Molecular Pathway of Phytochemicals in Preventing Sarcopenia

Desy Nofita Sari; Roman Ardian Goenarjo; Imelda Rosalyn Sianipar

doi:10.24036/eksakta/vol26-iss03/621

EKSAKTA: Berkala Ilmiah Bidang MIPA

Open Access

Molecular Pathway of Phytochemicals in Preventing Sarcopenia

Desy Nofita Sari ¹

, Roman Ardian Goenarjo ²

, Imelda Rosalyn Sianipar ³

¹ Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

² Department of Medical Physiology and Biophysics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

³ Metabolic Disorder, Cardiovascular, and Aging Research Cluster, The Indonesian Medical Educational and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Published 2025-09-30

Vol. 26 No. 03 (2025) PAGES 384-395

DOI 10.24036/eksakta/vol26-iss03/621

Views / Downloads 151 159

Download PDF

Abstract

Sarcopenia, the age-related decline in muscle mass and function, poses a significant global health challenge. This systematic review synthesizes evidence from preclinical studies published between 2020 and 2025 to elucidate the molecular pathways through which phytochemicals prevent sarcopenia. Following PRISMA guidelines, a systematic search of databases identified 16 eligible studies. The analysis reveals that phytochemicals, including flavonoids, polyphenols, and botanical extracts, mitigate muscle atrophy by concurrently enhancing anabolic signaling via the IGF-1/PI3K/Akt/mTOR axis, suppressing proteolysis, improving mitochondrial biogenesis, and reducing oxidative stress and inflammation. Notably, combinatorial formulations and multi-target extracts demonstrate superior efficacy. The review concludes that phytochemicals represent a promising multi-targeted strategy against sarcopenia; however, this promising potential necessitates future validation through standardized clinical trials to establish efficacy and safety in human populations.

References

1

[1] Wei, S., Nguyen, T. T., Zhang, Y., Ryu, D., & Gariani, K. (2023). Sarcopenic obesity: epidemiology, pathophysiology, cardiovascular disease, mortality, and management. Frontiers in endocrinology, 14, 1185221.

2

[2] Kim, J., Lee, J. Y., & Kim, C. Y. (2023). A comprehensive review of pathological mechanisms and natural dietary ingredients for the management and prevention of sarcopenia. Nutrients, 15(11), 2625.

3

[3] He, X., Song, Y., Ma, L., Ainsworth, B. E., Liu, Y., & Chen, N. (2022). Prevalence and factors influencing sarcopenia among community-dwelling older adults using the Asian Working Group for Sarcopenia Definition. Clinical interventions in aging, 1707-1727.

4

[4] He, X., Song, Y., Ma, L., Ainsworth, B. E., Liu, Y., & Chen, N. (2022). Prevalence and factors influencing sarcopenia among community-dwelling older adults using the Asian Working Group for Sarcopenia Definition. Clinical interventions in aging, 1707-1727.

5

[5] Ziemkiewicz, N., Hilliard, G., Pullen, N. A., & Garg, K. (2021). The role of innate and adaptive immune cells in skeletal muscle regeneration. International journal of molecular sciences, 22(6), 3265.

6

[6] Wang, D. T., Yang, Y. J., Huang, R. H., Zhang, Z. H., & Lin, X. (2015). Myostatin activates the ubiquitin‐proteasome and autophagy‐lysosome systems contributing to muscle wasting in chronic kidney disease. Oxidative medicine and cellular longevity, 2015(1), 684965.

7

[7] Dowling, P., Gargan, S., Swandulla, D., & Ohlendieck, K. (2023). Fiber-type shifting in sarcopenia of old age: proteomic profiling of the contractile apparatus of skeletal muscles. International Journal of Molecular Sciences, 24(3), 2415.

8

[8] Lim, J. Y., & Frontera, W. R. (2023). Skeletal muscle aging and sarcopenia: Perspectives from mechanical studies of single permeabilized muscle fibers. Journal of biomechanics, 152, 111559.

