Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites

Zhu, Meizhen; Wang, Xue; Wang, Kai; Zhao, Zhiqiang; Dang, Yanqi; Ji, Guang; Li, Fenghua; Zhou, Wenjun

doi:10.3389/fcimb.2023.1066053

Cited by 13 publications

(3 citation statements)

References 62 publications

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“…Continuous intake of ethanol induces the production of iNOS ( Davis and Syapin, 2004 ), an isoform of nitric oxide synthase which oxidizes L-arginine to L-citrulline and generates nitric oxide ( Chen et al, 2015 ). The nitric oxide combines with the superoxide anion to form an oxidant that causes lipid peroxidation, which damages the body ( Zhu et al, 2023 ). In addition, the intervention of YEH significantly reduced the levels of IL-1β, TNF-α, and IFN-γ ( Figures 3A – C ), with effects that were even better than those that were observed in the silymarin intervention group.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of yeast extract against alcohol-induced liver injury in rats

Lin

Wang

et al. 2023

Front. Microbiol.

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Oxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury. Previous research established that yeast extract (YE) has antioxidant, immune-boosting or microbiota-regulating properties. However, there is currently lack of information regarding the efficacy of YE on alcoholic liver injury. This study seeks to obtain data that will help to address this research gap using a Wistar male rat experimental model. Histologic and biochemical analysis results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of Peptococcus and Ruminococcus reduced in the low-dose yeast extract (YEL) group, while that of Peptococcus, Romboutsia, Parasutterella, and Faecalibaculum reduced in the high-dose (YEH) group. Furthermore, Spearman analysis showed that the gut microbes were significantly associated with several liver-related indicators. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5′ -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder. Besides, high-dose YE has been found to be more effective than low-dose YE in metabolic regulation, as well as in dealing with oxidative stress and inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Protective effects of yeast extract against alcohol-induced liver injury in rats

Lin

Wang

et al. 2023

Front. Microbiol.

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“…Regretfully, we were not able to select the most effective dose of probiotics by comparing our present data. However, from the analysis, we proposed that the probiotics supplementation, especially Lactobacillus and Bifidobacterium , may be beneficial in the patients with morbid obesity undergoing bariatric surgery, for 9 studies used either Lactobacillus or Bifidobacterium except the study of Kazzi and Han et al And the durations of probiotics supplementation mostly were 3 months postoperatively except the duration of Han and Woodard et al were 6 months (Results related with serum TNF-a and IL-6 levels in Sherf-Dagan were also 6 months) [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis

Wang,

Zheng,

Kuang

et al. 2023

Int J Obes

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Background Probiotics are commonly used after bariatric surgery. However, uncertainty remains regarding their effects. The purpose of this systematic review was to assess the effect of probiotics in patients with morbid obesity undergoing bariatric surgery. Methods PubMed, Cochrane Library, Embase, Science Direct, and Web of Science were searched from inception to April 4, 2023. No language restrictions were applied. Relevant randomized controlled trials and controlled clinical trials were included. We used the aggregated data extracted from the trials and assessed the heterogeneity. When severe heterogeneity was detected, a random effect model was used. All stages of the review were done by independent authors. Results We screened 2024 references and included 11 randomized controlled trials and controlled clinical trials. Compared with the protocol groups, probiotics showed significant effects on regulating aspartate amino transferase level (MD = −4.32 U/L; 95% CI [−7.10, −1.53], p = 0.002), triglycerides (MD = −20.16 mg/dL; 95% CI [−34.51, −5.82], p = 0.006), weight (MD = −1.99 kg; 95% CI [−3.97, −0.01], p = 0.05), vitamin B12 (MD = 2.24 pg/dL; 95% CI [−0.02, 4.51], p = 0.05), dietary energy (MD = −151.03 kcal; 95% CI [−215.68, −86.37], p < 0.00001), dietary protein (MD = −4.48 g/day, 95% CI [−8.76, −0.20], p = 0.04), dietary carbohydrate (MD = −34.25 g/day, 95% CI [−44.87, −23.62], p < 0.00001), and dietary fiber (MD = −2.17 g/day, 95% CI [−3.21, −1.14], p < 0.0001). There were no severe side effects related to probiotics. Conclusions Our meta-analysis suggested that probiotics may delay the progression of liver function injury, improve lipid metabolism, reduce weight, and reduce food intake, although the effects on other indicators were insignificant. Probiotics may be helpful for patients undergoing bariatric surgery. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42023407970. No primary source of funding.

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“…For example, Penthorum chinense Pursh has been shown to attenuate high-fat diet-induced NAFLD by regulating the gut microbiota and bile acid (BA) metabolism in mice ( Li X. et al, 2022 ). Lingguizhugan decoction has been shown to improve insulin resistance (IR), hepatic steatosis, and non-alcoholic steatohepatitis (NASH) by modulating the gut microbiota and correlated metabolites ( Ning et al, 2022 ; Zhu et al, 2023 ), such as BAs, amino acids (AAs), and short-chain fatty acids (SCFAs). Therefore, gut microbiota and correlated metabolites have emerged as novel therapeutic strategies for potential TCM interventions in NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites

Chen,

Wang,

Yang

et al. 2024

Front. Pharmacol.

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Purpose: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment of NAFLD. The new mechanism of “Shenling Baizhu San” (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level.Methods: Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl4 injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics.Results: SLBZS intervention for 6 weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (Bifidobacterium and Parvibacter) and inhibiting the growth of pro-inflammatory bacteria (Erysipelatoclostridium and Lachnoclostridium) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS.Conclusion: Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.

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Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites

Cited by 13 publications

References 62 publications

Protective effects of yeast extract against alcohol-induced liver injury in rats

Protective effects of yeast extract against alcohol-induced liver injury in rats

Effects of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites

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