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Germacrone, a kind of natural sesquiterpenoid compound, has been reported to exhibit many pharmacological properties, especially the anticancer effect. Many in vitro experiments have been performed on various cancer cell lines, trying to explore their anticancer mechanism. Aiming at investigating the anticancer effect of germacrone, this article reviews the extant information on existing literature about germacrone-related studies. The anticancer mechanisms and clinical usages of germacrone are summarized. Literature databases (such as PubMed and CNKI) are used to search the current studies and experimental research about the anticancer effect information of germacrone. Anticancer mechanism of germacrone includes cell cycle arrest inducing, programmed cell death (apoptosis, autophagy, pyroptosis and ferroptosis) inducing, and estrogen-related genes mediating. Structural modification and analogue design are worthy of further study in the future.

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OBJECTIVE: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis. METHODS: Murine left common carotid artery was injured by completely ligation, and paeonol was administrated by intraperitoneal injection. Hematoxylin and eosin (H&E) staining was performed to visualize vascular neointima formation. Rat aortic SMCs were used to determine whether paeonol suppresses cell proliferation and migration. And murine hind limb ischemia model was performed to confirm the function role of paeonol in suppressing vasculogenesis. RESULTS: Complete ligation of murine common carotid artery successfully induced neointima formation. Paeonol treatment dramatically reduced the size of injury-induced neointima. Using rat aortic primary SMC, we identified that paeonol strongly suppressed cell proliferation, migration, and decreased extracellular matrix deposition. And paeonol treatment dramatically suppressed vasculogenesis after hind limb ischemia injury. CONCLUSION: Paeonol could regulate SMC phenotypic switching through inhibiting proliferation and migration of SMC, which results in inhibiting ischemia-induced vasculogenesis.

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BACKGROUND: Sanguinarine, a kind of benzophenanthridine alkaloid, is a natural compound with potential development value for its anticancer activity. Hundreds of studies have been carried out in vivo or in vitro, trying to make it feasible for the anticancer clinic medication of sanguinarine. However, sanguinarine was branded as a toxicant or even a carcinogen according to some toxicological experiments and cancer investigations. OBJECTIVE: Aiming at safety and effectiveness of sanguinarine, this article reviews the extant information on present studies of sanguinarine, and both anticancer carcinogenesis mechanism details are summarized. The future potential research directions of this valued compound are also discussed to provide reference for future drugs development. METHODS: PubMed, Web of Science, CNKI and WanFang databases were used to search current studies and experimental researches about anticancer effect or carcinogenic information of sanguinarine. RESULTS: Our results indicated that sanguinarine exhibited anticancer effect through anti-proliferation, anti-invasion, anti-angiogenesis and apoptosis within cancer lesion. Also, many clinical investigations indicated that sanguinarine and its related products might be associated to pre-carcinoma within oral or skin potentially. CONCLUSION: Sanguinarine is a natural compound with good development value for its potent anticancer activity; however, its carcinogenesis effect should also be taken seriously. Studies on structural modification and analogue design should be carried out to improve its safety and efficiency in the future.

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INTRODUCTION: Zukamu granules may play a potential role in the fight against the Coronavirus, COVID-19. The purpose of this study was to explore the mechanisms of Zukamu granules using network pharmacology combined with molecular docking. METHODS: The Traditional Chinese Medicine systems pharmacology (TCMSP) database was used to filter the active compounds and the targets of each drug in the prescription. The Genecards and OMIM databases were used for identifying the targets related to COVID-19. The STRING database was used to analyze the intersection targets. Compound - target interaction and protein-protein interaction networks were constructed using Cytoscape to decipher the anti-COVID-19 mechanisms of action of the prescription. The Kyoto Encyclopedia of Genes and Genome (KEGG) pathway and Gene Ontology (GO) enrichment analysis was performed to investigate the molecular mechanisms of action. Finally, the interaction between the targets and the active compounds was verified by molecular docking technology. RESULTS: A total of 66 targets were identified. Further analysis identified 10 most important targets and 12 key compounds. Besides, 1340 biological processes, 43 cell compositions, and 87 molecular function items were obtained (P < 0.05). One hundred and thirty pathways were obtained (P < 0.05). The results of molecular docking showed that there was a stable binding between the active compounds and the targets. CONCLUSION: Analysis of the constructed pharmacological network results allowed for the prediction and interpretation of the multi-constituent, multi-targeted, and multi-pathway mechanisms of Zukamu granules as a potential source for supportive treatment of COVID-19.

