*Article* **Insuring Water Supply in Irrigated Agriculture: A Proposal for Hydrological Drought Index-Based Insurance in Spain**

#### **M. Dolores Guerrero-Baena \* and José A. Gómez-Limón**

Water Environmental and Agricultural Resources Economics (WEARE) Research Group, Faculty of Law and Business Sciences, University of Córdoba, Puerta Nueva s/n, E-14071 Córdoba, Spain<EMAIL_ADDRESS>**\*** Correspondence<EMAIL_ADDRESS>Tel.: +34-957-212-205

Received: 11 February 2019; Accepted: 2 April 2019; Published: 3 April 2019

**Abstract:** In Mediterranean-climate regions, irrigated agriculture is especially vulnerable to the risk of hydrological drought and irrigators are particularly concerned about its negative effects. During a hydrological drought episode, irrigators receive insufficient water to meet their crops' water needs, giving rise to the so-called 'water supply gap'. In such circumstances, agricultural production and irrigators' incomes are considerably reduced. In order to minimize the negative effects associated with water supply gaps, a new index-based drought insurance scheme for irrigation is proposed, linked to the variable 'stock of water available in reservoirs'. The proposal, although tailored to Spain, could be easily adapted to other countries or regions because the features of hydrological drought risk are similar worldwide. It is expected that the proposed scheme will improve drought risk management in irrigated agriculture, stabilizing irrigators' incomes and guaranteeing the sustainability of irrigated agriculture in the face of global change.

**Keywords:** drought risk; water supply risk; irrigation insurance; water use; Spain

#### **1. Introduction**

Agriculture is an economic activity exposed to multiple risks that can negatively influence farmers' income and wealth [1–3]. Particularly notable among all these agricultural risks are production and market risks: production risks such as hail, frost or drought reduce the quantity and/or quality of agricultural production, while market risks are related to potential increases in input prices and decreases in agricultural product prices.

In Mediterranean-climate agricultural regions, such as in Spain, production risks associated with climatological factors pose a more serious threat than market risks [3,4]. This is because this type of climate is characterized by a high frequency of extreme weather events (e.g., hail or heat waves) and by an irregular rainfall pattern, severely affecting agricultural production. Rainfall variability leads to sharp fluctuations in crop yields under rainfed conditions, where precipitations are the only source of water. This is not necessarily the case with irrigated agriculture, where the availability of irrigation water can solve problems related to meteorological drought (below-average rainfall). In fact, irrigation techniques have been developed worldwide as a strategy for both increasing agricultural production and reducing drought-related production risks. It is only when meteorological droughts last for a long time and become hydrological drought episodes (instream flows and reservoir levels below normal) that irrigated agriculture is affected: the availability of water for irrigation is reduced, and thus irrigators cannot fully meet all their crop water needs. This situation, the so-called 'water supply gap', entails notable losses of production and income for irrigation farmers.

In recent years, the changing climate has generated growing concern among irrigators in Mediterranean regions about irrigation water reliability, and they are becoming increasingly aware of the consequences of water supply gaps. Negative predictions about rainfall (lower water availability) and temperatures (higher crop water needs) in these regions could even threaten the sustainability of irrigated agriculture [5]. Furthermore, other global changes, such as increasing pressure from economic activities (mainly industry and tourism), population growth, rising living standards and worsening pollution, are likely to exacerbate the vulnerability of many Mediterranean regions to water scarcity and drought [6,7]. In fact, several studies have found a widespread interest among irrigators in reducing the uncertainty associated with the high variability of their water allotments for irrigation. That interest is manifested in their willingness to pay to reduce the said uncertainty [8–10]. Therefore, there is an urgent need to design new risk-management instruments that could be implemented by irrigators to minimize the foreseen negative impacts of hydrological droughts on irrigated agricultural production [11,12]. Of all the risk management tools suggested to date, insurance has been highlighted as a particularly efficient economic instrument to cope with this risk [13], as it can protect irrigators against financial losses resulting from droughts. In this sense, insurance is viewed as a key instrument forming part of the policy-mix to be implemented in order to adapt irrigated agriculture to climate change; it improves the resilience of the irrigation sector, which is facing increasing uncertainty and vulnerability due to changing climate conditions and other relevant drivers [14]. However, although agricultural insurance is highly developed in first-world countries such as Spain [4,15], the risk of water supply failure in irrigated agriculture is not covered because multiple factors hinder the development of hydrological drought insurance schemes.

Within this context, the main objective of this paper is to contribute to the debate on how to support irrigators in managing hydrological drought risk, by proposing a new insurance scheme for irrigated agriculture capable of overcoming the problems that currently make this risk uninsurable. This scheme is tailored to Spain, as it provides a particularly interesting case study. For this purpose, we exhaustively analyze the factors that currently limit the development of this type of insurance and review previous studies that have proposed insurance schemes to cope with hydrological drought risk. This has allowed us to propose a technically feasible and commercially viable index-based insurance scheme that relies on a variable measuring the stock of water in reservoirs. This scheme is best suited to highly inertial water supply systems, i.e., those with a large water storage capacity compared to annual inflows and annual water demands, as is the case with many basins in Mediterranean and semi-arid developed countries. In order to illustrate how the proposed drought index-based insurance could work in a real-world setting, this paper provides a quantitative example in the Guadalquivir River Basin (southern Spain).

Finally, it is also worth commenting that although the proposed insurance scheme is tailored to Spanish irrigators, the appeal of the developed proposal extends beyond this national scope. Indeed, most of the factors hindering the implementation of hydrological drought insurance for irrigated agriculture are universal, and the technical features of the suggested index-based scheme are applicable in many other countries.

#### **2. Hydrological Drought Insurance as an Instrument for Adaptation to Global Change**

#### *2.1. The Risk of Water Supply Gaps in Irrigated Agriculture*

As commented above, when faced with a 'water supply gap', irrigators cannot fully meet all their crop water needs because there is not enough irrigation water available in reservoirs and instream flows (hydrological drought episode). The consequences of these water supply gaps in irrigated agriculture can be categorized in three areas: economic (micro and macro), social and environmental. First, from an economic point of view, water supply gaps lessen farmers' income, since they have to choose their crop mixes depending on the availability of water, reducing the irrigated area and/or growing less water-intensive and less profitable crops. On a macroeconomic level, a water supply gap

diminishes total agricultural production and value-added of the farming sector and the other related economic sectors, such as the food industry or the agricultural input sectors. In addition, since farmers tend to be risk averse [16], in situations of high uncertainty about the availability of water for irrigation, they tend to reduce the use of inputs [17] and make fewer investments [18]. Therefore, in these situations, economic decision-making by farmers is not efficient from a public welfare perspective.

Second, from a social point of view, water supply gaps in irrigated agriculture may cause a considerable decline in agricultural employment, considering that one hectare of irrigated land generates, on average, 3.8 times more employment than the equivalent rainfed area [19]. In some cases, recurrent water supply gaps may even lead to the abandonment of certain crops that are especially vulnerable to the risk of insufficient water supply, such as fruit groves, which are much more labor-intensive than annual crops.

Third, it is worth mentioning the environmental consequences of water supply gaps: when water allotments for irrigation are below normal, many farmers might illegally extract water resources (i.e., groundwater extractions beyond those legally allowed) to cover their unsatisfied water needs partially. This may aggravate the problems related to the overexploitation of aquifers and surface water bodies (rivers, lakes, etc.) [20,21].

Due to all the aforementioned negative consequences of water supply gaps in irrigated agriculture, it is obvious that uncertainty about the availability of water for irrigation constitutes a major production risk for irrigators in Mediterranean-climate agricultural regions (microeconomic impact). It also poses a problem to society as a whole, taking into account its macroeconomic, social and environmental impacts on social welfare [22]. Therefore, the implementation of proactive measures to adapt to global change in irrigated agriculture must be a priority, in order to effectively manage this climate risk and mitigate its wide-ranging negative impacts [23,24].

Like any other entrepreneur running a business, irrigators are responsible for managing the set of risks that they face. However, public administrations should support farmers' decision-making by establishing an integrated public-private framework (with public incentives) to promote the appropriate adoption of risk management instruments [25]. Adequate management of risks in irrigated agriculture helps stabilize farmers' annual income and also, as previously mentioned, has positive economic, social and environmental consequences for society as a whole.

The strategy traditionally implemented to minimize hydrological drought risk has been to build new water infrastructures such as reservoirs, in order to capture and store a greater amount of water, a strategy known as 'supply-side policy'. However, increasing demands for water and the economic and environmental difficulties involved in enlarging storage reservoirs have ultimately forced policy-makers to stop implementing this kind of supply-side measure. This situation is especially evident in many river basins in Mediterranean and semi-arid regions that are considered hydrologically 'closed' [26,27], where any new demand for water can only be met if the water rights of other users are reduced.

River basin closure is motivating the scientific community and policy-makers to explore new demand-side instruments to manage hydrological drought risk [28]. Among these measures, it is worth highlighting the modernization of irrigation systems, as well as the implementation of water markets, water banks, water option contracts and hydrological drought insurance [29–33]. Moreover, several drought indicators, such as the Standardized Precipitation Index (SPI) [34], the Standardized Precipitation Evapotranspiration Index (SPEI) [35], the Surface Water Supply Index (SWSI) [36] and the Joint Deficit Index for Droughts (JDI) [37], have been proposed; the aim is to calculate these indicators regularly in order to provide accurate information to stakeholders and decision-makers involved in drought management. Of all these demand-side instruments, the hydrological drought insurance has been the focus of very little analysis in the literature as a potential tool for managing hydrological drought risk in irrigated agriculture. Moreover, there are virtually no reports of this kind of insurance scheme having been implemented in a real-life setting.

Despite this scarce analysis and lack of real-world experience, during the last decade the use of agricultural insurance has been promoted by international institutions such as the World Bank, the Organization for Economic Cooperation and Development (OECD) and the European Commission (EC) as a powerful instrument for managing the risks facing farmers, allowing them to transfer the risk of agricultural production to an insurance company [12,38,39]. In this regard, these institutions suggest that it is necessary to insure some risks that are not currently covered, such as the risk of water supply gaps in irrigated agriculture. Furthermore, it is acknowledged that public incentives should be provided in order to encourage the widespread adoption of agricultural insurance as a useful tool for risk management in the farming sector. Public incentives may make this instrument more financially attractive for farmers and for insurance companies. As mentioned above, this public support is justified because adequate risk management in agriculture contributes to enhancing social welfare, through the improvement of agricultural production and the reduction of negative social and environmental impacts.

