Baicalin suppresses renal fibrosis through microRNA-124/TLR4/NF-κB axis in streptozotocin-induced diabetic nephropathy mice and high glucose-treated human proximal tubule epithelial cells

Zhang, She-Feng; Xu, Li; Liang, Ruifeng; Yang, Chenhua; Wang, Peiren

doi:10.1007/s13105-020-00747-z

Cited by 48 publications

(28 citation statements)

References 39 publications

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“…Previous studies have indicated that BAI can prevent DN via suppressing renal fibrosis. [21][22][23] As we all know, renal fibrosis is not an initial factor in the development of CKD but may play an important role in the later stage. On the contrary, renal fibrosis is usually induced under chronic stress environment.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] Studies have demonstrated that BAI can protect against DN by inhibiting progressive renal fibrosis, and the related mechanisms were associated with the inhibition of NF-κB signaling. [21][22][23] Since organ fibrosis is a result of chronic stress and always occurs in the middle and late stages of chronic diseases, fibrogenesis may not be the foremost promoter in the early stage of DN. 24 However, current studies about BAI on DN were mainly focused on the renal fibrosis, few researches were conducted to explore the effects of BAI on the upstream events in DN: oxidative stress and inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Baicalin Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy via Nrf2 and MAPK Signaling Pathway

Shao

et al. 2021

DDDT

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Background: Oxidative stress and inflammation play essential roles in the development and progression of diabetic nephropathy (DN). Baicalin (BAI), a natural flavonoid, has been showed to have a renoprotective effect in various renal diseases. However, its underlying mechanisms in DN remain unclear. In this study, we explored the potential effects and underlying mechanisms of BAI on DN using a spontaneous DN model. Methods: The protective effects of BAI on DN have been evaluated by detecting DNrelated biochemical indicators, kidney histopathology and cell apoptosis. After that, we examined the level of renal oxidative stress and inflammation to explain BAI's renoprotective effects. Then, Nrf2 pathway was tested to clarify its antioxidant activity, and kidney transcriptomics was conducted to elucidate its anti-inflammatory activity. Finally, Western blot was applied for final mechanism verification. Results: Our results found that BAI effectively ameliorated diabetic conditions, proteinuria, renal histopathological changes and cell apoptosis in DN. BAI significantly improved the kidney levels of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT), and reduced malondialdehyde (MDA) level. Meanwhile, the infiltration of inflammatory cells including T-lymphocytes, T-helper cells, neutrophils and macrophages, and the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, MCP-1 and TNFα) were also obviously inhibited by BAI. Afterward, Western blot found that BAI significantly activated Nrf2 signaling and increased the expression of downstream antioxidant enzymes (HO-1, NQO-1). Kidney transcriptomics revealed that the inhibition of MAPK signaling pathway may contribute to BAI's anti-inflammatory activity, which has also been verified in later experiment. BAI treatment did obviously inhibit the activation of canonical proinflammatory signaling pathway MAPK family, such as Erk1/2, JNK and P38. Conclusion:In summary, our data demonstrated that BAI can treat DN by alleviating oxidative stress and inflammation, and its underlying mechanisms were associated with the activation of Nrf2-mediated antioxidant signaling pathway and the inhibition of MAPKmediated inflammatory signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Baicalin Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy via Nrf2 and MAPK Signaling Pathway

Shao

et al. 2021

DDDT

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“…Li investigated the reversal effect of baicalin on podocyte apoptosis induced by high glucose to discover the mechanism by which baicalin alleviates DN. The results indicated that baicalin can relieve DN by increasing the expression level of sirtuin 1 in high glucose-induced podocytes and inhibiting the NF-κB pathway [ 46 ]. Zhang and colleagues reported that baicalin at doses of 15–45 mg/kg/d reversed renal damage and efficiently prevented the progression of CKD in streptozotocin-induced DN mice.…”

