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Abstract Ethnopharmacological relevance Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. Aim of the study Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl 4 -induced liver injury in rats and to explore the underlying mechanisms. Materials and methods Hepatic fibrosis was induced by intraperitoneal injection of CCl 4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. Results HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. Conclusion This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Tibetan medicine Herpetospermum caudigerum Wall. (HCW) has long been employed to treat hepatitis, inflammatory diseases and jaundice according to the records of "The Four Medical Tantras" in China. This study was investigated to explore the protective effects of HCW on hepatic fibrosis and the possible mechanism in a rat model. Hepatic fibrosis was established by intragastric administration of 3 ml/kg carbon tetrachloride (CCl4 ) twice a week for 6 weeks. CCl4 -treated rats were received HCW (1 and 3 g/kg/d) and silymarin (0.1 g/kg/d) from 3 to 6 weeks. The results showed that HCW could significantly decrease the levels of AST, ALT, HA, LN, PCIII, Col IV, TNF-α, IL-1β and IL-6. Moreover, HCW could effectively inhibit collagen deposition and reduce the pathological damage. Analysis experiments finally exhibited that HCW was able to markedly inhibit hepatic fibrosis by modulating the expressions of NF-κB p65, IκBα, Samd3 and TGF-β1 proteins. Therefore, our results suggest that HCW has hepatoprotective activity against CCl4 -induced hepatic fibrosis in rats by regulating the inflammatory responses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease that represents an important public health challenge nowadays. Despite the growing number of studies assessing the rehabilitation outcome of Wuqinxi for COPD, their many variables and observations are often explored with a relatively small sample size, accordingly maybe lead to potential false-positive results. The aim of this systematic review and meta-analysis is to evaluate the rehabilitation efficacy of Wuqinxi for COPD.METHODS: A detailed search for articles up to June 2019 will be performed to identify randomized controlled trials for Wuqinxi in COPD. The following database will be used: PUBMED, Embase, Scopus, Web of Science, Google Scholar, Cochrane Library, Sino Med, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodicals Database, and Wanfang Database. Grey literature will be explored and the selection of studies, data extraction and validation will performed independently by 2 reviewers using predefined selection criteria and quality indicators. Stata V.13.0 and Review manager 5.3 software will be used for data synthesis, sensitivity analysis, subgroup analysis, and risk of bias assessment. We will use the grading of recommendations assessment, development, and evaluation system to assess the quality of evidence. RESULTS: This research will update previous evidence summaries and provide a quantitative and standardized assessment of the rehabilitation efficacy of Wuqinxi for COPD. CONCLUSION: This systematic review will generate the latest evidence for determining whether Wuqinxi has a positive rehabilitation effect for COPD.PROSPERO registration number: PROSPERO CRD 42019120960.

The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)-induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase (CK), lactate dehydrogenase, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), glutathione, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured after the rats were killed. iNOS, COX-2, NF-κB and PI3K/Akt/mTOR pathway proteins were detected by Western blot. In vitro, we evaluated the protective effect of Sal on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Reactive oxygen species (ROS) in H9c2 cells was measured by flow cytometry, and the activities of the antioxidant enzymes CAT, SOD, GSH-px, glutathione-S-transferase, TNF-α, IL-6 and IL-1β in cellular supernatant were measured. PI3K/Akt/mTOR signalling was examined by Western blot. As a result, Sal significantly attenuated the above indices. In addition, Sal exerts pronounced cardioprotective effect in rats subjected to LPS possibly through inhibiting the iNOS, COX-2, NF-κB and PI3K/Akt/mTOR pathway in vivo. Furthermore, the pharmacological effect of Sal associated with the ROS-mediated PI3K/Akt/mTOR pathway was proved by the use of ROS scavenger, N-acetyl-l-cysteine, in LPS-stimulated H9C2 cells. Our results indicated that Sal could be a potential therapeutic agent for the treatment of cardiovascular disease.

Liver fibrosis is a severe health problem, threatening the life quality and causing death, raising great concerns worldwide. Shi-Wei-Gan-Ning-Pill (SWGNP) is a traditional Tibetan recipe used to treat hepatic injuries; however, its hepatoprotective mechanism has not yet fully clarified. In this study, histological staining, biochemical assays, and elements determination were applied to evaluate the anti-fibrotic efficacy of SWGNP on a carbon tetrachloride (CCl4) induced hepato-fibrosis rat model. NMR-based metabolomics combined with orthogonal partial least squares-discriminant analysis (OPLS-DA), canonical regression analysis, and correlation networks analysis was used to characterize the potential biomarkers as well as metabolic pathways associated with the hepatoprotective activity of SWGNP. The results showed that SWGNP could significantly attenuate the pathological changes and decrease the levels of fibrosis markers (ColIV, HA, LN, and PCIII), and regulate the disordered elements distribution. Multivariate analysis and correlation network analysis revealed that SWGNP could protect rats against CCl4-induced liver fibrosis through anti-oxidation, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. In conclusion, this integrated metabolomics approach provided new insights into the mechanism of the hepatoprotective effect of SWGNP in liver fibrosis disease.

Two new polyhydroxy polyacetylenes, herpecaudenes A and B (1 and 2), were isolated from the ethanol extract of fruits of Herpetospermum caudigerum, an important Tibetan medicine. The structures of them were elucidated on the basis of extensive spectroscopic methods including UV, IR, HRESIMS, 1H and 13C NMR, HMBC, HSQC, and 1H-1H COSY. Compound 2 showed significant inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages with IC50 values of 7.05 ± 1.59 µM.