[Two new isoquinoline alkaloids from Corydalis hendersonii].

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(ß-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 µmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 µmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.

[Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia].

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

[Network pharmacology study of Tibetan medicine Corydalis Herba against acute myocardial ischemia].

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.

[Research progress on in vitro models of cardiomyocyte injury].

Cardiovascular diseases seriously endanger human health and life. The accompanying myocardial injury has been a focus of attention in society. Chinese medicine,serving as a natural and precious reservoir for the research and development of new drugs,is advantageous in resisting myocardial injury due to its multi-component,multi-pathway,and multi-target characteristics. In recent years,with the extensive application of culture method for isolated cardiomyocytes,a cost-effective,controllable in vitro model of cardiomyocyte injury with uniform samples is becoming a key tool for mechanism research on cardiomyocyte injury and drug development.A good in vitro model can reduce experimental and manpower cost,and also accurately stimulate clinical changes to reveal the mechanism. Therefore,the selection and establishment of in vitro model are crucial for the in-depth research. This study summarized the modeling principles,evaluation indicators,and application of more than ten models reflecting different clinical conditions,such as injuries induced by hypoxia-reoxygenation,hypertrophy,oxidative stress,inflammation,internal environmental disturbance,and toxicity. Furthermore,we analyzed advantages and technical difficulties,aiming to provide a reference for in-depth research on myocardial injury mechanism and drug development.

[Effect of total phenolic part of Rhus chinensis against myocardial ischemia in mice].

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.

[Analysis of bacterial community structure and diversity during mountain-agarwood formation].

As an important substitute for agarwood, mountain-agarwood, belonging to the family Oleaceae, comes from the root, stem and thick branch of Syringa pinnatifolia, which has a wide range of application in Inner Mongolia, China. It has good clinical efficacy in the use of cardiovascular diseases. However, the formation speed of mountain-agarwood is extremely slow, and its cultivated seedlings have low resin content. Therefore, how to speed up the formation of mountain-agarwood and increase the resin content is a hot research topic in this field. In this work, 16 S rDNA amplicon sequencing method was used to systematically analyze the bacterial communities of different samples of mountain-agarwood. Our data revealed that the samples of mountain-agarwood had more obvious species diversity than the ones of non-mountain-agarwood, especially the wild mountain-agarwood samples. By analysis of bacterial community composition and species abundance, Sphingomonas, Modestobacter and unidentified Cyanobacteria genus were three dominant bacterial genera in all samples. In addition, there are two identified genera of dominant bacteria, namely Actinoplanes and Microbacterium in both wild and cultivated mountain-agarwood, by bacterial community composition and species richness analysis. Meanwhile, Roseomonas was the dominant bacterial genus in both wild and cultivated non-mountain-agarwood samples. Our work could provides basic data for exploring the mechanism of the mountain-agarwood formation, and help to exploit resource of endophytic bacteria reasonably.

[Microscopic histochemical comparison during mountain-agarwood formation].

Mountain-agarwood plays an important role in ethnic medicine in China for its pharmaceutical value. Modern pharmacological researches demonstrated that mountain-agarwood was effective for its anti-myocardial ischemia, antibacterial, anti-inflammatory, antitumor and analgesic effects. Mountain-agarwood derives from the peeled roots, stems or twigs of Syringa pinnatifolia which belongs to Syringa genus. It often depends on the purple substance and fragrance to estimate the formation of mountain-agarwood. However, the mechanism of mountain-agarwood formation has not been reported. To observe the microcosmic change in the process during the formation of mountain-agarwood, this study described the microscopic and histochemical characteristics of mountain-agarwood formation through histochemical staining. Our results showed that a significant difference of the distribution of tyloses existed during mountain-agarwood formation. It was observed that inchoate mountain-agarwood had more starch granules and viable cells than mountain-agarwood formed with high level or low level. The amount of polysaccharide and degree of lignification were increased during the mountain-agarwood formation. The results indicated that the mountain-agarwood, which meets the quality requirements for pharmaceutical use, contained the following characteristics: a large amount of purple tyloses in heartwood; yellow-brown tyloses distributing in heartwood and sapwood which were less in the latter; lignification with high level; a few viable cells; lots of polysaccharide and few starch granules in xylem rays cell. This study is aimed to reveal the change of histochemical characteristics during mountain-agarwood formation, and lay the foundation for exploring the mechanism of mountain-agarwood formation.

[Advances on anti-tumor mechanisms of zerumbone].

Zerumbone(ZER), one of humulane-type sesquiterpenoids, showed its unique advantage against tumor activities. The main underlying mechanisms include inhibiting the growth and proliferation of cancer cells, inducing apoptosis of cancer cells and differentiation of cancer cells, regulating immune function, inhibiting invasion and metastasis of cancer cells, and reversing multidrug resistance of cancer cells. Studies on ZER focusing its cytotoxic or anti-tumor is one of hot topic. Currently, with the increasing studies on ZER, the clarified mechanisms are getting rich. The present paper describes a summary of its anti-tumor mechanism of action and helps to provide significant reference to more in-depth research.

