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IJSTR >> Volume 6 - Issue 1, January 2017 Edition

International Journal of Scientific & Technology Research  
International Journal of Scientific & Technology Research

Website: http://www.ijstr.org

ISSN 2277-8616

Evaluation of in vitro antioxidant potential, anti-inflammatory activity and melanogenesis inhibition of Artocarpus hirsutus Lam. extracts

[Full Text]



Mahadeva Nayak, A. Nagarajan, Muhammed Majeed, Lakshmi A. Mundkur



A. hirsutus Lam., melanogenesis, oxyresveratrol, TNF- α, tyrosinase.



Artocarpus hirsutus Lam. belongs to Moraceae family and is endemic to Western Ghats and Kerala in India. This species is found to be effective in traditional medicine for the treatment of ulcer, diarrhea and pimples. However, extensive biological evaluation on each component of this specific species rarely appears in the literature which restricts its applicability as medicinal herb. The leaf, bark and wood of Artocarpus hirsutus Lam. were separately extracted with hot ethanol. The wood extract was further fractionated to isolate major active molecule whose structure was determined from its NMR spectra and LCMS analysis. All the extracts of A. hirsutus Lam. were then studied in vitro to evaluate their potential on tyrosinase inhibition, free radical scavenging activity by 1,1-Diphenyl-2-picrylhydrazyl (DPPH) method and oxygen radical absorbance capacity (ORAC). Furthermore, their effects on melanogenesis inhibition were also evaluated by using murine melanoma cells. Activity guided fractionation of wood extract yielded a pure molecule that was characterized as oxyresveratrol. It was observed that antioxidant activity was higher in wood extract compared to the leaf and bark extracts. Isolated pure oxyresveratrol exhibited a significant antioxidant potential with ORAC value of 36,653±2570 µmol Trolox equivalent/g and having an IC50 of 4.3 µg/mL for DPPH free radical scavenging activity. This molecule was found to be effective for the tyrosinase inhibition with an IC50 of 0.1 µg/mL and melanogenesis inhibition in cultured melanoma cells by 44.62% at 0.2 µg/mL. Oxyresveratrol also exhibited significant inhibition of lipopolysaccharide (LPS) induced tumour necrosis factor alpha (TNF-α) secretion from J774A1 murine macrophage cell lines. This study provides substantial evidence for the presence of oxyresveratrol in the wood of A. hirsutus Lam. with promising anti-inflammatory, antioxidant and skin lightening property.



[1] Thakur, S., Vidyasagaran, K., 2014. Influence of zonal variation on physical characteristics of Artocarpus hirsutus fruit and size wise variation in biochemical composition of the fruit. Journal of Recent Advances in Agriculture 2(6), 263-270.

[2] Isaac, S.R., Nair, M.A., 2004. Decomposition of wild jack (Artocarpus hirsutus Lam.) leaf litter under subcanopy and open conditions. Journal of Tropical Agriculture 42(1-2), 29-32.

[3] Hari, A., Revikumar, K.G., Divya, D., 2014. Artocarpus: A review of its phytochemistry and pharmacology. Journal of Pharma Search 9(1), 7-12.

[4] Jagtap, U.B., Bapat, V.A., 2010. Artocarpus: A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethanopharmacology 129(2), 142-166.

[5] Asha, D.S., Ben, C.P., 2014. Least concerned bark and stipules of Artocarpus species (Moraceae) – an effective antibacterial agent. International Science Community Association 3(2), 25-29.

[6] Azeem, A.K., Rasheed, A., Dilip, C., Junise, V., Rani S., 2013. Diuretic activity of the fruits of Artocarpus hirsutus Lam. Journal of Current Science 1(1), 16-19.

[7] Dibinlal, D., Sathish Sekar, D., Senthil Kumar, K.L., 2010. Pharmacognostical Studies on the Bark of Artocarpus hirsutus Lam. Hygeia, Journal for Drugs and Medicines 2(1), 22-27.

[8] Lakshmi Pethakamsetty, Ganapaty, S., Mary Bharathi, K., 2013. Phytochemical and biological examination of the root extract of Artocarpus hirsuta, Lam. International Journal of Bioassays 02(04), 735-738.

[9] Vinay Suvarna, M.N., Ramesh, B.S., Venkatachalapathy, R., Makari, Hanumanthappa, K., Ramaganesh, C.K., 2013. Evaluation of antioxidant activity of Artocarpus hirsutus methanolic fruit extract: an in vitro study. International Journal of Scientific Research 2(12), 58–59.

[10] Vinay Suvarna, M.N., Venkatachalapathy, R., Makari, H.K., Ramesh, B.S., 2014. Phytochemical analysis and antimicrobial activity of Artocarpus hirsutus: an in vitro study. Journal of Recent Advances in Agriculture 5(3), 98–104.

[11] Arung, E.T., Shimizu, K., Kondo, R., 2011. Artocarpus plants as a potential source of skin whitening agents. Natural Product Communications 6(9), 1397-1402.

[12] Im, S., Kim, J., On W.Y., Kang, W.H., 2002. Increased expression of α-melanocyte-stimulating hormone in the lesional skin of melasma. British Journal of Dermatology 146(1), 165–167.

[13] Kang, W.H., Yoon, K.H., Lee, E.S., Kim, J., Lee, K.B., Yim, H., Sohn, S., Im, S., 2002. Melasma: histopathological characteristics in 56 Korean patients. British Journal of Dermatology 146(2), 228–237.

[14] Slominski, A., Zmijewski, M.A., Pawelek, J., 2012. L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions. Pigment Cell & Melanoma Research 25(1), 14-27.

