Anti-Aging Effects of Some Selected Iranian Folk Medicinal Herbs-Biochemical Evidences

Document Type : Original Article


1 Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran

2 Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

3 Pharmacognosy & Pharmaceutics Department of Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran



In the current study, the effects of selected folk medicinal herbs were evaluated in D-galactose-induced aging in male mice.
Materials and Methods:
Male BALB/c mice were randomly divided into 12 groups composing sham, control, and treated groups. Aging was induced by administration of D-galactose (500 mg/kg/day for 6 weeks). A positive control group was assigned that received vitamin E (200 mg/kg/day). The extract of herbs was prepared, lyophilized, and used in this study. The herbs were administered by gavage for 4 weeks to D-galactose-aged animals at the selected doses (mg/kg/day) as follows: Zingiber officinale (250), Glycyrrhiza glabra (150), Rosmarinus officinalis (300), Peganum harmala (50), Aloe vera (150), Satureja hortensis (200), Teucrium scordium (200), Hypericum perforatum (135) and Silybum marianum (150). One group of animals was assigned as sham and not given D-galactose.
At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), NF-kappaB (NF-κb), total antioxidant power (TAP), thiobarbituric acid reactive substances (TBARS) as lipid
peroxidation (LPO) marker and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood.
These data for the first time indicate significant anti-aging potential of examined herbs. Results showed that D-galactose induces a significant oxidative stress and promotes proinflammatory cascade of aging while all herbs more or less recovered these changes. Among 9 herbal extracts, Silybum marianum showed the best effect in restoring aging changes.


1. Momtaz S, Abdollahi M. A comprehensive review of biochemical and molecular evidences from animal and human studies on the role of oxidative stress in aging: An epiphenomenon or the cause. Asian J Anim Vet Adv 2012; 7:1
2. Ghanbari S, Yonessi M, Mohammadirad A, Gholami M, Baeeri M, Khorram
Khorshid HR, et al. Effects of IMOD and Angipars on mouse Dgalactose
induced model of aging. DARU J Pharm Sci 2012; 20:68.
3. Zhang X, Zhang A, Jiang B, Bao Y, Wang J, An L. Further pharmacological evidence of the neuroprotective effect of catalpol from Rehmannia glutinosa. Phytomedicine 2008; 15:484-
4. Chung HY, Sung B, Jung KJ, Zou Y, Yu BP. The molecular inflammatory process in aging. Antioxid Redox Signal 2006; 8:572-581.
5. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E,
et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 908:244-254
6. Song X, Bao M, Li D, Li YM. Advanced glycation in D-galactose induced mouse aging model. Mech Ageing Dev 1999; 108:239-251.
7. Wei H, Li L, Song Q, Ai H, Chu J, Li W. Behavioral study of the D-galactose induced aging model in C57BL/6 J mice. Behav Brain Res 2005; 157:245
8. Xu Y, Wu T, Jin Y, Fu Z. Effects of age and jet lag on d-galactose induced aging process. Biogerontology 2009; 10:153
9. Rahimi R, Abdollahi M. Herbal medicines for the management of irritable bowel syndrome: A comprehensive review. World J Gastroenterol 2012; 18:589
10. Rahimi R, Mozaffari S, Abdollahi M. On the use of herbal medicines in management of inflammatory bowel diseases: A systematic review of animal and human studies. Digestive Diseases and Sciences. Dig Dis Sci 2009; 54:471-480.
11. Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol 2009; 15:3073
12. Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 2005; 59:365
13. Mohseni
SalehiMonfared SS, Larijani B, Abdollahi M. Islet transplantation and antioxidant management: A comprehensive review. World J Gاastroenterol 2009; 15: 1153
14. Abdollahi M, Larijani B, Rahimi R, Salari P. Role of oxidative stress in osteoporosis. Therapy 2005; 2:787
15. Hasani-Ranjbar S, Nayebi N, Moradi L, Mehri A, Larijani B, Abdollahi M. The efficacy and safety of
herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr Pharm Des 2010; 16:2935
16. Hasani-Ranjbar S, Khosravi S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of anti-aging herbs in animals and human. Asian J Anim Vet Adv 2012; 7:621
17. Ho SC, Liu JH, Wu RY. Establishment of the mimetic aging effect in mice caused by D-galactose. Biogerontology 2003; 4:15
18. Jagetia G, Baliga M, Venkatesh P. Ginger (Zingiber officinale rosc.), a dietary supplement, protects mice against radiation-induced lethality: Mechanism of action. Cancer Biother Radiopharma 2004; 19:422-435.
19. Sofiabadi M, Esmaeili MH, Haghdost Yazdy H, Azhdari Zarmehri H. The prenatal consumption of aqueous extract of Glycyrrhiza glabra, improves memory retrieval in mice. J Med Plants 2011; 10:49-54.
20. Maistro EL, Mota SF, Lima EB, Bernardes BM, Goulart FC. Genotoxicity and mutagenicity of rosmarinus officinalis (labiatae) essential oil in mammalian cells in vivo. Gene Mol Res 2010; 9:2113-22. Lamchouri F, Settaf A, Cherrah Y, Zemzami M, Lyoussi B, Zaid A,
et al.
Antitumour principles from Peganum harmala seeds. Therapie 1999; 54:753-758.
21. Tanaka M, Yamada M, Toida T, Iwatsuki K. Safety evaluation of supercritical carbon dioxide extract of Aloe vera gel. J Food Sci 2010; 77:T2-T9.
22. Hajhashemi V, Ghannadi A, Pezeshkian SK. Antinociceptive and anti-inflammatory effects of Satureja hortensis L. extracts and essential oil. J Ethnopharmacol 2002; 82:83-87.
Kundaković T, Milenković M, Topić A, Stanojković T, Juranić Z, Lakušić B. Cytotoxicity and antimicrobial
activity of teucrium scordium L. (Lamiaceae) extracts. Afr J Microbiol Res 2011; 5:2950-2954.
24. Higuchi A, Yamada H, Yamada E, Jo N, Matsumura M. Hypericin inhibits pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy. Mol Vis 2008; 14:249-254.
25. Chou CH, Chen YC, Hsu MC, Tsai WL, Chang CY, Chiu CH. Effect of silymarin on lipid and alcohol metabolism in mice following long-term alcohol consumption. J Food Biochem 2012; 36:369-377.
26. Astaneie F, Afshari M, Mojtahedi A, Mostafalou S, Zamani MJ, Larijani B,
et al. Total antioxidant capacity and levels of epidermal growth factorand nitric oxide in blood and saliva of insulin-dependent diabetic patients. Arch Med Res 2005; 36:376
27. Maggio M, Basaria S, Ceda GP, Ble A, Ling SM, Bandinelli S,
et al. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest 2005; 28:116
28. Ahmed RS, Seth V, Banerjee BD. Influence of dietary ginger (Zingiber officinales Rosc) on antioxidant defense system in rat: comparison with ascorbic acid. Indian J Exp Biol 2000; 38:604-606.
29. Topic B, Tani E, Tsiakitzis K, Kourounakis PN, Dere E, Hasenöhrl RU,
et al
. Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat. Neurobiol Aging 2002; 23:135-143.
Anti-Aging Effects of
Mohammadirad A et al
Some Iranian Folk Medicinal Herbs
Iran J Basic Med Sci, Vol. 16, No. 11, Nov 2013
30. Topic B, Hasenöhrl RU, Häcker R, Huston JP. Enhanced conditioned inhibitory avoidance by a combined extract of Zingiber officinale and Ginkgo biloba. Phytother Res 2002; 16:312-315.
31. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther 2007; 20:308-313.
32. Cronin H, Draelos ZD. Top 10 botanical ingredients in 2010 anti-aging creams. J Cosmet Dermatol 2010; 9:218-225.
33. Altinier G, Sosa S, Aquino RP, Mencherini T, Della Loggia R, Tubaro A. Characterization of topical antiinflammatory compounds in Rosmarinus officinalis L. J Agric Food Chem 2007; 55:1718-1723.
