Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

[Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism].

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

[Treatment strategy and thought on classical herbal formulae for coronavirus disease 2019].

Coronavirus disease 2019(COVID-19) refers to the pneumonia caused by novel coronavirus(2019-nCoV) infection in 2019. It is highly infectious, with quick spreading and a wide range of impact. It has been broken out in many countries around the world and has become a public health emergency of international concern. Chinese medicine has a long history in treating plague, and viral disease is the clinical advantage in Chinese medicine. Under the premise that there is currently no specific drug treatment, Chinese medicine has achieved certain effects in the treatment of COVID-19, which has attracted much attention and has been upgraded to a national strategy. Regarding the treatment of COVID-19 with Chinese medicine, it is believed that in terms of the name of Chinese medicine, the modern connotation of "uniform of typhoid and febrile disease" should be re-recognized, and it is advisable to use drugs based on specific clinical prescriptions and indications. In terms of pathogenesis, the COVID-19 has the pathogenesis rules including from the mild to severe conditions, from the surface to the inside, from the excess syndrome to the deficiency syndrome. We should pay attention to the Taiyang syndrome damaged by wet disease in initial stage, Shaoyang syndrome complicated with Yangming syndrome in the middle stage, phlegm-heat obstructing lung in critical period, lung and spleen deficiency in the recovery stage. In terms of clinical treatment strategies, Dayuan Yin is recommended to induce sweat and disperse the stasis in early stage. Xiaochaihu Decoction and Maxing Shigan Decoction is used to relieve both exterior and interior symptoms in middle stage. In critical stage, Tingli Dazao Xiefei Decoction, Weijing Decoction, Xuanbai Chengqi Decoction, Xiaoxianxiong Decoction, and Sanzi Yangqin Decoction are considered to reduce phlegm and clear heat. We should pay attention to nourishing Qi and strengthening the spleen by Zhuye Shigao Decoction, Sha-shen Maidong Decoction, and Liujunzi Decoction in the later recovery period. It shall be noted that, no matter in the initial mild stage, the middle and critical stages, or in the later recovery stage, Chinese medicine plays an important role, including preventing mild to severe disease, shortening the fever time, improving cough symptoms, increasing blood oxygen saturation and reducing mortality. Many studies have shown that the classical herbal formulae can alleviate the cytokine storm, regulate the immune imbalance, and produce the potential effect of synergistic treatment for COVID-19 through multiple components, multiple targets, and multiple pathways.

[Application of cream formula in treatment of severe heart failure].

Cream formula has been mostly used to treat deficiency syndrome. Currently,it has been used to recuperate the body,promote health against aging,and prevent and treat chronic disease. In modern medicine,there are only treatment concepts and methods of diseases,but lack of concepts of " deficiency syndrome" and " restoring deficiency". The concepts of " deficiency syndrome" and " restoring deficiency" could effectively supplement and improve the diagnosis and treatment scheme of some modern diseases. Refractory heart failure,dilated cardiomyopathy,ischemic cardiomyopathy,and valvular heart disease belong to the traditional category of " consumptive disease". The cream formula with the efficacy of restoring deficiency can not only alleviate symptoms and improve the quality of life,but also improve the structure and function of the heart,reduce the dosage of diuretics and the number of hospitalizations,and achieve the purpose of secondary prevention in the treatment of severe heart failure,dilated cardiomyopathy,ischemic cardiomyopathy and valvular heart disease. The cream formula for treating chronic heart failure include Shenqi Pills,Zhenwu Decoction,Yougui Pills,Wuling Powder,Linggui Zhugan Decoction,Danggui Shaoyao Powder,Lizhong Decoction,Buzhong Yiqi Decoction,Guipi Decoction,Yupingfeng Powder,Guizhi Decoction. Long-term administration of cream formula could not only resist aging,but also play an irreplaceable role in the secondary prevention of acute and critical diseases.

[Thought and method of classic formulae in treatment of chronic cough].

Chronic cough is a common clinical disease with complex etiology, which is easily misdiagnosed and mistreated. Chronic cough guideline has been developed based on the modern anatomical etiology classification, and it may improve the level of diagnosis and treatment. Common causes of chronic cough are as follows: cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, gastroesophageal reflux-related cough, post-infectious cough, etc. There is a long history and rich experience in treatment of cough in traditional Chinese medicine which is characterized by syndrome differentiation. The four elements of pathogenesis for chronic cough include wind, phlegm, fire, and deficiency. Classic formula is widely used in the treatment of chronic cough, and the focus is on prescriptions corresponding to syndromes. This article attempts to explore the thought and method of classic formulae in treatment of chronic cough based on three perspectives: differentiation of etiology, pathogenesis and formula-syndrome. Three medical cases are selected at last in order to prove its correction.