In this sense, the primary objective of hydrological drought insurance for irrigation should be to guarantee a stable level of income to farmers when their water allotments are lower than their needs. This type of insurance would thus act as a buffer against the microeconomic effects of a water supply gap, reducing uncertainty and allowing farmers to adopt more efficient economic decisions. Moreover, it is worth noting that by achieving this primary objective, this kind of insurance scheme would have a positive effect on rural development since the macroeconomic and social impacts of hydrological drought would also be minimized.

#### *2.2. Factors Hindering the Development of Hydrological Drought Insurance for Irrigators*

There are many factors that can explain why hydrological drought insurance for irrigators has not been implemented in a real-life setting [33,40,41]. Some of these factors relate to information asymmetries between the insurer and the insured, which also affect other types of agricultural insurance schemes:

Both problems could be overcome in a drought insurance scheme for irrigated agriculture by applying the appropriate measures. To this end, it would be necessary to: (a) segment potential insurers (irrigators) according to their level of exposure to the risk of water supply gaps (e.g., dividing them into sub-basin levels) in order to apply premiums corresponding to the risk actually borne by each farmer; (b) implement bonus-malus incentive systems that individually correct the premiums based on farmers' historical behavior; (c) establish deductibles; and (d) apply evaluation rules that audit farmers' behavior in the event of a loss. In any case, it is worth noting that all these measures generate additional transaction costs that affect the cost of the premiums.

*Water* **2019**, *11*, 686

Moreover, the design and implementation of hydrological drought insurance for irrigated agriculture present some specific problems that also need to be solved:

for this month), there is typically zero probability of a water supply gap in that hydrological year. Consequently, water needs for irrigation are certain to be fully met, even if the year is drier than average. Under this circumstance, no one would be willing to take out insurance covering the risk of cuts in water allotments that year. In these basins, cuts in water allotments would occur only after two or three years with rainfall significantly below the average. Thus, the lower the volume of water stored at the beginning of the hydrological year, the greater the probability of allotment cuts during the year and, therefore, the higher the willingness to take out a drought insurance policy. This calls into question the design of a single-year hydrological drought insurance scheme, similar to other agricultural insurance schemes, because the probability of loss occurrence in a given year is not a statistically independent phenomenon; the probability of a water supply gap differs depending on whether the hydrological year starts with stored water levels above or below the historical average. This fact points to the need for multi-year policies or specific contract conditions that encourage the renewal of policies year after year.

While these limiting factors pose a problem in the design and implementation of hydrological drought insurance for irrigation, some authors have begun to analyze how to effectively overcome them. Although the literature on this topic is scarce, several studies have made interesting proposals about how to address these factors. In the next section, we will review the most relevant contributions.

#### **3. Design Alternatives for Insuring Hydrological Drought Risk in Irrigated Agriculture**

There are several types of agricultural insurance schemes (see Table 1). A common classification is based on the risks covered [49]: (a) single-risk or single-peril insurance, for example, to cover the risk of production or income losses due to hail or frost; (b) combined or multiple-peril insurance, which protects against income losses due to several risks, such as hail, frost, and floods; (c) yield insurance, which covers any risk affecting crop yields (income), including all climatic and biological (pests) risks, as well as systemic risks not usually covered by single- or multiple-peril insurance (e.g., meteorological drought in rainfed agriculture); and (d) revenue insurance, covering any risk impacting yields (income losses) or prices (drops in output prices or rises in input prices) in order to guarantee a predefined revenue for insured farmers.

**Table 1.** Types of agricultural insurance schemes 1.

1 The options included in the proposed hydrological drought insurance are marked in italics.

Agricultural insurance can also be classified according to how the damages suffered in the farms are assessed: (a) on-field loss assessment insurance (commonly known as 'traditional insurance'); and (b) index-based insurance (see below). In this sense, it is worth highlighting the study by Ruiz et al. [48] who proposed an in-field income loss assessment insurance in Spain to cover the risk of hydrological drought in irrigated agriculture, very similar to the other agricultural insurance schemes available in this country. However, it should be pointed out that the use of this type of loss assessment for cases of systemic risks (such as water supply gaps) has been criticized because it is difficult and expensive to implement when a large number of assessments must be carried out by qualified experts at the same time [46]. Moreover, this scheme proposal fails to address most of the aforementioned issues related to hydrological drought insurance. In fact, the only problem explicitly mentioned is that of water trading, with the assumption that the implementation of this insurance scheme would involve the prohibition of any water transfers by the irrigators insured; this requirement would be difficult to enforce in a real-life setting because of the existence of informal water markets.

In index-based insurance schemes, damage assessment is carried out indirectly through a variable or 'index' strongly correlated with the contingency covered (income or yield losses), without the need for individual loss declarations and in-field assessments. For example, an insurance scheme to cover drought risk in rainfed agriculture could be based on a cumulative rainfall index. Different types of index-based insurance schemes include the following [50]:

Although traditional agricultural insurance (in-field assessment) is the most widespread worldwide, index-based insurance offers a series of advantages that considerably reduce the cost of the premiums [38,46,51]:

However, the major drawback of index-based insurance is 'basis risk'; that is, the risk related to possible differences between the indemnity (calculated according to the index) and the actual loss suffered by the farmer. It may happen that when a farmer experiences a loss on his/her farm, the indemnity payment, based on the exogenous index, is either far above or below the actual loss. This situation may occur if there is not a strong positive correlation between the index measured and the loss experienced. Accordingly, it is evident that the main condition that a variable must meet to be considered as an index is a high correlation with the insured loss, in order to reduce basis risk. Other relevant requirements of index-based insurance are the following [52]:

The literature offers few proposals of index-based insurance schemes to cover the risk of hydrological drought in irrigated agriculture. In Australia, Zeuli and Skees [53] designed a rainfall index contract, compatible with transactions in a spot water market. However, the authors did not address the imperfect correlation between the rainfall variable used as the index and the risk of hydrological drought (actual farm losses).

For Mexican irrigators, Leiva and Skees [54] proposed a hydrological drought index-based insurance considering the variable 'inflow accumulation', also demonstrating that index-based insurance is fully compatible with water markets. Similarly, in Spain, Maestro et al. [55] have proposed an index-based insurance scheme to cover the risk of water supply failure in irrigation districts, which is based on reservoir inflows. However, this proposal is suitable only for water supply systems with low inertia (i.e., where reservoirs can only store enough water to meet users' needs for one year or less), where situations of hydrological drought cannot be forecasted at the beginning of the hydrological year. Nevertheless, this is not the case for most of the river basins in Mediterranean and semiarid developed countries with a high risk of supply gaps, where storage capacity is usually large enough to face long (interannual) drought periods.

The most recent proposal is that developed by Maestro et al. [56] for California, which suggests the use of an index currently calculated by the state's water management authority, aimed at estimating the availability of water in the basin to meet users' demand. The value of this index is calculated in early May every year (at the beginning of the irrigation season), accounting for the value of the same index in the previous year and the forecasted runoff for the current hydrological year. As the value of the index is affected by its own value in the previous year, there is a high risk of intertemporal adverse selection. To minimize this problem, the authors propose three alternative insurance designs: (a) 'early bird' insurance (the product must be bought one year before the irrigation season begins); (b) variable premium insurance; and (c) variable deductible insurance.

Finally, it should be noted that agricultural insurance can also be classified depending on the role of public authorities. If the function of the public sector is purely regulatory and in defense of competition, the agricultural insurance system is private. However, mixed public-private systems are also common. Under these public-private partnerships, agricultural insurance is part of the agricultural policy and the state creates the regulatory framework to promote this risk management instrument through subsidies and public reinsurance. The state is motivated to do so in view of the social benefits derived from its implementation [3,38,39].

#### **4. Proposal for a Hydrological Drought Index-Based Insurance for Irrigation in Spain**

Under Spanish law, all water resources are in the public domain, and consequently, any private water use (e.g., irrigation or industrial uses) is subject to administrative authorizations or legal concessions (water use rights), which are granted by the River Basin Agencies (RBAs) for extended periods (from 25 to 75 years). However, it is worth differentiating between the volumes set in these concessions or water rights, which theoretically are fixed in order to meet all users' needs, and water effectively delivered to rights holders (e.g., irrigators) each year (water allotments), which depends on the available water stored in reservoirs in the current hydrological year. Thus, the water volume specified in the water rights is only actually available for irrigators in average or wet hydrological years, when total water availability is higher than the aggregated water rights granted. In cases of resource scarcity (hydrological drought years), water resources are prioritized, and domestic water users are served first. For irrigation and other economic uses, the remaining water resources available are allocated proportionally. Thus, irrigators have to deal with interannual variability in their water allotments; they may sometimes receive a much smaller volume than that established in their concessions, and in some years may even receive no allotment at all, generating 'water supply gap' situations. In this regard, a new insurance scheme to cover this type of risk could play a fundamental role in enhancing irrigators' risk management in order to stabilize agricultural incomes.

The Spanish Agricultural Insurance System (SAIS) is one of the most well-developed and successful systems worldwide [4,15]. The maturity of the SAIS is evidenced by its penetration rates: in 2017, more than 234 thousand agricultural policies were contracted, covering 13.8 million hectares (36.9% of the total crop production area), insuring a capital of 9.93 billion Euros (34.6% of the total agricultural production value) [57]. Much of the success of the SAIS is due to the reduction in commercial insurance premiums thanks to the subsidies granted by the public sector. This public support averages 40% of the cost of the policies [57] and, in some insurance lines, reaches up to 65%, the maximum allowed by the European Union. Configured through a public-private partnership [58], the insurance policies offered cover multiple perils in many crop production, including all climatological risks (e.g., hail or frost, and even drought in rainfed crops). However, as previously mentioned, irrigated agriculture remains unprotected against the risk of irrigation water supply gaps.

In this paper, a hydrological drought index-based insurance scheme for irrigated agriculture is proposed as the most suitable insurance design, given the advantages of index-based insurance over traditional insurance, as explained in the previous section. The benefits derived from the lower management and administration costs and greater transparency of this type of insurance outweigh the shortcomings stemming from the basis risk, especially when the index chosen meets the aforementioned requirements.

