Journal of Isfahan Medical School

Journal of Isfahan Medical School

The effects of aerobic exercise and garlic extract on SEMA3C gene expression in the cerebral cortex of obese rats

Document Type : Original Article(s)

Authors
1 PhD Student, Department of Physical Education & Sports Sciences, AK. C., Islamic Azad University, Aliabad Katoul, Iran
2 Associate Professor, Department of Physical Education & Sports Sciences, AK. C., Islamic Azad University, Aliabad Katoul, Iran
10.48305/jims.v44.i865.0914
Abstract
Background a: Obesity is associated with increased systemic inflammation and disruption of neuroimmunological pathways. SEMA3C is considered an adipokine linked to metabolic disorders. This study aimed to investigate the effects of aerobic exercise and garlic extract on SEMA3C gene expression in the cerebral cortex of obese rats.
Methods: In this experimental study, 25 male Wistar rats were divided into five groups: healthy control, obese control, obese+garlic, obese+exercise, and obese+garlic+exercise. A high-fat diet was administered for 12 weeks to induce obesity. Moderate aerobic exercise was conducted and oral garlic extract was administered for eight weeks. SEMA3C gene expression in the cerebral cortex was determined using RT-PCR. Data were analyzed using one-way ANOVA.
Results: Obesity induction led to a significant increase in SEMA3C expression. Garlic extract supplementation significantly reduced SEMA3C expression, while exercise alone induced a non-significant decrease. The combined intervention of garlic and exercise resulted in the greatest reduction, which was statistically significant compared to the exercise-only group.
Conclusion: Garlic extract has a more potent effect than exercise in reducing SEMA3C expression, and its combination with exercise results in a synergistic effect. These findings highlight the importance of nutritional interventions, particularly garlic extract supplementation, in managing the adverse effects of obesity on brain health and neuroimmunological pathways.

