ZHAO Xiaopeng, DONG Dan, TAN Boxuan, et al. Mechanism of Litchi Semen Extract in Preventing Exercise-induced Muscle Damage Based on Network Pharmacology and in Vivo and in Vitro Experiments[J]. Science and Technology of Food Industry, 2025, 46(10): 371−382. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2024060142.
Citation: ZHAO Xiaopeng, DONG Dan, TAN Boxuan, et al. Mechanism of Litchi Semen Extract in Preventing Exercise-induced Muscle Damage Based on Network Pharmacology and in Vivo and in Vitro Experiments[J]. Science and Technology of Food Industry, 2025, 46(10): 371−382. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2024060142.

Mechanism of Litchi Semen Extract in Preventing Exercise-induced Muscle Damage Based on Network Pharmacology and in Vivo and in Vitro Experiments

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  • Received Date: June 11, 2024
  • Available Online: March 13, 2025
  • Objective: Based on network pharmacology combined with the GEO database and in vivo and in vitro experiments to explore the potential mechanisms of litchi semen extract (LZH) for preventing exercise-induced muscle damage (EIMD). Methods: Hematoxylin-eosin (HE) staining and comparison of the levels of indicators of skeletal muscle damage in serum were performed to detect the effectiveness of LZH in preventing EIMD. The main active ingredients of LZH were searched through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database in conjunction with the published literature, and the targets corresponding to the active ingredients were found through the relevant websites, which were intersected with the EIMD-related targets obtained from the GEO database. The STRING database screened the intersected targets and finally enriched them for analysis. The results of the network pharmacology predictions were validated in vivo using the centrifugal exercise-induced EIMD mouse model and in vitro using the H2O2-induced C2C12 cell model. Results: In vivo experiments showed that skeletal muscle fiber cross-sectional area (P<0.05), creatine kinase (CK) (P<0.001) and lactate dehydrogenase (LDH) (P<0.01) were significantly reduced after the intervention of LZH. The results of network pharmacology showed that LZH had 14 active ingredients, corresponding to 367 targets. The GEO database obtained 1015 targets related to EIMD. The intersection of the two yielded 37 intersecting targets. The enrichment analysis demonstrated p53-mediated cell cycle arrest as the primary target for validation. In vivo experiments showed that LZH significantly reduced the expression of p53 (P<0.01), p21 (P<0.001), BCL2-associated X (Bax) (P<0.05), and the expression of Cyclin D1 (P<0.05), B-cell lymphoma-2 (Bcl-2) (P<0.05) expression was significantly increased. In vitro experiments showed that low and high dose pretreatment of LZH significantly decreased the expression of apoptosis (P<0.001), p53 (P<0.05), p21 (P<0.01, P<0.001) and increased the expression of Cyclin D1 (P<0.05, P<0.001). Conclusion: LZH attenuates EIMD, and its mechanism is closely related to the activation of G1 phase arrest and attenuation of apoptosis in skeletal muscle cells. The results suggest that LZH can be used as a nutritional supplement to prevent EIMD.
  • [1]
    CABALLERO-GARCÍA A, NORIEGA-GONZÁLEZ D C, ROCHE E, et al. Effects of l-carnitine intake on exercise-induced muscle damage and oxidative stress:A narrative scoping review[J]. Nutrients,2023,15(11):2587. doi: 10.3390/nu15112587
    [2]
    OWENS D J, TWIST C, COBLEY J N, et al. Exercise-induced muscle damage:What is it, what causes it and what are the nutritional solutions?[J]. European Journal of Sport Science,2019,19(1):71−85. doi: 10.1080/17461391.2018.1505957
    [3]
    雷尚文, 元宝华, 刘学睿, 等. 中医药疗法治疗运动性骨骼肌损伤作用机制的研究进展[J]. 中医正骨,2024,36(1):57−62,68. [LEI S W, YUAN B H, LIU X R, et al. Research progress on the mechanism of traditional chinese medicine therapy in the treatment of exercise-induced skeletal muscle injury[J]. Chinese Medicine Zhenggu,2024,36(1):57−62,68.] doi: 10.3969/j.issn.1001-6015.2024.01.010

    LEI S W, YUAN B H, LIU X R, et al. Research progress on the mechanism of traditional chinese medicine therapy in the treatment of exercise-induced skeletal muscle injury[J]. Chinese Medicine Zhenggu, 2024, 36(1): 57−62,68. doi: 10.3969/j.issn.1001-6015.2024.01.010
    [4]
    TORRES R, RIBEIRO F, ALBERTO DUARTE J, et al. Evidence of the physiotherapeutic interventions used currently after exercise-induced muscle damage:Systematic review and meta-analysis [J]. Physical Therapy in Sport :Official Journal of the Association of Chartered Physiotherapists in Sports Medicine, 2012, 13(2):101-114.
