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FITOTERAPIA · 2025 · IF 2.6

Astragalus membranaceus improves blood glucose and renal function in diabetic kidney disease mice via gut microbial metabolite axis

Pei-Pei Zhang,Ming-Yang Cui,Shui-Yuan Yang,Bo Han,Wei Yu,Tian-Tian Wei,Ke-Wu Zeng,Peng-Fei Tu

Recent studies have demonstrated the therapeutic potential of Astragalus membranaceus in diabetic kidney disease (DKD); however, the underlying mechanisms remain incompletely elucidated. In this study, we established a streptozotocin-induced DKD mouse model to evaluate the effects of A. membranaceus extract (AME) on glycemic control, renal function, gut microbiota composition, and metabolic profiles. Biochemical analyzes revealed that A. membranaceus significantly attenuated hyperglycemia and improved renal function, as indicated by reduced serum creatinine and blood urea nitrogen levels. Metagenomic sequencing demonstrated that A. membranaceus reversed microbial dysbiosis by suppressing pathogenic bacteria (e.g., Aerococcus urinaeequi ) and enriching beneficial probiotics (e.g., Thomasclavelia cocleata ). Furthermore, LC/MS-based metabolomics identified key metabolic pathways, including glycerophospholipid metabolism and bile acid synthesis, as potential mediators of the therapeutic effects. These findings underscore the crucial role of the gut-renal axis in DKD pathogenesis and provide a mechanistic basis for the clinical application of A. membranaceus .

CAS / MDL: 68-04-2
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Food Bioscience · 2024 · IF 4.8

Collagen peptide and taurine synergistically improve hypertensive kidney injury induced by high salt diet through gut-kidney axis

Kai Shen,Shuqi He,WenDa Li,Siyi Song,Qianxia Lin,Huoxi Jin

Hypertensive kidney injury is significantly associated with oxidative stress, inflammation and gut microbiota. Collagen peptide and taurine (Tau) are key natural compounds known for their antioxidant, anti-inflammatory, and intestinal flora improvement. However, the potential synergistic actions of combining collagen peptides with Tau on hypertensive kidney damage remain unclear. Therefore, our study investigated the effects of collagen peptide LALFVPR (LR-7) derived from Harpadon nehereus in conjunction with Tau on renal injury in high salt (HS)-induced hypertension. The results showed that combination of LR-7 and Tau significantly alleviated renal fibrosis, glomerular atrophy, and impaired renal function in hypertensive mice. Furthermore, this combination outperformed individual treatments with either LR-7 or Tau alone in enhancing antioxidant enzyme activity while decreasing inflammatory factors and adhesion molecules levels in the kidneys. Moreover, LR-7 and Tau synergistically ameliorated HS-induced intestinal flora disturbance by promoting microbial diversity and adjusting the ratio of beneficial and harmful bacteria. Our research is pioneering in demonstrating that LR-7 combined with Tau may exert a synergistic effect on mitigating kidney damage in HS-induced hypertension through the gut-renal axis. This investigation provides a new strategy for utilizing combinations of food-derived functional compounds to effectively address complications arising from hypertension.

CAS / MDL: 107-35-7
研究领域: 药理学 · 肾病学 · 营养学 · 微生物学
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FOOD RESEARCH INTERNATIONAL · 2025 · IF 8

Exploring the mechanisms of torularhodin in alleviating diabetic kidney disease: a microbiome and metabolomics approach through the gut-kidney axis

Wenlong Deng,Yi Guo,Qigui Mo,Jiaqi Liu,Yanting Su,Zhihao Wei,Runtao Ma,Jiaqi Chen,Yue Song,Tianqi Chen,Peng Wang,Wei Yu,Surui Lu

This study primarily investigates the pivotal role of torularhodin in alleviating diabetic nephropathy in mice. Oral administration of torularhodin at a dose of 30 mg/kg/day for 8 weeks significantly improved diabetic symptoms and mitigated kidney tissue damage in a mouse model of diabetic nephropathy. Integrating findings from both network pharmacology and in vivo experiments, the study confirmed that torularhodin activates the Nrf2 signaling pathway, thereby promoting the expression of multiple antioxidant enzymes to directly reduce oxidative stress and mitochondrial damage in renal tissues. Moreover, combined analyses of metabolomics and gut microbiota profiling revealed that torularhodin increased the abundance of Muribaculaceae , Moraxellaceae , and Erysipelotrichaceae , while decreasing the abundance of Lactobacillaceae and Enterobacteriaceae . These microbial shifts were accompanied by increased levels of key metabolites, such as Glycerol 3-Phosphate and d -Fructose 6-Phosphate, which helped alleviate amino acid metabolic disorders, restore energy metabolism, and reduce oxidative stress in the kidneys via the gut-kidney axis. This study demonstrates that the protective effects of torularhodin against diabetic nephropathy arise both from its direct antioxidant and mitochondrial protective actions, and partly from modulation of the gut microbiota and their metabolites. These findings provide new insights into the mechanisms of torularhodin and establish a theoretical basis for its potential use as a therapeutic strategy for diabetic nephropathy.

