Natural products in traditional Chinese medicine: molecular mechanisms and therapeutic targets of renal fibrosis and state-of-the-art drug delivery systems.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Artemisia anomala S. Moore: A review of botany, traditional uses, phytochemistry, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia anomala S. Moore (family: Asteraceae) is a traditional herb that has been used for medicinal purposes in China for more than 1300 years. In traditional and local medicine, A. anomala is widely used in the treatment of rheumatic, dysmenorrhea, enteritis, hepatitis, hematuria and burn injury, and it is also considered as a natural botanical supplement in some areas, a traditional herb with both medicinal and edible properties. AIM OF THE REVIEW: The paper aims to provide a comprehensive overview of A. anomala, covering its botany, traditional uses, phytochemistry, pharmacological activity, and quality control, and to summarize the current research status in order to better understand the application value of A. anomala as a traditional herbal medicine and provide references for its further development and utilization. MATERIALS AND METHODS: The relevant information on A. anomala was collected by searching a range of literature and electronic databases using "Artemisia anomala" as the key search term. These sources included both ancient and modern books, the Chinese Pharmacopoeia, as well as various online databases such as PubMed, ScienceDirect, Wiley, ACS, CNKI, Springer, Taylor & Francis, Web of Science, Google Scholar, and Baidu Scholar. RESULTS: At present, 125 compounds have been isolated from A. anomala, including terpenoids, triterpenoids, flavonoids, phenylpropanoids, volatile oils and other compounds. Modern studies have confirmed that these active components have significant pharmacological activities, including anti-inflammatory, anti-bacterial, hepatoprotective, anti-platelet aggregation and anti-oxidation. In modern clinic, A. anomala is widely used in the treatment of rheumatoid arthritis, dysmenorrhea, irregular menstruation, traumatic bleeding, hepatitis, soft tissue contusion, burn and scald. CONCLUSIONS: Long-term traditional medicinal history and a large number of modern in vitro and in vivo studies have confirmed that A. anomala has a wide range of biological activities, which can provide rich resources for the discovery of promising drug candidates and the development of new plant supplements. However, the research on the active components and molecular mechanism of A. anomala is insufficient, and more mechanism-based pharmacological evaluation and clinical research should be carried out to provide a more powerful scientific basis for its traditional use. In addition, the index components and determination standards of A. anomala should be established as soon as possible, so as to establish a systematic and effective quality control system.

Mechanism of Citri Reticulatae Pericarpium as an Anticancer Agent from the Perspective of Flavonoids: A Review.

Citri Reticulatae Pericarpium (CRP), also known as "chenpi", is the most common qi-regulating drug in traditional Chinese medicine. It is often used to treat cough and indigestion, but in recent years, it has been found to have multi-faceted anti-cancer effects. This article reviews the pharmacology of CRP and the mechanism of the action of flavonoids, the key components of CRP, against cancers including breast cancer, lung cancer, prostate cancer, hepatic carcinoma, gastric cancer, colorectal cancer, esophageal cancer, cervical cancer, bladder cancer and other cancers with a high diagnosis rate. Finally, the specific roles of CRP in important phenotypes such as cell proliferation, apoptosis, autophagy and migration-invasion in cancer were analyzed, and the possible prospects and deficiencies of CRP as an anticancer agent were evaluated.

Zusanli (ST36) acupoint injection for acute diarrhea in children under 5 years old: A protocol of systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Acute diarrhea is the 2nd highest prevalence disease among children under 5 years of age. It can cause malnutrition and even death in children, especially in developing country. Traditional Chinese medicine therapy has been applied and already in the guidelines for clinical practice of acute infectious diarrhea in children in China, but there is no specific methods or recommendations due to lacking of evidence. Zusanli acupoint injection as a form of acupuncture therapy, which is proved to be effective in randomised controlled trials (RCTs) and very suitable for children, has been used in acute diarrhea in children for a long time; therefore, a systematic review is necessary to provide available evidence for further study. METHODS: Different studies from various databases will be involved in this study. Only RCTs of children under 5 years of age diagnosed with acute diarrhea using any recognized diagnostic criteria will be included. We will search manually the literature in the databases from China Conference Paper Database. Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet, WanFang, Chongqing VIP, and China Biomedical Literature CDROM Database. Primary outcomes: clinical cure rate (clinical cure is defined as the frequency, timing and character of stool back to normal status, as well as disappearance of diarrhea symptoms), diarrhea duration (from admission to the cessation of diarrhea). SECONDARY OUTCOMES: stool frequency within 24 hours, rate of adverse effect. Data will be extracted by 2 researchers independently; risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: This study will synthesize and provide evidence based on the data of the currently published zusanli (ST36) acupoint injection for acute diarrhea in children under 5 years old, especially in terms of clinical efficacy and safety. CONCLUSION: This systematic review aims to evaluate the benefits and harms of zusanli acupoint injection for acute diarrhea in children under 5 years old reported in RCTs, and provide evidence reference in TCM field for Chinese guidelines on the treatment of acute diarrhea in children. ETHICS AND DISSEMINATION: This study is a systematic review; the outcomes are based on the published evidence, and hence examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. PROSPERO REGISTRATION NUMBER: PROSPERO 2019 CRD42019135275.

A Significant Association Between Rhein and Diabetic Nephropathy in Animals: A Systematic Review and Meta-Analysis.

Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-clinical animal data to assess the current evidence for rhein effects and mechanisms in treating diabetic nephropathy. Methods: The databases of PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP information database, Wanfang Data Information Site, and Chinese Biomedical Literature were searched for this review. SYRCLE's risk of bias tool for animal studies was applied to assess the methodological quality of studies. A meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using RevMan 5.3 and STATA/SE 12.0 software. This study was registered with PROSPERO, number CRD42018105220. Results: Twenty-five studies involving 537 animals were included. There was significant association of rhein with levels of blood glucose (P < 0.05), serum creatinine (Scr) (P < 0.05), urine protein (P < 0.05), kidney tubules injury index (P < 0.05), relative area of kidney collagen (P < 0.05), transforming growth factor-ß1 (P < 0.05), malondialdehyde (P < 0.05), and superoxide dismutase (P < 0.05) compared with that in the control group. No significant association between rhein and endothelin (P > 0.05) was found. Subgroup analysis showed that the hypoglycemic effect of rhein on type 2 diabetic nephropathy was better than on type 1 diabetic nephropathy (P < 0.05). Conclusions: These findings suggested that rhein has beneficial effects on animal models of diabetic nephropathy, and that the mechanisms are mostly involved with ameliorating levels of TGF-ß1, renal fibrosis, metabolism, and oxidative stress status. However, some factors such as possible publication bias, methodological quality, and sample size may affect the accuracy of positive findings. These limitations suggested that a cautious interpretation of the positive results of this systematic review and meta-analysis is necessary. Therefore, high methodological quality and well-reported animal experiments are needed in future research.