Another relevant factor justifying the choice of index-based insurance to cover the risk of hydrological drought is related to the procedure followed in Spanish RBAs to set annual water allotments. In Spain, irrigators are represented in the Commissions on Reservoir Water Releases (*Comisiones de Desembalse*). In April each year (at the beginning of the irrigation season, when reservoirs reach their highest storage levels), the Commissions propose to RBAs the water allotments to be set for the irrigation season. RBAs have traditionally considered these proposals, taking into account the active farmers' lobbying activities. The possibility that the irrigators (potential insured parties) may have influenced the probability of loss occurrence (water allotments lower than water rights) made the risk of water supply gaps uninsurable (supply gaps could be artificially generated).

Nevertheless, since the approval of the Basin Drought Plans (BDPs) in 2007, RBAs' annual water allocation decisions must adhere to the action protocols established for that purpose, at least in theory (in practice, these guidelines have not always been fully implemented). Indeed, BDPs, in accordance with the requirements set by the European Water Framework Directive, have established a technical procedure for the distribution of available water resources based on a system of possible water availability scenarios (normality, pre-alert, alert and emergency), minimizing the previously-existing arbitrariness (allocation decisions swayed by pressure from lobbying groups). However, despite the existence of these action protocols, in cases of water scarcity, there is still a certain degree of arbitrariness in the allocation of water [40]. This means that some doubts remain as to whether water supply gaps in Spanish River Basins are an insurable event. This justifies the design of an index-based insurance scheme relying on a transparent and non-manipulable indicator that is highly correlated with the losses to be insured (actual and accidental supply gaps). In this regard, as stated by Brown and Carriquiry [59], Leiva and Skees [54] and Maestro et al. [56], an appropriate index for hydrological drought insurance for irrigation should be based on the river flow accumulation or, as with the approach adopted in this paper, the stock of water available in reservoirs.

In addition, we propose that this hydrological drought insurance for irrigation should be included in the SAIS, with a level of public support similar to the rest of the agricultural insurance schemes in Spain. The SAIS has effectively addressed the problem of covering systemic risks, such as drought in rainfed crops, using private coinsurance and public reinsurance [58]. Thus, it may be deduced that the risk of water supply gaps in irrigated agriculture could also be covered through a coinsurance pool and a public reinsurance program, guaranteeing the viability of this scheme.

Below, we discuss the elements of the proposed insurance contract, following the guidelines summarized in Table 2.

Regarding the *material elements* of the contract, the following design options are proposed:

• *Indemnity* (*I*): this is the estimated cash amount equivalent to the value of the damages caused by the loss. As it is an index-based insurance scheme, the calculation of the indemnity would not require in-field damage assessment. It would be calculated automatically, after determining the value of *SW*, as follows:

$$I = \begin{cases} 0 & \text{if } \quad SW \ge T \\ \text{IC} \times (1 - DED) \times f(SW) & \text{if } \quad T > SW > L \\ & \text{IC} \times (1 - DED) & \text{if } \quad SW \le L \end{cases} \tag{1}$$

As can be seen, the indemnity (*I*) depends on the deductible (*DED*, the percentage of the insured capital that the farmer is responsible for covering) and on the intensity of the loss, quantified by the function *f(SW)*. As already pointed out, according to the indemnity principle, the insurance should only cover the actual damage suffered; under no circumstances should the insured party receive an additional benefit. In this sense, to ensure compliance with this principle, and also in order to lower the cost of the premium, a deductible equal to 30% of the *IC* is proposed. Regarding the function measuring the intensity of the loss, it could be assumed to be linear: *f(SW) = (T* − *SW)/(T* − *L)*. This simplified way of measuring the intensity of the loss entails the assumption that the marginal value of the water allotment remains constant despite the volume of water allotted (i.e., the value of one cubic meter of irrigation water is the same regardless of the scarcity of the resource). In any case, other more accurate functional forms assuming an increasing marginal value of water could be used alternatively in order to measure the intensity of the loss. • *Premium*: an annual policy with an annual premium is proposed.

**Table 2.** Main features of the proposed hydrological drought index-based insurance in Spain. **Type of Element Element Main Feature 1**

1 *T*: minimum value of *SW* that allows the River Basin Agency (RBA) to approve full water allotments; *L*: lowest value of *SW* that allows the RBA to approve non-zero irrigation allotments; *DED*: deductible as a percentage of the insured capital.

With regard to the *formal elements* of the insurance contract, the following design options are proposed:

• *Contract term*: we propose that the contract is valid from the formalization of the policy during the pre-established contracting period and the corresponding payment of the annual premium (during the month of September every year), to 1 May of the following year, after the calculation of the *SW* index. However, the policy should be extendable for subsequent annuities. In addition, in order to minimize the existence of intertemporal adverse selection, if a pre-alert, alert or emergency situation occurs during the contracting period (September), only policies taken out in previous years would be eligible for renewal. The inclusion of new insured irrigators or modifications in the insured capital due to changes in the crop patterns would only be possible during the contracting period under normal hydrological conditions.

• *Claim*: as it is an index-based insurance, the irrigators do not have to inform the insurer about the occurrence of a loss. On 1 May, the value of the *SW* index is calculated and, if this value is lower than *T*, the compensation to be received by each insured irrigator is automatically determined.

Finally, in relation to the *personal elements* of the insurance contract, the following options are proposed:

#### **5. Illustrative Example**

The explanation of the proposal provided above is now complemented with a quantitative example illustrating how the drought index-based insurance proposed could work in a real-world setting. This example is aimed at further supporting the idea that this kind of insurance would be easily implementable, thereby enhancing the resilience of irrigated agriculture (the impact of droughts could be minimized).

For this purpose, the Guadalquivir River Basin (GRB), located in southern Spain, is taken as a case study. The stock of water available in reservoirs in the GRB at the end of April (index *SW* proposed above for insurance purposes) has already been modeled by Pérez-Blanco and Gómez [33], who reported that the Weibull distribution is the function that best fits historical data:

$$f(SW; \lambda, k) = \frac{k}{\lambda} \left(\frac{SW}{\lambda}\right)^{k-1} e^{-\frac{\xi W^k}{\lambda}} \tag{2}$$

$$F(SW; \lambda, k) = 1 - e^{-\frac{\text{Spl}^k}{\lambda}} \tag{3}$$

where, *f*(*SW*) and *F*(*SW*) are, respectively, the probability density function (PDF) and the cumulative distribution function (CDF) for the water stored in reservoirs (*SW*) expressed as a percentage of the maximum value in the historical data, *k* is the shape parameter and *λ* is the scale parameter of the distribution. More specifically, for the sub-basin of *Regulación General*, this PDF was fitted using the values *k* = 1.484 and *λ* = 0.347, as illustrated in Figure 1.

According to Basin Drought Plans (BDPs), the water storage capacity in reservoirs within the sub-basin of *Regulación General* is 4718 Mm3, although the historical maximum volume of water stored on 30 April is 4546 Mm3 (*SW* = 100%). Average inflows are 3799 Mm3/year, although there is a large interannual variability (standard deviation = 2808). From this stored water, a demand of 2034 Mm3/year must be met, most of it (94%) for irrigation purposes (293,762 irrigated hectares using an average of 1909 Mm3 annually). Hydrological drought events in this sub-basin are determined on the basis of the volume of water stored in reservoirs at the beginning of irrigation season (1 May), using the following thresholds:

**Figure 1.** Weibull CDF for water stored in reservoirs in the sub-basin of *Regulación General* (GRB).

This drought management arrangement means that the minimum stock of water in reservoirs on 30 April that would allow the RBA to approve full water allotments for irrigation (*T*) is *SWT* = 75%; in cases when *SW* < 75% it is expected that these allocations will be cut, which would thus lead to losses in farmers' gross margins. The threshold allowing the RBA to provide non-zero water allotments (*L*) is *SWL* = 5%, that is, when *SW* < 5% 'total' losses are expected to occur since only rainfed crops could be included in the crop mix.

Under this framework of uncertain irrigation water allotments, consider farmer X, who manages an irrigated farm of 50 hectares located in the Genil-Cabra irrigation district, and whose water resources are those provided by the RBA (surface water resources). When full water allotments are provided, he/she opts for the following crop-mix: olive (40% of farm area), cotton (30%) and corn (30%). However, under hydrological drought conditions (water allotments are cut), he/she must change the crop-mix in order to meet irrigation water needs with the water available. In fact, in extreme cases where water allotments are set at zero, he/she must choose a rainfed crop-mix, maintaining olive under rainfed conditions, and substituting irrigated crops with common rainfed options (wheat and sunflower in the case of the Genil-Cabra irrigation district). Table 3 shows the annual gross margin of farm X with full water allotment and under rainfed conditions (zero water allotment) based on average data from this irrigation district [60]. The difference between the two sets of figures (783 €/hectare, totaling 39,128 Euros for the whole farm area) is an estimate of the value of the annual full water allotment, i.e., the insured capital (*IC*). Similar assessments could be done for any other farm willing to be insured.

Consider that farmer X formalizes the proposed insurance every year during the contracting period (month of September), paying the annual premium set by the insurer. Note that this premium to be paid to the insurer is not fixed in this example since this would require the use of actuarial and financial methods that are beyond the scope of this paper. Thus, the farmer is able to claim an indemnity in the event of losses, calculated according to the value of the index *SW* on 1 May. In this sense, several scenarios are possible according to expression (1):

**Table 3.** Gross margins with full and zero water allotments. Assessment of insured capital (*IC*) 1.

1 Data obtained from Guerrero-Baena et al. [60] for the Genil-Cabra irrigation district.

Of course, it is true that the indemnities calculated following expression (1) may not be exactly the same as the actual losses suffered by the farmers due to allotment cuts (basis risk), but estimated and actual losses are expected to be similar. In any case, as pointed out earlier in this paper, this is the only drawback of index-based insurance schemes, and it is outweighed by the long list of advantages that reduce the cost of the premiums (e.g., no in-field damage assessment required, no room for conflict between farmers and insurers in indemnity assessment, and moral hazard and adverse selection problems are minimized).

#### **6. Conclusions**

Due to global change, the failure to guarantee water supply for irrigation is an increasingly pressing risk in Mediterranean-climate regions [61,62]. The severe consequences that hydrological droughts may entail for irrigated agriculture are prompting policy and academic debates about how to effectively manage this type of risk. As supply-side instruments, based on the construction of new water infrastructures, are no longer a viable option in most agricultural regions with mature water economies (i.e., closed basins), the development of new demand-side instruments is needed. In this regard, hydrological drought insurance is a promising instrument for managing the risk of water supply gaps in irrigated agriculture.