Section: Flavonoids For the Treatment Of Diabetic Nephropathymentioning

confidence: 99%

Flavonoids on diabetic nephropathy: advances and therapeutic opportunities

Xiaolin

et al. 2021

Chin Med

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With the advances in biomedical technologies, natural products have attracted substantial public attention in the area of drug discovery. Flavonoids are a class of active natural products with a wide range of pharmacological effects that are used for the treatment of several diseases, in particular chronic metabolic diseases. Diabetic nephropathy is a complication of diabetes with a particularly complicated pathological mechanism that affects at least 30% of diabetic patients and represents a great burden on public health. A large number of studies have shown that flavonoids can alleviate diabetic nephropathy. This review systematically summarizes the use of common flavonoids for the treatment of diabetic nephropathy. We found that flavonoids play a therapeutic role in diabetic nephropathy mainly by regulating oxidative stress and inflammation. Nrf-2/GSH, ROS production, HO-1, TGF-β1 and AGEs/RAGE are involved in the process of oxidative stress regulation. Quercetin, apigenin, baicalin, luteolin, hesperidin, genistein, proanthocyanidin and eriodictyol were found to be capable of alleviating oxidative stress related to the aforementioned factors. Regarding inflammatory responses, IL-1, IL-6β, TNF-α, SIRT1, NF-κB, and TGF-β1/smad are thought to be essential. Quercetin, kaempferol, myricetin, rutin, genistein, proanthocyanidin and eriodictyol were confirmed to influence the above targets. As a result, flavonoids promote podocyte autophagy and inhibit the overactivity of RAAS by suppressing the upstream oxidative stress and inflammatory pathways, ultimately alleviating DN. The above results indicate that flavonoids are promising drugs for the treatment of diabetic nephropathy. However, due to deficiencies in the effect of flavonoids on metabolic processes and their lack of structural stability in the body, further research is required to address these issues.

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“…In subsequent experiments, 1mM of captopril was used for deeper mechanism exploration for its effects on HSC in response to HG. Increased ratio of p-IκBα/IκBα and the ratio of p-p65/p65 are considered to be related to be involved in NF-κB activation [14][15][16]. As shown in results, captopril markedly decreased the ratio of p-IκBα/ IκBα and the ratio of p-p65/p65 when compared with HG alone (Figure 3).…”

Section: Captopril Suppressed Hsc-t6 Cell Activities Induced By Hgmentioning

confidence: 64%

The angiotensin-converting enzyme inhibitor, captopril, suppressed hepatic stellate cell activation via NF-kappaB or wnt3α/β-catenin pathway

Fang

2021

Bioengineered

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Activation of hepatic stellate cells (HSC) is associated with hepatic fibrogenesis, which is one of complications of diabetes mellitus. Captopril possesses potent anti-inflammation, oxidative stress and fibrosis effects. However, the specific molecular mechanism of captopril in high glucose (HG)-induced hepatic stellate cells has not been elucidated. Following the treatment of HG or captopril treatment for rat hepatic stellate cells (HSC-T6), cell activities were detected by Cell Counting Kit-8 (CCK8) assay. reactive oxygen species (ROS) levels were determined by ROS staining. The expression of inflammation-related proteins (Interleukin (IL)-1β, IL-6 and IL-8) and fibrosis-related proteins (fibronectin (FN), collagen I, collagen , collagen , matrix metallopeptidase (MMP)-2 and MMP-9) were determined by Western blot. Captopril significantly decreased HSC-T6 cell viability induced by HG in dose-dependent manner, as well as decreased levels of malondialdehyde (MDA), ROS, pro-inflammatory markers and fibrosis-related proteins while upregulated superoxide dismutase (SOD) activities. We further found that captopril decreased the ratio of p-IκBα/IκBα and the ratio of p-p65/p65. Intriguing, phorbol myristate acetate (PMA) or LiCl was able to significantly reverse the captopril-induced alteration of oxidative stress-, inflammation-and fibrosis-markers levels. In conclusion, in HG-stimulated HSC-T6 cells, captopril displayed a potent ability to inhibit oxidative stress, inflammation and hepatic fibrogenesis via NF-kappaB or wnt3α/β-catenin. These results demonstrated the mechanism of captopril as well as the role of the NF-kappaB or wnt3α/β-catenin on HSC-T6 activation induced by HG.

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Baicalin suppresses renal fibrosis through microRNA-124/TLR4/NF-κB axis in streptozotocin-induced diabetic nephropathy mice and high glucose-treated human proximal tubule epithelial cells

Cited by 48 publications

References 39 publications

Baicalin Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy via Nrf2 and MAPK Signaling Pathway

Baicalin Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy via Nrf2 and MAPK Signaling Pathway

Flavonoids on diabetic nephropathy: advances and therapeutic opportunities

The angiotensin-converting enzyme inhibitor, captopril, suppressed hepatic stellate cell activation via NF-kappaB or wnt3α/β-catenin pathway

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