Puerarin Mitigates Diabetic Hepatic Steatosis and Fibrosis by Inhibiting TGF‐<i>β</i> Signaling Pathway Activation in Type 2 Diabetic Rats

Hou, Biyu; Zhao, Yuerong; Qiang, Guifen; Yang, Xiuying; Xu, Chunyang; Chen, Xi; Liu, Chenge; Wang, Xiaobo; Zhang, Li; Du, Guanhua

doi:10.1155/2018/4545321

Cited by 50 publications

(30 citation statements)

References 47 publications

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“…In previous studies, puerarin significantly reduced levels of hydroxyproline and collagen type I in liver fibrosis (25,26). In the current study, hepatic inflammation and the protein expression levels of collagen type I and fibronectin were significantly alleviated following treatment with puerarin, which was consistent with previous reports (40,41). The results from the current study suggest that puerarin may have an anti-fibrotic effect in liver fibrosis.…”

Section: Discussionsupporting

confidence: 92%

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide‑induced hepatic fibrosis in rats

Zhang

Pan

et al. 2019

Exp Ther Med

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Liver fibrosis is a complex pathological process and an early step in the progression of liver cirrhosis, which can eventually develop into hepatocellular carcinoma. Currently, there is no effective treatment for liver fibrosis. Puerarin is a traditional Chinese herb, which is commonly used in the treatment of various diseases. In addition, it is also believed to have a therapeutic effect in liver fibrosis. However, whether puerarin reduces liver fibrosis via the ERK1/2 signaling pathway to inhibit the activation of hepatic stellate cell (HSC) and excessive collagen deposition in liver fibrosis remains unknown. The aim of the current study was to establish a liver fibrosis in vivo model by intraperitoneal injection of thioacetamide (TAA) and investigate the effect of puerarin in the treatment of liver fibrosis. Hematoxylin and eosin and Van Gieson's staining were used to examine histopathological changes associated with liver fibrosis. Liver hydroxyproline content was examined to determine the total amount of collagen in the liver. The relative protein expression levels of transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA), collagen type I, fibronectin, ERK1/2 and p-ERK1/2 were determined by western blot analysis. In the TAA group, histopathological changes and collagen fiber content in rat liver tissue samples were significantly increased compared with the control group (P<0.05). In addition, treatment with puerarin significantly decreased histopathological changes and collagen fiber content in rat liver tissue samples (P<0.05). The relative protein expression levels of TGFβ1, α-SMA, collagen type I, fibronectin and p-ERK1/2 were significantly upregulated in the TAA group compared with the control group (P<0.05), whereas puerarin treatment reversed these changes. These findings suggest that treatment with puerarin may reduce HSC activation and alleviate extracellular matrix protein expression levels by inhibiting the TGF-β/ERK1/2 pathway in liver fibrosis.

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Section: Discussionsupporting

confidence: 92%

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide‑induced hepatic fibrosis in rats

Zhang

Pan

et al. 2019

Exp Ther Med

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“…In fact, puerarin also plays an important role in the treatment of many other diseases. Puerarin has beneficial effects on osteoporosis, neurological disorders, and cardiovascular diseases (Wong and Rabie, 2007;Lin et al, 2012;Li et al, 2016;Hou et al, 2018). The role of autophagy in mediating the effect of puerarin was reported previously for other diseases.…”

Section: Discussionmentioning

confidence: 54%

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Zhu

Zheng

et al. 2020

Front. Physiol.