In this paper, hydrological drought insurance indexed to the variable 'stock of water available in reservoirs' has been proposed to cover the risk of water supply gaps in irrigated agriculture. This new insurance scheme would be a viable option, since it minimizes many of the problems associated with traditional agricultural insurance, such as adverse selection and moral hazard. It also reduces the cost of the premium because there is no need to make in-field damage evaluations in the event of drought losses. Moreover, the proposed index-based insurance solves certain limitations related to arbitrariness in RBAs' water allotments decision-making. Likewise, the proposed insurance scheme allows this

strategy to be combined with other risk management instruments, such as spot water markets and water banks.

The implementation of the proposed insurance in a real-life setting requires additional studies from a supply-side perspective, in order to calculate the commercial premium of the insurance scheme using actuarial and financial methods. Also, further studies from the demand perspective are needed to determine the potential acceptance of this risk management instrument by irrigators through their willingness to pay for such an insurance policy. The comparison of the results of supply- and demand-side studies will allow an exploration of the commercial viability of the scheme proposed. If a significant share of irrigators has a willingness to pay greater than the commercial premium, then the insurance would be viable without the need for public subsidies. In any case, there will be a percentage of irrigators whose willingness to pay is lower than the commercial premium and, therefore, their decision will be to not take out the proposed insurance. Obviously, the existence of public subsidies (and thus cheaper premiums) would mean that a higher percentage of irrigators will choose to take out these insurance policies. In light of this situation, it would be worth analyzing the heterogeneity of irrigators' preferences regarding hydrological drought insurance and the impact of public subsidies on the insurance adoption rate. This information would help support efficient policy decision-making regarding this agricultural insurance scheme.

All the studies outlined above indicate the future lines of research to be developed in order to implement this new insurance scheme and, consequently, improve the economic, social and environmental performance of irrigated agriculture while guaranteeing its resilience in the face of global change.

**Author Contributions:** M.D.G.-B. and J.A.G.-L. contributed equally to the conceptualization, development, writing, and editing of the manuscript.

**Funding:** The authors acknowledge the financial support from the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (ERDF) through the research project IRRIDROUGHT (AGL2018-48080). These funding institutions had no involvement in the conduct of the research nor the preparation of the paper.

**Acknowledgments:** The authors are particularly grateful to the anonymous reviewers and the editors for their very helpful comments on previous versions of the paper.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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**2. Phage library and sensitivity**

Availability of a library with a range of therapeutic bacteriophages is the foundation for the success of phage therapy. Bacteriophages are observed to show off a narrow to broad host specificity [30–32].  For a safe medical use of the phage, genes of toxins, antibiotic-resistance, and multidrug-resistant genes should not be present in the genome of the phage', whilst the lytic phage must have the potential to kill the multidrug-resistant bacteria such as *Acinetobacter baumannii, Enterococcus, Escherichia coli*, *Klebsiella pneumoniae, Pseudomonas aeruginosa,* and *Staphylococcus aureus* [34–38]. Confirmation of phage-sensitive bacteria is the prerequisite for

### **Figure 1.**

*Transmission electron micrograph (TEM) bacteriophages infected Bacillus. Note the capsid, nucleic acid, tail fibers [2].*

### **Figure 2.**

*A magnified portion of a Bacillus infected with bacteriophages is seen in this Transmission electron micrograph (TEM). The capsid, nucleic acid, tail fibers should all be noted [2].*

initiation of antibacterial therapy. First, the bacterium inflicting the infection in the patient has to be received and identified; second, phage in the library that are effective against the pathogenic bacterium need to be screened, and selected for therapeutic use. If there are specific phage or cocktails of phage in the library that kill the identical bacterial strain, are preferred for the therapy [39, 40]. Reports have shown that phage cocktail preparations would possibly decorate bactericidal efficacy and additionally limit the chance of the emergence of phage-resistant isolates for the duration of the therapy [30–32]. Bacteriophages (phage) have a unique sorting mechanism for their target bacteria since they have a number of necessary characteristics such as inherent natural specificity, ease of use of cell signalling and receptor molecules, and simple phage or phage-derived product processing. These characteristics make bacteriophages more suitable for use as bacterial detectors and

### **Figure 3.**

*TEM showing* V. vulnificus *(VV-1) bacteriophage particles (Bp) within the cytolyzed cytoplasm (c) of the host cell bacterium* Vibrio *sp. Note the presence of phage within the cytoplasm [10].*

### **Figure 4.**

*Electron micrograph showing* V. vulnificus *(VV-2) bacteriophage (Bp) particles within the lysed cytoplasm (c) of the host cell bacterium* Vibrio *sp [10].*

as aids in the detection of human pathogens. Phage-based systems are currently being used to diagnose *Staphylococcus aureus, Mycobacterium tuberculosis, Bacillus anthracis*, and *Yersinia pestis* in the clinical setting.

### **3. Production and purification of bacteriophages**

Appropriate cultural media used for the growth, proliferation, and fermentation process of cells of bacterial hosts of bacteriophages for therapeutic applications. The fundamental processing of bacteriophages consists of several stages of purification (**Table 1**). These are broth specifications with low-speed centrifugation or filtering, cell removal, and cellular debris. Chloroform will be added to the lysate to form lysis and release the phage from non-lytic cells. Specified bacteriophage lysate can be used in many applications but clinical applications require additional purification of the lysate to eliminate endotoxins, metabolites, hydrophilic O-specific polysaccharide, phosphorylated oligosaccharides, phage, bacterial cells, and other wastes. Impure preparations of bacteriophages should not be used for injection [41, 47]. Occurrences of such as endotoxins in the bacteriophage preparations may aggravate

**Table**

**1.**

the immune system responses viz. fever, leucocytosis, leukopenia, fatal endotoxin shock, can open up macrophages, and release inflammatory mediators such as TNFα, IL-6, and IL-1 and cause serious side effects. The final limit of endotoxins recommended for intravenous administration is 5 Endotoxin Unit (100 pg) (EU)/ kg. The elimination of endotoxin from bacteriophages is a multidisciplinary procedure. Two-Phase fluid extraction processes viz. LPS affinity resins, ultrafiltration, and chromatographic methods for removal of well-charged endotoxin proteins. Ion exchange, size exclusion chromatography, interaction with histidine or polymyxin B, and anion-exchange chromatographic exchange were methods used for further phage purification. Diafiltration was used to exchange phage particles from lysate media with a suitable buffer. Cesium chloride density gradient centrifugation, ultracentrifugation, PEG precipitation, and ultrafiltration used for the removal of endotoxins and purification of phages. Bacteriophage CM8-1/SJT-2 stock solution mixed with bacterial culture in the mid-log phase spread on a double-layer agar Petri plate, Sodium magnesium (SM) buffer added after the bacteriophage had grown of the entire Petri plate and placed on a shaker at 120 rpm/min for 2 hours. The SM-bacteriophage lysate solution was filtered through a 0.22 μm filter, PEG8000 (10%) was once added to the bacteriophage stock solution, left the solution overnight at 4°C, and centrifuged at 10,000 g for 10 min to obtain bacteriophage precipitation [46]. By contrast, T4 bacteriophages had prepared by using a stepwise gradient of anion-exchange quaternary amine (QA) CIM column and NaCl elution buffer [48, 49]. Purified bacteriophages of *Mycobacterium smegmatis* and *S. aureus* were prepared by using columns such as QA CIM and diethylamine (DEAE) while QA and DEAE CIM columns, were employed to remove endotoxins from pre-purified phage preparations by using the Endotrap HD column (Cambrex BioScience, EndoTraptm Blue) [50]. Enterococcal bacteriophages, viz. ENB6 and C33 were prepared from the raw wastewater by using caesium chloride density gradient centrifugation and stored at 4°C. Thus, there was a great deal of variation in the elution conditions between the different phages. A common operating procedure for varied phage preparations, storage, and transport is lacking [51]. Standard operating procedure (s) for large scale-bacteriophage cultivation, isolation, titration, and purification and to produce sufficient plaqueforming units of bacteriophages (PFUs) per milliliter of *Pseudomonas, Klebsiella, and Serratia* were established [41, 52]. Such a universal process and production of the final phage preparations for use could reduce endotoxins, might be pivotal in alleviating fears and the phage therapy shall be readily accepted all the world over.


**Frankincense (Heaven's Gift) — Chemistry, Biology, and Clinical Applications**

Farid A. Badria

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/59006

## **1. Introduction**

Frankincense, gold, and myrrh were the three gifts from the wise men (the Magi, or the three kings) brought from the East to celebrate the birth of baby Jesus Christ (Bible, Matthew 2:11) According to the Christian belief (Botros et.al. 2003). Nine compounds with immunostimulant and antiviral activity were isolated from the oleogum resin of frankincense (*Boswellia carterii* Birdwood). The frankincense essential oil (3%) found to contain monoterpenes (13.1 %), sesquiterpenes (1 %), and diterpenes (42.5 %). Both isolated oil and resins exhibited strong immunostimulant activity. Badria et al. (2003) proved that the of boswellia, curcumin, and glycyrrhizin exhibited the highest activity against *Herpes simplex* virus. However, boswellia extract retained a significant increase in both FEV1 and PEFR (P ≤ 0.05 and ≤ 0.01 respectively) with no significant change in FVC in the severe persistent bronchial asthma (Badria et. al. 2003). Boswellia-Curcumin preparation was investigated clinically for treatment of knee osteoar‐ thirits (Badria et. al. 2002). Meanwhile, glycyrrhizin, curcumin and *Boswellia carterii* formula exhibited a hepatoprotective effect and used as endogenous interferon inducer, demonstrating that two phases of the induction of IFN in serum takes place; the induced IFN was regarded as IFN-γ. This induction may be followed by activation of macrophages and augmentation of natural killer (NK) activity through the action of the induced IFN (Badria 2001). This combi‐ nation was successfully tried in a clinical study as endogenous interferon inducer for treatment of hepatitis C (Badria 2001).

