IMMUNOMODULATORY ACTIVITY OF AN ACETONE EXTRACT OF TERMINALIA BELLERICA ROXB FRUIT ON THE MOUSE IMMUNE RESPONSE IN VITRO
Keywords:
Lymphocytes, Proliferation, Macrophages, Phagocytosis, Cytokines, Anti-inflammatoryAbstract
Objectives: To investigate the immunomodulatory activity of an acetone extract of T. bellerica fruit.
Methods: Mitogen induced-lymphocyte proliferation using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) technique, Th1- and Th2-related cytokine production by lymphocytes using ELISA and peritoneal macrophage function in ICR mice were assayed.
Results: The results show that the extract had a mild inhibitory effect on the generation of oxidase enzyme (Phagocytic Index 0.8, 100 mg/ml) but did not influence acid phosphatase enzyme function during phagocytosis. The extract stimulated the proliferation of both T and B lymphocytes. The maximal activation (Stimulation Index 3.2, 100 mg/ml) was presented with concanavalin A induction, indicating a major effect on T lymphocyte proliferation. The extract reduced the production of IFN-γ (89%, 100 mg/ml) and IL-2 (98%, 100 mg/ml) but increased IL-10 secretion (231%, 100 mg/ml) compared to concanavalin A. Gallic acid, a pharmacological component contained in this plant, presented a similar effect as that of T. bellerica extract and may contribute to the immunomodulatory activity of T. bellerica fruits in cooperation with other phytocompounds. The decrease in the IFN-g/IL-10 ratio indicated a shift in the Th1/Th2 balance towards a Th2-type response, which might lead to a treatment for Th1-mediated inflammatory immune diseases.
Conclusion: Our investigations show that the acetone extract of T. bellerica fruit possesses immunomodulatory activity, which could be used to explain its folklore applications and provide a pharmacological basis for its usefulness in immune-related disorders.
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References
WHO. The World Medicines Situation, Traditional medicines: Global situation, issues and challenges. Geneva: World Health Organization; 2011.
Mukherjee PK, Nema NK, Venkatesh P, Debnath PK. Changing scenario for promotion and development of Ayurveda–way forward. J Ethnopharmacol 2012;143:424–34.
Huang C, Lin S, Liao P, Young S, Yang C. The immunopharmaceutical effects and mechanisms of herb medicine. Cell Mol Immunol 2008;5:23-31.
Hackett CJ. Innate immune activation as a broad-spectrum biodefense strategy: Prospects and research challenges. J Allergy Clin Immun 2003;112:686-94.
Bunyapraphatsara N. Medicine plants (4). Bangkok: Prachachon Publishing Ltd; 2000. p. 477-82.
Duke JA, Bogenschutz-Godwin MJ, Ducelliar J, Duke PAK. Handbook of medicinal herbs. 2nd ed. Boca Raton: CRC Press; 2002. p. 70-1.
Jagetia GC, Baliga MS, Malagi KL, Kamath MS. The evaluation of the radioprotective effect of Tripala (an ayurvedic rejuvenating drug) in the mice exposed to radiation. Phytomed 2002;9:99-108.
Sandhya T, Mishra KP. Cytotoxic of breast cancer cell line, MCF 7 and T 47D to triphala and its modification by antioxidants. Cancer Lett 2006;238:304-13.
Nandy AK, Podda G, Sahu M, Manto P, Shashi B. Triterpenoids and their glucosides from Terminalia bellerica. Phytochem 1989;28:2769-72.
Row LR, Murty PS. Chemical examination of Terminalia belerica Roxb. Indian J Chem 1970;8:1047-8.
Biswajit D, Suvakanta D, Chandra CR. Pharmaceutical properties of Terminalia bellerica (Bahera)-an overview. RJPT 2014;7:592-7.
Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal plants for their antimicrobial properties. J Ethnopharmacol 1998;62:183-93.
Nithya Devi P, Kaleeswari S, Poonkothai M. Antimicrobial activity and phytochemical analysis of fruit extracts of Terminalia Bellerica. Int J Pharm Pharm Sci 2014;6:639-42.
Naik GH, Priyadarsini KI, Bhagirathi RG, Mishra B, Mishra KP, Banavalikar MM, et al. In vitro antioxidant studies and free radical reactions of triphala, an ayurvedic formulation and its constituents. Phytother Res 2005;19:582-6.
Chaudhary SK, Mukherjee PK, Nema NK, Bhadra S, Saha BP. ACE inhibiton activity of standardized extract and fractions of Terminalia bellerica. Orient Pharm Exp Med 2012;12:273-7.
Valsaraj R, Pushpangadan P, Smitt UW, Adsersen A, Christensen SB, Sittie A, et al. New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica. J Nat Prod 1997;60:739-42.
