Astragaloside IV acts through multi-scale mechanisms to effectively reduce diabetic nephropathy

Wang, Enyu; Wang, Liang; Ding, Rui; Zhai, Mengting; Ge, Ruirui; Zhou, Peng; Wang, Tingting; Fang, Haiyan; Wang, Jinghui; Huang, Jinling

doi:10.1016/j.phrs.2020.104831

Cited by 75 publications

(47 citation statements)

References 87 publications

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“…15 In the treatment of DN, anti-oxidative stress or anti-inflammation therapies have been widely investigated and proven to have certain effects. 16,17 Given that, compared with single anti-oxidative stress or antiinflammation therapies, multiple pathways (anti-oxidative and anti-inflammation)-targeted strategy may exert a better efficacy and have gained substantial interest.…”

Section: Introductionmentioning

confidence: 99%

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

Shao

et al. 2021

DDDT

116

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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: Introductionmentioning

confidence: 99%

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

Shao

et al. 2021

DDDT

116

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“…Astragaloside IV (AS-IV) is a natural saponin isolated from the plant Astragalus membranaceus. Recent studies have revealed that AS-IV has anti-oxidation, anti-inflammation and anti-apoptosis effects, and can enhance immunity (16)(17)(18). Our previous studies also showed that AS-IV exerts protective effects on the endoplasmic reticulum stress-induced apoptosis of renal tubular epithelial cells and diabetic cardiomyopathy in T2DM rats (18,19).…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV alleviates liver injury in type 2 diabetes due to promotion of AMPK/mTOR‑mediated autophagy

Zhu

Zhang

et al. 2021

Mol Med Rep

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Diabetic liver injury is a serious complication of type 2 diabetes mellitus (T2DM), which is often irreversible in the later stage, and affects the quality of life. Autophagy serves an important role in the occurrence and development of diabetic liver injury. For example, it can improve insulin resistance (IR), dyslipidaemia, oxidative stress and inflammation. Astragaloside IV (AS-IV) is a natural saponin isolated from the plant Astragalus membranaceus , which has comprehensive pharmacological effects, such as anti-oxidation, anti-inflammation and anti-apoptosis properties, as well as can enhance immunity. However, whether AS-IV can alleviate diabetic liver injury in T2DM and its underlying mechanisms remain unknown. The present study used high-fat diets combined with low-dose streptozotocin to induce a diabetic liver injury model in T2DM rats to investigate whether AS-IV could alleviate diabetic liver injury and to identify its underlying mechanisms. The results demonstrated that AS-IV treatment could restore changes in food intake, water intake, urine volume and body weight, as well as improve liver function and glucose homeostasis in T2DM rats. Moreover, AS-IV treatment promoted suppressed autophagy in the liver of T2DM rats and improved IR, dyslipidaemia, oxidative stress and inflammation. In addition, AS-IV activated adenosine monophosphate-activated protein kinase (AMPK), which inhibited mTOR. Taken together, the present study suggested that AS-IV alleviated diabetic liver injury in T2DM rats, and its mechanism may be associated with the promotion of AMPK/mTOR-mediated autophagy, which further improved IR, dyslipidaemia, oxidative stress and inflammation. Thus, the regulation of autophagy may be an effective strategy to treat diabetic liver injury in T2DM.

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“…On the TCMSP platform, the ADME parameters of OB ≥ 30% and DL ≥ 0.18 were selected 20 active compounds were obtained, and then, according to the relevant literature [ 29 ], additional 4 active compounds were obtained and merged with the former, and finally, a total of 24 compounds of AM were identified ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy

Jin

Hao

Xie

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life’s quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. Methods. Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. Results. 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. Conclusion. AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.

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Astragaloside IV acts through multi-scale mechanisms to effectively reduce diabetic nephropathy

Cited by 75 publications

References 87 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

Astragaloside IV alleviates liver injury in type 2 diabetes due to promotion of AMPK/mTOR‑mediated autophagy

A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy

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