San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism

Su, Xiuhai; Yu, Wenxia; Liu, Airu; Wang, Congxiang; Li, Xiuzhen; Gao, Juanjuan; Liu, Xiaofei; Jiang, Wenhui; Yang, Yue; Lv, Shuquan

doi:10.3389/fphar.2021.808867

Cited by 29 publications

(24 citation statements)

References 76 publications

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“…Christensenellaceae _R-7_group, Clostridia_UCG-014 and Parasutterella were all increased in the combined treatment group. Evidence showed that Christensenellaceae _R-7_group was increased with a special traditional Chinese medicine capsule intervention, which could ameliorated hyperglycemia and pathological changes in diabetic nephropathy in rat models ( Su et al, 2021 ). Clostridia_UCG-014 was identified as a probiotic associated with tryptophan metabolism in colitis mice and might mediate the improvement of gut barrier disruption, colon inflammation and the pathological phenotype ( Yang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Potential benefits of metformin and pioglitazone combination therapy via gut microbiota and metabolites in high-fat diet-fed mice

et al. 2022

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Metformin and pioglitazone monotherapy have been proven to alter gut microbiota in diabetes and obesity. The present study aimed to investigated whether the combined administration of pioglitazone and metformin achieved superior protective effects on high-fat diet (HFD)-fed obese mice and elucidated its molecular mechanism via the gut microbiota and its metabolites. C57BL/6 males were randomly divided into five groups: the control group, fed a normal control diet; the HFD group, fed an HFD; the metformin monotherapy group, fed an HFD and treated with metformin; the pioglitazone monotherapy group, fed an HFD and treated with pioglitazone; and the combination therapy group, fed an HFD and treated with metformin and pioglitazone combination therapy. The cecal contents were collected for 16S rDNA amplicon sequencing and untargeted metabolomics analysis. The results showed that the combination therapy of metformin and pioglitazone significantly improved insulin sensitivity and glucolipid metabolism in HFD-fed mice. Combination therapy markedly altered gut microbiota by increasing beneficial bacteria, such as Bifidobacterium, Christensenellaceae_R-7_group, Faecalibacterium and Roseburia, and decreasing harmful bacteria, such as Oscillibacter and Eubacterium_xylanophilum_group. Fecal metabolites were significantly changed in the combination therapy group, including a reduction in amino acid metabolism and augmentation of lipid metabolism, such as citrulline, sarcosine, D-glutamine, lipoxin A4, prostaglandin E2, stearidonic acid and lucidenic acid A. These results revealed that combined metformin and pioglitazone therapy had synergistic effects or at least have an additive effect on modifying gut microbiota and metabolites, closely associated with improved glucolipid metabolic parameters in HFD-fed mice, which provides novel evidence and promising targets for metformin and pioglitazone combination therapy in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Potential benefits of metformin and pioglitazone combination therapy via gut microbiota and metabolites in high-fat diet-fed mice

et al. 2022

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“…Exogenous supplementation of L-proline can enhance the antioxidant capacity of rats [ 34 ]. The results of metabonomics showed that proline metabolism was disordered, and excessive production of ROS caused by downregulation of proline would lead to intracellular damage of biomolecules, including cell cycle blocking, autophagy and apoptosis [ 35 ]. HMOX1 is a downstream target gene of HIF-1α.…”

Section: Discussionmentioning

confidence: 99%

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network

Chen

Zhang

Jiao

et al. 2022

Toxins

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Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (p < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.

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“…Phytochemical resveratrol treatment significantly reduced body and kidney weights but not the fasting blood sugar (FBS) of db/db mice, which were associated with the decrease in the F/B ratio after resveratrol treatment ( Cai et al, 2020 ). Qing-Re-Xiao-Zheng formula ( Gao Y. et al, 2021 ), Cordyceps cicadae polysaccharides ( Yang J. et al, 2020 ), and San-Huang-Yi-Shen capsule ( Su et al, 2022 ) significantly lowered serum glucose and the ratio of Firmicutes -to- Bacteroidetes in mice with diabetic kidney disease. While treatment with QiDiTangShen granules and Tangshen formula had no significant effects on the F/B ratio in db/db mice, this maybe partly explains why they do not alter body weight and glycemic levels in those mice ( Zhao et al, 2020 ; Wei et al, 2021 ).…”

Section: Animal Studies Of Natural Products For the Treatment Of Ckd ...mentioning

confidence: 99%

Natural products from plants and microorganisms: Novel therapeutics for chronic kidney disease via gut microbiota regulation

et al. 2023

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Dysbiosis of gut microbiota plays a fundamental role in the pathogenesis and development of chronic kidney disease (CKD) and its complications. Natural products from plants and microorganisms can achieve recognizable improvement in renal function and serve as an alternative treatment for chronic kidney disease patients with a long history, yet less is known on its beneficial effects on kidney injury by targeting the intestinal microbiota. In this review, we summarize studies on the effects of natural products from plants and microorganisms, including herbal medicines and their bioactive extracts, polysaccharides from plants and microorganisms, and phytochemicals, on the prevention and treatment of chronic kidney disease through targeting gut microflora. We describe the strategies of these anti-CKD effects in animal experiments including remodulation of gut microbiota structure, reduction of uremic toxins, enhancement of short-chain fatty acid (SCFA) production, regulation of intestinal inflammatory signaling, and improvement in intestinal integrity. Meanwhile, the clinical trials of different natural products in chronic kidney disease clinical practice were also analyzed and discussed. These provide information to enable a better understanding of the renoprotective effects of these effective natural products from plants and microorganisms in the treatment of chronic kidney disease. Finally, we propose the steps to prove the causal role of the intestinal microflora in the treatment of chronic kidney disease by natural products from plants and microorganisms. We also assess the future perspective that natural active products from plants and microorganisms can beneficially delay the onset and progression of kidney disease by targeting the gut flora and highlight the remaining challenges in this area. With the continuous deepening of studies in recent years, it has been proved that gut microbiota is a potential target of natural active products derived from plants and microorganisms for chronic kidney disease treatment. Fully understanding the functions and mechanisms of gut microbiota in these natural active products from plants and microorganisms is conducive to their application as an alternative therapeutic in the treatment of chronic kidney disease.

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San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism

Cited by 29 publications

References 76 publications

Potential benefits of metformin and pioglitazone combination therapy via gut microbiota and metabolites in high-fat diet-fed mice

Potential benefits of metformin and pioglitazone combination therapy via gut microbiota and metabolites in high-fat diet-fed mice

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network

Natural products from plants and microorganisms: Novel therapeutics for chronic kidney disease via gut microbiota regulation

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