    [5]
    BAZZUCCHI I, PATRIZIO F, CECI R, et al. The effects of quercetin supplementation on eccentric exercise-induced muscle damage[J]. Nutrients,2019,11(1):205. doi: 10.3390/nu11010205
    [6]
    CHEN H Y, CHEN Y C, TUNG K, et al. Effects of caffeine and sex on muscle performance and delayed-onset muscle soreness after exercise-induced muscle damage:A double-blind randomized trial[J]. Journal of Applied Physiology, 2019, 127(3):798-805.
    [7]
    WHITE S H, WARREN L K. Submaximal exercise training, more than dietary selenium supplementation, improves antioxidant status and ameliorates exercise-induced oxidative damage to skeletal muscle in young equine athletes[J]. Journal of Animal Science,2017,95(2):657-670. doi: 10.1093/jas/skaa065
    [8]
    MURPHY R M, DUTKA T L, HORVATH D, et al. Ca2+-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and cardiac muscle[J]. The Journal of Physiology,2013,591(3):719−729. doi: 10.1113/jphysiol.2012.243279
    [9]
    国春鼎, 杨军霞, 李鹏程, 等. 萝卜硫素通过抑制pink1/parkin信号通路介导的线粒体自噬减轻力竭运动诱导的骨骼肌损伤和疲劳[J]. 中国食品卫生杂志,2022,34(6):1158−1165. [GUO C D, YANG J X, LI P C, et al. Sulforaphane Alleviates exhaustive exercise-induced skeletal muscle injury and fatigue by inhibiting mitophagy mediated by PINK1/Parkin signaling pathway[J]. China Journal of Food Hygiene,2022,34(6):1158−1165.]

    GUO C D, YANG J X, LI P C, et al. Sulforaphane Alleviates exhaustive exercise-induced skeletal muscle injury and fatigue by inhibiting mitophagy mediated by PINK1/Parkin signaling pathway[J]. China Journal of Food Hygiene, 2022, 34(6): 1158−1165.
    [10]
    RA S G, MIYAZAKI T, KOJIMA R, et al. Effect of bcaa supplement timing on exercise-induced muscle soreness and damage:A pilot placebo-controlled double-blind study[J]. The Journal of Sports Medicine and Physical Fitness,2018,58(11):1582−1591.
    [11]
    FEDEWA M V, SPENCER S O, WILLIAMS T D, et al. Effect of branched-chain amino acid supplementation on muscle soreness following exercise:A meta-analysis[J]. International Journal for Vitamin and Nutrition Research,2019,89(5−6):348−356. doi: 10.1024/0300-9831/a000543
    [12]
    MS S A B, WALDMAN PH D H, KRINGS PH D B, et al. Effect of curcumin supplementation on exercise-induced oxidative stress, inflammation, muscle damage, and muscle soreness[J]. Journal of Dietary Supplements,2020,17(4):401−414. doi: 10.1080/19390211.2019.1604604
    [13]
    DA SILVA W, MACHADO Á S, SOUZA M A, et al. Effect of green tea extract supplementation on exercise-induced delayed onset muscle soreness and muscular damage[J]. Physiology & Behavior,2018,194:77−82.
    [14]
    MAN S L, MA J, YAO J W, et al. Systemic perturbations of key metabolites in type 2 diabetic rats treated by polyphenol extracts from litchi chinensis seeds[J]. Journal of Agricultural and Food Chemistry,2017,65(35):7698−7704. doi: 10.1021/acs.jafc.7b02206
    [15]
    PAN M H, LI M Y, TSAI M L, et al. A mixture of citrus polymethoxyflavones, green tea polyphenols and lychee extracts attenuates adipogenesis in 3t3-l1 adipocytes and obesity-induced adipose inflammation in mice[J]. Food & Function,2019,10(12):7667−7677.
    [16]
    LEE W Y, LEE C Y, KIM Y S, et al. The methodological trends of traditional herbal medicine employing network pharmacology[J]. Biomolecules,2019,9(8):362. doi: 10.3390/biom9080362
    [17]
    LI S, ZHANG B. Traditional chinese medicine network pharmacology:Theory, methodology and application[J]. Chinese Journal of Natural Medicines,2013,11(2):110−120. doi: 10.1016/S1875-5364(13)60037-0
    [18]
    YAO Y, LIU T H, YIN L J, et al. Polyphenol-rich extract from litchi chinensis seeds alleviates hypertension-induced renal damage in rats[J]. Journal of Agricultural and Food Chemistry,2021,69(7):2138−2148. doi: 10.1021/acs.jafc.0c07046
    [19]
    CHANG M, ZHU D, CHEN Y J, et al. Total flavonoids of litchi seed attenuate prostate cancer progression via inhibiting akt/mtor and NF-KB signaling pathways[J]. Frontiers in Pharmacology,2021,12:758219. doi: 10.3389/fphar.2021.758219
    [20]
    KIM Y A, OH S H, LEE G H, et al. Platycodon grandiflorum-derived saponin attenuates the eccentric exercise-induced muscle damage[J]. Food and Chemical Toxicology, 2018, 112:150-156.