#### **1.1. Historical Background and Folkloric use (Ryman, 1997)**

The earliest recorded use of frankincense is found in an inscription on the tomb of a 15th century BC Egyptian queen named Hathsepsut who exported it from Punt's Land "Somalia" to prepare her cosmetics, skin care lotions, and perfumes. Ancient Egyptians burned frankincense as

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

incense in religious ceremonies and rituals. They used it also in embalming and mummification of dead bodies. As an evidence for incense burning, burners with a shape of long handle spoon from the old kingdom in ancient Egypt have been found in which the resin was burnt to provide aromatic warmth on the braziers of their homes in chilly weather. The ancient Egyptians used to grind the resin after charring to provide the black powder that called "Kohl" which used in manufacturing of distinctive eyeliner as seen in a lot of Egyptian art figures. This is the cause of employment of frankincense in the worship of the Egyptian sun God "Horus", a primordial symbol for who was the sacred "All-seeing" eye that burned with judgment.

The use of resin as incense was not confined to ancient Egyptians but extended to Babylonians, Greeks, Romans and Assyrians. It was Herodotus who reported that "in ancient Babylon, 1000 talents weight was offered every year during the feast of Bel, on the great altar of his temple". Nero burnt frankincense by the ton. Romans burnt large quantities of the resin along the routes of the Roman triumphs or victory parades.

The frankincense was a kings' gift, it is said that the queen of Sheba presented a large amount of frankincense, brought by her from Yemen, to the wise King Solomon in 1950 B.C. The original use of the word "incense" was to descripe the aromatic smoke that produced from a substance upon burning, the term has been gradually limited now to frankincense. Interest‐ ingly, several myths surrounded the harvest of frankincense; it was believed that valleys where frankincense is collected were guarded by huge horrible winged creatures and red poisonous snakes that attack any one trying to touch the frankincense tree. These mysterious stories tells also that the mythological bird Phoenix, when ready to die, makes its final nest from frankin‐ cense and *Cassia* and there; its spirit ascends to the heavens with the perfume of this sacred herb (Miller and Morris, 1988).

The use of camels in transport flourished frankincense trade in the 11th century BC. One of the oldest international trade routes, the frankincense route, runs parallel to the Red Sea outseting from Yemen through a distance of almost 3,400 Km towards Palestine. Such huge trade made Pliny the Elder, the first century Greek Writer, to claim that "the control of the frankincense trade had made the South Arabians the richest people on earth".

Frankincense is one of the crude drugs that are heavily associated with religious rituals and cults; it was thought that incense smokes carried the prayers to the heaven. In Judaism, frankincense was one of the four sweet scents used in compounding the ceremonial incense of Jewish temples. As a part of the meet offering as well as the chew-bread on Sabbath day, pure frankincense was utilized. It was preserved with many other spices in great chamber of the GOD house at Jerusalem.

In Christianity, Frankincense occupied a distinguished place; it was mentioned 22 times in the Bible. According to the Christian belief; gold, frankincense, and myrrh were the three gifts from the wise men (the Magi, or the three kings) brought from the East to celebrate the birth of baby Jesus Christ (Bible, Matthew 2:11). Frankincense enters into the composition of incense now used in the Christian churches.

Frankincense was one of the most prized and costly substance in the ancient world, worth more than its weight in gold. Dioscorides and others mentioned the therapeutic use of the resin Frankincense (Heaven's Gift) — Chemistry, Biology, and Clinical Applications http://dx.doi.org/10.5772/59006 5

**Figure 1.** *Boswellia carterii* Birdwood Tree; Frankincense

incense in religious ceremonies and rituals. They used it also in embalming and mummification of dead bodies. As an evidence for incense burning, burners with a shape of long handle spoon from the old kingdom in ancient Egypt have been found in which the resin was burnt to provide aromatic warmth on the braziers of their homes in chilly weather. The ancient Egyptians used to grind the resin after charring to provide the black powder that called "Kohl" which used in manufacturing of distinctive eyeliner as seen in a lot of Egyptian art figures. This is the cause of employment of frankincense in the worship of the Egyptian sun God "Horus", a primordial

The use of resin as incense was not confined to ancient Egyptians but extended to Babylonians, Greeks, Romans and Assyrians. It was Herodotus who reported that "in ancient Babylon, 1000 talents weight was offered every year during the feast of Bel, on the great altar of his temple". Nero burnt frankincense by the ton. Romans burnt large quantities of the resin along the routes

The frankincense was a kings' gift, it is said that the queen of Sheba presented a large amount of frankincense, brought by her from Yemen, to the wise King Solomon in 1950 B.C. The original use of the word "incense" was to descripe the aromatic smoke that produced from a substance upon burning, the term has been gradually limited now to frankincense. Interest‐ ingly, several myths surrounded the harvest of frankincense; it was believed that valleys where frankincense is collected were guarded by huge horrible winged creatures and red poisonous snakes that attack any one trying to touch the frankincense tree. These mysterious stories tells also that the mythological bird Phoenix, when ready to die, makes its final nest from frankin‐ cense and *Cassia* and there; its spirit ascends to the heavens with the perfume of this sacred

The use of camels in transport flourished frankincense trade in the 11th century BC. One of the oldest international trade routes, the frankincense route, runs parallel to the Red Sea outseting from Yemen through a distance of almost 3,400 Km towards Palestine. Such huge trade made Pliny the Elder, the first century Greek Writer, to claim that "the control of the frankincense

Frankincense is one of the crude drugs that are heavily associated with religious rituals and cults; it was thought that incense smokes carried the prayers to the heaven. In Judaism, frankincense was one of the four sweet scents used in compounding the ceremonial incense of Jewish temples. As a part of the meet offering as well as the chew-bread on Sabbath day, pure frankincense was utilized. It was preserved with many other spices in great chamber of

In Christianity, Frankincense occupied a distinguished place; it was mentioned 22 times in the Bible. According to the Christian belief; gold, frankincense, and myrrh were the three gifts from the wise men (the Magi, or the three kings) brought from the East to celebrate the birth of baby Jesus Christ (Bible, Matthew 2:11). Frankincense enters into the composition of incense

Frankincense was one of the most prized and costly substance in the ancient world, worth more than its weight in gold. Dioscorides and others mentioned the therapeutic use of the resin

trade had made the South Arabians the richest people on earth".

symbol for who was the sacred "All-seeing" eye that burned with judgment.

4 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

of the Roman triumphs or victory parades.

herb (Miller and Morris, 1988).

the GOD house at Jerusalem.

now used in the Christian churches.

in the treatment of skin disorders, in ophthalmology, hemorrhages and pneumonia. Pliny the Elder (1st century) mentions it as antidote to hemlock (Encyclopedia Britannica web site). The Iranian physician Avicenna "Ibn Sina" (10 th century) in his book "El-Kanon Fi El-Tibb" thought that frankincense was useful in many disorders and disease as fever, gastric disorders and tumors. *B. carterii* is used almost for everything in China.. In Ayurvedic medicine (Kapoor, 1990) the resin is prescribed in chronic lung diseases, diarrhea, dysentery, pulmonary diseases, menorrhea, dysmenorrhea, syphilis, piles, and liver disorders. The oil extracted from the gum resin is prescribed with a demulcent drink in gonorrhea. A paste made of the gum resin with coconut oil or lemon juice is applied to ulcers, swellings, boils, and ringworm (Chopra *et al*., 1956). The antiseptic action of the resin encourages healing so it is used to treat ulcers and wounds. The resin is used nowadays in manufacture of incense, and as ingredient in plasters and fumigating pastilles (Wallis, 1967). It is also important as a scent and a fixative in perfum‐ ery industry. The recommended dosage of frankincense in inflammatory or bronchoconstric‐ tive conditions is 400 mg three times daily. The frankincense is one of the safest herbals. Toxicity studies of *Boswellia* in rats and primates showed that LD50 was established at more than 2 g/kg (Murray, 1995).

Frankincense is an oleogum resin obtained through a deep longitudinal incision the trunk of the Boswellia tree.The milk-like juice which exudes is hardened by exposure to the air. In about three months, the resin attains the required degree of consistency, hardening into yellowish tears (Fig. 2). (Miller and Morris, 1988).

Even the frankincense collected from the wounds is graded into several grades (Singh and Atal, 1988) of which are, Grade I (Tears); which is the best and most carefully selected grade of white color; Grade II (Reddish) that is mixed white and reddish quality which contains some particles of the bark; and Grade III (Dust and Sifting). The latter grade, because of its low price and finer size, is the most suitable quality for distillation of volatile oil. The harvest lasts from May till the middle of September, when the first shower of monsoon rain puts a close to the gathering for that year. Once the collection season is completed, the raw frankincense is allowed to cure for three months before being sold. It is stored on the floor of dry caves during

**Figure 2.** Oleogum Resin Tears of *Boswellia carterii* Birdwood

that period of maturation. The resin occurs in small tears (Fig. 2) varying from 0.5 to 3 cm in length and usually ovoid, pear-shaped, or club-shaped. It is usually of pale yellowish color, frequently with a greenish, bluish or reddish tinge, semi-translucent and covered with a dull white dust, the surface of the tear being dull even after the dust has been removed. They are brittle and internally are opalescent and translucent, the fractured surface being dull and waxy. The drug has a fragrant, balsamic odor and an aromatic, slightly bitter taste, and softens to a plastic mass when chewed. The oleogum resin when triturated with water yields a whitish emulsion (Wallis, 1967).

After such presentation of the deep-rooted usage of frankincense, one can really understand how frankincense is a truly Kings' gift. The oleogum resin of different *Boswellia* species that has various vernacular names *viz*. Frankincense, Incense, or Olibanum in English; Luban Dakar, Bakhor, Kendar in Arabic; Salai guggal In Ayurveda, and H-15 in Germany and Switzerland; was subject to various phytochemical investigations. It is noteworthy that the word Frankincense comes from a 10th century French word meaning "luxuriant incense". The word olibanum is derived from the Hebrew word "Lebonah" and the Greek word "Libanos" meaning white.

The genus takes its name from Professor John Boswell (Miller and Morris, 1988) the uncle of the famous novelist James Boswell, the writer of the well-known Story of Samuel Johnson. The genus comprises several species; all of which are trees (Guenther, 1972 and Lawerence, 1969); of which the most reputed are:

#### **1.2.** *Boswellia carterii* **Birdwood (Syn.** *Boswellia sacra* **Flüeckiger)**

A tree which is native to Somalia, Southern Yemen (in Hadra'mout valley), and Oman (in Dhofar region). Miller and Morris (Kapoor, 1990) stated that the only species of *Boswellia* present in the Arabian Peninsula is *Boswellia carterii*. This species was named after the English surgeon H.G. Carter who was the first to discover it in his expedition in Southern Arabia at 1846. In 1876, the Swiss chemist and botanist Flüeckiger re-examined the same plant describing it as new species and called it *Boswellia sacra*. Three years later, The English botanist Birdwood reviewed the whole genus and found that the specimens described earlier by Carter and Flüeckiger are identical to those found in Somalia and Known as *Boswellia carterii* so that the two species should be considered synonymous (Miller and Morris, 1988).