[Phytochemical and pharmacological progress on genus Syringa].

The genus Syringa, belonging to the family Oleaceae, are distributed naturally in the European and Asian regions.This genus is composed of more than 20 species worldwide, among which about 16 species including 10 endemic ones are discovered in China.The Syringa sp.are extensively used as herbal medicine and ornamental aspects, such as the roots and stems of S. pinnatifolia, which is one of the typical Mongolian folk medicines in China for the treatment of cardiovascular and pulmonary symptoms. As a continuous research following the previous summary in 2015, the present reriew describes the phytochemical and pharmacological progress of the genus, which hopes to provide a valuable reference to its research, development and clinic application.

[Chemical and pharmacological progress on a Tibetan folk medicine formula Bawei Chenxiang Powder].

Bawei Chenxiang Powder is a traditional Tibetan folk medicine formula, consisting of resinous wood of Aquilaria sinensis, kernel of Myristica fragrans, fruit of Choerospondias axillaris, travertine, resin of Boswellia carterii or B. bhaw-dajiana, stem of Aucklandia lappa, fruit of Terminalia chebula(roasted), and flower of Gossampinus malabarica. It has the function of clearing heart heat, nourishing heart, tranquilizing mind, and inducing resuscitation, which has been used for the treatment of coronary heart disease and angina pectoris. Modern research shows that the medicine materials of this formula mainly contain terpenoids like sesquiterpenes and triterpenes and polyphenols like flavonoids, lignans, and tannins, displaying some pharmacological activities such as anti-myocardial ischemia, anti-cerebral ischemia, and spatial learning and memory promotion. This review summaries the traditional uses, chemical constituents, and pharmacological activities research progress, hopefully to provide a reference for clarification of its pharmacological active ingredients.

[Advances on terpenoids from genus Syringa].

Syringa plants are of important value in ornamental, economic and medical fields. The terpenoids in Syringa plants mainly include iridoids, sesquiterpenoids, and triterpenoids, most showing activities such as cardioprotective, neuroprotective, hypoglycemic, anti-flu virus, anti-bacterial, anti-inflammatory, and anti-oxidation effects. Among the above active compounds, sesquiterpenoids have attracted increasing attention. In this review, the phytochemical and pharmacological activities of Syringa terpenoids were summarized in order to provide an overview for further research and development of Syringa plants.

[Research progress on terpenes and pharmacological effects of Saussurea lappa].

Saussurea lappa originates in India, and now mainly grow in Yunnan, Sichuan and other places in China. It is one of the commonly used traditional herbal medicines in Tibet and other minority regions, with effects in regulating qi to relieve pain and invigo-rating spleen to promote food. It has been used in clinic for gastrointestinal diseases, such as Qi stagnation syndrome of spleen and stomach, diarrhea and tenesmus. More than 200 compounds have been identified from S. lappa. Among them, sesquiterpenoids attracted much attention. In terms of the number of compounds, eudesmanetype is dominant, guaiane and germacranetypes have also been reported frequently. Pharmacological studies have involved extracts, volatile oils and monomeric components represented by dehydrocostus lactone. Anti-tumor, anti-inflammatory and anti-bacterial effects on digestive system have attracted great attention. However, due to the complex sources of S. lappa and widely used in clinical practice, there is few research progress on relevant chemical constituents and pharmacological activities. This paper systematically summarizes terpenes and the pharmacological effects of S. lappa, in order to provide basis for further studies and clinical applications.

Alashanoids K-M, bioactive eremophilane sesquiterpenoids from Syringa pinnatifolia.

Three new eremophilane-type sesquiterpenoids, alashanoids K-M (1-3), and one known analogue (4) were isolated from the peeled stems of Syringa pinnatifolia. All the compounds were isolated from the genus Syringa for the first time. Structures of these compounds were established using 1D and 2D NMR and MS data. The absolute configurations were determined by experimental and calculated electronic circular dichroism analysis, a modification of Mosher's method, and X-ray diffraction. Compounds 2 and 3 inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC50 values of 14.23 and 12.20 µM, respectively, and showed cytotoxic activities against HepG2 cells with the IC50 values of 34.41 and 40.86 µM, respectively.

[Advances on network pharmacology in ethnomedicine research].

Ethnomedicine is the precious wealth left by ethnic minorities in their struggle against diseases. It is similar to traditional Chinese medicine in a narrow sense and has the characteristics of multi-component,multi-target and multi-channel synergy. Under the guidance of the theory of ethnomedicine,the combination of ethnomedicine and network pharmacology will help to understand the essence of the prevention and treatment of ethnomedicines in a dynamic and holistic manner. This paper reviews the research progress of network pharmacology applied in ethnomedicine,analyses the problems and challenges existing in the application of network pharmacology in ethnomedicine research at present,such as inaccurate data and information,lack of network analysis platform for effective analysis of dose-effect relationship of chemical constituents and weak basic research of ethnomedicine,and puts forward corresponding prospects.