9

[9] Pascual-Fernández, J., Fernández-Montero, A., Córdova-Martínez, A., Pastor, D., Martínez-Rodríguez, A., & Roche, E. (2020). Sarcopenia: molecular pathways and potential targets for intervention. International Journal of Molecular Sciences, 21(22), 8844.

10

[10] Vainshtein, A., & Sandri, M. (2020). Signaling pathways that control muscle mass. International journal of molecular sciences, 21(13), 4759.

11

[11] Mankhong, S., Kim, S., Moon, S., Kwak, H. B., Park, D. H., & Kang, J. H. (2020). Experimental models of sarcopenia: bridging molecular mechanism and therapeutic strategy. Cells, 9(6), 1385.

12

[12] Marzetti, E., Privitera, G., Simili, V., Wohlgemuth, S. E., Aulisa, L., Pahor, M., & Leeuwenburgh, C. (2010). Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. The Scientific World Journal, 10(1), 340-349.

13

[13] Sakuma, K., & Yamaguchi, A. (2010). Molecular mechanisms in aging and current strategies to counteract sarcopenia. Current aging science, 3(2), 90-101.

14

[14] Li, M., Qin, Y., Geng, R., Fang, J., Kang, S. G., Huang, K., & Tong, T. (2025). Effects and mechanisms of phytochemicals on skeletal muscle atrophy in glucolipid metabolic disorders: current evidence and future perspectives. Food Innovation and Advances, 4(1), 83-98.

15

[15] Yoon, Y. E., Ju, S. H., Kim, Y., & Lee, S. J. (2025). Natural Flavonoids for the Prevention of Sarcopenia: Therapeutic Potential and Mechanisms. International journal of molecular sciences, 26(15), 7458.

16

[16] Sun, Y., Zheng, Q., Sun, J., Wang, L., & Li, Y. (2024). Phytonutrients as potential dietary supplements to ameliorate sarcopenia via the involvement of autophagic pathway. Food Reviews International, 40(9), 2539-2579.

17

[17] Vargas-Mendoza, N., Madrigal-Santillán, E., Álvarez-González, I., Madrigal-Bujaidar, E., Anguiano-Robledo, L., Aguilar-Faisal, J. L., ... & Morales-González, J. A. (2022). Phytochemicals in skeletal muscle health: effects of curcumin (from Curcuma longa Linn) and sulforaphane (from Brassicaceae) on muscle function, recovery and therapy of muscle atrophy. Plants, 11(19), 2517.

18

[18] Medoro, A., Scapagnini, G., & Davinelli, S. (2024). Polyphenol supplementation and sarcopenia: A systematic review and Meta-Analysis of clinical trials. The Journal of frailty & aging, 13(4), 432-440.

19

[19] Jeong, H. Y., & Kwon, O. (2021). Dietary phytochemicals as a promising nutritional strategy for sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Applied Biological Chemistry, 64(1), 60.

20

[20] Calvani, R., Picca, A., Coelho-Júnior, H. J., Tosato, M., Marzetti, E., & Landi, F. (2023). Diet for the prevention and management of sarcopenia. Metabolism, 146, 155637.

21

[21] Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., ... & Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. bmj, 372.

22

[22] Hooijmans, C. R., Rovers, M. M., De Vries, R. B., Leenaars, M., Ritskes-Hoitinga, M., & Langendam, M. W. (2014). SYRCLE’s risk of bias tool for animal studies. BMC medical research methodology, 14(1), 43.

23

[23] de Castro, J. M., da Silva Melo, A., Silveira, B. L., Martins, I. A. S., Marçal, M. M., Dal Bosco, T., ... & Torres, I. L. (2025). Oral apigenin prevents obesity-related muscular atrophy, but not obesity itself, in middle-aged rats fed a high-calorie diet. Biomedicine & Pharmacotherapy, 189, 118342.

24

[24] Cano-Martínez, A., Méndez-Castro, J. A., García-Vázquez, V. E., Carreón-Torres, E., Díaz-Díaz, E., Sánchez-Aguilar, M., ... & Rubio-Ruíz, M. E. (2025). A Combination of Resveratrol and Quercetin Prevents Sarcopenic Obesity: Its Role as a Signaling Inhibitor of Myostatin/ActRIIA and ActRIIB/Smad and as an Enhancer of Insulin Actions. International Journal of Molecular Sciences, 26(10), 4952.