#### **1.3.** *Boswellia frereana* **Birdwood**

A species which is grown in small scale in northern regions of Somalia.

#### **1.4.** *Boswellia serrata* **Roxb. Ex Colebr.**

A species which is grown in India and have been differentiated botanically into two varieties (var. *serrata* with serrated and pubescent leaves, and var. *glabra* with glabrous leaves). Both varieties yield Indian Olibanum.

#### **1.5.** *Boswellia papyrifera* **(Delile ex Caill.) Hochst**

A species which is grown in North Eastern tropical Africa, especially in Sudan (Benson, 1967). The Egyptians supply of the oleogum resin of Frankincense, Olibanum, or Luban dakar comes mainly from Somalia, and rarely from Sudan or Kenya, therefore it is considered to be originated from *Boswellia carterii* Birdwood.

### **2. Chemistry**

that period of maturation. The resin occurs in small tears (Fig. 2) varying from 0.5 to 3 cm in length and usually ovoid, pear-shaped, or club-shaped. It is usually of pale yellowish color, frequently with a greenish, bluish or reddish tinge, semi-translucent and covered with a dull white dust, the surface of the tear being dull even after the dust has been removed. They are brittle and internally are opalescent and translucent, the fractured surface being dull and waxy. The drug has a fragrant, balsamic odor and an aromatic, slightly bitter taste, and softens to a plastic mass when chewed. The oleogum resin when triturated with water yields a whitish

After such presentation of the deep-rooted usage of frankincense, one can really understand how frankincense is a truly Kings' gift. The oleogum resin of different *Boswellia* species that has various vernacular names *viz*. Frankincense, Incense, or Olibanum in English; Luban Dakar, Bakhor, Kendar in Arabic; Salai guggal In Ayurveda, and H-15 in Germany and Switzerland; was subject to various phytochemical investigations. It is noteworthy that the word Frankincense comes from a 10th century French word meaning "luxuriant incense". The word olibanum is derived from the Hebrew word "Lebonah" and the Greek word "Libanos"

The genus takes its name from Professor John Boswell (Miller and Morris, 1988) the uncle of the famous novelist James Boswell, the writer of the well-known Story of Samuel Johnson. The genus comprises several species; all of which are trees (Guenther, 1972 and Lawerence, 1969);

A tree which is native to Somalia, Southern Yemen (in Hadra'mout valley), and Oman (in Dhofar region). Miller and Morris (Kapoor, 1990) stated that the only species of *Boswellia* present in the Arabian Peninsula is *Boswellia carterii*. This species was named after the English surgeon H.G. Carter who was the first to discover it in his expedition in Southern Arabia at 1846. In 1876, the Swiss chemist and botanist Flüeckiger re-examined the same plant describing it as new species and called it *Boswellia sacra*. Three years later, The English botanist Birdwood reviewed the whole genus and found that the specimens described earlier by Carter and

**1.2.** *Boswellia carterii* **Birdwood (Syn.** *Boswellia sacra* **Flüeckiger)**

emulsion (Wallis, 1967).

**Figure 2.** Oleogum Resin Tears of *Boswellia carterii* Birdwood

6 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

meaning white.

of which the most reputed are:

A review of the chemistry of Frankincense is made by (Khalid, 1983).

#### **A-The Essential oil:**

There has been considerable work done on the composition of olibanum oil from different species and commercial brands of *Boswellia*(Peyron *et al.,* 1980). The volatile oil was found to contain a variety of components *viz*.

#### **Monoterpenes:**

In 1978, Obermann investigated the essential oil derived from Aden and Eritrean frankincense and reported that α-pinene is the main component in the Aden oil, whereas n-octyl acetate and n-octanol are the dominant compounds in the Eritrean oil.

In 1978, De Rijke *et al*. isolated traces of the monoterpene acid α-campholytic acid [1] from olibanum oil. This acid was synthesized and showed a rather strong odor reminiscent of the oil. Thus in spite of being a trace constituent, it influences the olfactory character of the oil greatly.

In 1987, Abdel Wahab *et al*. examined the oil of Somali frankincense using GC/MS and found a variety of monoterpene hydrocarbons *viz*. sabinene, camphene, and myrcene; oxides *viz*. cineole; alcohols *viz*. decanol, α-terpineol, and linalol; esters *viz*. bornyl acetate, neryl acetate, and geranyl acetate.

Olibanum oil is reported to contain several odorless cembranoid diterpenes *viz*. cembrene [2], isocembrene [3] (Khalid, 1983) that was initially identified in pine tree resins, whereas

incensole [4] and the 1-hydroxy derivative [5] occur only in olibanum. These cembranoid macromolecules may in part account for the reported fixative properties of frankincense oil (Ohloff, 1994); just like the macromolecules of Musk oil.

The yield of steam distillation of frankincense essential oil (3%); and its physicochemical constants were determined. Capillary GC/MS technique was used for the analysis of the oil. Several oil components were identified based upon comparison of their mass spectral data with those of reference compounds published in literature or stored in a computer library. The oil was found to contain monoterpenes (13.1 %), sesquiterpenes (1 %), and diterpenes (42.5 %). The chemical profile of the oil is considered as a chemotaxonomical marker that confirmed the botanical and geographical source of the resin (Mikhaeil BR, 2003)

**B. The Gum:** In 1992, Sen *et al*. were able to isolate and elucidate the structure of 4-O-methylglucurono arabinogalactan from the oleogum resin of *Boswellia serrata* Roxb.

#### **C-The Resin:**

Several authors reported the isolation and identification of various triterpenes of different skeletons from the resin of different species of the genus *Boswellia*.

#### **2.1. Pentacylic Triterpenes**

**•** Olean-12-ene (β-amyrin type) Triterpenoids:

Classical acid-base extraction procedure led to isolation of α-boswellic acid [58].

In 1972, Elkhadem *et al*. isolated the 3-acetoxy derivative [59] of α-boswellic acid (acetyl αboswellic acid) by precipitation from ether extract of the resin of the Somaliland variety of olibanum by barium hydroxide followed by acetylation with acetic anhydride and hydrolysis.

Urs-12-ene (α-amyrin type) Triterpenoids: Elkhadem *et al.* were able to eliminate that diene impurity completely by treatment of β-boswellic acid with maleic anydride twice, followed by filtration of the adduct and crystallization. They were able also to prepare different synthetic derivatives of α-, and β-boswellic *viz*. ethyl, ethyl acetyl, and methyl benzoyl esters.

The configurations of such groups and double bond position were later unveiled through progress in NMR spectroscopic techniques especially after 2D-NMR has emerged. Recent advances in crystallographic analysis confirmed the α-configuration of 3-acetoxyl group in 8 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine Frankincense (Heaven's Gift) — Chemistry, Biology, and Clinical Applications http://dx.doi.org/10.5772/59006 9

incensole [4] and the 1-hydroxy derivative [5] occur only in olibanum. These cembranoid macromolecules may in part account for the reported fixative properties of frankincense oil

The yield of steam distillation of frankincense essential oil (3%); and its physicochemical constants were determined. Capillary GC/MS technique was used for the analysis of the oil. Several oil components were identified based upon comparison of their mass spectral data with those of reference compounds published in literature or stored in a computer library. The oil was found to contain monoterpenes (13.1 %), sesquiterpenes (1 %), and diterpenes (42.5 %). The chemical profile of the oil is considered as a chemotaxonomical marker that confirmed the

**B. The Gum:** In 1992, Sen *et al*. were able to isolate and elucidate the structure of 4-O-methyl-

Several authors reported the isolation and identification of various triterpenes of different

In 1972, Elkhadem *et al*. isolated the 3-acetoxy derivative [59] of α-boswellic acid (acetyl αboswellic acid) by precipitation from ether extract of the resin of the Somaliland variety of olibanum by barium hydroxide followed by acetylation with acetic anhydride and hydrolysis. Urs-12-ene (α-amyrin type) Triterpenoids: Elkhadem *et al.* were able to eliminate that diene impurity completely by treatment of β-boswellic acid with maleic anydride twice, followed by filtration of the adduct and crystallization. They were able also to prepare different synthetic

The configurations of such groups and double bond position were later unveiled through progress in NMR spectroscopic techniques especially after 2D-NMR has emerged. Recent advances in crystallographic analysis confirmed the α-configuration of 3-acetoxyl group in

(Ohloff, 1994); just like the macromolecules of Musk oil.

**C-The Resin:**

**2.1. Pentacylic Triterpenes**

**•** Olean-12-ene (β-amyrin type) Triterpenoids:

botanical and geographical source of the resin (Mikhaeil BR, 2003)

skeletons from the resin of different species of the genus *Boswellia*.

glucurono arabinogalactan from the oleogum resin of *Boswellia serrata* Roxb.

Classical acid-base extraction procedure led to isolation of α-boswellic acid [58].

derivatives of α-, and β-boswellic *viz*. ethyl, ethyl acetyl, and methyl benzoyl esters.

both acetyl-β-boswellic acid, and 3-acetoxyl-11-keto-β-boswellic acid (AKBA) (Schweizer *et* al., 2000).

In 1995, Mahajan *et al*. isolated 3α-hydroxy-urs-9,12-diene-4β-oic acid [64] and 2α, 3αdihydroxy-urs-12-ene-4-β-oic acid [65] together with other known boswellic acid derivatives by repeated chromatography of the acidic fraction from the ethanolic extract of *Boswellia serrata* Roxb. oleogum resin. They separated also urs-12-ene-3α,24-diol [66] by chromato‐ graphic fractionation of the neutral fraction of the resin.

Lupane Triterpenoids:

Proietti *et al*., 1981 managed to isolate 2 lupane-skeleton triterpenoids from resin exudate of *Boswellia frereana* distributed in the northern regions of Somalia namely, lupeol [67] and epilupeol [68].

Frankincense (Heaven's Gift) — Chemistry, Biology, and Clinical Applications http://dx.doi.org/10.5772/59006 11

#### **2.2. Tetracyclic triterpenes**

Tirucallane Triterpenoids:

Liang *et al*., (22) reported the presence of a variety of tirucallane triterpenoids in family Burseraceae.

