<em>Saururus chinensis</em> (Lour.) Baill. extract promotes skeletal muscle cell differentiation by positively regulating mitochondrial biogenesis and AKT/mTOR signaling <em>in vitro</em>

Eun,So Young; Chung,Chong Hyuk; Cheon,Yoon-Hee; Park,Gyeong Do; Lee,Chang Hoon; Kim,Ju-Young; Lee,Myeung Su

doi:10.3892/mmr.2024.13250

Saururus chinensis (Lour.) Baill. extract promotes skeletal muscle cell differentiation by positively regulating mitochondrial biogenesis and AKT/mTOR signaling in vitro

Authors:
- So Young Eun
- Chong Hyuk Chung
- Yoon-Hee Cheon
- Gyeong Do Park
- Chang Hoon Lee
- Ju-Young Kim
- Myeung Su Lee
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Affiliations: Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea
Published online on: May 20, 2024 https://doi.org/10.3892/mmr.2024.13250
Article Number: 125

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Abstract

Promotion of myoblast differentiation by activating mitochondrial biogenesis and protein synthesis signaling pathways provides a potential alternative strategy to balance energy and overcome muscle loss and muscle disorders. Saururus chinensis (Lour.) Baill. extract (SCE) has been used extensively as a traditional herbal medicine and has several physiological activities, including anti‑asthmatic, anti‑oxidant, anti‑inflammatory, anti‑atopic, anticancer and hepatoprotective properties. However, the effects and mechanisms of action of SCE on muscle differentiation have not yet been clarified. In the present study, it was investigated whether SCE affects skeletal muscle cell differentiation through the regulation of mitochondrial biogenesis and protein synthesis in murine C2C12 myoblasts. The XTT colorimetric assay was used to determine cell viability, and myosin heavy chain (MyHC) levels were determined using immunocytochemistry. SCE was applied to C2C12 myotube at different concentrations (1, 5, or 10 ng/ml) and times (1,3, or 5 days). Reverse transcription‑quantitative PCR and western blotting were used to analyze the mRNA and protein expression change of factors related to differentiation, mitochondrial biogenesis and protein synthesis. Treatment of C2C12 cells with SCE at 1,5, and 10 ng/ml did not affect cell viability. SCE promoted C2C12 myotube formation and significantly increased MyHC expression in a concentration‑ and time‑dependent manner. SCE significantly increased the mRNA and protein expression of muscle differentiation‑specific markers, such as MyHC, myogenic differentiation 1, myogenin, Myogenic Factor 5, and β‑catenin, mitochondrial biosynthesis‑related factors, such as peroxisome proliferator‑activated receptor‑gamma coactivator‑1α, nuclear respirator factor‑1, AMP‑activated protein kinase phosphorylation, and histone deacetylase 5 and AKT/mTOR signaling factors related to protein synthesis. SCE may prevent skeletal muscle dysfunction by enhancing myoblast differentiation through the promotion of mitochondrial biogenesis and protein synthesis.