Highlights

Habib Asgharpour : Google Scholar

Keywords
Subjects

1.     Gholabi A, Ghalavand A, Barmala A, Sadegh Joola M, Gholami A. Effect of exercise training on insulin dysfunction related to obesity across the lifespan. Razi Journal of Medical Sciences 2025; 32(1): 1-20.
2.     Kokkorakis M, Chakhtoura M, Rhayem C, Al Rifai J, Ghezzawi M, Valenzuela-Vallejo L, et al. Emerging pharmacotherapies for obesity: a systematic review. Pharmacol Rev 2025; 77(1): 100002.
3.     Ghalavand A, RahmaniGhobadi M. Effect of exercise and insulin signaling on glucose transporter type 4 in skeletal muscles: a narrative review [in Persian]. J Shahid Sadoughi Univ Med Sci 2023; 31(1): 6244-57.
4.     Johansson K, Neovius M, Hemmingsson E. Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2014; 99(1): 14-23.
5.     Mambrini SP, Grillo A, Colosimo S, Zarpellon F, Pozzi G, Furlan D, et al. Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility. Front Nutr 2024; 11: 1426551.
6.     Halagali P, Inamdar A, Singh J, Anand A, Sadhu P, Pathak R, et al. Phytochemicals, herbal extracts, and dietary supplements for metabolic disease management. Endocr Metab Immune Disord Drug Targets 2025; 25(12): 993-1016.
7.     Ettehad-Marvasti F, Ejtahed H-S, Siadat S-D, Soroush A-R, Hoseini-Tavassol Z, Hasani-Ranjbar S, et al. Effect of garlic extract on weight loss and gut microbiota composition in obese women: A double-blind randomized controlled trial. Front Nutr 2022; 9: 1007506.
8.     Varade S, Nadella M, Hirake A, bhausaheb Mungase S, Ali A, Adela R. Effect of garlic on the components of metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials. J Ethnopharmacol 2024; 318(Pt B): 116960.
9.     Sánchez-Sánchez MA, Zepeda-Morales ASM, Carrera-Quintanar L, Viveros-Paredes JM, Franco-Arroyo NN, Godínez-Rubí M, et al. Alliin, an Allium sativum nutraceutical, reduces metaflammation markers in DIO mice. Nutrients 2020; 12(3): 624.
10.  Lu Q, Zhu L. The role of semaphorins in metabolic disorders. Int J Mol Sci 2020; 21(16): 5641.
11.  Nam JS, Ahn CW, Park HJ, Kim YS. Semaphorin 3 C is a novel adipokine representing exercise-induced improvements of metabolism in metabolically healthy obese young males. Sci Rep 2020; 10(1): 10005.
12.  Dehghan F, Cheragh BS. Effect of obesity on skeletal muscle semaphorin 3c levels in male and female Wistar Rats [in Persian]. J North Khorasan Univ Med Sci 2022; 14(3): 92-9.
13.  Ghalavand A, Nasiri M, Kardan H, Azari BB, Dalaramnasab M, Dadvar N. The effect of a short period of aerobic training on serum Asprosin, glycemic control, and lipid profile in women with type 2 diabetes. Int J Basic Sci Med 2024; 9(1): 10-4.
14.  Saeidi A, Haghighi MM, Kolahdouzi S, Daraei A, Abderrahmane AB, Essop MF, et al. The effects of physical activity on adipokines in individuals with overweight/obesity across the lifespan: A narrative review. Obesity reviews 2021; 22(1): e13090.
15.  EbadiAsl H, Mirzaei B, Damirchi A. The effect of high-intensity functional training on semaphorin-3E levels in obese men. Iranian journal of diabetes and obesity. 2025; 17(1): 48-53.
16.  Sezgin G, Kar F, Uslu S. The effect of nutrition and exercise training on irisin and semaphorin-3E levels in obese patients. Arch Physiol Biochem 2022; 128(2): 558-67.
17.  Tafazoli M, Cheragh-Birjandi S. The effect of resistance and high intensity interval training on the expression of Semaphorin 3C and lipocalin 2 in the subcutaneous fat tissue of obese elderly rats [in Persian]. Journal of Practical Studies of Biosciences in Sport 2024; 14(37): 104-19.
18.  Pranoto NW, Fauziah V, Anugrah S, Fitriady G, Setyawan H, Geantă VA, et al. The effectiveness of diet and exercise in the management of obesity. Retos, número 2024; (58): 951-9.
19.  Shabihi M, Asgharpour H, Askari A. Effect of Aerobic Physical Activity While Fasting on Liver Lipophagy-Related Factors (ULK1 and LC3-II) in Male Wistar Rats [in Persian]. Jundishapur Scientific Medical Journal 2024; 22(6): 745-55.
20.  Cho DK, Choi DH, Cho JY. Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet. J Exerc Nutrition Biochem 2017; 21(3): 26-34.
21.  Bernardis L, Patterson B. Correlation between'Lee index'and carcass fat content in weanling and adult female rats with hypothalamic lesions. J Endocrinol 1968; 40(4): 527-8.
22.  Kyohara M, Takayanagi R, Tsuno T, Ong Yajima E, Inoue R, Yamashita N, et al. Expression analysis and possible functional roles of semaphorin/plexin/CRMP families in mouse pancreatic islets. Sci Rep 2025;15: 10546.
23.  Farazandeh Nia D, Hosseini M, Riyahi Malayeri S, Daneshjoo A. Effect of eight weeks of swimming training with garlic intake on serum levels of IL-10 and TNF-α in obese male rats. Jundishapur Scientific Medical Journal 2018; 16(6): 665-71.
24.  Van Der Klaauw AA, Croizier S, De Oliveira EM, Stadler LK, Park S, Kong Y, et al. Human semaphorin 3 variants link melanocortin circuit development and energy balance. Cell 2019; 176(4): 729-42. e18.
25.  Woo A, Botta A, Shi SS, Paus T, Pausova Z. Obesity-related neuroinflammation: magnetic resonance and microscopy imaging of the brain. Int J Mol Sci 2022; 23(15): 8790.
26.  Shen J, Gong L, Sun Y, Lin J, Hu W, Wei J, et al. Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury. Iscience. 2024; 27(5): 109649.
27.  Mizuno Y, Nakanishi Y, Kumanogoh A. Pathophysiological functions of semaphorins in the sympathetic nervous system. Inflamm Regen 2023; 43(1): 30.
28.  Yasmin T, Ali MT, Haque S, Hossain M. Interaction of quercetin of onion with axon guidance protein receptor, NRP-1 plays important role in cancer treatment: an in silico approach. Interdiscip Sci 2017; 9(2): 184-91.
29.  Gonthier B, Nasarre C, Roth L, Perraut M, Thomasset N, Roussel G, et al. Functional interaction between matrix metalloproteinase-3 and semaphorin-3C during cortical axonal growth and guidance. Cereb Cortex 2007; 17(7): 1712-21.
30.  Ross IA. The Neuroprotective Effect of Garlic. Plant-Based Therapeutics, Volume 3: Allium sativum (Garlic): Springer; 2025. p. 83-206.
31.  Bautista-Perez SM, Silva-Islas CA, Sandoval-Marquez OU, Toledo-Toledo J, Bello-Martínez JM, Barrera-Oviedo D, et al. Antioxidant and Anti-Inflammatory Effects of Garlic in Ischemic Stroke: Proposal of a New Mechanism of Protection through Regulation of Neuroplasticity. Antioxidants (Basel) 2023; 12(12): 2126.
32.  Song H, Lu Y, Qu Z, Mossine VV, Martin MB, Hou J, et al. Effects of aged garlic extract and FruArg on gene expression and signaling pathways in lipopolysaccharide-activated microglial cells. Sci Rep 2016; 6(1): 35323.
33.  Daniela M, Catalina L, Ilie O, Paula M, Daniel-Andrei I, Ioana B. Effects of exercise training on the autonomic nervous system with a focus on anti-inflammatory and antioxidants effects. Antioxidants (Basel) 2022; 11(2): 350.
34.  Šamadan L, Papić N, Mijić M, Knežević Štromar I, Gašparov S, Vince A. Do semaphorins play a role in development of fibrosis in patients with nonalcoholic fatty liver disease? Biomedicines 2022; 10(12): 3014.
35.  Oyovwi MO, Ogenma UT, Onyenweny A. Exploring the impact of exercise-induced BDNF on neuroplasticity in neurodegenerative and neuropsychiatric conditions. Mol Biol Rep 2025; 52(1): 140.
36.  de Sousa Fernandes MS, Aidar FJ, da Silva Pedroza AA, de Andrade Silva SC, Santos GCJ, dos Santos Henrique R, et al. Effects of aerobic exercise training in oxidative metabolism and mitochondrial biogenesis markers on prefrontal cortex in obese mice. BMC Sports Sci Med Rehabil 2022; 14(1): 213.
Volume 44, Issue 847
1st Week, August
July and August 2026
Pages 914-921

  • Receive Date 23 January 2026
  • Accept Date 26 July 2026