PMID- 36846003 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230228 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 11 IP - 3 DP - 2023 Feb 15 TI - Jian Pi Sheng Sui Gao (JPSSG) alleviation of skeletal myoblast cell apoptosis, oxidative stress, and mitochondrial dysfunction to improve cancer-related fatigue in an AMPK-SIRT1- and HIF-1-dependent manner. PG - 156 LID - 10.21037/atm-22-6611 [doi] LID - 156 AB - BACKGROUND: Jian Pi Sheng Sui Gao (JPSSG), a Chinese traditional herbal paste, possesses certain efficacy in patients with cancer-related fatigue (CRF); however, its related mechanism remains unclear. Hence, network pharmacology analysis, followed by in vivo and in vitro experiments were conducted in this study with the aim to evaluate the effect of JPSSG on CRF and clarify its potential mechanism. METHODS: Network pharmacology analysis was performed. Subsequently, 12 mice were injected with CT26 cells to establish CRF mouse models and randomly divided into a model group (n=6) and JPSSG group (n=6); meanwhile, another 6 normal mice served as a control group. Then, 3.0 g/kg JPSSG was given to mice in JPSSG group for 15 days, while mice in the n control and model groups received phosphate-buffered saline (PBS) of the same volume for 15 days. For the in vitro experiment, CT26 conditioned medium (CM) was established; meanwhile, the mitochondrial damage model was constructed through C2C12 myotubes stimulated with H(2)O(2). C2C12 myotubes were divided into 5 groups: control group (without treatment), CM group, CM + JPSSG group, H(2)O(2) group, and H(2)O(2) + JGSSP group. RESULTS: Network pharmacology analysis identified 87 bioactive compounds and 132 JPSSG-CRF interaction targets. Moreover, according to the Kyoto Encyclopedia of Genes and Genomes enrichment analysis and the subsequent in vivo and in vitro experiments, JPSSG activated adenosine 5'-monophosphate-activated protein kinase-silent-information-regulator factor 2-related-enzyme 1 (AMPK-SIRT1) and hypoxia-inducible factor-1 (HIF-1) signaling pathways during CRF. Moreover, the in vivo experiment showed that JPSSG attenuated CRF in mice, reflected by increased distance traveled, mobile time in open field test, and swimming time in exhaustive swimming test, and decreased absolute rest time and tail suspension test in the JPSSG group (vs. model group). Furthermore, JPSSG upregulated gastrocnemius weight, adenosine triphosphate (ATP), superoxide dismutase (SOD), and the cross-sectional area of the gastrocnemius. With regard to in vitro study, JPSSG elevated cell viability, B-cell lymphoma-2, ATP, SOD, and mitochondrial membrane potential, while it decreased apoptosis rate, cleaved-caspase3, malondialdehyde, and reactive oxygen species in C2C12 myotubes. CONCLUSIONS: JPSSG ameliorates CRF via alleviating skeletal myoblast cell apoptosis, oxidative stress, and mitochondrial dysfunction in an AMPK-SIRT1- and HIF-1-dependent manner. CI - 2023 Annals of Translational Medicine. All rights reserved. FAU - Xiao, Min AU - Xiao M AD - Clinical Discipline of Integrated Chinese and Western Medicine, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Rheumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. FAU - Guo, Wei AU - Guo W AD - Clinical Discipline of Integrated Chinese and Western Medicine, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhang, Chi AU - Zhang C AD - Clinical Discipline of Integrated Chinese and Western Medicine, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhu, Yukun AU - Zhu Y AD - Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. FAU - Li, Zhiling AU - Li Z AD - Department of Rheumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. FAU - Shao, Cui AU - Shao C AD - Clinical Discipline of Integrated Chinese and Western Medicine, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Jiang, Jiling AU - Jiang J AD - Department of General Surgery, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. FAU - Yang, Zhenjiang AU - Yang Z AD - Department of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. FAU - Zhang, Jianyong AU - Zhang J AD - Department of Rheumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China. FAU - Lin, Lizhu AU - Lin L AD - Clinical Discipline of Integrated Chinese and Western Medicine, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC9951005 OTO - NOTNLM OT - Jian Pi Sheng Sui Gao (JPSSG) OT - cancer-related fatigue (CRF) OT - molecular mechanism OT - network pharmacology OT - oxidative stress COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6611/coif). The authors have no conflicts of interest to declare. EDAT- 2023/02/28 06:00 MHDA- 2023/02/28 06:01 PMCR- 2023/02/15 CRDT- 2023/02/27 05:30 PHST- 2022/12/14 00:00 [received] PHST- 2023/02/02 00:00 [accepted] PHST- 2023/02/27 05:30 [entrez] PHST- 2023/02/28 06:00 [pubmed] PHST- 2023/02/28 06:01 [medline] PHST- 2023/02/15 00:00 [pmc-release] AID - atm-11-03-156 [pii] AID - 10.21037/atm-22-6611 [doi] PST - ppublish SO - Ann Transl Med. 2023 Feb 15;11(3):156. doi: 10.21037/atm-22-6611.