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Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines to treat patients with diabetic nephropathy (DN). In the previous studies, we showed that puerarin exerts renoprotective effects in Streptozocin (STZ)induced diabetic mice through activation of Sirt1 and anti-oxidative effects. Here, we further investigated the underlying mechanism mediating the renal protective effects of puerarin in DN. We studied the effects and mechanism of puerarin in STZ-induced diabetic mice and in cultured immortalized mouse podocytes treated with high glucose. We confirmed that puerarin ameliorated urinary albumin creatinine ratio and kidney injury in STZ-induced DN mice. We found that expression of heme oxygenase 1 (HMOX-1) and Sirt1 was suppressed in diabetic glomeruli but restored by puerarin treatment at both mRNA and protein levels. Additionally, we found that puerarin induced autophagy in the kidney of DN mice. In conditionally immortalized mouse podocytes, puerarin inhibited HG-induced apoptosis and restored the mRNA and protein levels of HMOX-1 and Sirt1. Interestingly, we showed that puerarin decreased liver kinase B1 (LKB1) acetylation, thereby promoting adenosine 5-monophosphate-activated protein kinase-dependent autophagy. Knockdown of HMOX-1 and Sirt1 expression or treatment with the autophagy inhibitor 3-methyladenine abolished the protective effects of puerarin in HG-treated podocytes. Taken together, these results suggest that puerarin protects podocytes from diabetes-induced injury through HMOX1 and Sirt1-mediated upregulation of autophagy, a novel mechanism explaining its renal protective effects in DN.

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“…Diabetes mellitus (DM) is a chronic metabolic disease characterized by persistent blood hyperglycemia; it causes profound long-term effects on a variety of organs, such as the kidneys, heart, brain, eyes, and liver [1][2][3][4][5]. In recent years, increasing evidence suggests that the lung is also one of the target organs for diabetic microangiopathy with DM [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats

Yang

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Diabetes affects a variety of organs such as the kidneys, eyes, and liver, and there is increasing evidence that the lung is also one of the target organs of diabetes and imbalance of Sirt3-mediated stress responses such as inflammation, oxidative stress, apoptosis, autophagy, and ER stress may contribute to diabetic lung fibrosis. Although previous studies have reported that mesenchymal stem cells (MSCs) have beneficial effects on various diabetic complications, the effect and mechanisms of MSCs on diabetes-induced lung injury are not clear. In this study, the STZ-induced diabetes model was constructed in rats, and the effect and potential mechanisms of bone marrow MSCs on diabetic lung fibrosis were investigated. The results revealed that fibrotic changes in the lung were successfully induced in the diabetic rats, while MSCs significantly inhibited or even reversed the changes. Specifically, MSCs upregulated the expression levels of Sirt3 and SOD2 and then activated the Nrf2/ARE signaling pathway, thereby controlling MDA, GSH content, and iNOS and NADPH oxidase subunit p22phox expression levels in the lung tissue. Meanwhile, high levels of Sirt3 and SOD2 induced by MSCs reduced the expression levels of IL-1β, TNF-α, ICAM-1, and MMP9 by suppressing the NF-κB/HMGB1/NLRP3/caspase-1 signaling pathway, as well as regulating the expression levels of cleaved caspasese-3, Bax, and Bcl2 by upregulating the expression level of P-Akt, thereby inhibiting the apoptosis of the lung tissue. In addition, MSCs also regulated the expression levels of LC3, P62, BiP, Chop, and PERK, thereby enhancing autophagy and attenuating endoplasmic reticulum stress. Taken together, our results suggest that MSCs effectively attenuate diabetic lung fibrosis via adjusting Sirt3-mediated responses, including inflammation, oxidative stress, apoptosis, autophagy, and endoplasmic reticulum stress, providing a theoretical foundation for further exploration of MSC-based diabetic therapeutics.

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Puerarin Mitigates Diabetic Hepatic Steatosis and Fibrosis by Inhibiting TGF‐β Signaling Pathway Activation in Type 2 Diabetic Rats

Cited by 50 publications

References 47 publications

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide‑induced hepatic fibrosis in rats

Puerarin alleviates liver fibrosis via inhibition of the ERK1/2 signaling pathway in thioacetamide‑induced hepatic fibrosis in rats

Puerarin Attenuates Diabetic Nephropathy by Promoting Autophagy in Podocytes

Mesenchymal Stem Cells Attenuate Diabetic Lung Fibrosis via Adjusting Sirt3-Mediated Stress Responses in Rats

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