PMID- 33050143 OWN - NLM STAT- MEDLINE DCOM- 20210521 LR - 20210521 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 25 IP - 20 DP - 2020 Oct 9 TI - Water Extract of Lotus Leaf Alleviates Dexamethasone-Induced Muscle Atrophy via Regulating Protein Metabolism-Related Pathways in Mice. LID - 10.3390/molecules25204592 [doi] LID - 4592 AB - Muscle atrophy is an abnormal condition characterized by loss of skeletal muscle mass and function and is primarily caused by injury, malnutrition, various diseases, and aging. Leaf of lotus (Nelumbo nucifera Gaertn), which has been used for medicinal purposes, contains various active ingredients, including polyphenols, and is reported to exert an antioxidant effect. In this study, we investigated the effect of water extract of lotus leaf (LL) on muscle atrophy and the underlying molecular mechanisms of action. Amounts of 100, 200, or 300 mg/kg/day LL were administered to dexamethasone (DEX)-induced muscle atrophy mice for 4 weeks. Micro-computed tomography (CT) analysis revealed that the intake of LL significantly increased calf muscle volume, surface area, and density in DEX-induced muscle atrophy mice. Administration of LL recovered moving distance, grip strength, ATP production, and body weight, which were decreased by DEX. In addition, muscle damage caused by DEX was also improved by LL. LL reduced the protein catabolic pathway by suppressing gene expression of muscle atrophy F-Box (MAFbx; atrogin-1), muscle RING finger 1 (MuRF1), and forkhead box O (FoxO)3a, as well as phosphorylation of AMP-activated kinase (AMPK). The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. The HPLC analysis and pharmacological test revealed that quercetin 3-O-beta-glucuronide (Q3G) is a major active component in LL. Thus, Q3G decreased the gene expression of atrogin-1 and MuRF1 and phosphorylation of AMPK. This compound also increased phosphorylation levels of mTOR and its upstream enzyme AKT in DEX-treated C2C12 cells. We identified that LL improves muscle wasting through regulation of muscle protein metabolism in DEX-induced muscle atrophy mice. Q3G is predicted to be one of the major active phenolic components in LL. Therefore, we propose LL as a supplement or therapeutic agent to prevent or treat muscle wasting, such as sarcopenia. FAU - Park, Sang Hee AU - Park SH AUID- ORCID: 0000-0003-1175-4222 AD - Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Korea. FAU - Oh, Jieun AU - Oh J AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Jo, Minkyeong AU - Jo M AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Kim, Jin Kyeong AU - Kim JK AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Kim, Dong Seon AU - Kim DS AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Kim, Han Gyung AU - Kim HG AUID- ORCID: 0000-0002-4730-9801 AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Yoon, Keejung AU - Yoon K AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Yang, Yoonyong AU - Yang Y AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Geum, Jeong-Ho AU - Geum JH AD - COSMAX NBT, INC., Seoul 06132, Korea. FAU - Kim, Jung-Eun AU - Kim JE AD - Biological and Genetic Resources Assessment Division, National Institute of Biological Resources, Incheon 22689, Korea. FAU - Choi, Su-Young AU - Choi SY AD - Biological and Genetic Resources Assessment Division, National Institute of Biological Resources, Incheon 22689, Korea. FAU - Kim, Ji Hye AU - Kim JH AUID- ORCID: 0000-0002-7881-9599 AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Cho, Jae Youl AU - Cho JY AUID- ORCID: 0000-0001-8141-9927 AD - Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Korea. AD - Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. LA - eng GR - Grant S2435140/Ministry of SMEs and Startups (MSS)/ PT - Journal Article DEP - 20201009 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Plant Extracts) RN - 059QF0KO0R (Water) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Blotting, Western MH - Cell Line MH - Chromatography, High Pressure Liquid MH - Dexamethasone/*toxicity MH - Lotus/*chemistry MH - Male MH - Mice MH - Muscle, Skeletal/*drug effects/*metabolism MH - Muscular Atrophy/*drug therapy/*metabolism MH - Plant Extracts/chemistry/*therapeutic use MH - Plant Leaves/*chemistry MH - Real-Time Polymerase Chain Reaction MH - Water/*chemistry MH - X-Ray Microtomography PMC - PMC7587191 OTO - NOTNLM OT - Atrogin-1 OT - C2C12 myoblast cells OT - MuRF1 OT - Nelumbo nucifera Gaertn OT - Quercetin 3-O-beta-glucuronide OT - dexamethasone-induced muscle atrophy OT - leaf of lotus OT - muscle wasting COIS- The authors declare no conflict of interest. EDAT- 2020/10/15 06:00 MHDA- 2021/05/22 06:00 PMCR- 2020/10/09 CRDT- 2020/10/14 01:03 PHST- 2020/09/10 00:00 [received] PHST- 2020/09/30 00:00 [revised] PHST- 2020/10/02 00:00 [accepted] PHST- 2020/10/14 01:03 [entrez] PHST- 2020/10/15 06:00 [pubmed] PHST- 2021/05/22 06:00 [medline] PHST- 2020/10/09 00:00 [pmc-release] AID - molecules25204592 [pii] AID - molecules-25-04592 [pii] AID - 10.3390/molecules25204592 [doi] PST - epublish SO - Molecules. 2020 Oct 9;25(20):4592. doi: 10.3390/molecules25204592.