Nephrotoxicity of Herbal Medicine and Its Prevention.

Herbal medicine (HM) has been widely used to treat diseases for thousands of years and has greatly contributed to the health of human beings. Many new drugs have been developed from HM, such as artemisinin. However, artemisinin has adverse effects, such as renal toxicity. In 1993, a study conducted in Belgium reported for the first time that the root extracts of Aristolochia obliqua S. M. Hwang led to progressive interstitial renal fibrosis. The nephrotoxicity of HM has attracted worldwide attention. More than 100 kinds of HM induce renal toxicity, including some herbs, animal HMs, and minerals. This paper aimed to summarize the HM compounds that cause nephrotoxicity, the mechanisms underlying the toxicity of these compounds, biomarkers of renal injury, and prevention strategies. These findings provide a basis for follow-up studies on the prevention and treatment of HM nephrotoxicity.

The Phytochemistry, Pharmacology, and Quality Control of Tetrastigma hemsleyanum Diels & Gilg in China: A Review.

Tetrastigma hemsleyanum Diels & Gilg (TDG), the family member of Vitaceae, is a traditional herbal medicine in China. The root of TDG can be immediately used after cleaning the muddy soil, and can be dehydrated for dry use. TDG is able to be collected all year round, which is commonly used in the treatment of hepatitis, infantile high fever, snake bite, etc. Based on phytochemistry, the chemical components of TDG are divided into flavonoids, phenolic acids, terpenes, steroids, polysaccharide, and other compounds, showing many pharmacological effects which include anti-tumor, anti-oxidation, anti-inflammatory, antipyretic, analgesic, and immunomodulatory activity, as well as other activities. Currently, TDG involves some problems of the reduction of wild resources, the backward processing methods, and storage difficulties as well as the imperfection of detection methods. Therefore, this review summarizes the literature of the past 20 years, and the purpose of this review is to summarize the recent researches on the phytochemistry, pharmacology, quality control, and clinical application of TDG. The above discussions provide new insights for the future research on TDG.

Danshensu, a novel indoleamine 2,3-dioxygenase1 inhibitor, exerts anti-hepatic fibrosis effects via inhibition of JAK2-STAT3 signaling.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1), an important intracellular rate-limiting enzyme in the development of Hepatic fibrosis (HF), and has been proposed as a hallmark of HF. Danshensu (DSS) is a major bioactive component that isolated from a edible traditional Chinese medicinal herb Salviae Miltiorrhizae Radix et Rhizoma (Danshen), while, the anti-HF mode and mechanism of action of DSS have not been fully elucidated. METHODS: Carbon tetrachloride (CCl4)-induced rat HF model and TGF-ß1-induced hepatic stellate cell (HSC) model were employed to assess the in vivo and in vitro anti-HF effects of DSS. HSC-T6 cells stably expressing IDO1, a constitutively active IDO1 mutant, was used to determine the role of JAK2-STAT3 signaling in the DSS's anti-HF effects. RESULTS: We found that intragastric administration of DSS potently reduced fibrosis, inhibited IDO1 expression and STAT3 activity both in vitro and in vivo. Using molecular docking and molecular dynamics analysis, DSS was identified as a novel IDO1 inhibitor. Mechanistic studies indicated that DSS inhibited JAK2-STAT3 signaling, it reduced IDO1 expression, STAT3 phosphorylation and STAT3 nuclear localization. More importantly, overexpression of IDO1 diminished DSS's anti-HF effects. CONCLUSION: Our findings provide a pharmacological justification for the clinical use of DSS in treating HF, and suggest that DSS has the potential to be developed as a modern alternative and/or complimentary agent for HF treatment and prevention.

Total Glycosides of Peony Protects Against Inflammatory Bowel Disease by Regulating IL-23/IL-17 Axis and Th17/Treg Balance.

Inflammatory bowel disease (IBD) is a group of autoimmune diseases, including ulcerative colitis and Crohn's disease, characterized by nonspecific inflammation in the gut. Total glycoside of peony (TGP) has been widely used for treatment of autoimmune diseases because of its pharmacological effects. However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD. Hence, the aim of this study was to investigate the effects of TGP on experimental colitis mice and the related mechanisms. In the present study, we demonstrated that administration of TGP effectively attenuates colonic inflammation of TNBS-induced colitis mice, mainly reflected in significantly improved clinical parameters, reduced inflammatory response and myeloperoxidase (MPO) activity, even stronger systemic immune ability and effective improvement of Th17/Treg immune disorders. In addition, there was a stronger immunosuppressive ability in a positive cluster of differentiation 4 (CD4 + ) T-lymphocytes from the TGP treated mouse colon, characterized by the inhibition of high levels of inflammatory factors and increased regulatory T cells. Importantly, high-dose TGP has similar therapeutic effects as salicylazosulfapyridine (SASP) on IBD treatment. The potential mechanisms might be, at least in part, related to the adjustment of imbalance of Th17/Treg cells and the inhibition of IL-23/IL17 inflammatory signal axis.