Protective effect of crocin against d-galactose-induced aging in mice

Document Type: Original Research Article

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective: Aging is a multifactorial phenomenon, which attribute to different diseases and abnormalities in living systems. Oxidative stress, which is an important factor in aging, exacerbates this process via different mechanisms. Crocin (CR), one of the active components of saffron showed strong antioxidant effects. In the present study, anti-aging property of crocin was investigated in mice.
Materials and Methods: The model of aging was induced using administration of d-galactose (500 mg/kg, s. c.) for 42 days. Animals were treated with crocin (10, 20, 40 mg/kg, i.p.) during treatment with d-galactose.  At the end of treatment, levels of malondialdehyde (MDA) as a lipid peroxidation marker and glutathione content (GSH) in the liver and brain were measured. Also, biochemical factors including liver enzymes (ALT and AST), male sex hormones including testosterone and dehydroepiandrosterone-sulfate (DHEA-SO4) and pro-inflammatory markers such as tumor necrosis factor -α (TNF-α) and interlukine-6 (IL-6) in serum, were evaluated.
Results: Administration of d-galactose led to induction of lipid peroxidation in liver and brain tissues, as well as elevation of AST, ALT, and pro-inflammatory cytokines and reduction of male sex hormones levels in serum. Interestingly, treatment of animals with crocin (10, 20 and 40 mg/kg) diminished lipid peroxidation in the liver and brain tissues while elevated GSH content. Also, a decline in serum levels of TNF-α and IL-6 and an elevation of male sex hormones were observed following treatment with crocin.
Conclusion: Administration of crocin reduced d-galactose-induced aging in mice through inhibition of oxidative stress, reduction of inflammation and elevation of sex hormones.

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Main Subjects


Alavizadeh SH, Hosseinzadeh H. 2014. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol, 64: 65-80.

Anderson FH, Zeng L,Rock NR, Yoshida EM. 2000. An assessment of the clinical utility of serum ALT and AST in chronic hepatitis C. Hepatol Res,18: 63-71.

Asadi MH, Zafari F, Sarveazad A, Abbasi M, Safa M, Koruji M, Yari A, Alizadeh Miran R. 2014. Saffron improves epididymal sperm parameters in rats exposed to cadmium. Nephrourol Mon, 6: Doi:  10.5812/numonthly.12125

Bahashwan SA, Hassan MH, Tamer M. Abdelghany TM,Gamil MA.  Ghobara MM. 2015. Crocin mitigates carbon tetrachloride-induced liver toxicity in rats. J Taibah Univ  Med Sci, 10: 140-149.

Ghanbari S, Yonessi M, Mohammadirad A, Gholami M, Baeeri M, Khorram-Khorshid HR, Gharibdoost F, Abdollahi M. 2012. Effects of IMOD and Angipars on mouse D-galactose-induced model of aging. Daru, 20: 68.

Hadizadeh F, Mohajeri SA, Seifi M.. 2010. Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method. Pak J Biol Sci, 13: 691-698.

Hadzi-Petrushev N, Stojkovski V, Mitrov D, Mladenov M. 2014. D-galactose induced inflammation lipid peroxidation and platelet activation in rats. Cytokine, 69: 150-153.

Haider S, Liaquat L, Shahzad S, Sadir S, Madiha S, Batool Z, Tabassum S, Saleem S, Naqvi F, Perveen T. 2015. A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process. Life Sci, 124:110-119.

Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H. 2010. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: Protective effects of crocin and safranal. Food Chem Toxicol, 48: 2803-2808.

Hosseinzadeh H, Abootorabi A, Sadeghnia HR 2008. Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate-induced DNA damage in mice organs. DNA Cell Biol, 27: 657-664.

Hosseinzadeh H, Sadeghi Shakib S, Khadem Sameni A, Taghiabadi E. 2013. Acute and Subacute Toxicity of Safranal, a Constituent of Saffron, in Mice and Rats.  Iran J Pharm Res, 12 : 93-99.

Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA. 2012. Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res, 26: 381-386.

Hsieh HM, WM Wu, Hu ML. 2009. Soy isoflavones attenuate oxidative stress and improve parameters related to aging and Alzheimer’s disease in C57BL/6J mice treated with D-galactose. Food Chem Toxicol, 47: 625-632.

Jauslin ML, Vertuani S, Durini E, Buzzoni L, Ciliberti N, Verdecchia S, Palozza P, Meier T, Manfredini S. 2007. Protective effects of Fe-Aox29, a novel antioxidant derived from a molecular combination of Idebenone and vitamin E, in immortalized fibroblasts and fibroblasts from patients with Friedreich Ataxia. Mol Cell Biochem, 302: 79-85.

Jin SL and Yin YG. 2012. In vivo antioxidant activity of total flavonoids from indocalamus leaves in aging mice caused by D-galactose. Food Chem Toxicol, 50: 3814-3818.