Rashed KN, Koekemoer T, Van de Venter M. In vitro gastro-protective effect and bioactive compounds from Terminalia bellerica Roxb. seeds. Pharm Res 2013;10:41-53.
Saraphanchotiwitthaya A, Sripalakit P, Ingkaninan K. Effects of Terminalia bellerica Roxb. methanolic extract on mouse immune response in vitro. Maejo Int J Sci Technol 2008;2:400-7.
Manosroi A, Saraphanchotiwitthaya A, Manosroi J. Immunomodulatory activities of Clausena excavata Burm. f wood extracts. J Ethnopharmacol 2003;89:155-60.
Rainard P. A colorimetric microassay for opsonins by reduction of NBT in phagocytosing bovine polymorphs. J Immunol Methods 1986;90:197-201.
Suzuki I, Tanaka H, Adachi Y, Yadomae T. Rapid measurement of phagocytosis by macrophages. Chem Pharm Bull 1998;36:4871-5.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55-63.
Xie P, Chen S, Liang Y, Wang X, Tian R, Upton R. Chromatographic fingerprint analysis-a rational approach for quality assessment of traditional Chinese herbal medicine. J Chromatogr A 2006;1112:171-80.
Kang NS, Park SY, Lee KR, Lee SM, Lee BG, Shin DH, et al. Modulation of macrophage function activity by ethanolic extract of larvae of Holotrichia diomphalia. J Ethnopharmacol 2002;79:89–94.
Tam PR, Hinsdill RD. Screening for immunomodulators: effects of xenobiotics on macrophage chemiluminescence in vitro. Fundam Appl Toxicol 1990;14:542-53.
Kim BH, Cho SM, Chang YS, Han SB, Kim Y. Effect of quercitrin gallate on zymosan A-induced peroxynitrite production in macrophage. Arch Pharm Res 2007;30:733-8.
Horsmanheimo M. Correlation of tuberculin-induce lymphocyte transformation with skin test reactivity and with clinical sarcoidosis. Cell Immunol 1974;10:329-37.
Nakamura A, Nagai K, Suzuki S, Ando K, Tamura G. A novel method of screening for immunomodulating substances, establishment of an assay system and its application to culture broths of microorganisms. J Antibiot 1986;39:1148–54.
Ho CY, Lau CBS, Kim CF, Leung KN, Fung KP, Tse TF, et al. Differential effect of Coriolus versicolor (Yunzhi) extract on cytokine production by murine lymphocytes in vitro. Int Immunopharmacol 2004;4:1549-57.
Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138-46.
Romagnani S. The role of lymphocytes in allergic diseases. J Allergy Clin Immun 2000;105:399-408.
Swain SL, Bradley LM, Crof M, Tonkonoggy S, Atkins G, Weinberg AD, et al. Helper T-cell subset: phenotype, function and the role of lymphokines in regulating their development. Immuno Rev 1991;123:115-44.
Pedotti R, De Voss JJ, Steinman L, Galli SJ. Involvement of both ‘allergic’ and ‘autoimmune’ mechanisms in EAE, MS and other autoimmune diseases. Trends Immunol 2003;24:479-84.
Abbas AK, Murphy KM, Sher A. A functional diversity of helper T lymphocytes. Nat 1996;383:787-93.
Guerrini A, Mancini I, Maietti S, Rossi D, Poli F, Sacchetti G, et al. Expression of pro-inflammatory interleukin-8 is reduced by Ayurvedic decoctions. Phytother Res 2014;28(8):1173-81.
Kroes BH, Van den Berg AJ, Quarles van Ufford HC, Van Dijk H, Labadie RP. Anti-inflammatory activity of gallic acid. Planta Med 1992;58:499–504.
Kubo I, Xiao P, Fujita K. Antifungal activity of octyl gallate: Structural criteria and mode of action. Bioorg Med Chem Lett 2001;11:347–50.
Hu ZQ, Toda M, Okubo S, Hara Y, Shimamura T. Mitogenic activity of (-) epigallocatechin gallate on B-cells and investigation of its structure-function relationship. Int J Immunopharmacol 1992;14:1399-407.
Serrano A, Palacios C, Roy G, Cespon C, Villar ML, Nocito M, et al. Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys 1998;350:49-54.
Kim S, Jun C, Suk K, Choi B, Lim H, Park S, et al. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicol Sci 2006;91:123-31.
Kato K, Yamashita S, Kitanaka S, Toyoshima S. Effect of gallic acid derivatives of Th1 cytokines and Th2 cytokines from anti-CD3-stimulated spleen cells. Yakugaku Zasshi 2001;121:451-7.