القاء چاقی، عصاره سیر و استویا به‌همراه فعالیت هوازی، بر بیان ژن سمافورین4D و گیرنده‌ی پلکسین-B2 در موش‌های نر صحرائی
محورهای موضوعی : فیزیولوژی تجربی و آسیب شناسی
ملیحه اردکانی زاده
1
(دانشگاه دامغان، گروه علوم ورزشی)
سید جواد ضیاءالحق
2
(گروه فیزیولوژی ورزشی واحد شاهرود، دانشگاه آزاد اسلامی ، شاهرود، ایران.)
کلید واژه: چاقی, عصاره سیر, عصاره استویا, سمافورینD4, پلکسینB2.,
چکیده مقاله :
زمینه و هدف: ازدیرباز، میوه سیر و برگ استویا در کنار فعالیت بدنی هوازی، به‌عنوان یک ضد التهاب بیان شده‌اند، ازطرفی به‌تازگی سمافورین‌ها به‌عنوان پروتئین‌های اثرگذار بر التهاب سیستم عصبی مرکزی شناسائی شده‌اند. مواد و روش‌ها: تعداد 35 سر رت نژاد ویستار نر چاق شده (شاخص لی) بصورت تصادفی به 7 گروه (پنج تایی)؛ کنترل سالم، چاق، سیر، استویا، هوازی، سیر+هوازی، و استویا+هوازی تقسیم شدند. تمرینات هوازی شامل30 دقیقه/روز، پنج روز/هفته بود، و عصاره سیر و استویا با غلظت 250 میلی‌گرم/کیلوگرم به آب مصرفی روزانه اضافه شد. جهت مطالعات بیان ژن سمافورین 4Dو گیرنده آن بنام پلکسینB2 به روش real-time PCR بافت مغز به آزمایشگاه ارسال شد. از آزمون آنالیز واریانس یک‌طرفه و آزمون تعقیبی توکی جهت تعیین اختلاف بین گروه‌ها استفاده گردید (05/0p≤). نتایج: مقادیر بیان ژن سمافورینD4 گروه چاق نسبت به گروه کنترل سالم افزایش معنی‌دار داشت، و همه گروه‌ها غیر از گروه استویا+هوازی، کاهش معنی‌داری در میزان این ژن نشان دادند. مقادیر پلکسینB2 گروه استویا+هوازی از مقادیر گروه کنترل چاق نیز فراتر بود، و گروه سیر با/بدون فعالیت هوازی مقادیر کمتری نسبت به گروه کنترل سالم و چاق تجربه کردند (05/0>p). نتیجه گیری: به‌نظر می‌رسد که القاء چاقی موجب افزایش بیان ژن سمافورین4D و گیرنده پلکسینB2 می‌گردد، و عصاره سیر و ترکیب آن با فعالیت هوازی اثرات مفیدی بر کاهش التهاب سیستم عصبی مرکزی ایفا می‌کنند.
Background and aim: For a long time, garlic fruit and stevia leaves have been expressed as an anti-inflammatory along with aerobic physical activity, on the other hand, semaphorins have recently been identified as proteins that affect central nervous system inflammation. Materials & Methods: the number of 35 obese male Wistar rats (Lee's index) randomly divided into 7 groups (n=5); healthy control, obese, garlic, stevia, aerobic, garlic+aerobic, and stevia+aerobic. Aerobic exercises consisted of 30 M/D, five D/W, and garlic and stevia extract with a concentration of 250 mg/kg was added to the water consumed daily. In order to study the expression of semaphoring-4D gene and its receptor called plexin-B2, brain tissue was sent to the laboratory by real-time PCR method. One-way analysis of variance and Tukey's post hoc test were used to determine the difference between groups (p≤0.05). Results: The expression levels of semaphoring-D4 gene in the obese group increased significantly compared to the healthy control group, and all groups showed a significant decrease in the amount of this gene, except for the aerobic+stevia group. The values of plexin-B2 in the aerobic+stevia group exceeded the values of the obese control group, and the garlic group with/without aerobic activity experienced lower values than the healthy and obese control group (p<0.05). Conclusion: It seems that induction of obesity increases the expression of semaphoring-4D gene and plexin-B2 receptor, and garlic extract and its combination with aerobic activity have beneficial effects on reducing central nervous system inflammation.
1. Polak-Szczybyło E. Low-Grade Inflammation and Role of Anti-Inflammatory Diet in Childhood Obesity. International Journal of Environmental Research and Public Health. 2023;20(3):1682.
2. Malik MFA, Ye L, Jiang WG. Reduced expression of semaphorin 4D and plexin-B in breast cancer is associated with poorer prognosis and the potential linkage with oestrogen receptor. Oncology Reports. 2015;34(2):1049-57.
