PMID- 32855685 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 20 IP - 4 DP - 2020 Oct TI - Rhodiola Crenulata ameliorates exhaustive exercise-induced fatigue in mice by suppressing mitophagy in skeletal muscle. PG - 3161-3173 LID - 10.3892/etm.2020.9072 [doi] AB - The aim of present study was to evaluate the potential effects of Rhodiola crenulata oral liquid (RCOL) on exhaustive exercise (EE)-induced fatigue in mice. Male Institute of Cancer Research mice from five treatment groups (n=10 per group) were orally administered with sterilized water for the Control and EE groups and/or RCOL at doses of 1.02, 3.03 and 6.06 ml/kg/day, once daily for 2 weeks. Anti-fatigue activity was subsequently evaluated by measuring the levels of creatine kinase (CK), lactic acid (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and total anti-oxidative capability (T-AOC). Histopathology was assessed using hematoxylin and eosin staining. Ultrastructures of mitochondria were observed by transmission electron microscopy. Energy supply capacity was assessed using citrate synthase (CS), succinate dehydrogenase (SDH), Na(+)-K(+)-ATPase, and liver and quadriceps glycogen content assays. Expression levels of mRNA and protein associated with mitophagy in the skeletal muscle were measured by reverse transcription-quantitative PCR and western blotting, respectively. RCOL was observed to markedly inhibit fatigue-induced oxidative stress by increasing the activities of SOD, CAT and T-AOC, whilst reducing the accumulation of LA, CK, LDH and MDA. Histological analysis of the quadriceps femoris tissue suggested increased numbers of muscle fibers in the RCOL groups compared with those in the EE group. RCOL administration was found to reverse EE-induced mitochondrial structural damage and alleviated defects inflicted onto the energy supply mechanism by increasing CS, SDH, Na(+)-K(+)-ATPase and glycogen levels. Additionally, RCOL reduced the protein expression of PTEN-induced kinase 1 (PINK1), Parkin, microtubule-associated proteins 1A/1B light chain 3, sequestosome 1 and ubiquitin, whilst lowering the gene expression of PINK1 and Parkin. Taken together, results from the present study clarified the anti-fatigue effect of RCOL, where the underlying mechanism may be associated with increased antioxidant activity, enhanced energy production and the inhibition of mitophagy by suppressing the PINK1/Parkin signaling pathway. CI - Copyright: (c) Hou et al. FAU - Hou, Ya AU - Hou Y AD - Department of Pharmacology of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Tang, Yan AU - Tang Y AD - Department of Pharmacology of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Wang, Xiaobo AU - Wang X AD - Department of Pharmacology of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Ai, Xiaopeng AU - Ai X AD - Department of Pharmacology of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Wang, Hongling AU - Wang H AD - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Li, Xuanhao AU - Li X AD - Department of Pharmacology of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Chen, Xiaorui AU - Chen X AD - Department of Pharmacology of Chinese Materia Medica, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Zhang, Yi AU - Zhang Y AD - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Hu, Yao AU - Hu Y AD - Interdisciplinary Laboratory of Exercise and Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Meng, Xianli AU - Meng X AD - Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. FAU - Zhang, Jing AU - Zhang J AD - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China. LA - eng PT - Journal Article DEP - 20200729 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC7444336 OTO - NOTNLM OT - Rhodiola crenulata oral liquid OT - anti-fatigue OT - loaded swimming OT - mitophagy OT - quadriceps femoris EDAT- 2020/08/29 06:00 MHDA- 2020/08/29 06:01 PMCR- 2020/07/29 CRDT- 2020/08/29 06:00 PHST- 2019/09/29 00:00 [received] PHST- 2020/05/20 00:00 [accepted] PHST- 2020/08/29 06:00 [entrez] PHST- 2020/08/29 06:00 [pubmed] PHST- 2020/08/29 06:01 [medline] PHST- 2020/07/29 00:00 [pmc-release] AID - ETM-0-0-9072 [pii] AID - 10.3892/etm.2020.9072 [doi] PST - ppublish SO - Exp Ther Med. 2020 Oct;20(4):3161-3173. doi: 10.3892/etm.2020.9072. Epub 2020 Jul 29.