34. Ramírez P, Señoráns FJ, Ibañez E, Reglero G. Separation of rosemary antioxidant compounds by supercritical fluid chromatography on coated packed capillary columns. J Chromatogr A 2004; 1057:241-245.
35. Posadas SJ, Caz V, Largo C, De la Gándara B, Matallanas B, Reglero G,
et al.
Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats. Exp Gerontol 2009; 44:383-389.
36. Bastianetto S, Quirion R. Natural extracts as possible protective agents of brain aging. Neurobiol Aging 2002; 23:891-
37. Hamden K, Carreau S, Ayadi F, Masmoudi H, El Feki A. Inhibitory effect of estrogens, phytoestrogens, and caloric restriction on oxidative stress and hepato-toxicity in aged rats. Biomed Environ Sci 2009; 22:381-387.
38. Monsef
Esfahani HR, Ghobadi A, Iranshahi M, Abdollahi M. Antinociceptive effects of Peganum harmala L. alkaloid on mouse formalin test. J Pharm Pharm Sci 2004; 7:70
39. Berrougui H, Isabelle M, Cloutier M, Hmamouchi M, Khalil A. Protective effects of Peganum harmala L. extract, harmine and harmaline against human low-density lipoprotein oxidation. J Pharm Pharmacol 2006; 58:967-974.
40. Hamden K, Masmoudi H, Ellouz F, ElFeki A, Carreau S. Protective effects of Peganum harmala extracts on thiourea-induced diseases in adult male rat. J Environ Biol 2008; 29:73-77.
41. Asadi-Shahmirzadi A, Mozaffari S, Sanei Y, Baeeri M, Hajiaghaee R, Monsef-Esfahani HR,
et al.
Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects. Chin J Integr Med 2012; [Epub ahead of print]
42. Yoo EA, Kim SD, Lee WM, Park HJ, Kim SK, Cho JY,
et al
. Evaluation of antioxidant, antinociceptive, and anti-inflammatory activities of ethanol extracts from Aloe saponaria Haw. Phytother Res 2008; 22:1389-1395.
43. Ikeno Y, Hubbard GB, Lee S, Yu BP, Herlihy JT. The influence of long-term Aloe vera ingestion on age-related disease in male Fischer 344 rats. Phytother Res 2002; 16:712-218.
44. Lim BO, Seong NS, Choue RW, Kim JD, Lee HY, Kim SY,
et al.
Efficacy of dietary aloe vera supplementation on hepatic cholesterol and oxidative status in aged rats. J Nutr Sci Vitaminol (Tokyo) 2003; 49:292-296.
45. Mosaffa F, Behravan J, Karimi G, Iranshahi M. Antigenotoxic effects of Satureja hortensis L. on rat lymphocytes exposed to oxidative stress. Arc Pharm Res 2006; 29:159-164.
46. Momtaz S, Abdollahi M. An update on pharmacology of Satureja species; from antioxidant, antimicrobial, antidiabetes and anti
hyperlipidemic to reproductive stimulation. Int J Pharmacol 2010; 6:454
47. Momtaz S, Abdollahi M. A systematic review of the biological activities of Satureja L. Species. Pharmacologyonline 2008; 2:34
48. Vosough
Ghanbari S, Rahimi R, Kharabaf S, Zeinali S, Mohammadirad A, Amini A, et al. Effects of Satureja khuzestanica on serum glucose, lipids andmarkers of oxidative stress in patients with type 2 diabetes mellitus: A doubleblind randomized controlled trial. Evid Based Complement Alternat Med 2010; 7:465
49. Abdollahi M, Salehnia A, Mortazavi SH, Ebrahimi M, Shafiee A, Fouladian F,
et al. Antioxidant, antidiabetic, antihyperlipidemic, reproduction stimulatory properties and safety of essential oil of Satureja Khuzestanica in rat in vivo
: a oxicopharmacological study. Med Sci Monit 2003; 9:BR331-BR335.