3. Fujii T, Uchiyama H, Yamamoto N, Hori H, Tatsumi M, Ishikawa M, et al. Possible association of the semaphorin 3D gene (SEMA3D) with schizophrenia. Journal of psychiatric research. 2011;45(1):47-53.
4. Negishi-Koga T, Shinohara M, Komatsu N, Bito H, Kodama T, Friedel RH, et al. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nature medicine. 2011;17(11):1473-80.
5. Ch'ng ES, Kumanogoh A. Roles of Sema4D and Plexin-B1 in tumor progression. Molecular cancer. 2010;9(1):1-9.
6. Gabrovska P, Smith R, Tiang T, Weinstein S, Haupt L, Griffiths L. Semaphorin–plexin signalling genes associated with human breast tumourigenesis. Gene. 2011;489(2):63-9.
7. Lu Q, Zhu L. The role of semaphorins in metabolic disorders. International Journal of Molecular Sciences. 2020;21(16):5641.
8. Zhao H, He Z, Yun H, Wang R, Liu C. A Meta-Analysis of the Effects of Different Exercise Modes on Inflammatory Response in the Elderly. International Journal of Environmental Research and Public Health. 2022;19(16):10451.
9. Schulz JM, Birmingham TB, Atkinson HF, Woehrle E, Primeau CA, Lukacs MJ, et al. Are we missing the target? Are we aiming too low? What are the aerobic exercise prescriptions and their effects on markers of cardiovascular health and systemic inflammation in patients with knee osteoarthritis? A systematic review and meta-analysis. British Journal of Sports Medicine. 2020;54(13):771-5.
10. Morze J, Rücker G, Danielewicz A, Przybyłowicz K, Neuenschwander M, Schlesinger S, et al. Impact of different training modalities on anthropometric outcomes in patients with obesity: A systematic review and network meta‐analysis. Obesity Reviews. 2021;22(7):e13218.
11. Mofrad MD, Rahmani J, Varkaneh HK, Teymouri A, Mousavi SM. The effects of garlic supplementation on weight loss: A systematic review and meta-analysis of randomized controlled trials. Int J Vitam Nutr Res. 2019;1:13.
12. Mirzavandi F, Mollahosseini M, Salehi-Abargouei A, Mozaffari-Khosravi H. Effects of garlic supplementation on serum inflammatory markers: a systematic review and meta-analysis of randomized controlled trials. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(5):1153-61.
13. Gauer JS, Ajjan RA, Ariëns RA. Platelet–Neutrophil Interaction and Thromboinflammation in Diabetes: Considerations for Novel Therapeutic Approaches. Journal of the American Heart Association. 2022;11(20):e027071.
14. Rojas E, Bermúdez V, Motlaghzadeh Y, Mathew J, Fidilio E, Faria J, et al. Stevia rebaudiana Bertoni and its effects in human disease: emphasizing its role in inflammation, atherosclerosis and metabolic syndrome. Current nutrition reports. 2018;7(3):161-70.
15. Chowdhury AI, Rahanur Alam M, Raihan MM, Rahman T, Islam S, Halima O. Effect of stevia leaves (Stevia rebaudiana Bertoni) on diabetes: A systematic review and meta‐analysis of preclinical studies. Food Science & Nutrition. 2022.
16. Kassi E, Landis G, Pavlaki A, Lambrou G, Mantzou A, Androulakis I, et al., editors. Long-term effects of Stevia rebaduiana on glucose and lipid profile, adipocytokines, markers of inflammation and oxidation status in patients with metabolic syndrome. Endocrine Abstracts; 2016: Bioscientifica.
17. Giles ED, Jackman MR, MacLean PS. Modeling diet-induced obesity with obesity-prone rats: implications for studies in females. Frontiers in Nutrition. 2016;3:50.
18. Soares TS, Andreolla AP, Miranda CA, Klöppel E, Rodrigues LS, Moraes-Souza RQ, et al. Effect of the induction of transgenerational obesity on maternal-fetal parameters. Systems biology in reproductive medicine. 2018;64(1):51-9.
19. Choi DH, Kwon IS, Koo JH, Jang YC, Kang EB, Byun JE, et al. The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type. Journal of exercise nutrition & biochemistry. 2014;18(2):225.
20. Liu M, Xie S, Liu W, Li J, Li C, Huang W, et al. Mechanism of SEMA3G knockdown-mediated attenuation of high-fat diet-induced obesity. Journal of Endocrinology. 2020;244(1):223-36.
21. Eidi A, Eidi M, Oryan S, Esmaeili A. Effect of garlic (Allium sativum) extract on levels of urea and uric acid in normal and streptozotocin-diabetic rats. Iranian Journal of Pharmaceutical Research. 2004;3(2):52-.
