Anti-inflammatory and Analgesic Properties of Salvigenin, Salvia officinalis Flavonoid Extracted

Document Type: Original Article


1 1Immunology Dept., Shahid Sadoughi University of Medical Sciences, Yazd, I.R. Iran

2 2Physiology Dept, Shahid Sadoughi University of Medical Sciences, Yazd, I.R. Iran

3 3Shahrekord University of Medical Sciences, Shahrekord, I.R. Iran


Background and aims: Inflammation is one of the defense mechanisms of body and unpleasant sensation of pain is caused by tissue damage. Mostly, inflammation occurs through the release of inflammatory mediators. Salvia officinalis is one of the most valuable medicinal kind of mint order. Salvigenin is one of the active flavonoids existing in this plant. The aim of this study was to evaluate the anti-inflammatory and analgesic effect of salvigenin, Salvia officinalis flavonoid extracted. Methods: In this laboratory experimental study, plant was extracted and the column chromatography was used to purify prepared extracts. 100 male albino mice and 48 male wistar rats were selected. In the hot plate test and in the writhing test, animals were divided randomly into 5 groups. Group 1 (received 10 mg/kg normal saline), groups 2, 3 and 4 (received Salvigenin 25, 50 and 100 mg/kg intraperitoneally, espectively), group 5 (received 10 mg/kg morphine in hot plate test and 10 mg/kg indomethacin in writhing test). In the inflammatory test, animals were divided into 6 groups. Group 1 was assigned as a control group which received 0.05 ml of carrageenin. Groups 2, 3 and 4 (received Salvigenin, at doses of 25, 50 and 100 mg/kg). Group 5 (received 10 mg/kg indomethacin) and then changes of the volume of all groups were measured. Data were analyzed using ANOVA and Tukey test and PResults: In writhing test, Salvigenin reduced the number of abdominal contractions at doses of 50 and 100 mg/kg. Increasing dose of Salvigenin, with reduction in abdominal cramps resulted in the increasing of pain inhibition, and the percentage of this inhibition was statistically significant (P<0.001). In hot plate test, also 30, 45 and 60 minutes after injection of Salvigenin and morphine showed significant difference compared to the control group (P<0.001). Also, Salvigenin increased the maximum percentage of analgesic compared to the control group (P<0.001). Salvigenin could reduce inflammation and in the group that received Salvigenin at 100 mg/kg, the inflammation was significantly lower than the control group (P<0.05). Discussion: Our findings showed that Salvigenin has dose-dependent analgesic effect so that it can be useful in controlling of inflammations, acute and chronic pain.  


Main Subjects


1. Koo EG, Lai LM, Choi GY, Chan MT. Systemic inflammation in the elderly. Best Pract Res Clin Anaesthesiol.. 2011; 25(3): 413-25.

2. Sollid LM, Jabri B. Is celiac disease an autoimmune disorder? Curr Opin Immunol. 2005; 17(6): 595-600.

3. Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol. 2006; 97(2): 3-11.

4. Dahners LE, Mullis BH. Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing. J Am Acad Orthop Surg. 2004; 12(3): 139-43.

5. Ejaz P, Bhojani K, Joshi VR. NSAIDs and kidney. J Assoc Physicians India. 2004; 52: 632-40.

6. Foss JF. A review of the potential role of methylnaltrexone in opioid bowel dysfunction. Am J Surg. 2001; 182(5A Suppl): 19S-26S.

7. Hochain P, Capet C, Colin R. [Digestive complications of aspirin]. La Revue de medecine interne/fondee par la Societe nationale francaise de medecine interne. 2000; 21(Suppl 1): 50s-9s.

8. Pilotto A, Franceschi M, Leandro G, Paris F, Niro V, Longo MG, et al. The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs. Aging Clin Exp Res. 2003; 15(6): 494-9.

9. Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000; 47(2): 123-8.

10. Rodrigues MR, Kanazawa LK, das Neves TL, da Silva CF, Horst H, Pizzolatti MG, et al. Antinociceptive and anti-inflammatory potential of extract and isolated compounds from the leaves of Salvia officinalis in mice. J Ethnopharmacol. 2012; 139(2): 519-26.

11. Imanshahidi M, Hosseinzadeh H. The pharmacological effects of Salvia species on the central nervous system. Phytother Res: 2006; 20(6): 427-37.

12. Raus K, Pleschka S, Klein P, Schoop R, Fisher P. Effect of an echinacea-based hot drink versus Oseltamivir in influenza treatment: A Randomized, double-blind, double-dummy, multicenter, noninferiority clinical trial. Curr Ther Res Clin Exp. 2015; 77: 66-72.

13. Lima CF, Azevedo MF, Araujo R, Fernandes-Ferreira M, Pereira-Wilson C. Metformin-like effect of Salvia officinalis (common sage): is it useful in diabetes prevention? Br J Nutr. 2006; 96(2): 326-33.

14. Sa CM, Ramos AA, Azevedo MF, Lima CF,  Fernandes-Ferreira M, Pereira-Wilson C. Sage tea drinking improves lipid profile and antioxidant defences in humans. Int J Mol Sci. 2009; 10(9): 3937-50.

15. Clebsch B, Barner CD. The new book of salvias: sages for every garden: Portland: Timber Press; 2003.

16. Lu Y, Foo LY. Antioxidant activities of polyphenols from sage (Salvia officinalis). Food Chem. 2001; 75(2):197-202.

17. Ollanketo M, Peltoketo A, Hartonen K, Hiltunen R, Riekkola M-L. Extraction of sage (Salvia officinalis L.) by pressurized hot water and conventional methods: antioxidant activity of the extracts. Eur Food Res Technol. 2002; 215(2): 158-63.

