Effects of Tylophora yunnanensis Schltr on regulating the gut microbiota and its metabolites in non-alcoholic steatohepatitis rats by inhibiting the activation of NOD-like receptor protein 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Tylophora yunnanensis Schltr (TYS) is widely distributed in Yunnan, Guizhou, and other places in China. It is commonly used by folks to treat hepatitis and other liver-related diseases; however, its mechanism of action is still unclear. AIM OF THE STUDY: This study aimed to determine the effects of TYS on regulating gut microbiota and its metabolites in non-alcoholic steatohepatitis (NASH) rats by inhibiting the activation of NOD-like receptor protein3 (NLRP3). MATERIAL AND METHODS: An HFD-induced rat model was established to investigate if the intragastric administration of TYS could mediate gut microbiota and their metabolites to ultimately improve the symptoms of NASH. The improving effects of TYS on NASH rats were assessed by measuring their body weight, lipid levels, histopathology, and inflammatory factor levels in the rat models. The regulatory effects of TYS on NLRP3 in the NASH rats were analyzed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), which determined the levels of NLRP3-related factors. The changes in the composition of the gut microbiota of NASH rats were analyzed using 16S rRNA gene sequencing technology. Meanwhile, the Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for the non-targeted analysis of metabolites in the cecum contents. RESULTS: The results showed that TYS could improve NASH by decreasing the body weight and levels of lipid, AST, ALT, LPS, FFA, VLDL, IL-1ß, IL-6, TNF-α, TGF-ß, NLRP3, ASC, and Caspase-1 in the NASH rats. The analysis of gut microbiota showed that TYS could improve the diversity and abundance of gut microbiota and alter their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio and relative abundances of Lachnospiraceae, Christensenellaceae, Blautia, etc. while increasing those of Muribaculaceae, Rumiaococcus, Ruminococcaceae, etc. The analysis of metabolites in the cecum contents suggested that the arachidonic acid metabolism, bile secretion, serotonergic synapse, Fc epsilon RI signaling pathway, etc. were regulated by TYS. The metabolites enriched in these pathways mainly included chenodeoxycholic acid, prostaglandin D2, TXB2, 9-OxoODE, and 13(S)-HOTrE. CONCLUSIONS: These findings suggested that TYS could alleviate the NASH symptoms by decreasing the body weight, regulating the lipid levels, reducing the inflammatory response, and inhibiting the expression levels of NLRP3, ASC, and Caspase-1 in the NASH rats. The changes in the composition of gut microbiota and their metabolic disorder were closely related to the activation of NLRP3. TYS could significantly inhibit the activation of NLRP3 and regulate the composition of gut microbiota and the disorder of metabolites during NASH modeling.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. METHODS: The effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. RESULTS: SAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of ß-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. CONCLUSION: SAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

[Determination of ursolic acid of Sambucus adnata].

HPLC was used to determine the content of ursolic acid of Sambucus adnata from different origins. The content of ursolic acid range between 1.14 to 5.7 microg, r = 0.999 8, the recovery range from 99.8% to 101.3%. The method is quick, sensitive and repeatable for determination of the content of ursolic acid of S. adnata.

[Studies on the chemical constituents of the leaves of Polygonum multiflorum].

OBJECTIVE: To study the chemical constituents of the leaves of Polygonum multiflorum. METHODS: The chemical constituents were extracted with water and separated by manifold chromatography technique, and their structures were determined by spectral analysis. RESULTS: Eleven compounds were isolated and identified as physcion (I), emodin (II), noreugenin (III), apigenin (IV), hyperoside (V), rutin (VI), vitexin (VII), 2,3,5 ,4'-tetrahydroxy-stibene-2-O-beta-D-glucoside (VIII), beta-amyrin (IX), beta-sitosterol (X), daucosterol( XI). CONCLUSION: Among these compounds, I - IV, VI - XI are isolated from the leaves of Polygonum multiflorum for the first time.

[Studies on chemical constituents from rattan of Polygonum multiflorum].

OBJECTIVE: To study on the chemical constituents from rattan of Polygonum multiflorum. METHODS: The chemical constituents were extracted with alcohol and were separated with manifold chromatography technique. Their structures were determined by spectral analysis. RESULTS: Thirteen compounds were isolated and identified as Chrysophanol(I), Physcion(II), Emodin(III), Aloeemodin(IV), Rhein(V), Physcion-8-O-beta-D-glucoside(VI), Emodin-8-O-beta-D-glucoside (VII),2,3,5,4'-Tetrahydroxy-stibene-2-O-beta-D-glucoside(VIII), Noreugenin(IX), Apigenin(X), Daucosterol(XI), beta-Sitosterol(XII), Stearic acid(XIII). CONCLUSION: Among these, compounds I, IV-VI, VIII-XI, XIII are isolated from rattan of Polygonum multiflorum for the first time.