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1	Hargreaves M and Spriet LL: Skeletal muscle energy metabolism during exercise. Nat Metab. 2:817–828. 2020. View Article : Google Scholar : PubMed/NCBI
2	Thyfault JP and Bergouignan A: Exercise and metabolic health: Beyond skeletal muscle. Diabetologia. 63:1464–1474. 2020. View Article : Google Scholar : PubMed/NCBI
3	Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Rubin SM and Harris TB: Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci. 61:72–77. 2006. View Article : Google Scholar : PubMed/NCBI
4	Landi F, Liperoti R, Russo A, Giovannini S, Tosato M, Capoluongo E, Bernabei R and Onder G: Sarcopenia as a risk factor for falls in elderly individuals: Results from the ilSIRENTE study. Clin Nutr. 31:652–658. 2012. View Article : Google Scholar : PubMed/NCBI
5	Peng P, Hyder O, Firoozmand A, Kneuertz P, Schulick RD, Huang D, Makary M, Hirose K, Edil B, Choti MA, et al: Impact of sarcopenia on outcomes following resection of pancreatic adenocarcinoma. J Gastrointest Surg. 16:1478–1486. 2012. View Article : Google Scholar : PubMed/NCBI
6	Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, Abellan van Kan G, Andrieu S, Bauer J, Breuille D, et al: Sarcopenia: An undiagnosed condition in older adults. Current consensus definition: Prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 12:249–256. 2011. View Article : Google Scholar : PubMed/NCBI
7	Mankhong S, Kim S, Moon S, Kwak HB, Park DH and Kang JH: Experimental models of sarcopenia: Bridging molecular mechanism and therapeutic strategy. Cell. 9:13852020. View Article : Google Scholar
8	Ma J, Meng X, Kang SY, Zhang J, Jung HW and Park YK: Regulatory effects of the fruit extract of Lycium chinense and its active compound, betaine, on muscle differentiation and mitochondrial biogenesis in C2C12 cells. Biomed Pharmacother. 118:1092972019. View Article : Google Scholar : PubMed/NCBI
9	Shin EJ, Jo S, Choi S, Cho CW, Lim WC, Hong HD, Lim TG, Jang YJ, Jang M, Byun S and Rhee Y: Red ginseng improves exercise endurance by promoting mitochondrial biogenesis and myoblast differentiation. Molecules. 25:8652020. View Article : Google Scholar : PubMed/NCBI
10	Kim YH, Jung JI, Jeon YE, Kim SM, Oh TK, Lee J, Moon JM, Kim TY and Kim EJ: Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes. Nutr Res Pract. 16:14–32. 2022. View Article : Google Scholar : PubMed/NCBI
11	National Institute of Biological Resources, . Korean Red List of Threatened Species. 2nd edition. National Institute of Biological Resources 2014; 2nd edition. Suh MH, Lee BY, Kim ST, Park CH, Oh HK, Kim HY, Lee JH and Lee SY: National Institute of Biological Resources; Incheon: 2014
12	Chang CS, Lee JS, Park TY and Kim H: Reconsideration of rare and endangered plant species in Korea based on the IUCN red list categories. Korean J Pl Taxon. 31:107–142. 2001. View Article : Google Scholar
13	Ryu SY, Oh KS, Kim YS and Lee BH: Antihypertensive, vasorelaxant and inotropic effects of an ethanolic extract of the roots of Saururus chinensis. J Ethnopharmacol. 118:284–289. 2008. View Article : Google Scholar : PubMed/NCBI
14	Yoo HJ, Kang HJ, Jung HJ, Kim K, Lim CJ and Park EH: Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of Saururus chinensis extract. J Ethnopharmacol. 120:282–286. 2008. View Article : Google Scholar : PubMed/NCBI
15	Nho JH, Lee HJ, Jung HK, Jang JH, Lee KH, Kim AH, Sung TK and Cho HW: Effect of Saururus chinensis leaves extract on type II collagen-induced arthritis mouse model. BMC Complement Altern Med. 19:22019. View Article : Google Scholar : PubMed/NCBI
16	Cheng Y, Yin Z, Jiang F, Xu J, Chen H and Gu Q: Two new lignans from the aerial parts of Saururus chinensis with cytotoxicity toward nasopharyngeal carcinoma. Fitoterapia. 141:1043442020. View Article : Google Scholar : PubMed/NCBI
17	Sung SH, Lee EJ, Cho JH, Kim HS and Kim YC: Sauchinone, a lignan from Saururus chinensis, attenuates CCl4-induced toxicity in primary cultures of rat hepatocytes. Biol Pharm Bull. 23:666–668. 2000. View Article : Google Scholar : PubMed/NCBI
18	Hwang BY, Lee JH, Nam JB, Hong YS and Lee JJ: Lignans from Saururus chinensis inhibiting the transcription factor NF-kappaB. Phytochemistry. 64:765–771. 2003. View Article : Google Scholar : PubMed/NCBI
19	Quan Z, Lee YJ, Yang JH, Lu Y, Li Y, Lee YK, Jin M, Kim JY, Choi JH, Son JK and Chang HW: Ethanol extracts of Saururus chinensis suppress ovalbumin-sensitization airway inflammation. J Ethnopharmacol. 132:143–149. 2010. View Article : Google Scholar : PubMed/NCBI
20	Alaklabi A, Arif IA, Ahamed A, Surendra Kumar R and Idhayadhulla A: Evaluation of antioxidant and anticancer activities of chemical constituents of the Saururus chinensis root extracts. Saudi J Biol Sci. 25:1387–1392. 2018. View Article : Google Scholar : PubMed/NCBI
21	Zhang J, Rho Y, Kim MY and Cho JY: TAK1 in the AP-1 pathway is a critical target of Saururus chinensis (Lour.) Baill in its anti-inflammatory action. J Ethnopharmacol. 279:1144002021. View Article : Google Scholar : PubMed/NCBI
22	Yoo SR, Ha H, Shin HK and Seo CS: Anti-inflamatory activity of neolignan compound isolated from the roots of Saururus chinensis. Plants (Basel). 9:9322020. View Article : Google Scholar : PubMed/NCBI