    [21]
    XIA Z, CHOLEWA J, ZHAO Y, et al. Hypertrophy-promoting effects of leucine supplementation and moderate intensity aerobic exercise in pre-senescent mice[J]. Nutrients,2016,8(5):246. doi: 10.3390/nu8050246
    [22]
    RU J L, LI P, WANG J N, et al. Tcmsp:A database of systems pharmacology for drug discovery from herbal medicines[J]. Journal of Cheminformatics,2014,6:13. doi: 10.1186/1758-2946-6-13
    [23]
    XIANG J Y, CHI Y Y, HAN J X, et al. Litchi chinensis seed prevents obesity and modulates the gut microbiota and mycobiota compositions in high-fat diet-induced obese zebrafish[J]. Food & Function,2022,13(5):2832−2845.
    [24]
    CHUKWUMA C I, IZU G O, CHUKWUMA M S, et al. A review on the medicinal potential, toxicology, and phytochemistry of litchi fruit peel and seed[J]. Journal of Food Biochemistry,2021,45(12):e13997.
    [25]
    YAO P, GAO Y, SIMAL-GANDARA J, et al. Litchi (Litchi chinensis sonn.):A comprehensive review of phytochemistry, medicinal properties, and product development[J]. Food & Function,2021,12(20):9527−9548.
    [26]
    CAO S, HAN Y, LI Q, et al. Mapping pharmacological network of multi-targeting litchi ingredients in cancer therapeutics[J]. Frontiers in Pharmacology,2020,11:451. doi: 10.3389/fphar.2020.00451
    [27]
    IBRAHIM S R, MOHAMED G A. Litchi chinensis:Medicinal uses, phytochemistry, and pharmacology[J]. Journal of Ethnopharmacology,2015,174:492−513. doi: 10.1016/j.jep.2015.08.054
    [28]
    KIM S, CHEN J, CHENG T J, et al. Pubchem in 2021:New data content and improved web interfaces[J]. Nucleic Acids Research,2021,49(D1):D1388−D1395. doi: 10.1093/nar/gkaa971
    [29]
    DAINA A, MICHIELIN O, ZOETE V. Swisstargetprediction:Updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Research,2019,47(W1):W357−W364. doi: 10.1093/nar/gkz382
    [30]
    WANG X, SHEN Y, WANG S, et al. Pharmmapper 2017 update:A web server for potential drug target identification with a comprehensive target pharmacophore database[J]. Nucleic Acids Research,2017,45(W1):W356−w360. doi: 10.1093/nar/gkx374
    [31]
    MENDEZ D, GAULTON A, BENTO A P, et al. Chembl:Towards direct deposition of bioassay data[J]. Nucleic Acids Research,2019,47(D1):D930−D940. doi: 10.1093/nar/gky1075
    [32]
    BARRETT T, WILHITE S E, LEDOUX P, et al. Ncbi geo:Archive for functional genomics data sets--update [J]. Nucleic Acids Research, 2013, 41:D991−D995.
    [33]
    WARREN G L, SUMMAN M, GAO X, et al. Mechanisms of skeletal muscle injury and repair revealed by gene expression studies in mouse models[J]. The Journal of Physiology, 2007, 582(Pt 2):825-841.
    [34]
    Uniprot:The universal protein knowledgebase in 2021[J]. Nucleic Acids Research, 2021, 49(D1):D480-D489.
    [35]
    SZKLARCZYK D, GABLE A L, LYON D, et al. String v11:Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Research,2019,47(D1):D607−D613. doi: 10.1093/nar/gky1131
    [36]
    HUANG DA W, SHERMAN B T, LEMPICKI R A. Systematic and integrative analysis of large gene lists using david bioinformatics resources[J]. Nature Protocols,2009,4(1):44−57. doi: 10.1038/nprot.2008.211
    [37]
    LUO W, BROUWER C. Pathview:An r/bioconductor package for pathway-based data integration and visualization[J]. Bioinformatics (Oxford, England),2013,29(14):1830−1.
    [38]
    CHEN X L, LIANG D H, HUANG Z Q, et al. Anti-fatigue effect of quercetin on enhancing muscle function and antioxidant capacity[J]. Journal of Food Biochemistry,2021,45(11):e13968.
    [39]
    SHIBUYA S C, WATANABE K, SAKURABA D, et al. Natural compounds that enhance motor function in a mouse model of muscle fatigue[J]. Biomedicines,2022,10(12):3073. doi: 10.3390/biomedicines10123073
    [40]
    BEYFUSS K, HOOD D A. A systematic review of p53 regulation of oxidative stress in skeletal muscle[J]. Redox Report:Communications in Free Radical Research, 2018, 23(1):100−117.
    [41]
    KUMARI R, JAT P. Mechanisms of cellular senescence:Cell cycle arrest and senescence associated secretory phenotype[J]. Frontiers in Cell and Developmental Biology,2021,9:645593. doi: 10.3389/fcell.2021.645593
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