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L-arginine/NOS/NO signaling pathway plays a critical role in controlling variety of vascular diseases. However, whether NOS inhibition by L-NAME suppresses late embryonic development is undefined. The aim of this study is to determine whether NOS inhibition by L-NAME is critical for late embryonic rat hind limb development. The pregnant rat at E13.5 administrated L-NAME by consecutive intraperitoneal injection. The embryos been harvested from E16.5 to E 20.5. Hematoxylin and Eosin Staining, Immunofluorescence and Immunohistochemistry performed to determine hind limb Vasculogenesis, HUVEC culture, Adenoviral PFKFB3 infection, Real time PCR and western blot were performed to determine whether L-arginine/NOS/NO pathway controlling late embryonic hind limb development through PFKFB3 mediated angiogenetic pathway. NOS inhibition by L-NAME resulting in late embryonic hind limb developmental defects characterized by severe hemorrhage. The in vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis. For underlie mechanism, our studies indicated that L-NAME treatment dramatically suppresses PFKFB3 expression in hematopoietic progenitor cells, tubulogenetic endothelial cells and smooth muscle cells. Knockdown of PFKFB3 dramatically inhibits the expression of angiogenetic genes, as well as tubulogenesis and extracellular matrix related genes. Taken together, our data in this study demonstrated that L-arginine-eNOS-NO pathway is important for rat hind limb development during late embryonic stage. This could be both a useful animal model and a promising therapeutic treatment for defects of late embryonic developmental hind limbs.

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Metabolic diseases constitute a major public health burden and are linked with high morbidity and mortality. They comprise atherosclerosis dyslipidemia, diabetes, hypertension, and obesity. However, there is no single drug that can simultaneously treat multiple diseases with complex underlying mechanisms. Therefore, it is necessary to identify a class of adjuvant drugs that block the development of metabolic diseases from a preventive perspective. Red yeast rice is a food fermentation product widely used to promote blood circulation and remove blood stasis. Modern pharmacology has shown that red yeast rice exerts potential protective effects on the liver, pancreas, blood vessels, and intestines. Therefore, this study was carried out to analyze and summarize the effect of red yeast rice on several metabolic diseases and the mechanisms of action involved. It was found that red yeast rice may be beneficial in the prevention and treatment of metabolic diseases.

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Myopathy is a muscle disease in which muscle fibers do not function properly, and eventually cause severe diseases, such as muscular dystrophy. The properly regeneration of skeletal muscle plays a pivotal role to maintain the muscle function after muscle injury. The aim of this study is to determine whether andrographolide plays an effect role on regulating skeletal muscle regeneration. Mouse satellite cells, C2C12 cells and Cardiotoxin (CTX) intramuscular injection induced acute skeletal muscle injury model were used to evaluate whether andrographolide is essential for skeletal muscle regeneration. The underling mechanism detected using immunohistochemistry stain, western blot, real time PCR. Andrographolide promotes mouse skeletal muscle regeneration. In cardiotoxin induced skeletal muscle injury model, andrographolide treatment enhanced myotube generation and promoted myotube fusion. Andrographolide treatment dramatically increased expression of myotube differentiation related genes, including Desmin, MyoD, MyoG, Myomaker, Tnni2, Dmd, Myoz1 and Myoz3. For the mechanism studies, we observed that andrographolide treatment significantly promoted histone modification, such as H3K4Me2, H3K4Me3 and H3K36Me2, both in vivo and in vitro. Treatment with DZNep, a Lysine methyltransferase EZH2 inhibitor, significantly attenuated andrographolide-induced expression of Myf5, Myomaker, Skeletal muscle α-actin, MyoD and MyoG. Taken together, our data in this study demonstrate andrographolide epigenetically drives differentiation and fusion of myotube, eventually promotes skeletal muscle regeneration. This should be a therapeutic treatment for skeletal muscle regeneration after muscle damage.