23	Jung YW, Lee BM, Ha MT, Tran MH, Kim JA, Lee S, Lee JH, Woo MH and Min BS: Lignans from Saururus chinensis exhibit anti-inflammatory activity by influencing the Nrf2/HO-1 activation pathway. Arch Pharm Res. 42:332–343. 2019. View Article : Google Scholar : PubMed/NCBI
24	Choi MS, Kim EC, Lee HS, Kim SK, Choi HM, Park JH, Han JB, An HJ, Um JY, Kim HM, et al: Inhibitory effects of Saururus chinensis (LOUR.) BAILL on the development of atopic dermatitis-like skin lesions in NC/Nga mice. Biol Pharm Bull. 31:51–56. 2008. View Article : Google Scholar : PubMed/NCBI
25	Jeong HJ, Koo BS, Kang TH, Shin HM, Jung S and Jeon S: Inhibitory effects of Saururus chinensis and its components on stomach cancer cells. Phytomedicine. 22:256–261. 2015. View Article : Google Scholar : PubMed/NCBI
26	Wang L, Cheng D, Wang H, Di L, Zhou X, Xu T, Yang X and Liu Y: The hepatoprotective and antifibrotic effects of Saururus chinensis against carbon tetrachloride induced hepatic fibrosis in rats. J Ethnopharmacol. 126:487–491. 2009. View Article : Google Scholar : PubMed/NCBI
27	Jung MH, Song MC, Bae K, Kim HS, Kim SH, Sung SH, Ye SK, Lee KH, Yun YP and Kim TJ: Sauchinone attenuates oxidative stress-induced skeletal muscle myoblast damage through the down-regulation of ceramide. Biol Pharm Bull. 34:575–579. 2011. View Article : Google Scholar : PubMed/NCBI
28	Liu H, Lee SM and Joung H: 2-D08 treatment regulates C2C12 myoblast proliferation and differentiation via the Erk1/2 and proteasome signaling pathways. J Muscle Res Cell Motil. 42:193–202. 2021. View Article : Google Scholar : PubMed/NCBI
29	Kim JY, Cheon YH, Ahn SJ, Kwak SC, Chung CH, Lee CH and Lee MS: Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice. BMC Complement Med Ther. 22:2142022. View Article : Google Scholar : PubMed/NCBI
30	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
31	Sayer AA, Robinson SM, Patel HP, Shavlakadze T, Cooper C and Grounds MD: New horizons in the pathogenesis, diagnosis and management of sarcopenia. Age Ageing. 42:145–150. 2013. View Article : Google Scholar : PubMed/NCBI
32	Oh KS, Choi YH, Ryu SY, Oh BK, Seo HW, Yon GH, Kim YS and Lee BH: Cardiovascular effects of lignans isolated from Saururus chinensis. Planta Med. 74:233–238. 2008. View Article : Google Scholar : PubMed/NCBI
33	Dumont NA, Bentzinger CF, Sincennes MC and Rudnicki MA: Satellite cells and skeletal muscle regeneration. Compr Physiol. 5:1027–1059. 2015. View Article : Google Scholar : PubMed/NCBI
34	Langley B, Thomas M, Bishop A, Sharma M, Gilmour S and Kambadur R: Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem. 277:49831–49840. 2002. View Article : Google Scholar : PubMed/NCBI
35	Tanaka S, Terada K and Nohno T: Canonical Wnt signaling is involved in switching from cell proliferation to myogenic differentiation of mouse myoblast cells. J Mol Signal. 6:122011. View Article : Google Scholar : PubMed/NCBI
36	Kang C and Li Ji L: Role of PGC-1α signaling in skeletal muscle health and disease. Ann N Y Acad Sci. 1271:110–117. 2012. View Article : Google Scholar : PubMed/NCBI
37	Taherzadeh-FardE SC, Akkad DA, Wieczorek S, Haghikia A, Chan A, Epplen JT and Arning L: PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease. Mol Neurodegener. 6:322011. View Article : Google Scholar : PubMed/NCBI
38	Hardie DG, Ross FA and Hawley SA: AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 13:251–262. 2012. View Article : Google Scholar : PubMed/NCBI
39	Gasparrini M, Giampieri F, Alvarez Suarez J, Mazzoni L, Y Forbes Hernandez T, Quiles JL, Bullon P and Battino M: AMPK as a new attractive therapeutic target for disease prevention: The role of dietary compounds AMPK and disease prevention. Curr Drug Targets. 17:865–889. 2016. View Article : Google Scholar : PubMed/NCBI
40	Fu X, Zhao JX, Liang J, Zhu MJ, Foretz M, Viollet B and Du M: AMP-activated protein kinase mediates myogenin expression and myogenesis via histone deacetylase 5. Am J Physiol Cell Physiol. 305:C887–C895. 2013. View Article : Google Scholar : PubMed/NCBI
41	Tao R, Gong J, Luo X, Zang M, Guo W, Wen R and Luo Z: AMPK exerts dual regulatory effects on the PI3K pathway. J Mol Signal. 5:12010. View Article : Google Scholar : PubMed/NCBI
42	Simone C, Forcales SV, Hill DA, Imbalzano AN, Latella L and Puri PL: p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci. Nat Genet. 36:738–743. 2004. View Article : Google Scholar : PubMed/NCBI
43	Bae GU, Lee JR, Kim BG, Han JW, Leem YE, Lee HJ, Ho SM, Hahn MJ and Kang JS: Cdo interacts with APPL1 and activates Akt in myoblast differentiation. Mol Biol Cell. 21:2399–2411. 2010. View Article : Google Scholar : PubMed/NCBI
44	Glass DJ: Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol. 5:87–90. 2003. View Article : Google Scholar : PubMed/NCBI
45	Bodine SC, Stitt TN, Gonalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ and Yancopoulos GD: Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 3:1014–1019. 2001. View Article : Google Scholar : PubMed/NCBI
46	Lipina C, Kendall H, McPherron AC, Taylor PM and Hundal HS: Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice. FEBS Lett. 584:2403–2408. 2010. View Article : Google Scholar : PubMed/NCBI