Astragalus polysaccharide alleviated hepatocyte senescence via autophagy pathway

Yao, Ting; Chen, Jinmei; Shen, Leer; Yu, Yongsheng; Tang, Zhenghao; Zang, Guoqing; Zhang, Yi; Chen, Xiaohua

doi:10.1002/kjm2.12495

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…The NLRP3 inflammasome triggers the activation of Caspase-1, and cleavage of pro-IL-1β and Gasdermin D (GSDMD), thereby resulting in the formation of membrane openings and the release of inflammatory cytokine (IL-18 and IL-1β), ultimately leads to cell pyroptosis. A large amount of studies confirmed that ROS can cause mitochondrial damage in various liver cells (HL7702, AML12, LO2, LM3, and Huh7) though activating the NLRP3 mediated-pyroptosis pathway [20][21][22]. Recent evidence demonstrated that Esc has good anti-inflammation effects and can treat intestinal inflammatory diseases (IBD) by inhibiting the NLRP3 mediated-pyroptosis pathway [23,24].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells

Luo,

Chang,

Huang

et al. 2024

Molecules

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Oxidative stress plays a crucial role in the pathogenesis of many diseases. Esculetin is a natural coumarin compound with good antioxidant and anti-inflammatory properties. However, whether esculetin can protect HepG2 cells through inhibiting H2O2-induced apoptosis and pyroptosis is still ambiguous. Therefore, this study aimed to investigate the protective effects and mechanisms of esculetin against oxidative stress-induced cell damage in HepG2 cells. The results of this study demonstrate that pretreatment with esculetin could significantly improve the decrease in cell viability induced by H2O2 and reduce intracellular ROS levels. Esculetin not only apparently reduced the apoptotic rates and prevented MMP loss, but also markedly decreased cleaved-Caspase-3, cleaved-PARP, pro-apoptotic protein (Bax), and MMP-related protein (Cyt-c) expression, and increased anti-apoptotic protein (Bcl-2) expression in H2O2-induced HepG2 cells. Meanwhile, esculetin also remarkably reduced the level of LDH and decreased the expression of the pyroptosis-related proteins NLRP3, cleaved-Caspase-1, Il-1β, and GSDMD-N. Furthermore, esculetin pretreatment evidently downregulated the protein expression of p-JNK, p-c-Fos, and p-c-Jun. Additionally, anisomycin, a specific activator of JNK, blocked the protection of esculetin against H2O2-induced HepG2 cells apoptosis and pyroptosis. In conclusion, esculetin can protect HepG2 cells against H2O2-induced oxidative stress, apoptosis, and pyroptosis via inhibiting the JNK signaling pathway. These findings indicate that esculetin has the potential to be used as an antioxidant that improves oxidative stress-related diseases.

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Section: Discussionmentioning

confidence: 99%

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells

Luo,

Chang,

Huang

et al. 2024

Molecules

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“…Choline metabolism had been found to be altered during senescence of different cell types, suggesting a crucial role of choline metabolism in senescence [ 56 ]. Astragalus polysaccharide reduces reactive oxygen species levels through the AMPK/mTOR pathway, inhibits apoptosis, and promotes autophagy, thereby attenuating hepatocyte senescence in vitro and in vivo [ 57 ]. All of these active ingredients have important roles, but there are few studies on other active ingredients of Radix Astragali, such as Astragaloside II, Astragaloside III, Astragaloside, choline, and so on, in the mechanism of delaying kidney aging.…”

Section: Discussionmentioning

confidence: 99%

Study on the Mechanism of Radix Astragali against Renal Aging Based on Network Pharmacology