Jnaneshwari S, Hemshekhar M, Santhosh MS, Sunitha K, Thushara R, Thirunavukkarasu C, Kemparaju K, Girish KS. 2013. Crocin, a dietary colorant mitigates cyclophosphamide‐induced organ toxicity by modulating antioxidant status and inflammatory cytokines. J Pharm Pharmacol, 65: 604-614.

Kumar A, Prakash A, Dogra S. 2011. Centella asiatica attenuates D-galactose-induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. Int J Alzheimers Dis, 2011, Article ID 347569.

Lan Z, Liu J, Chen L, Fu Q, Luo J, Qu R, Kong L, Ma S. 2012. Danggui-Shaoyao-San ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in d-galactose-induced senescent mice. J Eethnopharmacol, 141: 386-395.

Lari P, Abnous KH, Imenshahidi M, Rashedinia M, Razavi M, Hosseinzadeh H3. 2015. Evaluation of diazinon-induced hepatotoxicity and protective effects of crocin. Toxicol Ind Health, 31: 367-376.

Li K, Li Y, Ma Z, Zhao J. 2015. Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK.  Int J Mol Med, 36: 1291-1299.

Lu J, Zheng YL, Luo L, Wu DM, Sun DX, Feng YJ. 2006. Quercetin reverses D-galactose induced neurotoxicity in mouse brain. Behav brain Res, 171: 251-260.

Maggio M, Basaria S, Ceda GP, Ble A, Ling SM, Bandinelli S, Valenti G, Ferrucci L. 2005. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest, 28: 116-119.

Mehri S, Abnous KH, Khooei A, Mousavi SH, Motamed Shariaty V, Hosseinzadeh H 2015. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran J Basic Med Sci,18: 902-908.

Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, Cesari M, Nourhashemi F. 2013. Proinflammatory Cytokines, Aging, and Age-Related Diseases. J Am Med Dir Assoc, 14: 877-882.

Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H. 2013. Safety Evaluation of Crocin (a constituent of saffron) Tablets in Healthy Volunteers. Iran J Basic Med Sci, 16: 39-46.

Mohammadirad A, Aghamohammadali-Sarraf F, Badiei S, Faraji Z, Hajiaghaee R, Baeeri M, Gholami M Abdollahi M. 2013. Anti-Aging Effects of Some Selected Iranian Folk Medicinal Herbs-Biochemical Evidences. Iran J Basic Med Sci, 16: 1170-1180.

Mollazadeh H, Emami SA,Hosseinzadeh  H. 2015. Razi’s Al-Hawi and saffron (Crocus sativus): a review. Iran J Basic Med Sci 18: 1153-1166.

Moron MS, Depierre JW, Mannervik B. 1979. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582: 67-78.

Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, Jung WS, Cho KH, Park JH, Kang I, Hong JW, Lee EH. 2010. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol, 648: 110-116.

Nazem H, Modaresi M, Messripour M,  Asadi M, Ebadi A. 2009. Effect of Saffron Extract on Pituitary-Testis Axis in Mice. Asian J Chem,  21: 1616-1618.

Razavi BM, Hosseinzadeh H, Movassaghi AR, Imenshahidi M, Abnous K. 2013. Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem Biol Interact, 203: 547-555.

Rikans LE and Hornbrook KR. 1997. Lipid peroxidation, antioxidant protection and aging.Biochim Biophys Acta, 1362: 116-127.

Ruan Q, F Liu, , Gao Z, Kong D, Hu X, Shi D, Bao Z, Yu Z. Author informationet al. 2013. The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats. Mech. Ageing Dev,134: 89-97.

Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O. 2009. Evaluation of Crocus sativus L. (saffron) on male erectile dysfunction: A pilot study. Phytomedicine, 16: 690-693.

Uchiyama M and Mihara M.1978. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem, 86: 271-278.

Umare V, Pradhan V, Nadkar M, Rajadhyaksha A, Patwardhan M, Ghosh KK1, Nadkarni AH. 2014. Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients. Mediators Inflamm 2014; Doi: 10.1155/2014/385297

Wang D, Liu M, Cao J, Cheng Y, Zhuo C, Xu H, Tian S, Zhang Y, Zhang J, Wang F. 2012. Effect of Colla corii asini (E’jiao) on D-galactose induced aging mice. Biol Pharm Bull, 35: 2128-2132.

Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, Hu B. 2009. Purple sweet potato color attenuates oxidative stress and inflammatory response induced by d-galactose in mouse liver. Food Chem Toxicol 47: 496-501.

Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, Hu B. 2009. Troxerutin Protects the Mouse Liver against Oxidative Stress-Mediated Injury Induced by d-Galactose. J Agric Food Chem, 57: 7731-7736.

Zhen YZ, Lin YJ, Li KJ, Zhang GL, Zhao YF, Wang MM, Wei JB, Wei J, Hu G. 2016. Effects of rhein lysinate on D-galactose-induced aging mice. Exp Ther Med, 11: 303-308.

Zheng YQ, Liu JX, Wang JN, Xu L. 2007. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res, 1138: 86-94.

Zhong SZ, Ge QH, Qu R, Li Q, Ma SP. 2009. Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice.  J Neurol Sci, 277: 58-64.