18. Pietta P, Minoggio M, Bramati L. Plant polyphenols: Structure, occurrence and bioactivity. Stud Nat Prod Chem. 2003; 28(1): 257-312.

19. Han X, Shen T, Lou H. Dietary polyphenols and their biological significance. Int J Mol Sci. 2007; 8(9): 950-88.

20. Brieskorn CH, Kapadia R. XXIII. 5-Methoxy salvigenin in leaves of Salvia officinolis. Planta Med. 1979; 35: 376-8.

21. Rafatian G, Khodagholi F, Farimani MM, Abraki SB, Gardaneh M. Increase of autophagy and attenuation of apoptosis by salvigenin promote survival of SH-SY5Y cells following treatment with H2O2. Mol Cell Biochem. 2012; 371(1-2): 9-22.

22. Habibi Z, Hassan ZM, Noori S, Mozafari V, Yoosefi-Mohammadi M-M, Hassani L. Interaction of salvigenin with DNA. Daneshvar. 2011; 18(92): 69-76.

23. Uydeş-Doğan BS, Takır S, Özdemir O, Kolak U, Topçu G, Ulubelen A. The comparison of the relaxant effects of two methoxylated flavones in rat aortic rings. Vascul Pharmacol. 2005; 43(4): 220-6.

24. Rathee P, Chaudhary H, Rathee S, Rathee D, Kumar V, Kohli K. Mechanism of action of flavonoids as anti-inflammatory agents: a review. Inflamm Allergy Drug Targets. 2009; 8(3): 229-35.

25. Aherne SA, O’Brien NM. Dietary flavonols: chemistry, food content, and metabolism. Nutrition. 2002; 18(1):75-81.

26. Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev. 1998; 56(11): 317-33.

27. Wang M, Li J, Rangarajan M, Shao Y, LaVoie EJ, Huang T-C, et al. Antioxidative phenolic compounds from sage (Salvia officinalis). J Agric Food Chem. 1998; 46(12): 4869-73.

28. Pan S, Mukherjee B, Ganguly A, Mitra S, Bhattacharyya A. Antifungal activity of some naturally occurring flavenoids. Z Pflanzenkr Pflanzenschutz. 1985; 92(4): 392-395.

29. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983; 16(2): 109-10.

30. Ferreira J, Campos MM, Araújo R, Bader M, Pesquero JB, Calixto JB. The use of kinin B1 and B2 receptor knockout mice and selective antagonists to characterize the nociceptive responses caused by kinins at the spinal level. Neuropharmacology. 2002; 43(7): 1188-97.

31. Najafabadi MK, Atyabi S. Evaluation of analgesic effect of Datura stramonium seed extract in hot plate and formalin tested on male rats. Iranian J Med Aromat Plants Res. 2004; 20(3): 309-22.

32. Farzin D, Âsghari L. Effect of different thisamine receptor agonists and antagonists on the pain threshold caused by hot plate and abdominal writhing in mice. J Mazandaran Univ Med Sci. 2000; 10(28): 40-54.

33. Collier HO, Dinneen LC, Johnson CA, Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother. 1968; 32(2): 295-310.

34. Shamsi Meymandi M, Keyhanfar F. Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain. Can J Anaesth. 2013; 60(1): 44-9.

35. Ghahhari J, Vaezi G, Shariatifar N, Zendehdel KHM. The study of hydroalcoholic extract of Ziziphora tenuior on visceral pain with writhing test in mice. Ofogh-e-Danesh. 2009; 15(2): 24-9.

36. Onasanwo S, Pal A, George B, Olaleye S. Pharmacological and toxicity studies of the crude extracts and fractions of Hedranthera barteri leaf in rats and mice. Afr J Biomed Res. 2008; 11(3):311-321.

37. Samsam-Shariat H. Medicinal plants propagation. Tehran: Mani Publ; 1990.

38. Qnais EY, Abu-Dieyeh M, Abdulla FA, Abdalla SS. The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts. Pharm Biol. 2010; 48(10): 1149-56.

39. Hoodgar F, Nasri S, Amin G. Investigation of Antinociceptive and anti-inflammatory effects of hydro-alcoholic extract of Securigera Securidaca L. Ofogh-e-Danesh. 2011; 17(1): 12-9.

40. Bahmani M, Shirzad H, Majlesi M, Shahinfard N, Rafieian-Kopaei M. A review study on analgesic applications of Iranian medicinal plants. Asian Pac J Trop Med. 2014; 7: S43-S53.

41. Pilehvarian A, Shirani M, Kheiri S, Taji F, Asgari A. Effect of Euphorbia helioscopia on acetic acid-induced abdominal constrictions in Balb/c mice. J Shahrekord Univ Med Sci. 2010; 11(4): 9-14.

42. Lopes LS, Pereira SS, Silva LL, Figueiredo KA, Moura BA, Almeida FR, et al. Antinociceptive effect of topiramate in models of acute pain and diabetic neuropathy in rodents. Life Sci. 2009; 84(3-4): 105-10.

43. Dashti-Rahmatabadi M, Vahidi Merjardi A, Pilavaran A, Farzan F. Antinociceptive effect of cinnamon extract on formalin induced pain in rat. J Shaheed Sadoughi Univ Med Sci. 2009; 17(2): 190-199.

44. Ramezani M, Amin G, Jalili E. Antinociceptive and anti-inflammatory effects of hydroalcoholic extract of Vitex agnus castus fruit in mice. J Shahrekord Univ Med Sci. 2010; 11(4): 46-51.

45. Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001; 74(4): 418-25.