PMID- 34962345 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220426 IS - 2410-8650 (Electronic) IS - 1607-551X (Linking) VI - 38 IP - 5 DP - 2022 May TI - Astragalus polysaccharide alleviated hepatocyte senescence via autophagy pathway. PG - 457-468 LID - 10.1002/kjm2.12495 [doi] AB - Aging is characterized by inevitable organ function decline over time, with consequent body deterioration and increased susceptibility to death. Astragalus polysaccharide (APS) has been reported to have anti-oxidative, anti-apoptotic, and anti-inflammatory properties. We investigated the potential protective effects of APS on hydrogen peroxide (H(2) O(2) ) induced hepatocyte senescence and identified related mechanisms in L02, Huh7, and LM3 cell lines. Aged female C57BL/6 mice were given APS for 1 week by intraperitoneal injection, and APS provided the strongest protective effect against H(2) O(2) -induced damage at 100 muM. APS reduced the expression of cell senescence markers and alleviated pathological damage in aged mouse liver. APS treatment decreased oxidative stress, apoptosis, NOD-like receptor protein-3-mediated pyroptosis, and maintained mitochondrial homeostasis. Notably, the protective effect of APS was weakened in the presence of chloroquine. APS might enrich autophagy by activating AMP-activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR). In conclusion, APS reduced reactive oxygen species levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo. CI - (c) 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University. FAU - Yao, Ting AU - Yao T AUID- ORCID: 0000-0003-0132-8027 AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Chen, Jin-Mei AU - Chen JM AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Shen, Le-Er AU - Shen LE AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Yu, Yong-Sheng AU - Yu YS AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Tang, Zheng-Hao AU - Tang ZH AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Zang, Guo-Qing AU - Zang GQ AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Zhang, Yi AU - Zhang Y AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. FAU - Chen, Xiao-Hua AU - Chen XH AD - Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. LA - eng GR - 81770589/National Natural Science Foundation of China/ PT - Journal Article DEP - 20211228 PL - China (Republic : 1949- ) TA - Kaohsiung J Med Sci JT - The Kaohsiung journal of medical sciences JID - 100960562 RN - 0 (Polysaccharides) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - *AMP-Activated Protein Kinases/genetics/metabolism MH - Animals MH - Apoptosis MH - *Astragalus Plant/metabolism MH - Autophagy MH - Hepatocytes/metabolism MH - Mammals/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Polysaccharides/pharmacology MH - Signal Transduction MH - TOR Serine-Threonine Kinases/genetics/metabolism OTO - NOTNLM OT - AMPK OT - Astragalus polysaccharide OT - autophagy OT - cell death OT - hepatocyte senescence EDAT- 2021/12/29 06:00 MHDA- 2022/04/27 06:00 CRDT- 2021/12/28 08:55 PHST- 2021/10/10 00:00 [revised] PHST- 2021/08/15 00:00 [received] PHST- 2021/12/08 00:00 [accepted] PHST- 2021/12/29 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2021/12/28 08:55 [entrez] AID - 10.1002/kjm2.12495 [doi] PST - ppublish SO - Kaohsiung J Med Sci. 2022 May;38(5):457-468. doi: 10.1002/kjm2.12495. Epub 2021 Dec 28.