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The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.

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Cancer has become a significant public health problem with high disease burden and mortality. At present, radiotherapy and chemotherapy are the main means of treating cancer, but they have shown serious safety problems. The severity of this problem has caused further attention and research on effective and safe cancer treatment methods. Polysaccharides are natural products with anti-cancer activity that are widely present in a lot of plants, and many studies have found that inducing apoptosis of cancer cells is one of their important mechanisms. Therefore, this article reviews the various ways in which plant polysaccharides promote apoptosis of cancer cells. The major apoptotic pathways involved include the mitochondrial pathway, the death receptor pathway, and their upstream signal transduction such as MAPK pathway, PI3K/AKT pathway, and NF-κB pathway. Moreover, the paper has also been focused on the absorption and toxicity of plant polysaccharides with reference to extant literature, making the research more scientific and comprehensive. It is hoped that this review could provide some directions for the future development of plant polysaccharides as anticancer drugs in pharmacological experiments and clinical researches.

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Diabetes mellitus is a chronic and common metabolic disease that seriously endangers human health. Hyperglycemia and long-term metabolic disorders in diabetes will cause damage to the whole body tissues and organs, resulting in serious complications. Nowadays, drugs for treating diabetes on the market has strong side effects, new treatments thus are urgently needed. Natural therapy of natural ingredients is a promising avenue, this is because natural ingredients are safer and they also show strong activity in the treatment of diabetes. Diosgenin is such a very biologically active natural steroidal sapogenin. The research of diosgenin in the treatment of diabetes and its complications has been widely reported. This article reviews the effects of diosgenin through multiple targets and multiple pathways in diabetes and its complications which including diabetic nephropathy, diabetic liver disease, diabetic neuropathy, diabetic vascular disease, diabetic cardiomyopathy, diabetic reproductive dysfunction, and diabetic eye disease.

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INTRODUCTION: The novel coronavirus pneumonia that broke out in 2019 has become a global epidemic. According to the diagnosis and treatment plan issued in China and the existing clinical data, Shufeng Jiedu (SFJD) Capsule can be effectively used in the treatment of COVID-19 patients. This study aimed to explore its mechanism of action by network pharmacology and molecular docking technology. METHODS: The Chinese Medicine System Pharmacology Analysis Platform (TCMSP), a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM), the Encyclopedia of Traditional Chinese Medicine (ETCM) and related literature records were used to search the composition and main active compounds of SFJD, and to screen out the targets of drug components. Disease-associated genes were obtained by the Human Gene Database (GeneCards), the Human Online Mendelian Inheritance Platform (OMIM) and the DisGeNET database, and the co-targeted genes/proteins as targets of both SFJD and COVID-19 were selected by the Comparative Toxicogenomics Database (CTD). Co-targeted genes/proteins were analyzed by STRING, the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Reactome for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment, and predicted by AutoDock for their high-precision docking simulation. In addition, the therapeutic effect for SFJD treatment on COVID-19 was validated by the Chinese medicine anti-novel coronavirus pneumonia drug effect prediction and analysis platform (TCMCOVID). RESULTS: Screening resulted in 163 compounds and 463 targeted genes. The PPI core network contains 76 co-targeted proteins. The Reactome pathways were enriched in signaling by interleukins, immune system, etc. Finally, 6 key proteins of TNF, IL-10, IL-2, IL-6, STAT1 and CCL2 were selected and successfully docked with 4 active ingredients of quercetin, luteolin, wogonin and kaempferol. CONCLUSION: SFJD may play a role in the prevention and treatment of COVID-19 through multiple active compounds acting on multiple targets and then multiple pathways.

