Effects of Foeniculum vulgare ethanol extract on osteogenesis in human mecenchymal stem cells

Document Type : Original Research Article


1 Department of Biotechnology, Faculty of New Technologies and Energy Engineering, Shahid Beheshti University, Tehran, I. R. Iran

2 Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, I. R. Iran

3 Department of Hematology, School of Medicine, Boushehr University of Medical Science, Boushehr, I. R. Iran

4 Department of Biotechnology, Faculty of Agriculture, Bu-ali Sina University, Hamedan, I. R. Iran


Objective: Osteoporosis or silent disease is a major bone disorder in elderly women in current century. Estrogen has an important role in osteogenesis and prevention of bone fractures. Hormone replacement therapy (HRT) is usually accompanied by such effects as breast and ovary cancers. Thus, there is an increasing demand for replacement with plant phytoestrogens. This study is focused on determining the effects of Foeniculum vulgare extract on proliferation and osteogenesis progress in human mesenchymal stem cells.
Material and Methods: Human mesenchymal stem cells were isolated and treated with different amount of plant extracts (0.5 to 100 µg/ml). Extract cytotoxicity was measured using MTT assay. The alkaline phosphatase enzyme activity was measured to evaluate the differentiation progress.
Results: Results of MTT assay and alkaline phosphatase activity showed that Foeniculum vulgare extract, at range of 5 to 50 µg/ml, may positively affect cell proliferation and mineralization. The most proliferation and enzyme activity were seen with dose of 5 µg/ml.
Conclusions: Foeniculum vulgare has been used in Iranian folk medicine for many years. Our in vitro study showed that Foeniculum vulgare extract has osteoprotective effects.


Adams M, Gmünder F, et al. 2007. Plants traditionally used in age related brain disorders-A survey of ethnobotanical literature. J Ethnopharmacol, 113: 363-381.
Amjad H. and Jafary HA. 2000. Foeniculum vulgare therapy in irritable bowel syndrome. Am J Gastroenterol, 95: 2491.
Bhargavan B, Gautam AK, et al. 2009. Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. J Cell Biochem, 108: 388-399.
Choi EM and Hwang JK. 2004. Antiinflammatory, analgesic and antioxidant activities of the fruit of Foeniculum vulgare. Fitoterapia, 75: 557-565.
Christensen C , Christensen MS, et al. 1982. Pathophysiological Mechanisms of Estrogen Effect on Bone Metabolism. Dose-Response Relationships in Early Postmenopausal Women.  J Clin Endocrinol Metab, 55: 1124-1130.
Gronholz  MJ. 2008. Prevention, Diagnosis, and Management of Osteoporosis-Related Fracture: A Multifactoral Osteopathic Approach. J Am Osteopath Assoc, 108: 575-585.
Horiuchi  T,  Onouchi  T, et al. 2000 . Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women. Osteoporos Int, 11: 721-724.
Hsu JT, Hsu WL, et al. 1999. Dietary phytoestrogen regulates estrogen receptor gene expression in human mammary carcinoma cells. Nut Res, 19: 1447-1457.
Jaffary  F, Ghannadi A, Najafzadeh H, et al. 2006.  Evaluation of the Prophylactic Effect of Fennel Essential Oil Experimental Osteoporosis Model in Rats. Int J Pharmacol,2: 588-592.
Jung EM, Choi  KC, et al. 2010. Effects of 17β-estradiol and xenoestrogens on mouse embryonic stem cells. Toxicol in Vitro, 24: 1538-1545.
Knight DC, Eden JA. 1996 . A review of the clinical effects of phytoestrogens. Obstet Gynecol, 87: 897-904.
Kushida K, Takahashi M, et al, 1995. Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients. J Clin Endocrinol Metab, 80: 2447-2450.
Meunier PJ, Delmas PD, et al. 1999 . Diagnosis and management of osteoporosis in postmenopausal women: Clinical guidelines. Clinl Ther, 21: 1025-1044.
Nakagawa  Y, Suzuki T, 2003. Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rat hepatocytes and cultured MCF-7 human breast cancer cells. Biochem J, 66: 63-73.
Namavar Jahromi B, Tartifizadeh A, et al . 2003. Comparison of fennel and mefenamic acid  for the treatment of primary dysmenorrhea. Int J Gynecol Obstet, 2: 80: 153.    
Neuner J, Zimmer  MJ, et al. 2003. Diagnosis and Treatment of Osteoporosis in Patients with Vertebral Compression Fractures. A J Clin Nutr,71: 142-151.
New  SA , Robins SP, et al. 2000. Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr, 71: 142-151.
Oktay M, Gülçin İ, et al. 2003. Determination of in vitro antioxidant activity of fennel (Foeniculum vulgare) seed extracts. LWT - Food Sci Technol, 36: 263-271.
Ostad SN, Soodi M, et al. 2001. The effect of Fennel essential oil on urine contraction as a model for dysmenorrhea, pharmacology and toxicology study. J Ethnopharmacol, 76: 299-304.
Özbek H, Uğraş S, et al. 2003. Hepatoprotective effect of Foeniculum vulgare essential oil. Fitoterapia, 74: 317-319.
Peretz A, Moris M, et al. 1996. Is bone alkaline phosphatase an adequate marker of bone metabolism during acute corticosteroid treatment? Clin Chem, 42: 102-103.
Rather M, Dar AB, et al. 2012.  Foeniculum vulgare: A comprehensive review of its traditional use,phytochemistry, pharmacology, and safety. Arab J Chem, Article in press.
Rubin C, Turner  AS, et al.  2001. Anabolism: Low mechanical signals strengthen long bones. Nature, 412: 603-604.
Setchell  KD, Lydeking-Olsen E. 2003. Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. Am J Clin Nutr, 78: 593-609.
Singh G, Maurya S, et al. 2006. Chemical constituents, antifungal and antioxidative potential of Foeniculum vulgare volatile oil and its acetone extract. Food Control, 17: 745-752.
Suh SJ, Yun WS , et al. 2007. Stimulative effects of Ulmus davidiana Planch (Ulmaceae) on osteoblastic MC3T3-E1 cells. J Ethnopharmacol, 109: 480-485.
Tielens  S, Wymeersch F, et al. 2008. Effect of 17β-estradiol on the in vitro differentiation of murine embryonic stem cells into the osteogenic lineage.  In Vitro Cell Dev-An, 44: 368-378.
Tognolini M, Ballabeni V, et al. 2007.  Protective effect of Foeniculum vulgare essential oil and anethole in an experimental model of thrombosis. Pharmacol Res, 56: 254-260.
Wei Y, Tsai K, et al. 2011. Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells. Osteoporos Int, 22: 1469-1479.