CAS / MDL: 18883-66-4
研究领域: 药理学 · 代谢组学 · 微生物组学 · 分子生物学 · 肾脏病学 · 氧化应激
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Food & Function · 2025 · IF 5.4

Lactiplantibacillus plantarum MPB-65 combined with epicatechin alleviates hyperuricemia by modulating the gut–kidney axis

Zihao Tian,Jing Zhang,Zhongmei Tan,Xiaolei Duan,He Zhang,Bailiang Li,Enyu Wang,Vicky Yang Wang,Dong Xu,Jiage Ma,Wei Yu

Hyperuricemia (HUA) is a metabolic disorder induced by excessive generation or underexcretion of uric acid (UA), leading to abnormally elevated levels of serum UA beyond the normal range. This study explored the potential effects of Lactiplantibacillus plantarum MPB-65 combined with epicatechin (EC) as a synbiotic supplement in alleviating HUA. The results showed that the combination of L. plantarum MPB-65 and EC effectively reduced the levels of serum UA, creatinine (CRE), and blood urea nitrogen (BUN). It also alleviated kidney and colon inflammatory responses, reduced kidney oxidative stress, and relieved tissue injury in the kidneys and colon. Furthermore, L. plantarum MPB-65 combined with EC could inhibit liver xanthine oxidase (XOD) activity, downregulate the expression of URAT1 and GLUT9 in the kidneys and upregulate the expression of ABCG2 in the colon. It was also shown to significantly suppress the expression of key proteins in the JAK2/STAT3 signaling pathway in the kidneys. Meanwhile, the HUA-induced gut microbiota dysbiosis was ameliorated by intervention with L. plantarum MPB-65 combined with EC, particularly in the species composition and structure of the gut microbiota. L. plantarum MPB-65 combined with EC increased the short-chain fatty acid levels. Overall, L. plantarum MPB-65 combined with EC exerted alleviating effects on potassium oxonate- and adenine-induced HUA through modulating the gut–kidney axis.

CAS / MDL: 490-46-0 73-24-5
研究领域: 微生物学 · 药理学 · 代谢紊乱 · 胃肠病学 · 肾脏病学 · 分子生物学
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CELL BIOCHEMISTRY AND FUNCTION · 2025 ·Vol. 43 ·期 7 ·e70100 · IF 2.7

Smilax glabra Roxb. Meliorates Hyperuricemia via Regulating Renal Urate Transporter and Remodelulating Intestinal Microbiota in Mice

Jie Xiao,Weiwei He,Xiaoyang Fang,Rongrong Zhou,Ao Huang,Yikun Wang,Qing Du,Linben Xu,Fei Cheng,Hongliang Zeng

Smilax glabra Roxb. is a natural herb, exhibits significant uric acid lowering effect in clinical. However, the specific mechanism remains to be clarified. To study this problem, intraperitoneal injection of Potassium oxazinate (PO) and Hypoxanthine (HX) induced hyperuricemia in mice model, and mice were divided into control, model, and model plus ethanol extract (TFL), ethyl acetate extract (TFL_Y), n-butanol extract (TFL_Z), and residual aqueous extract (TFL_S) of Smilax glabra Roxb., And then a follow-up test. Furthermore, possible pharmacological components were detected by UPLC-Q-TOF-MS. The results showed that serum creatinine, blood urea nitrogen, d -lactate, lipopolysaccharide levels and xanthine oxidase. They could upregulate renal OAT1 and ABCG2, downregulate renal URAT1, reduce renal tubular dilation and interstitial inflammatory cell infiltration. Moreover, they could upregulate intestinal tight junction proteins, increase the number of intestinal goblet cells, and repair damage to the intestinal barrier. Moreover, 16S rRNA sequencing analysis showed that restored intestinal microbiota by increasing probiotic bacteria ( Candidatus Saccharimonas , Lachnospiraceae NK4A136_group ) and reducing pathogenic bacteria ( Helicobacter ). Furthermore, it was found that all control taint flavonoids such as Neoastalbin, Astibin, Neoiosastilbin, Isoastalbin, Engeletin, and Isoengeletin. Summary This study elucidates the multi-target mechanisms underlying the urate-lowering effects of Smilax glabra Roxb., including modulation of renal urate transporters (OAT1/ABCG2/URAT1), improvement of intestinal barrier function, and restoration of gut microbiota homeostasis. Flavonoid (e.g., neoastilbin and isoastilbin) were identified as the main active ingredients through UHPLC-Q-TOF-MS analysis. For the first time, we comprehensively revealed the “gut-kidney axis” mechanism of Smilax glabra Roxb., identified critical targets in renal transporters and gut microbiota, discovered bioactive flavonoid markers for quality control, and provided theoretical support for its clinical application and drug development.

研究领域: 药理学 · 民族药理学 · 植物化学 · 微生物学 · 肾脏病学 · 代谢性疾病
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