Zhang

Fang

Sun

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Radix Astragali is widely used in the traditional Chinese medicine with the effect of antiaging. The purpose of this study is to explore the main active ingredients and targets of Radix Astragali against renal aging by network pharmacology and further to verify the mechanism of the main active ingredients in vitro. TCMSP, ETCM, and TCMID databases were used to screen active ingredients of Radix Astragali. Targets of active ingredients were predicted using BATMAN-TCM and cross validated using kidney aging-related genes obtained from GeneCards and NCBI database. Pathways enrichment and protein-protein interaction (PPI) analysis were performed on core targets. Additionally, a pharmacological network was constructed based on the active ingredients-targets-pathways. HK-2 cell was treated with D-galactose to generate a cell model of senescence. CCK-8 and β-galactosidase were used to detect the effect of Radix Astragali active components on cell proliferation and aging. ELISA was used to detect the expression of senescence-associated secreted protein (TGF-β and IL-6) in the cell culture supernatant. Western blot was used to detect the expression of key proteins in the SIRT1/ p 53 pathway. Five active ingredients (Astragaloside I, II, III, IV and choline) were identified from Radix Astragali, and all these active ingredients target a total of 128 genes. Enrichment analysis showed these genes were implicated in 153 KEGG pathways, including the p 53 , FoxO, and AMPK pathway. 117 proteins and 572 interactions were found in PPI network. TP53 and SIRT1 were two hub genes in PPI network, which interacted with each other. The pharmacological network showed that the five main active ingredients target on some coincident genes, including TP53 and SIRT1. These targeted genes were involved in the p53, FoxO, and AMPK pathway. Proliferation of HK-2 cells was increased by Astragaloside IV treatment compared with that of the D-Gal treatment group. However, the proliferation of the SA-β-gal positive cells were inhibited. The expression of TGF-β and IL-6 in the D-Gal group was higher than that in the normal group, and the treatment of Astragaloside IV could significantly reduce the expression of TGF-β and IL-6. The expression of SIRT1 in the Astragaloside IV group was higher than that in the D-Gal group. However, the expression of p 53 and p 21 was less in the Astragaloside IV group than that in the D-Gal group. This study suggested that Astragaloside IV is an important active ingredient of Radix Astragali in the treatment of kidney aging via the SITR1- p 53 pathway.

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“…75 APSs reduced ROS levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via the AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo. 134 ArMPs alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/ HO-1 signaling pathways. ArMPs reduce brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family.…”

Section: Insulin/insulin-like Growth Factor-1 (Insulin/igf-1) Signali...mentioning

confidence: 97%

“…AMPK can integrate multiple signal pathways such as FOXO, mTOR, and SIRT1, and it is a major kinase that regulates aging-related physiological processes such as autophagy, oxidative stress, and inflammation. , Activation of AMPK can promote adenosine triphosphate (ATP) production, prolong the life of nematodes, Drosophila , and mice, and effectively resist aging. − Jiang et al found that AMPK/SIRT1 activity was significantly increased during LBP improvement of POF induced by d -Gal in mice, and AMPK inhibitors could weaken the role of LBPs in activating autophagy and alleviating POF . APSs reduced ROS levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via the AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo . ArMPs alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways.…”

Section: Antiaging Targets and Signal Pathways Of Polysaccharidesmentioning

confidence: 99%

Advances in Plant Polysaccharides as Antiaging Agents: Effects and Signaling Mechanisms

Deng

Wang

et al. 2023

J. Agric. Food Chem.

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Aging refers to the gradual physiological changes that occur in an organism after reaching adulthood, resulting in senescence and a decline in biological functions, ultimately leading to death. Epidemiological evidence shows that aging is a driving factor in the developing of various diseases, including cardiovascular diseases, neurodegenerative diseases, immune system disorders, cancer, and chronic low-grade inflammation. Natural plant polysaccharides have emerged as crucial food components in delaying the aging process. Therefore, it is essential to continuously investigate plant polysaccharides as potential sources of new pharmaceuticals for aging. Modern pharmacological research indicates that plant polysaccharides can exert antiaging effects by scavenging free radicals, increasing telomerase activity, regulating apoptosis, enhancing immunity, inhibiting glycosylation, improving mitochondrial dysfunction regulating gene expression, activating autophagy, and modulating gut microbiota. Moreover, the antiaging activity of plant polysaccharides is mediated by one or more signaling pathways, including IIS, mTOR, Nrf2, NF-κB, Sirtuin, p53, MAPK, and UPR signaling pathways. This review summarizes the antiaging properties of plant polysaccharides and signaling pathways participating in the polysaccharide-regulating aging process. Finally, we discuss the structure–activity relationships of antiaging polysaccharides.

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Astragalus polysaccharide alleviated hepatocyte senescence via autophagy pathway

Cited by 11 publications

References 34 publications

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells

Study on the Mechanism of Radix Astragali against Renal Aging Based on Network Pharmacology

Advances in Plant Polysaccharides as Antiaging Agents: Effects and Signaling Mechanisms

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