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CONTEXT: Coptidis rhizome (CR), also known as Huanglian in Chinese, is the rhizome of Coptis chinensis Franch., C. deltoidea C.Y. Cheng et Hsiao, or C. teeta Wall (Ranunculaceae). It has been widely used to treat bacillary dysentery, diabetes, pertussis, sore throat, aphtha, and eczema in China. OBJECTIVES: The present paper reviews the latest advances of CR, focusing on the botany, phytochemistry, traditional usages, pharmacokinetics, pharmacology and toxicology of CR and its future perspectives. METHODS: Studies from 1985 to 2018 were reviewed from books; PhD. and MSc. dissertations; the state and local drug standards; PubMed; CNKI; Scopus; the Web of Science; and Google Scholar using the keywords Coptis, Coptidis Rhizoma, Huanglian, and goldthread. RESULTS: Currently, 128 chemical constituents have been isolated and identified from CR. Alkaloids are the characteristic components, together with organic acids, coumarins, phenylpropanoids and quinones. The extracts/compounds isolated from CR cover a wide pharmacological spectrum, including antibacterial, antivirus, antifungal, antidiabetic, anticancer and cardioprotective effects. Berberine is the most important active constituent and the primary toxic component of CR. CONCLUSIONS: As an important herbal medicine in Chinese medicine, CR has the potential to treat various diseases. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs and pharmacokinetics, and to establish criteria for quality control, for CR and its related medications. In addition, the active constituents, other than alkaloids, in both raw and processed products of CR should be investigated.

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Different kinds of factors contribute to gastric ulcer development which characterized by damaging gastric mucosal layer. However, gastric vascular homeostasis is not well defined and whether andrographolide has a protective function is largely unknown. The goal of this study is to investigate the potential function roles and underlying mechanism by which andrographolide regulates gastric vascular homeostasis in vivo and in vitro. Gastric ulcer animal model induced on andrographolide pretreated C57/BL6 mouse by ethanol intragastric administration. Hematoxylin and Eosin Stain, Masson's trichrome stain and Immunohistochemistry stain performed to observe gastric vascular homeostasis, which associated hemorrhage, extracellular matrix deposition and macrophage infiltration. The activity of vascular endothelial cells were associated with the proliferation and migration, which were detected using cell counting, MTS, and wound scratch healing assay. The underlying endothelial glycolytic mechanism investigated in vivo and in vitro. Andrographolide pretreatment dramatically attenuates ethanol intragastric administration induced imbalance of gastric vascular homeostasis which characterized by severe hemorrhage, increase extracellular matrix deposition and augment macrophage infiltration. Andrographolide treatment conspicuous inhibits HUVEC-C activity characterized by suppressing proliferation and migration of endothelial cells. Mechanically, andrographolide treatment significant suppresses the expression of glycolytic genes, especially decrease PFKFB3 expression. The treatment with PFKFB3 inhibitor, 3-PO, exacerbates the inhibitory function of andrographolide on vascular endothelial cell proliferation and migration. Those data Suggests that andrographolide contributes to maintain gastric vascular homeostasis, at least partially, by inhibiting PFKFB3 mediated glycolysis pathway. Andrographolide plays a crucial role in maintaining gastric vascular homeostasis during gastric ulcer development through regulating vascular endothelial cell glycolytic pathway.

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Obesity is a chronic metabolic disease caused by multiple factors and is considered to be a risk factor for type 2 diabetes, cardiovascular disease, hypertension, stroke and various cancers. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against obesity diseases. Our review discusses mechanisms of hesperidin in the treatment of obesity. Hesperidin regulates lipid metabolism and glucose metabolism by mediating AMPK and PPAR signaling pathways, directly regulates antioxidant index and anti-apoptosis, and indirectly mediates NF-κB signaling pathway to regulate inflammation to play a role in the treatment of obesity. In addition, hesperidin-enriched dietary supplements can significantly improve symptoms such as postprandial hyperglycemia and hyperlipidemia. Further clinical trials are also required for confirming lipid-lowering efficacy of this natural flavonoid and evaluating its safety profile.

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