In 2001, Boden *et al*. reported isolation of three triterpenoids having tirucallane nucleus from the oleogum resin of *Boswellia serrata* Roxb. ; namely 3-keto-8,24-diene-21-β-oic acid (3-oxotirucallic acid) [69], 3-β-hydroxy-tirucall-8,24-diene-21-β-oic acid (3-hydroxy-tirucallic acid) [70], and 3-β-acetoxy-tirucall-8,24-diene-21-β-oic acid (3-acetoxy- tirucallic acid) [71].

#### **Dammarane triterpenoids:**

both acetyl-β-boswellic acid, and 3-acetoxyl-11-keto-β-boswellic acid (AKBA) (Schweizer *et*

In 1995, Mahajan *et al*. isolated 3α-hydroxy-urs-9,12-diene-4β-oic acid [64] and 2α, 3αdihydroxy-urs-12-ene-4-β-oic acid [65] together with other known boswellic acid derivatives by repeated chromatography of the acidic fraction from the ethanolic extract of *Boswellia serrata* Roxb. oleogum resin. They separated also urs-12-ene-3α,24-diol [66] by chromato‐

Proietti *et al*., 1981 managed to isolate 2 lupane-skeleton triterpenoids from resin exudate of *Boswellia frereana* distributed in the northern regions of Somalia namely, lupeol [67] and

graphic fractionation of the neutral fraction of the resin.

10 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

al., 2000).

Lupane Triterpenoids:

epilupeol [68].

In 1985, Fattorusso *et al*. isolated four dammarane triterpenes from the most polar fractions of the chloroformic extract of the exudate of *Boswellia frereana*, namely 3β-acetoxy-16(S),20(R) dihydroxy dammar-24-ene [72], 3β,20(S)-dihydroxy dammar-24-ene [73], its 3-acetyl deriva‐ tive [74], and 20(S)-protopanaxdiol [75].

**•** 3,4- Secotriterpenoids:

3,4-secotriterpenic acids carrying an isopropyl group at position 5 are very rare as naturally occurring compounds. They are considered to be degradation products originating through

geochemical process involving photochemical or photomimetic reactions. In 1983, Fattorusso *et al*. managed to isolate a member of such group of compounds, namely 4(23)-dihydro roburic acid [76] from the acidic fraction of incense *Boswellia carterii* Birdwood after methylation with diazomethane followed by catalytic hydrogenation of the produced methyl ester and column chromatography.

#### **Analysis of the oleogum resin:**

In 2001, Ganzera and Khan developed a reversed phase HPLC method for the separation of boswellic acids from *Boswellia serrata* oleogum resin. The first accurate determination of 6 individual acids was possible in the resin as well as in multi-component preparations. By using an acidic mobile phase, raised temperature, and a 4 μm Synergi MAX-RP 80 A column, the acids could be detected at levels as low as 0.9 μg/ml. The study of market products revealed significant variations in the content of these pharmacologically active compounds in commer‐ cial samples. (Ganzera & Khan, 2001)

Assignment of other atoms was made by referring to reported compilation data of a variety of similar compounds (Mahato *et al*., 1994), and by using data from DEPT spectrum combined with 1 H-1 H COSY, HMQC correlations and long range C-H correlation data from HMBC spectrum which is illustrated by (Fig. 3). EI/MS fragments corroborated the aforementioned assignments showing a molecular ion peak [M]+ at m/z 512.35 corresponding for the molecular formula C32H48O5.

**Figure 3.** HMBC Correlation for 3-acetyl 11-keto β-Boswellic acid [63]

geochemical process involving photochemical or photomimetic reactions. In 1983, Fattorusso *et al*. managed to isolate a member of such group of compounds, namely 4(23)-dihydro roburic acid [76] from the acidic fraction of incense *Boswellia carterii* Birdwood after methylation with diazomethane followed by catalytic hydrogenation of the produced methyl ester and column

12 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

In 2001, Ganzera and Khan developed a reversed phase HPLC method for the separation of boswellic acids from *Boswellia serrata* oleogum resin. The first accurate determination of 6 individual acids was possible in the resin as well as in multi-component preparations. By using an acidic mobile phase, raised temperature, and a 4 μm Synergi MAX-RP 80 A column, the acids could be detected at levels as low as 0.9 μg/ml. The study of market products revealed significant variations in the content of these pharmacologically active compounds in commer‐

chromatography.

**Analysis of the oleogum resin:**

cial samples. (Ganzera & Khan, 2001)

From the above mentioned data, and from literature data; one can conclude that compound A-6 is 3α-acetoxy-urs-12-ene-11-Keto-24β-oic acid known as acetyl-11-Keto-β-Boswellic acid (AKBA). A computer- generated model for that compound after energy minimization using

**Figure 4.** Computer-generated Model of 3-acetyl 11-keto β-Boswellic acid [63]

CSChem3D program pro-version 4.0 (Cambridge Soft Corp.) is shown in Fig. 4.

The aforementioned data; it was suggested that 3α-hydroxy-urs-12-ene-11-keto-24β-oic acid known as 11-keto β-Boswellic acid (Kβ-BA). A computer-generated model for that compound after energy minimization using CSChem3D program pro-version 4.0 (Cambridge Soft Corp.) is shown in (Fig. 5).

**Figure 5.** Computer-generated Model of 11-Keto-β-Boswellic acid [62]

#### **3. Biology**

**•** Rough based Granular computing approach had been used to predict response to new medication from Boswellia and other components for treatment of HCV patients as presented in Fig. 6 (Badria et. Al al. 2013).

**Figure 6.** Rough based Granular Approach (RGA) Used in HCV Dataset Classification

**Figure 7.** Classifications Accuracy for Each Reduct During Experiment

The aforementioned data; it was suggested that 3α-hydroxy-urs-12-ene-11-keto-24β-oic acid known as 11-keto β-Boswellic acid (Kβ-BA). A computer-generated model for that compound after energy minimization using CSChem3D program pro-version 4.0 (Cambridge Soft Corp.)

14 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

**•** Rough based Granular computing approach had been used to predict response to new medication from Boswellia and other components for treatment of HCV patients as

is shown in (Fig. 5).

**3. Biology**

**Figure 5.** Computer-generated Model of 11-Keto-β-Boswellic acid [62]

presented in Fig. 6 (Badria et. Al al. 2013).

**Figure 6.** Rough based Granular Approach (RGA) Used in HCV Dataset Classification

galactosamine -endotoxin. The non acid part of the gum has pain relieving and sedative qualities, and in high doses can lower blood pressure, and reduce heart rate in dogs but increase in frogs observed benefits of *Boswellia* include reduction in joint swelling, increased mobility, steroid sparing action, less morning stiffness, improved grip strength, and general improvement in quality of life, for both osteoarthritis and rheumatoid arthritis. (Pachnanda et al. 1996).

**•** Boswellia gum has been used for the treatment of diabetes, skin and blood diseases, fever, cardiovascular disorders, neurological disorders, dysentery and diseases of the tests (Adrian, 1998).

#### **3.1. Predicting the Effect of Boswellic Acid**

If the boswellic acid was just another leukotriene inhibitor, then its effects probably could be predicted on the basis of these drugs: It probably works sometimes, it probably doesn't work for everyone, it probably is very effective for aspirin-induced asthma, it isn't going to be quite as strong as corticosteroids, and it isn't going to have as big an effect on the amount of air that can be expelled in one second as it does on other symptoms. These are, in fact, reasonable expectations (Safahyi *et al*., 1992). However, the boswellic acids neutralize elastase (Safahyi *et al*., 1997). It is not known how important this is. First, it is not known to what extent elastase contributes to the problem of asthma. Second, it is not known to what extent elastase is a problem when taking a leukotriene inhibitor (Safahyi *et al*., 1997). Boswellic acid's ability to neutralize elastase is superfluous, or it might nicely complement the inhibition of leukotrienes. Also, we don't know how much the boswellic acids actually neutralize elastase.

#### **3.2. Experimental Autoimmune Encephalomyelitis (Multiple Sclerosis)**

Wildfeuer et al., 1998 administered a mixture of acetyl-boswellic acids to guinea pigs with experimental autoimmune encephalomyelitis. Multiple sclerosis occurs when the myelin insulating the neurons in the brain is destroyed. Researchers wishing to study this can't wait for rats to get multiple sclerosis. Instead, they create a problem that is much like multiple sclerosis, which is called experimental autoimmune encephalomyelitis (Wildfeuer et al., 1998). Two studies (Safayhi *et al.,* 1992) had previously found that leukotriene inhibitors reduced the development of experimental autoimmune encephalomyelitis. Of course, there is a jump from experimental autoimmune encephalomyelitis in a rodent to multiple sclerosis in a human. Curiously, the role of leukotrienes in multiple sclerosis seems to have garnered more attention. People with multiple sclerosis do have increased leukotrienes (Sailer *et al*. 1996).

#### **4. Blocking the formation of leukotrienes**

#### **4.1. Leukotrienes Inhibitors**

Safahyi *et al*., 1992, observed the ability of the different boswellic acids to inhibit the formation of the leukotriene LTB4. As noted, the other leukotrienes are more important with regard to asthma. However, the mode of action of the boswellic acids should be equally effective for all leukotrienes, because they inhibit 5-lipoxygenase, the key enzyme needed for starting the synthesis of all leukotrienes. Safahyi and his group (1992) measured the concentration needed to block the activity of LTB4 by 50%. For AKBA, the needed concentration was 1.5 micromoles.

For the other boswellic acids, it was 4-7 micromoles, which means that 3 to 4 times greater a concentration was needed. A factor of 3 or 4 might not be that important as things go, but this finding singled out AKBA as being the most powerful boswellic acids (Safahyi *et al*., 1992). Wildfeuer et al., 1998, found that boswellic acids reduce leukotriene formation, and AKBA is the most effective.

