The immunoinhibitory and apoptosis-inducing activities of Foeniculum vulgare on human peripheral blood lymphocytes

Salimeh Ebrahimnezhad Darzi, Seyedeh Parvin Khazraei, Zahra Amirghofran

Abstract


Foeniculum vulgare (F. vulgare, Apiaceae) is an important plant currently used in folk medicine to treat various diseases including infections and inflammatory conditions. In this study we have investigated the immunomodulatory and apoptosis-inducing activities of the fractions from this plant. We prepared dichloromethane, hexane, butanol, and water fractions from the aerial parts of the plant. We examined the growth inhibitory effects of the fractions on proliferative lymphocytes by the BrdU incorporation assay. Cell viability was determined by the propidium iodide (PI) assay. AnnexinV/PI staining and cell cycle analysis by flow cytometry was performed to investigate the apoptosis-inducing effects of the plant fractions. Cytokine levels were measured by enzyme-linked immunosorbent assay. All fractions reduced cell proliferation of the activated lymphocytes. The dichloromethane fraction with the highest inhibitory effect (IC50, 19.8 µg/mL) significantly reduced cell viability. Although the butanol fraction inhibited cell growth (IC50, 88.2 µg/mL) it did not affect cell viability. Annexin V/PI and cell cycle analysis showed the maximum apoptosis-inducing effect of the dichloromethane fraction at 200 µg/mL. Cytokines, that included interleukin (IL)-4 (22.8 ± 0.9 pg/mL, P < 0.05) and interferon (IFN)-γ (651 ± 37.5 pg/mL, P < 0.01) reduced the activated lymphocyte levels in cultures in the presence of 100 μg/mL concentration of butanol fraction compared to the untreated control. In conclusion, the dichloromethane fraction of F. vulgare had the capability of inducing apoptosis in the activated lymphocytes, whereas the butanol fraction reduced cell activation and cytokine secretion. These data suggested the potential of these examined fractions for more studies in terms of their beneficial effects on immune-mediated diseases.


Keywords


Foeniculum vulgare; Apoptosis; Lymphocytes; Cytokines

Full Text:

PDF

References


Fishman JA. Infection in solid-organ transplant recipients. New Engl J Med. 2007;357:2601-2614.

Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102:322-328.

Ansil PN, Wills PJ, Varun R, Latha MS. Cytotoxic and apoptotic activities of Amorphophallus campanulatus tuber extracts against human hepatoma cell line. Res Pharm Sci. 2014;9:269-277.

Amirghofran Z, Bahmani M, Azadmehr A, Javidnia K, Miri R. Immunomodulatory activities of various medicinal plant extracts: effects on human lymphocytes apoptosis. Immunol Invest. 2009;38:181-192.

Amirghofran Z, Bahmani M, Azadmehr A, Javidnia K. Immunomodulatory and apoptotic effects of Stachys obtusicrena on proliferative lymphocytes. Med Sci Monit. 2007;13:BR145-50.

Badgujar SB, Patel VV, Bandivdekar AH. Foeniculum vulgare Mill.: a review of its botany, phytochemistry, pharmacology, contemporary application, and toxicology. Biomed Res Int. 2014;2014:842674.

Amirghofran Z. Medicinal plants as immunosuppressive agents in traditional Iranian medicine. Iran J Immunol. 2010;7:65-73.

Rahimi R, Shams Ardekani MR. Medicinal properties of Foeniculum vulgare Mill. in traditional Iranian medicine and modern phytotherapy. Chin J Integr Med. 2013;19:73-79.

Amirghofran Z. Herbal medicines for immunosuppression. Iran J Allergy Asthma Immunol. 2012;11:111-119.

Khaghanzadeh N, Mojtahedi Z, Ramezani M, Erfani N, Ghaderi A. Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells. Daru. 2012;20(1):69.

Amirghofran Z, Hashemzadeh R, Javidnia K, Golmoghaddam H, Esmaeilbeig A. In vitro immunomodulatory effects of extracts from three plants of the Labiatae family and isolation of the active compound(s). J mmunotoxicol. 2011;8: 265-273.

Amirghofran Z, Ahmadi H, Karimi MH. Immunomodulatory activity of the water extract of Thymus vulgaris, Thymus daenensis, and Zataria multiflora on dendritic cells and T cells responses. J Immunoassay Immunochem. 2012;33:388-402.

Wlodkowic D, Skommer J, Darzynkiewicz Z. Flow cytometry-based apoptosis detection. Methods Mol Biol. 2009;559:19-32.

Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol. 2016;28:163-171.

Mansouri E, Kooti W, Bazvand M, Boroon MG, Amirzargar A, Afrisham R, et al. The effect of hydro-alcoholic extract of Foeniculum vulgare Mill. on leukocytes and hematological tests in male rats. Jundishapur J Nat Pharm Prod. 2015;10(1). e18396. Published online.

Naeini A, Khosravi A, Tajbakhsh H, Ghazanfari T, Yaraee R. Anticandida and immunomodulatory effects of Foeniculum vulgare Mill. In vitro. Daneshvar Med. 2009;16:7-20.

Kaileh M, Vanden Berghe W, Boone E, Essawi T, Haegeman G. Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. J Ethnopharmacol. 2007;113: 510-516

Mimica‐Dukić N, Kujundžić S, Soković M, Couladis M. Essential oil composition and antifungal activity of Foeniculum vulgare Mill. obtained by different distillation conditions. Phytother Res. 2003;17:368-371.

Yea SS, Jeong HS, Choi CY, Park KR, Oh S, Shin JG, et al. Inhibitory effect of anethole on T-lymphocyte proliferation and interleukin-2 production through down-regulation of the NF-AT and AP-1. Toxicol In Vitro. 2006;20:1098-1105.

Marín I, Sayas-Barberá E, Viuda-Martos M, Navarro C, Sendra E. Chemical composition, antioxidant and antimicrobial activity of essential oils from organic fennel, parsley, and lavender from Spain. Foods. 2016;5: E18.


Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.