22. Ajagannanavar SL, Shamarao S, Battur H, Tikare S, Al-Kheraif AA, Al Sayed MSAE. Effect of aqueous and alcoholic Stevia (Stevia rebaudiana) extracts against Streptococcus mutans and Lactobacillus acidophilus in comparison to chlorhexidine: An in vitro study. Journal of International Society of Preventive & Community Dentistry. 2014;4(Suppl 2):S116.
23. Saunders NA, Lee MA. Real-time PCR: advanced technologies and applications: Horizon Scientific Press; 2013.
24. Walker RE, Harvatine KJ, Ross AC, Wagner EA, Riddle SW, Gernand AD, et al. Fatty acid transfer from blood to milk is disrupted in mothers with low milk production, obesity, and inflammation. The Journal of Nutrition. 2022;152(12):2716-26.
25. Karczewski J, Śledzińska E, Baturo A, Jończyk I, Maleszko A, Samborski P, et al. Obesity and inflammation. European cytokine network. 2018;29(3):83-94.
26. Pati S, Irfan W, Jameel A, Ahmed S, Shahid RK. Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management. Cancers. 2023;15(2):485.
27. Deng T, Lyon CJ, Bergin S, Caligiuri MA, Hsueh WA. Obesity, inflammation, and cancer. Annu Rev Pathol. 2016;11(1):421-49.
28. Chen G, Doumatey AP, Zhou J, Lei L, Bentley AR, Tekola-Ayele F, et al. Genome‐wide analysis identifies an african‐specific variant in SEMA4D associated with body mass index. Obesity. 2017;25(4):794-800.
29. Chapoval SP. Neuroimmune semaphorins as costimulatory molecules and beyond. Molecular Medicine. 2018;24(1):1-20.
30. Mumtaz S, Ali S, Khan R, Shakir HA, Tahir HM, Mumtaz S, et al. Therapeutic role of garlic and vitamins C
and E against toxicity induced by lead on various organs. Environmental Science and Pollution Research. 2020;27(9):8953-64.
31. Kagawa Y, Ozaki‑Masuzawa Y, Hosono T, Seki T. Garlic oil suppresses high‑fat diet induced obesity in rats through the upregulation of UCP‑1 and the enhancement of energy expenditure. Experimental and Therapeutic Medicine. 2020;19(2):1536-40.
32. Xu C, Mathews AE, Rodrigues C, Eudy BJ, Rowe CA, O'Donoughue A, et al. Aged garlic extract supplementation modifies inflammation and immunity of adults with obesity: A randomized, double-blind, placebo-controlled clinical trial. Clinical Nutrition ESPEN. 2018;24:148-55.
33. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, et al. Adiponectin as a biomarker of the metabolic syndrome. Circulation journal. 2004;68(11):975-81.
34. Gómez-Arbeláez D, Lahera V, Oubiña P, Valero-Muñoz M, De las Heras N, Rodríguez Y, et al. Aged garlic extract improves adiponectin levels in subjects with metabolic syndrome: a double-blind, placebo-controlled, randomized, crossover study. Mediators of inflammation. 2013;2013.
35. Ha C, Tian S, Sun K, Wang D, Lv J, Wang Y. Hydrogen sulfide attenuates IL-1β-induced inflammatory signaling and dysfunction of osteoarthritic chondrocytes. International Journal of Molecular Medicine. 2015;35(6):1657-66.
36. Gu X, Zhu YZ. Therapeutic applications of organosulfur compounds as novel hydrogen sulfide donors and/or mediators. Expert review of clinical pharmacology. 2011;4(1):123-33.
37. Fiuza-Luces C, Garatachea N, Berger NA, Lucia A. Exercise is the real polypill. Physiology. 2013.
38. Sang H, Yao S, Zhang L, Li X, Yang N, Zhao J, et al. Walk-run training improves the anti-inflammation properties of high-density lipoprotein in patients with metabolic syndrome. The Journal of Clinical Endocrinology & Metabolism. 2015;100(3):870-9.
39. Abd El-Kader S, Gari A, El-Den AS. Impact of moderate versus mild aerobic exercise training on inflammatory cytokines in obese type 2 diabetic patients: a randomized clinical trial. African Health Sciences. 2013;13(4):857-63.
40. Stolarczyk E. Adipose tissue inflammation in obesity: a metabolic or immune response? Current opinion in pharmacology. 2017;37:35-40.
41. Wang Z, Xue L, Guo C, Han B, Pan C, Zhao S, et al. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-κB pathway. Biochemical and biophysical research communications. 2012;417(4):1280-5.
42. Ray J, Kumar S, Laor D, Shereen N, Nwamaghinna F, Thomson A, et al. Effects of Stevia rebaudiana on glucose homeostasis, blood pressure and inflammation: a critical review of past and current research evidence. International journal of clinical research & trials. 2020;5.