اثر هشت هفته تمرین هوازی و مکمل سیر بر بیان ژنی نشانگرهای التهاب عصبی در پارکینسون القاشده با رزرپین در موش‌های صحرایی

Extended Abstract
Background and Aim:  Parkinson’s disease (PD) is the second most common age‑related neurodegenerative disorder after Alzheimer’s disease. Experimental studies in animal models of PD indicate that regular aerobic training can improve motor performance, reduce neuronal damage, and decrease inflammatory cytokine expression in the brain. Dietary and herbal interventions have also been investigated for their anti‑inflammatory and neuroprotective effects. Garlic (Allium sativum) is widely studied because of its bioactive compounds including allicin, diallyl sulfide, and S‑allyl cysteine. Considering that exercise influences systemic immune regulation and neurotrophic signaling while garlic directly targets inflammatory pathways and oxidative stress, their combination may produce synergistic effects. Therefore, the present study aimed to investigate the effects of 8 weeks of aerobic exercise combined with garlic supplementation on the expression of pro‑ and anti‑inflammatory cytokines (IL‑17, IL‑23, IL‑10, and IL‑8) in the brain tissue of rats with experimentally induced Parkinson’s disease.
Materials and Methods: This experimental study used a post‑test control group design. Thirty male Sprague‑Dawley rats (250–270 g, 8–10 weeks old) were obtained from the animal laboratory of Islamic Azad University, Marvdasht Branch. Animals were maintained under controlled conditions (22 ± 2°C, 50–60% humidity, and a 12‑h light/dark cycle) with free access to food and water. After one week of acclimatization, rats were randomly assigned to five groups (n=6): healthy control, PD control, aerobic exercise, garlic supplementation, and aerobic exercise plus garlic supplementation. Parkinson’s disease was induced using a reserpine‑based protocol under Ketamine/Xylazine anesthesia to simulate dopaminergic depletion and PD‑like symptoms. To confirm the development of a parkinsonian phenotype and evaluate the severity of reserpine-induced motor deficits, the following standardized behavioral tests were performed: the rotarod test, the rearing test, and the load test .  The aerobic training protocol was adapted from Moradi et al. (2019). Rats performed treadmill running three sessions per week for eight weeks, including warm‑up, moderate‑intensity running, and cool‑down periods with gradually increased duration and intensity. Animals in the garlic group received garlic extract by oral gavage at a dose of 500 mg/kg body weight daily for eight weeks. The combined group received both aerobic training and garlic supplementation. Forty‑eight hours after the final training session, animals underwent a 12‑hour fasting period. Rats were anesthetized with intraperitoneal ketamine (75 mg/kg) and xylazine (25 mg/kg). Brain tissues were collected and stored at −70 °C until analysis. The expression levels of IL‑8, IL‑10, IL‑17, and IL‑23 were measured using ELISA and quantitative real‑time PCR (qRT‑PCR). Statistical analysis was performed using SPSS version 22. Group differences were assessed using one‑way ANOVA followed by Tukey’s post hoc test. A significance level of p<0.05 was considered statistically significant. All procedures were approved by the Ethics Committee of Islamic Azad University, Behbahan Branch.
 
Findings: The results demonstrated that parkinsonian mice exhibited a significant impairment in motor performance compared with healthy control mice. Specifically, muscle strength and balance, as assessed by the rotarod test, as well as motor function and exploratory activity, as assessed by the rearing test, were significantly reduced in parkinsonian mice relative to the healthy control group (p < 0.05). Furthermore, the load test revealed a significant increase in muscular rigidity in parkinsonian mice compared with healthy controls (p<0.05).
The mean ± standard deviation values of IL-10, IL-23, IL-17, and IL-8 are presented in Table 3. The findings indicated significant differences among the study groups in IL-10 (F = 109.04, p = 0.001), IL-23 (F = 1408.57, p = 0.001), IL-17 (F = 203.78, p = 0.001), and IL-8 (F = 215.24, p = 0.001). Fold-change analysis demonstrated a 1.6-fold increase in IL-10 levels in the garlic supplementation group and a 1.9-fold increase in the exercise plus garlic supplementation group. For IL-23, the greatest reduction was observed in the exercise plus garlic supplementation group (0.35-fold). Similarly, the largest decrease in IL-17 was found in the exercise plus garlic supplementation group (0.42-fold), whereas IL-8 showed the greatest increase in the same group (2.36-fold).
Tukey’s post hoc analysis revealed that IL-10 (p = 0.035), IL-23 (p = 0.001), IL-17 (p = 0.001), and IL-8 (p = 0.001) levels were significantly lower in the disease control group than in the healthy control group. In the garlic supplementation and exercise plus garlic supplementation groups, IL-8 levels were significantly higher than those observed in both the disease control and exercise-only groups (p < 0.05). Moreover, IL-10 concentrations in the exercise plus garlic supplementation group were significantly higher than those in the garlic supplementation group alone (p = 0.002).
IL-23 levels were significantly lower in the garlic supplementation (p = 0.001), exercise (p = 0.004), and exercise plus garlic supplementation (p = 0.001) groups compared with the disease control group. Likewise, IL-17 concentrations were significantly reduced in the garlic supplementation (p = 0.001), exercise (p = 0.004), and exercise plus garlic supplementation (p = 0.001) groups relative to the disease control group. Furthermore, IL-17 levels in the exercise plus garlic supplementation group were significantly lower than those in both the garlic supplementation group alone (p = 0.004) and the exercise-only group (p = 0.001).
Conclusion: In this study, reserpine-induced PD models exhibited a pronounced dysregulation of inflammatory cytokines in brain tissue, characterized by elevated levels of the pro-inflammatory mediators IL-17 and IL-23 and reduced levels of the anti-inflammatory cytokines IL-10 and IL-8. Both aerobic exercise and garlic supplementation significantly improved this inflammatory profile, underscoring their potential as effective non-pharmacological strategies for modulating PD-associated neuroinflammation. Importantly, the combined intervention produced greater improvements than either treatment alone, indicating a synergistic interaction between structured physical activity and targeted nutritional supplementation. These findings emphasize the therapeutic relevance of integrating lifestyle-based approaches to attenuate inflammation-driven mechanisms implicated in PD pathology. Collectively, the results support the combined use of aerobic exercise and garlic supplementation as a promising complementary strategy to reduce neuroinflammation and potentially enhance neuroprotective pathways in PD. Further experimental and clinical studies are required to elucidate the mechanisms involved and confirm translational applicability.
Keywords: Aerobic exercise, Garlic Supplement, Inflammation, Parkinson, Neuroprotection.
 
Ethical Considerations: The study was approved by the Ethics Committee of Islamic Azad University, Behbahan Branch (IR.IAU.BEHBAHAN.REC.1402.024).
Compliance with ethical guideline: In this study, compliance with ethical guidelines was ensured.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.
Keywords: Aerobic exercise, Garlic, Inflammation, Brain, Experimental Parkinson’s disease model