Effect Of Celery (Apium Graveolens) Seeds Extract On Protease Inhibitor (Ritonavir) Induced Dyslipidemia
Apium Graveolens Seeds Extract & Ritonavir Induced Dyslipidemia
DOI:
https://doi.org/10.70284/njirm.v3i1.1967Keywords:
celery seed extract, protease inhibitor, dyslipidemiaAbstract
Objective: The present study was carried out to explore protective effects of ethanolic extract of Apium graveolens (celery seeds) on ritonavir, a protease inhibitor induced dyslipidemia. Materials & Methods: Thirty mice were divided into 5 groups. Group 1 mice served as healthy control. Group 2 mice were given drug ritonavir at doses of 33.33 mg/kg (200mg/day, human dose), group 3 received same dose of ritonavir and ethanolic extract of celery seeds(CSE) at the doses of 75mg/kg. Group 4 was treated with same dose of ritonavir and CSE at high doses i.e.150mg/kg. Group 5 mice were given ritonavir and hypolipidemic drug, fenofibrate. All groups of mice were given the drug and extract by oral gavage route for the period of 12 weeks. Blood lipid profile and liver lipids of all the groups were tested at the end of 12 weeks. Results: Blood lipid profile was found to be deranged in the group of mice treated with ritonavir. Concurrent treatment of ritonavir with low dose of CSE showed no significant improvement in blood lipid profile in group 3 mice but high dose CSE along with ritonavir with the same dose of ritonavir exhibited significant improvement (p<0.05) in group 4 mice. Effect of fenofibrate in group 5 was almost equally effective as that of high dose of CSE. There was a similar pattern of decrease in liver lipids in all the groups (p<0.05). Conclusion: Above results suggest that ethanolic extract of celery seeds possess potential for improving blood lipid profile & liver lipids deranged by ritonavir when given concurrently. Its efficacy approaches that of fenofibrate. Its intake along with ritonavir would be better in terms of cost and side effects as compared to fenofibrate.
References
2. Flexner C. Dual protease inhibitor therapy in HIV infected patients: Pharmacologic rationale & clinical benefits. Annu Rev Pharmacol Toxicol 2000; 40: 649-674.
3. Flexner C. Antiretroviral agents and treatment of HIV infection . Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman’s, The Pharmacological Basis Of Therapeutics ,12th ed : Mc Graw-Hill, 2011: 1623-1663.
4. Spector AA. HIV protease inhibitors & hyperlipidemia: a fatty acid connection. Arterioscler Thromb vasc Biol 2006; 26: 7-9.
5. Martinet W, Kockx MM. Apoptosis in atherosclerosis: implications for plaque destabilization. Verh K Acad Geneeskd Belg 2004; 66: 61-79.
6. Le QT, Elliott WJ: Dose response relationship of blood pressure and serum cholesterol to 3-n-butylphthalide, a component of celery oil. Clin Res 1991; 39: 750A
7. Mimura Y, Kobayashi S, Naitoh T, Kimura I, Kimura M. The structure activity relationship between synthetic butylidenephthalide derivatives regarding competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells. Biol Pharm Bull 1995; 18: 1203-6.
8. Momin RA, Nair MG. Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from A. graveolens seeds, phytochemistry 2002; 9: 312-318.
9. Tsi D, Das NP, Tan BK. Effects of celery (A. graveolens) extract on lipid parameters of rats fed a high fat diet. Planta Med 1995; 6: 18-21.
10. Tsi D, Tsi BKH. The mechanism underlying the hypocholesterolemic activity of aqueous celery extract, its butanol and aqueous fractions in genetically hypocholesterolemic rico rats. J Life Sci 2000; 66: 755-767.
11. Palmer R. Use of complementary therapies to treat patients with HIV-AIDS. Nurs stand 2008; 22: 35-41.
12. Ahmad AH, Rekhe DS, Ravikanth K, Maini S. Acute toxicity study of Vilocym Premix in wistar albino rat. Veterinary World 2009; 2(3): 100-102
13. Folch J, Lee M, Sloane-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem; 226: 497-509.
14. Wybenga DR, Pileggi VJ, Dirstine PH, Giorgio DJ. Direct manual determination of serum total cholesterol with a single stable agent. Clin chem 1970; 16: 980.
15. Demacker PNM, Vos-Jansees HE, Jansen AP, Vont Laar A. Evaluation of the dual –precipitation method by comparison with the ultracentrifugation method f or measurements of lipoproteins in serum. Clin Chem 1977; 23: 1238.
16. Cole TG, Klotzch SG, Namara M J. Measurement of TG concentration . Rifai N. Warnick GR, Domnizeck MH (Washington, AACC press) 1997: 115.
17. Friedwald WT, Levy RI, Friedrickson DS. Estimation of concentration of LDL cholesterolin plasma without preparation or ultracentrifugation . Clin Chem 1972; 18: 449.
18. Kellner A, Corell JW, Ladd AT. Sustained hyperlipidemia induced in rabbits by means of intravenously injected surface active agents. J Exp. Med. 1951; 93: 373-384.
19. Fichtenbaum CJ, Hui DY. Leptin replacement therapy but not dietary polyunsaturated fatty acid alleviates HIV protease inhibitor –induced dyslipidemia and lipodystrophy in mice. Journal of Acquired Immune Deficiency Syndromes 2003; 33(5): 564-70.
20. Aimin X, Shinan Y, Laiching W, Kok WC, Karen SL. Adiponectin ameliorates dislipidemia induced by human immunodeficiency virus protease inhibitor ritonavir in mice. Endocrinology 2004; 145(2):487-494.
21. Maurya R, Srivastavas S, Kulshreshtha DK, Gupta CM. Traditional remedies for fertility regulation. Curr Med Chem 2004; 11: 1350-1431.
22. Weibin Z, Guang L, Jian X, Elaine J S, Phillip BH, William MP et al. Berberine inhibits HIV protease inhibitor –induced inflammatory response by modulating ER stress signalling pathways in murine macrophages. PloS One 2010; 5(2): e9069.
23. Shafran SD, Mashinter LD, Roberts SE. The effect of low dose ritonavir monotherapy on fasting serum lipid concentration. HIV Medicine 2005; 6(6): 421-425.
24. Kamal M, Adel MA, Ahmad D, Talal A. Hypolipidemic effects of seed extract of celery(Apium graveolens) in rats. Phcog Mag (serial online) 2009;5: 301-5.