25

[25] Oh, H. J., Jin, H., & Lee, B. Y. (2023). Hesperidin ameliorates sarcopenia through the regulation of inflammaging and the AKT/mTOR/FoxO3a signaling pathway in 22–26-month-old mice. Cells, 12(15), 2015.

26

[26] Lee, H., Lee, J., Kim, H. J., & Kwon, O. (2023). Short-term treatment of Agastache rugosa extract combined with voluntary wheel running exercise alters the size and type of skeletal muscle fibers and improves anabolic resistance in middle-aged mice. Journal of Functional Foods, 109, 105803.

27

[27] Tian, S., Zhao, H., Liu, J., Ma, X., Zheng, L., Guo, H., & Jiang, Y. (2022). Metabolomics reveals that alcohol extract of propolis alleviates D-gal-induced skeletal muscle senescence in mice. Food Bioscience, 49, 101885.

28

[28] Sakata, Y., Okamoto, T., Oshio, K., Nakamura, H., Iwamoto, H., Namba, K., ... & Yoshizawa, F. (2016). Dietary supplementation with shiikuwasha extract attenuates dexamethasone-induced skeletal muscle atrophy in aged rats. Springerplus, 5(1), 816.

29

[29] Lee, J. H., Kang, H., Ban, G. T., Kim, B. K., Lee, J., Hwang, H., ... & Choi, J. S. (2023). Proteome network analysis of skeletal muscle in lignan-enriched nutmeg extract-fed aged mice. Journal of Analytical Science and Technology, 14(1), 11.

30

[30] Kim, C., Kang, M., Kim, Y., & Hwang, J. K. (2025). Inhibitory effect of standardized Kaempferia parviflora extract on sarcopenia by improving protein metabolism pathways in aged C57BL/6J mice. Journal of Traditional and Complementary Medicine.

31

[31] Lee, H., Eo, Y., Kim, S. Y., & Lim, Y. (2024). Guava leaf extract attenuated muscle proteolysis in dexamethasone induced muscle atrophic mice via ubiquitin proteasome system, mTOR-autophagy, and apoptosis pathway. Nutrition Research, 127, 97-107.

32

[32] Lee, H., Eo, Y., Kim, S. Y., & Lim, Y. (2024). Guava leaf extract attenuated muscle proteolysis in dexamethasone induced muscle atrophic mice via ubiquitin proteasome system, mTOR-autophagy, and apoptosis pathway. Nutrition Research, 127, 97-107.

33

[33] Li, Y., Liu, Z., Yan, H., Zhou, T., Zheng, L., Wen, F., ... & Zhang, Z. (2025). Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging and mitochondrial dysfunction via PI3K/Akt/mTOR signaling pathway. Phytomedicine, 136, 156316.

34

[34] Huang, J., Tong, Y., Wang, S., Tagawa, T., Seki, Y., Ma, S., ... & Suzuki, K. (2024). 8-Week Kaempferia parviflora Extract Administration Improves Submaximal Exercise Capacity in Mice by Enhancing Skeletal Muscle Antioxidant Gene Expression and Plasma Antioxidant Capacity. Antioxidants, 13(9), 1147.

35

[35] Long, Y., Wu, Y., Zhong, Y., Wu, Y., Ye, H., Luo, Y., ... & Wang, M. (2024). Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments. Biomedicine & Pharmacotherapy, 179, 117396.

36

[36] Zhaoyu, L., Xiaomeng, Y., Na, L., Jiamin, S., Guanhua, D., & Xiuying, Y. (2024). Roles of natural products on myokine expression and secretion in skeletal muscle atrophy. General and Comparative Endocrinology, 355, 114550.

Molecular Pathway of Phytochemicals in Preventing Sarcopenia

Abstract

References

How to Cite

Cite Article

Article Update