Yishen capsule promotes podocyte autophagy through regulating SIRT1/NF-κB signaling pathway to improve diabetic nephropathy

Liu, Yuxiang; Liu, Wenyuan; Zhang, Ziyuan; Hu, Yaling; Zhang, Xiaodong; Sun, Ying; Lei, Qingqing; Sun, Dalin; Liu, Ting; Fan, Yun; Li, Hui; Ding, Wujie; Fang, Jingai

doi:10.1080/0886022x.2020.1869043

Cited by 21 publications

(23 citation statements)

References 30 publications

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“…Recent research team found that Yishen Capsule has the function of improving diabetic nephropathy by promoting autophagy and inhibiting inflammation. 9 …”

Section: Discussionmentioning

confidence: 99%

“…The successfully modeled DN rats were randomly divided into diabetic nephropathy group (DN) and Yishen capsule group (YS). The YS group was given Yishen capsule gavage solution at 1.25 g/kg/d by gavage (The previous study of the research has carried out different doses of intervention treatment, and it is confirmed that 1.25 g/kg/d is the effective dose of gavage treatment), 9 and the N group and DN group were given the same amount of normal saline gavage for 8 consecutive weeks. After 8 weeks of treatment, the right kidney specimens of each group of rats were collected for subsequent immunohistochemistry and Western Blotting detection.…”

Section: Methodsmentioning

confidence: 96%

“…8 Previous studies have indicated that Yishen Capsule can improve kidney function through multiple targets and mechanisms, which effectively delays the progression of DN. 9–15 …”

Section: Introductionmentioning

confidence: 99%

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Potential Molecular Mechanism of Yishen Capsule in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

Liu

et al. 2022

DMSO

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Purpose Using network pharmacology and molecular docking to explore the mechanism of Yishen Capsule in the treatment of diabetic nephropathy. Materials and Methods Active components of Yishen Capsule were obtained using database such as TCMSP and TCMID. UniProt protein database was used to screen and standardize the human-derived targets of the active chemical components. Diabetic nephropathy (DN) targets were obtained from databases such as GeneCards, OMIM, TTD, DisGeNET and DrugBank. A network of “Yishen Capsule Components-diabetic nephropathy Targets-Pathways” was constructed by analyzing data above to screening out core targets for molecular docking verification. DN is induced by streptozocin in rats after left nephrectomy. Renal tubular epithelial cells (RTECs) was isolated and cultured under high glucose conditions. Based on these experimental models, key pathway target genes screened by network pharmacology were verified both in vitro and in vivo. Results The main active components of Yishen Capsule in the treatment of DN include quercetin, kaempferol, gallic acid, astragaloside IV, etc. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE, HIF-1 and JAK-STAT signal pathway) were included in the treatment of DN with Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsule. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP-1 were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β was decreased. Conclusion This study revealed the mechanism of Yishen Capsule in the treatment of DN, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsule interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy.

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“…Recent research team found that Yishen Capsule has the function of improving diabetic nephropathy by promoting autophagy and inhibiting inflammation. 9 …”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 96%

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Potential Molecular Mechanism of Yishen Capsule in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

Liu

et al. 2022

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“…This phenomenon may be due to a self-protective stress response. Podocytes maintain their function and homeostasis by increasing autophagy within a short period of time after HG stimulation [ 20 ]. The expression of p62 proteins increased significantly ( P < 0.01), indicating that autophagy activity in podocytes was inhibited under high glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models

Yang

Han

Wen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

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“…Low expression of Sirt1 has been found in podocyte injury during DN [13,14]. Moreover, speci c knockdown of Sirt1 in podocytes induced severe podocyte damage and increased proteinuria, whereas kidney damage was signi cantly alleviated after Sirt1 overexpression in diabetic mice [15,16]. Therefore, the expression of Sirt1 in podocytes in uence the occurrence and development of DN.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of Risa Improves Podocyte Injury by Enhancing Autophagy in Diabetic Nephropathy

Zhou

et al. 2021

Preprint

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BackgroundLncRNA AK044604 (Risa), Sirt1 and GSK3β are autophagy related genes that can play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.MethodsTransgenic db/db mice were fed and injected with Risa inhibition of adeno-associated virus by tail vein injection, as well as intraperitoneally injected with LiCl. Blood, urine, kidney tissue samples, and clinical data were collected at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with Risa inhibition of lentivirus, EX-527, and LiCl. MPCs were collected under different stimulations. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blot analysis, transmission electron microscope, PAS staining, and immunofluorescence staining. ResultsRisa and activated GSK3β were overexpressed, but Sirt1 decreased in Renal tissues of DN mice and high-glucose-treated MPCs and correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated the injury of podocytes by inhibiting the expression of Sirt1. In contrast, Risa inhibition enhanced Sirt1-induced autophagy and attenuated podocyte injury, but this effect could be abrogated by EX-527, suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy. ConclusionsRisa inhibits autophagy by regulating the Sirt1/GSK3β axis and thereby aggravates podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.

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Yishen capsule promotes podocyte autophagy through regulating SIRT1/NF-κB signaling pathway to improve diabetic nephropathy

Cited by 21 publications

References 30 publications

Potential Molecular Mechanism of Yishen Capsule in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

Potential Molecular Mechanism of Yishen Capsule in the Treatment of Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models

Down-regulation of Risa Improves Podocyte Injury by Enhancing Autophagy in Diabetic Nephropathy

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