50. Misharina TA, Burlakova EB, Fatkullina LD, Terenina MB, Krikunova NI, Vorob'eva AK,
et al.
Changes in fatty acid composition in the brain and liver in aging mice of high cancer risk AKR strain and effect of savory essential oil administration on leukemic process. Biomed Khim 2011; 57:604-614.
51. Abdolghaffari AH, Baghaei A, Moayer F, Esmaily H, Baeeri M, Monsef-Esfahani HR,
et al.
On the benefit of Teucrium in murine colitis through improvement of toxic inflammatory mediators. Hum Exp Toxicol 2010; 29:287-295.
52. Hasani P, Yasa N, Vosough-Ghanbari S, Mohammadirad A, Dehghan G, Abdollahi M.
In vivo
antioxidant potential of Teucrium polium, as compared to alpha-tocopherol. Acta Pharm 2007; 57:123-129.
53. Abdollahi M, Karimpour H, Monsef-Esfehani HR. Antinociceptive effects of Teucrium polium L total extract and essential oil in mouse writhing test. Pharmacol Res 2003; 48:31-35.
54. Morteza-Semnani K, Saeedi M, Akbarzadeh M. Essential oil composition of Teucrium scordium L. Acta Pharm 2007; 57:499-504.
55. Tambe Y, Tsujiuchi H, Honda G, Ikeshiro Y, Tanaka S. Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, beta-caryophyllene. Planta Med 1996; 62:469-470.
56. Reichling J, Weseler A, Saller R. A current review of the antimicrobial activity of Hypericum perforatum L. Pharmacopsychiatry 2001; 34:S116-S118.
57. Mozaffari S, Esmaily H, Rahimi R, Baeeri M, Sanei Y, Asadi
Shahmirzadi A, et al. Effects of Hypericum perforatum extract on rat irritable bowel syndrome. Pharmacogn Mag 2011; 7:213
58. Martarelli D, Martarelli B, Pediconi D, Nabissi MI, Perfumi M, Pompei P. Hypericum perforatum methanolic extract inhibits growth of human prostatic carcinoma cell line orthotopically implanted in nude mice. Cancer Lett 2004; 210:27-33.
Anti-Aging Effects of Some Iranian Folk Medicinal Herbs
Mohammadirad A et al
Iran J Basic Med Sci, Vol. 16, No. 11, Nov 2013
59. Rahimi R, Abdollahi M. An update on the ability of
St. John’s wort to affect the metabolism of other drugs. Exp Opin Drug Met Toxicol 2012; 8: 691
60. Hänsgen KD, Vesper J, Ploch M. Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. J Geriatr Psychiatry Neurol 1994; 7:S15-S18.
61. Das SK, Vasudevan DM. Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver. Indian J Biochem Biophys 2006; 43:306-311.
62. Hasani-Ranjbar S, Larijani B, Abdollahi M. A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflamm Allergy Drug Targets 2009; 8:2
63. Esmaily H, Hosseini
Tabatabaei A, Rahimian R, Khorasani R, Baeeri M, BarazeshMorgani A, et al.
the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells. Cent Eur J Biol 2009; 4: 204
64. Malihi F, Hosseini
Tabatabaei A, Esmaily H, Khorasani R, Baeeri M, Abdollahi M. Improvement of inflammatory and toxic stress biomarkers by silymarin in a murine model of type one diabetes mellitus. Cent Eur J Biol 2009; 4:369
Metodiewa D, Kośka C. Reactive oxygen species and
reactive nitrogen species: relevance to cyto(neuro)toxic events and neurologic disorders. An overview. Neurotox Res 2000; 1: 197-233.
66. Galhardi F, Mesquita K, Monserrat JM, Barros DM. Effect of silymarin on biochemical parameters of oxidative stress in aged and young rat brain. Food Chem Toxicol 2009; 47:2655-2660.