Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats

Zhao, Tingting; Zhang, Haojun; Yin, Xingbin; Zhao, Hailing; Ma, Liang; Yan, Meihua; Peng, Liang; Wang, Qian; Dong, Xi; Li, Ping

doi:10.1016/j.biopha.2020.110325

Cited by 44 publications

(44 citation statements)

References 54 publications

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“…DKD is a chronic inflammatory disease accompanied by lipid disorders ( 47 , 48 ). Evidence shows that gut-derived LPS may be crucial in chronic inflammation and progression of DKD ( 14 , 17 ). In our study, we have shown that damage to the gut barrier led to a lower expression of tight junction proteins ZO-1, higher levels of the serum FITC-dextran and subsequently increased intestinal permeability, which may facilitate the passage of gut-derived LPS into the blood.…”

Section: Discussionmentioning

confidence: 99%

“…Studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD ( 12 , 13 ). In particular, gut-derived endotoxins such as LPS, an inflammatory marker involved in the pathogenesis of DKD ( 14 ), Gut dysbiosis suppresses the expression of tight junction proteins, leading to increased intestinal permeability and the translocation of Gram-negative bacteria-derived LPS into the blood ( 15 ), that might be involved in metabolic inflammation and DKD progression ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

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Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease

et al. 2021

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Evidence indicates that the metabolic inflammation induced by gut microbiota dysbiosis contributes to diabetic kidney disease. Prebiotic supplementations to prevent gut microbiota dysbiosis, inhibit inflammatory responses, and protect the renal function in DKD. Qing-Re-Xiao-Zheng formula (QRXZF) is a Traditional Chinese Medicine (TCM) formula that has been used for DKD treatment in China. Recently, there are growing studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD. However, it is unknown whether QRXZF is effective for DKD by regulating of gut microbiota. In this study, we investigated the reno-protective effect of QRXZF by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney. High-fat diet (HFD) and streptozotocin injection-induced DKD mice model was established to assess the QRXZF effect in vivo. Mice treated with QRXZF for 8 weeks had significantly lower levels of urinary albumin, serum cholesterol and triglycerides. The renal injuries observed through histological analysis were attenuated as well. Also, mice in the QRXZF group had higher levels of Zonula occludens protein-1 (ZO-1) expression, lower levels of serum fluorescein-isothiocyanate (FITC)-dextran and less-damaged colonic mucosa as compared to the DKD group, implying the benefit role for the gut barrier integrity. QRXZF treatment also reversed gut dysbiosis and reduced levels of gut-derived LPS. Notably, the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), which are important inflammation pathways in DKD, were suppressed in the QRXZF groups. In conclusion, our results indicated that the reno-protective effects of QRXZF was probably associated with modulating gut microbiota and inhibiting inflammatory responses in the kidney.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease

et al. 2021

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“…To date, studies have focused on the effects of traditional Chinese medicine in treating DKD by modulating the composition or function of gut microbiota, such as Cordyceps cicadae polysaccharides, Tangshen formula and Shenyan Kangfu tablets. 39 , 40 , 41 Recently, researchers found that QiDiTangShen (QDTS) granules, a traditional Chinese medicine composed of seven herbs, could reverse mucosal injury, reduce proteins in urine and KIM‐1 and relieve pathological damage to the kidney. However, QDTS granules did not impact body weight, blood glucose, or urea nitrogen.…”

Section: Gut Microbiota the Central Regulators Of Dkdmentioning

confidence: 99%

“… 50 In fact, some agents can improve the intestinal mucosal barrier, lower the intestinal permeability, reduce inflammation by regulating gut microbiota and alleviating diabetes or DKD. 40 , 51 However, the underlying association between intestinal flora and inflammation needs to be investigated in detail.…”

Section: Mechanisms Behind the Effects Of Gut Microbiota On Dkdmentioning

confidence: 99%

Gut microbiota, key to unlocking the door of diabetic kidney disease

Wang

Zheng

et al. 2021

Nephrology

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“…Through liquid chromatography-mass spectrometry (LC-MS), we have successfully detected 40 compounds in TSF and 12 compounds in the serum of TSF-treated mice (supplementary Tables S1 and S2 ). Six compounds, including loganin, neohesperidin, naringenin, calycosin-7-O- β -D-glucoside, naringenine-7-rhamnosidoglucoside, and aloe-emodin, were selected to describe the quality of TSF by comparing the high-performance liquid chromatography (HPLC) fingerprints of 10 sample batches [ 17 , 18 ]. The results confirmed that these six compounds exhibit renal protective effects [ 19 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Role of Tangshen Formula on the Progression of Renal Damage indb/dbMice by TRPC6/Talin1 Pathway in Podocytes

Wang

Tian

Zhou

et al. 2020

Journal of Diabetes Research

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Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of TSF on podocytes was investigated using the murine model of type 2 DKD db/db mice in vivo and advanced glycation end products (AGEs)-stimulated primary mice podocytes in vitro. Results revealed that TSF treatment could significantly mitigate reduction of podocyte numbers and foot process effacement, reduce proteinuria, and protect renal function in db/db mice. There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice. The results of AGEs-stimulated primary mice podocytes showed increased cell migration and actin-cytoskeleton rearrangement. Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca2+ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2. These dysregulations in mice primary podocytes stimulated by AGEs could be significantly attenuated after TSF treatment. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, blocked the protective role of TSF on podocyte cell-matrix adherence. In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.

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Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats

Cited by 44 publications

References 54 publications

Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease

Qing-Re-Xiao-Zheng Formula Modulates Gut Microbiota and Inhibits Inflammation in Mice With Diabetic Kidney Disease

Gut microbiota, key to unlocking the door of diabetic kidney disease

Protective Role of Tangshen Formula on the Progression of Renal Damage indb/dbMice by TRPC6/Talin1 Pathway in Podocytes

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