[Analgesic and sedative effects of Mongolian medicine Syringa pinnatifolia].

The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,ß1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.

[Pharmacological evaluation of Mongolian medicine Syringa pinnatifolia fraction I against acute myocardial ischemia in mice].

Syringa pinnatifolia Hemsl.( SP) is a representative Mongolian folk medicine with the effects of inhibiting Heyi related diseases,clearing heat and relieving pain. It has been used for the treatment of Heyi-induced heart tingling,heart palpitations,upset,insomnia and other symptoms. Total ethanol extract( T) and major fraction( M) of SP have been evaluated its anti-ischemic effects,and the mechanism was related to the regulation of cyclooxygenase( COX)-mediated inflammatory pathway and p53-mediated apoptosis pathway in our previous studies. This study reports the chemical fractionation on M by which to obtain subfractions( I and M_3),and the pharmacological evaluation of M,I,and M_3 against myocardial ischemia in mice. The result showed that I and M reduced the values of LVEDd and LVEDs,significantly increased EF and FS values,increased serum CK-MB and LDH levels in mice,and reduced in inflammatory cells infiltration and collagen deposition in the infarcted myocardial tissue,suggesting that M and I possess the same degree anti-myocardial is chemia equally whereas M_3 has no this effect. Related mechanism studies suggested that I can reduce the expression of COX-1,COX-2 and p53 protein in myocardial tissue in a dose-dependent manner. This study lays the foundation for further chemical segmentation and clarification of pharmacological substance groups,paving the way for the full use and benefits to be use of systematic biological methods to analyze the pharmacological basis of SP against myocardial ischemia.

[Phytochemical and pharmacological progress on humulane-type sesquiterpenoids].

Humulane-type sesquiterpenoids, widely distributed in plants and microbes, include three types: α-humulene, ß-humulene, and γ-humulene. Up to now, 98 humulane-type sesquiterpenoids have been reported, which possessed anti-tumor, anti-inflammatory, antibacterial, and antiviral activities. Herein, this paper describes their chemical constituents and pharmacological activities, hoping to bring benefits for further research and lay a foundation for investigating the structure-activity relationships.

[Phenolic constituents from stems of Ilex asprella].

Phytochemical investigation on Ilex asprella stems by using various chromatographic techniques led to the isolation of 18 phenolic constituents. Based on spectroscopic data analyses and/or comparison of the spectroscopic data with those in literature, these constituents were identified, including two lignans (1, 2), five phenylpropanes (3-7), six chlorogenic analogues (8-13), and five benzoic analogues (14-18). Among them, compounds 3-7, 9, 11, 13, 14, 17, and 18 were isolated from genus Ilex for the first time, and 2, 8, 10, 15, and 16 were isolated from this species for the first time. The in vitro anti-inflammatory assay results showed that compounds 8, 9, 11, 13, and 15 possessed moderate inhibition on the NO production in RAW264.7 cells with IC50 values of 51.1-85.8 µmol·L⁻¹. The present study brought preliminary reference for the clarification of therapeutic ingredients of I. asprella with anti-inflammatory efficacy and its quality evaluation.

[Chemical and pharmacological progress on usnic acid and its derivatives].

Usnic acid and its derivatives, a group of organic molecules with great importance, are characteristic to lichens, possessing pharmacological activities such as anti-virus, anti-bacteria, anti-humor, anti-inflammatory, analgesic, and anaesthetic effects. Many of them have been widely used as medicine, but also bring side effects such as dermatitis and liver damages. In the past decades, great efforts by isolation, organic synthesis, and structure modification methods were put on discovery of UA derivatives with higher biological activities or less side effects. This paper describes herein the most progress on natural sources, isolation and structure elucidation, structural characteristics, synthesis and modification results, pharmacological activities and toxicities of UA and its derivatives, hopefully to provide valuable reference for further research.

[Chemical constituents from a Tibetan herbal medicine Corydalis hendersonii].

Nine alkaloids and two phenolic glycosides were isolated from EtOH extract of the whole plants of Corydalis hendersonii by various chromatographic techniques including silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified as groenlandicine (1), berberine (2), protopine (3), cryptopine (4), N-trans-feruloyloctopamine(5), 3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl] acrylamide (6), N-cis-p-coumaroyloctopamine (7), N-trans-p-coumaroylnoradrenline (8),N-cis-feruloyloctopamine (9), apocynin (10), and glucoacetosyringone (11) by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 10 and 11 were isolated from this genus for the first time, and 1, 2, and 5-9 were isolated from the species for the first time. All isolates were tested for their protection for in vitro PC12 cell line and antiplatelet aggregation activity. The results showed that compounds 5 and 7 displayed protective effects at a concentration of 10 µmol·L⁻¹, and compound 2 showed antiplatelet aggregation activity induced by THR, ADP, and AA, and compound 3 exhibted inhibitory effect induced by THR.