text: Pulmonary fibrosis (PF) is a kind of disease with normal lung tissue structure changing and function losing, which is caused by cell excessive repairing and excessive accumulation of extracellular matrix resulting from sustained alveolus injury due to pneumonia. Clinical manifestations of this disease include dyspnea, shortness of breath and tiredness. This disease is characterized by a continuous progress. Say popularly, pulmonary fibrosis is that the alveolus is gradually replaced by fiber materials, and the lung tissue becomes tough and thick, therefore the ability of oxygen exchange of the lung tissue fades away. The patients will suffer respiratory difficulty and respiratory failure in turn as a result of anoxia until death. In the past 20 years, the incidence of pulmonary fibrosis is rising year by year because of the environmental pollution. At present, glucocorticoid and immunosuppressant, such as prednison, cytoxan and colchicines, are main drugs for treating the pulmonary fibrosis. Clinical practices of recent years have proved that drugs, such as glucocorticoid, antibiotic and immunosuppressant, can relieve early inflammation of alveolus and clinical symptoms of patients, but cannot suppress the development of fibrosis effectually. Furthermore, long-term uses of high doses of hormone and antibiotic not only lead to serious complications but also aggravate the process of fibrosis. Because the etiology and pathogenesis are unclear, the treatment of pulmonary fibrosis is still a difficult problem in the medicine field. Although new drugs are continually developed, there′re no effective therapeutic methods and professional therapeutic drugs yet. The prognosis is poor, the mean survival time is only 3 years and five-year survival rate is less than 50%, therefore pulmonary fibrosis is called cancer but not cancer actually.
  Pathogenesis of pulmonary fibrosis is still unclear, but it has a common feature that collagen metabolism in the body is out-of-balance and the synthesis of collagen exceeds the degradation of collagen. Therefore, the occurrence of pulmonary fibrosis results from the activation of cytokines and the dysregulation of collagen metabolism. In recent years, studies focus on cytokines which play an important role in regulating proliferation, transformation and secretion of lung fibroblasts. Inflammation and fibrosis of tissue can be observed in most of the pulmonary fibrosis patients. Sustained Inflammation injuries may cause fibrosis. Cytokines, such as TGF-β1, FGFs, PDGFs and VEGFs, play a key role in the process of the occurrence of pulmonary fibrosis. Wherein TGF-β1, a recognized pro-fibrogenic marker, is a mediator which is most closely associated with the occurrence and formation of pulmonary fibrosis. The up-regulation of TGF-β1 can activate the classic Smad signaling pathway downstream, and stimulate cells to synthesize and excrete a large number of extracellular matrix. With the increase of deposition of extracellular matrix and epithelial-mesenchymal transition in the process of fibrosis, development of fibrosis is accelerated. Based on the above reasons, TGF-β1 has become the main target of anti-fibrosis. The contents of hydroxyproline in lung tissues indicate the contents of collagen and the expression level of TGF-β1 shows the possible mechanism of drugs intervening in pulmonary fibrosis. That is, drugs can relieve pulmonary fibrosis, though decreasing the level of TGF-β1 to inhibit the TGF-β1/Smad pathway rather than anti-inflammatory. For an example, pirfenidone, a drug which has just come into the market in Japan, India and European Union, can inhibit the pro-fibrogenic factors such as TGF-β1 but have clinical side effects such as photosensitization.
  Cough is one of the common symptoms in respiratory diseases. Similar to other respiratory diseases, early pulmonary fibrosis also shows general symptoms like cough. Although there is some relationship between cough and pulmonary fibrosis, in fact they are totally different. Strictly speaking, cough is a pattern of manifestation in respiratory diseases but not a real illness. Cough may occur in early stage or developing period of pulmonary fibrosis, and symptoms including cough and asthma occurring in early fibrosis can be alleviated by using anti-cough drugs, but the drugs will be ineffective if the condition is serious and in this situation only hormone and antibiotic can be used to alleviate the symptoms of the disease. However, the above treatments only scratch the surface but cannot radically cure or prevent pulmonary fibrosis. Furthermore, a long-term uses of hormone and antibiotic may even aggravate pulmonary fibrosis.
  In summary, there still lacks effective treatment for pulmonary fibrosis and it is urgent to develop new drugs with better curative effect to relieve even cure the pulmonary fibrosis.
  Traditional Chinese Medicine stemonae belongs to Stemona of Stemonaceae, and has the function of moistening lung along with gas, suppressing cough, deinsectization and delousing. Stemonae is mainly used in treating for pertussis, tuberculosis, new or old cough, and treatment of enterobiasis of head and body in clinic. Stemona alkaloids are the major bioactive components of stemonae. Studies have shown that compounds such as tuberostemonine J, tuberostemonine H, isostenine and neotuberostemonine isolated from stemona tuberosa have a very good antitussive effect in cough of guinea pig induced by citric acid. Wherein, isostenine and neotuberostemonine have a similar antitussive effect as codein while tuberostemonine J and tuberostemonine H have a weaker antitussive effect than that of codein. Studies have also shown that antitussive activities of croomine, neotuberostemonine and stemoninine in stemona tuberosa are similar while that of tuberostemonine is weaker. Besides, mechanism researches have shown that neotuberostemonine, tuberostemonine and stemoninine target the peripheral cough reflex pathway which belongs to peripheral antitussive, while croomine works by inhibiting cough center. Although cough is one of the symptoms in pulmonary fibrosis, there is no any report showing that anti-cough drugs can improve or treat pulmonary fibrosis so far.
  
  There are few patents regarding stemona alkaloids and most of them are relating to preparation methods of total alkaloids or cough suppressing and deinsectization of alkaloids. Besides, there is only one patent (201210149954.X) regarding alkaloid represented by Formula (I) and the alkaloid is used in preparation of acetylcholinesterase inhibitors. There are no any reports regarding effects of stemona tuberosa alkaloids in preventing or treating pulmonary fibrosis and application of the drugs in treating pulmonary fibrosis.