## **5. Clinical applications**

galactosamine -endotoxin. The non acid part of the gum has pain relieving and sedative qualities, and in high doses can lower blood pressure, and reduce heart rate in dogs but increase in frogs observed benefits of *Boswellia* include reduction in joint swelling, increased mobility, steroid sparing action, less morning stiffness, improved grip strength, and general improvement in quality of life, for both osteoarthritis and rheumatoid arthritis. (Pachnanda

16 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

**•** Boswellia gum has been used for the treatment of diabetes, skin and blood diseases, fever, cardiovascular disorders, neurological disorders, dysentery and diseases of the tests

If the boswellic acid was just another leukotriene inhibitor, then its effects probably could be predicted on the basis of these drugs: It probably works sometimes, it probably doesn't work for everyone, it probably is very effective for aspirin-induced asthma, it isn't going to be quite as strong as corticosteroids, and it isn't going to have as big an effect on the amount of air that can be expelled in one second as it does on other symptoms. These are, in fact, reasonable expectations (Safahyi *et al*., 1992). However, the boswellic acids neutralize elastase (Safahyi *et al*., 1997). It is not known how important this is. First, it is not known to what extent elastase contributes to the problem of asthma. Second, it is not known to what extent elastase is a problem when taking a leukotriene inhibitor (Safahyi *et al*., 1997). Boswellic acid's ability to neutralize elastase is superfluous, or it might nicely complement the inhibition of leukotrienes.

Wildfeuer et al., 1998 administered a mixture of acetyl-boswellic acids to guinea pigs with experimental autoimmune encephalomyelitis. Multiple sclerosis occurs when the myelin insulating the neurons in the brain is destroyed. Researchers wishing to study this can't wait for rats to get multiple sclerosis. Instead, they create a problem that is much like multiple sclerosis, which is called experimental autoimmune encephalomyelitis (Wildfeuer et al., 1998). Two studies (Safayhi *et al.,* 1992) had previously found that leukotriene inhibitors reduced the development of experimental autoimmune encephalomyelitis. Of course, there is a jump from experimental autoimmune encephalomyelitis in a rodent to multiple sclerosis in a human. Curiously, the role of leukotrienes in multiple sclerosis seems to have garnered more attention.

Safahyi *et al*., 1992, observed the ability of the different boswellic acids to inhibit the formation of the leukotriene LTB4. As noted, the other leukotrienes are more important with regard to

Also, we don't know how much the boswellic acids actually neutralize elastase.

People with multiple sclerosis do have increased leukotrienes (Sailer *et al*. 1996).

**4. Blocking the formation of leukotrienes**

**4.1. Leukotrienes Inhibitors**

**3.2. Experimental Autoimmune Encephalomyelitis (Multiple Sclerosis)**

et al. 1996).

(Adrian, 1998).

**3.1. Predicting the Effect of Boswellic Acid**

#### **5.1. For treatment of knee osteoarthritis**

After one month of treatment there was a significant reduction of pain on active movement, passive movement, tenderness, nocturnal pain and a significant improvement of pain free walking time. After two months of therapy, there was a highly significant reduction of pain on active movement, pain on passive movement, tenderness, nocturnal pain, and highly significant prolongation of pain free walking time. At the end of three months, there was a significant reduction of grade of knee effusion, with highly significant reduction of pain on passive movement, pain on active movement, tenderness, and significant prolongation of pain free walking time (Badria *et al*. 2004).

Efficacy and tolerability of *Boswellia* and turmeric in this work is superior to clinical trial of NSAIDs in treatment of active osteoarthritis. The efficacy of NSAIDs (diclofenace) were tested in a double blind clinical trail in 50 OA patients at dose of 50 mg bid for three weeks and follow up visit after seven weeks. At the end of the trial, there was a significant reduction in pain, joint tenderness (P < 0.05) and swelling *(*Badria *et al*. 2002).

#### **5.2. For treatment of bronchial asthma**

Badria *et. al, 2002* and Gupta *et al,* 1998 performed the best type of research study in a doubleblind, placebo-controlled study. Some subjects with bronchial asthma. During the 6 week treatment period, the subjects taking boswellic acid had an average of.3 asthmatic attacks and the subjects taking the placebo had an average of 1.2. despite worse starting signs, the subjects taking boswellic acid actually had fewer asthmatic attacks. Therefore, Gupta's study stands as good evidence that boswellic acid at least reduces the probability of an asthmatic attack (Gupta *et al,* 1998).

After 2 weeks treatment with boswellia, there was a significant increase in both FEV1 and PEFR (P ≤ 0.05 and ≤ 0.01 respectively) with no significant change in FVC in the severe persistent asthma subgroup (C1) when compared to those received placebo (C2). The potent inhibitory action of boswellia extract on blood eosinophils, can be explained by a potent anti-inflamma‐ tory action extends beyond the leukotriene inhibition (Badria et al. 2004).

#### *5.2.1. Ulcerative colitis*

Badria *et al.*, 2001 and Gupta *et. al*. 1997 compared boswellic acid to a typical therapy for ulcerative colitis, sulfasalazine. To roughly characterize the finding, there was no observable difference between the two treatments (Badria *et al.*, 2001)

#### **5.3. For treatment of hepatitis C**

Inclusion Criteria:

Participants were enlisted from a group of HCV-infected patients currently enrolled in a large observational study in Egypt. Participants received the supplements daily for 18 months, with measures obtained every 6 months.

Measures to be assessed will include: compliance with assignment, retention in the study, Liver enzymes levels, serum collagen markers, self-described symptoms, viral load and clearance, abdominal ultrasound. It is hypothesized that the supplements led to clearance of HCV infections and/or at least prevent progression of liver disease in participants with chronic HCV hepatitis and, in some cases, reverse hepatic lesions that are already present, as well as improving the quality of life in individuals who use this dietary supplement. (Badria *et al*. 2002)

#### **Author details**

Farid A. Badria\*

Address all correspondence to<EMAIL_ADDRESS>
Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

#### **References**

[3] Badria F., Mohammed E., El-Badrawy M., and El-Desouky M., (2004), Natural Leuko‐ triene Inhibitor from Boswellia: A Potential New Alternative for Treating Bronchial Asthma, Alternative Complementary Therapies; 10(5), 257-265.

*5.2.1. Ulcerative colitis*

Inclusion Criteria:

than HCV

**Author details**

Farid A. Badria\*

**References**

**•** positive PCR for HCV.

**5.3. For treatment of hepatitis C**

measures obtained every 6 months.

Badria *et al.*, 2001 and Gupta *et. al*. 1997 compared boswellic acid to a typical therapy for ulcerative colitis, sulfasalazine. To roughly characterize the finding, there was no observable

**•** Elevated liver enzymes within 6 months of the Entry, with no attribution to causes other

Participants were enlisted from a group of HCV-infected patients currently enrolled in a large observational study in Egypt. Participants received the supplements daily for 18 months, with

Measures to be assessed will include: compliance with assignment, retention in the study, Liver enzymes levels, serum collagen markers, self-described symptoms, viral load and clearance, abdominal ultrasound. It is hypothesized that the supplements led to clearance of HCV infections and/or at least prevent progression of liver disease in participants with chronic HCV hepatitis and, in some cases, reverse hepatic lesions that are already present, as well as improving the quality of life in individuals who use this dietary supplement. (Badria *et al*. 2002)

Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

[1] Abdel wahab S. M., Aboutabl E. A., Elzalabani S. M., Fouad H. A., De Pooter H. L., and El Fallaha B.; (1987), The Essential Oil of Olibanum, *Planta Medica*, 53, 382.

[2] Adrian AL(1996), Boswellia serrata. A unique Ayuvredic Anti-rheumatic. Issue of

**•** Chronic HCV confirmed histologically with Liver biopsy within 2 years of entry

difference between the two treatments (Badria *et al.*, 2001)

18 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

**•** Both genders were eligible within age of 18-70 years old.

Address all correspondence to<EMAIL_ADDRESS>
VRP's Nutritional News.

[16] El-Khadem H., El-Shafei Z. M., El-Sekeily M. A. S., and Abdel Rahman M. M. A.;

[17] Fattorusso E., Santacroce C., and Xaasan C.F.; (1983), 4(23)-Dihydroroburic acid from

[18] Fattorusso E., Santacroce C., and Xaasan C.F.; (1985), Dammarane Triterpenes from

[19] Ganzera M., and Khan I. A.; (2001), A Reversed Phase High Performance Liquid Chromatography Method for the Analysis of Boswellic acids in *Boswellia serrata*,

[20] Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R, (2001), Therapy of active Crohn disease with Boswellia serrata extract H15Z. Gastroenterol; 39(1): 11-7.

[21] Guenther E.; (1972), "*The Essential Oils*", Vol. IV, Robert E. Krieger Publishing Co.,

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[23] Gupta I, Parihar A, Malhorta P(1997), : Effects of *Boswellia serrata* gum resin in pa‐

[24] Huan MT, Badmaev V, Ding Y, Liu Y, Xie JG, Ho CT, (2000), Antitumor and anticar‐ cinogenic activities of triter period, beta-boswellic acid. In Biofactors; 13(1-4): 225-30.

[25] Kapoor L. D.; (1990), "*CRC Handbook of Ayurvedic Medicinal Plants*", CRC Press, Flori‐

[26] Khalid S. A.; (1983), "*Chemistry of the Burseraceae*", Annual Proceedings Phytochemi‐

[27] Knaus U, Wagner H, (1996), Effects of boswellic acid of Boswellia serrata and other

[28] Krieglstein CF, Anthoni C, Rijcken EJ, Laukotter M, Spiegel HU, Boden SE, Schweiz‐ er S, Safayhi H, Senninger N and Schurmann G, (2001), Acetyl-11-Keto-beta-boswel‐ lic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates

[29] Lawrence G. H.; (1969), "*Taxonomy of Vascular Plants*"; 2nd Indian reprint, Oxford &

[30] Liang G. Y., Gray A. I., Waterman P. G.;. (1988), Tirucallane and Oleanane Triter‐

[31] Mahajan B., Taneja S. C., Sethi V. K., and Dhar K. L.; (1995), Two Triterpenoids from

penes from the Resin of Aucoumea Klaineana, *Phytochemistry*, 27, 2283.

triterpenic acids on the complement system. Phytomedicine; 3: 77-81.

the Resin (Incense) of *Boswellia Carterii*, Phytochemistry, 22, 2868.

the Resin of *Boswellia freerana*, Phytochemistry; 24, 1035.

20 Evidence-based Strategies in Herbal Medicine, Psychiatric Disorders and Emergency Medicine

(1972), *Planta Medica*, 22, 157.

Planta *Medica*, 67, 778.

3(11): 511-4.

da, USA, p. 83.

Huntington, New York; pp. 352-356.

cal, Society of Europe, 22, 281-299.

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*Boswellia serrata* gum resin, *Phytochemistry*, 39, 453-5.

IBH Publishing Co., Calcutta, India, p. 559.

**Chapter 2**