[15] Slominski, A., Wortsman, J., Luger, T., Paus, R., Solomon, S., 2000. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiological Reviews 80(3), 979–1020.

[16] Slominski, A., Tobin, D.J., Shibahara, S., Wortsman, J., 2004. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiological Reviews 84(4), 1155-1228.

[17] Handel, A.C., Lima, P.B., Tonolli, V.M., Miot, L.D., Miot, H.A., 2014. Risk factors for facial melasma in women: a case-control study. British Journal of Dermatology 171(3), 588-594.

[18] Yamakoshi, J., Otsuka, F., Sano, A., Tokutake, S., Saito, M., Kikuchi, M., Kubota, Y., 2003. Lightening effect on ultraviolet-induced pigmentation of guinea pig skin by oral administration of a proanthocyanidin-rich extract from grape seeds. Pigment Cell Research 16(6), 629-638.

[19] Bubici, C., Papa, S., Dean, K., Franzoso, G., 2006. Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene 25(51), 6731-6748.

[20] Nakagawa, M., Kawai, K., Kawai, K., 1995. Contact allergy to kojic acid in skin care products. Contact Dermatitis 32(1), 9-13.

[21] Clarke, G., Ting, K.N., Wiart, C., Fry, J., 2013. High correlation of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing activity potential and total phenolics content indicates redundancy in use of all three assays to screen for antioxidant activity of extracts of plants from the malaysian rainforest. Antioxidants 2, 1-10.

[22] Ou, B., Hampsch-Woodill, M., Prior, R.L., 2001. Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. Journal of Agricultural and Food Chemistry 49(10), 4619–4626.

[23] Vichai, V., Kirthikara, K., 2006. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nature protocols 1(3), 1112-1116.

[24] Jeong, C.H., Shim, K.H., 2004. Tyrosinase inhibitor isolated from the leaves of Zanthoxylum piperitum. Bioscience Biotechnology and Biochemistry Journal 68(9), 1984-1987.

[25] Choi, S.Y., Kim, S., Kim, H., Suk, K., Hwang, J.S., Lee, B.G., Kim, A.J., Sun, Y. K., 2002. (4-Methoxy-benzylidene)-(3-methoxy-phenyl)-amine, a nitrogen analog of stilbene as a potent inhibitor of melanin production. Chemical & Pharmaceutical Bulletin 50(4), 450-452.

[26] Djapic, N., Djarmati, Z., Filip, S., Jankov, R.M., 2003. A stilbene from the heartwood of Maclura pomifera. Journal of the Serbian Chemical Society 68(3), 235–237.

[27] Soekamto, N.H., Achmad, S.A., Ghisalberti, E.L., Hakim, E.H., Syah, Y.M., 2005. Lunularin and oxyresveratrol: two stilbene derivatives from Morus macroura. Indonesian Journal of Chemistry 5(3), 207 – 210.

[28] Gupta, D., Mann, S., Sood, A., Gupta, R.K., 2011. Phytochemical, nutritional and antioxidant activity evaluation of seeds of jackfruit (Artocarpous heterolphyllus Lam.). International Journal of Pharma and Bio Sciences. 2(4), 336-345.

[29] Haytowitz, D.B., Bhagwat, S., 2010. USDA Database for the Oxygen Radical Absorbance Capacity (ORAC) of selected foods, release 2. Page:1–46.

[30] Li, Xu., Chao, L., Wei, X., Hu C., Xiaoli Q., Xianzhi H., 2014. Advances in the Study of Oxyresveratrol. International Journal of Pharmacology 10(1), 44-54.

[31] Lim, Y.H., Kim, K.H., Kim, J.K., 2015. Source, biosynthesis, biological activities and pharmacokinetics of oxyresveratrol. Korean Journal of Food Science and Technology. 47(5), 345-555.

[32] Kim, Y.M., Yun, J., Lee, C.K., Lee, H., Min, K.R., Kim, Y., 2002. Oxyresveratrol and hydroxystilbene compounds - inhibitory effect on tyrosinase and mechanism of action. The Journal of Biological Chemistry 277(18), 16340–16344.

[33] Likhitwitayawuid, K., Sornsute, A., Sritularak, B., Ploypradith, P., 2006. Chemical transformations of oxyresveratrol (trans-2,4,3′,5′-tetrahydroxystilbene) into a potent tyrosinase inhibitor and a strong cytotoxic agent. Bioorganic & Medicinal Chemistry Letters 16(21):5650-5653.

[34] Tengamnuay, P., Pengrungruangwong, K., Pheansri, I., Likhitwitayawuid, K., 2006. Artocarpus lakoocha heartwood extract as a novel cosmetic ingredient: evaluation of the in vitro anti-tyrosinase and in vivo skin whitening activities. International Journal of Cosmetic Science 28(4), 269-276.

[35] Shin, N.H., Ryu, S.Y., Lee, H., Min, K.R., Kim, Y., 1998. Inhibitory effects of hydroxystilbenes on cyclooxygenase from sheep seminal vesicles. Planta Medica 64, 283—284.

[36] Li, H., Wu, W.K., Zheng, Z., Che, C.T., Li, Z.J., Xu, D.D., Wong, C.C., Ye, C.G., Sung, J.J., Cho, C.H., Wang, M., 2010. 3,3',4,5,5'-Pentahydroxy-trans-stilbene, a resveratrol derivative, induces apoptosis in colorectal carcinoma cells via oxidative stress. European Journal of Pharmacology 637(1-3), 55-61.

[37] Andrabi, S.A., Spina, M.G., Lorenz, P., Ebmeyer, U., Wolf, G., Horn, T.F.W., 2004. Oxyresveratrol (trans-2, 3′, 4, 5′-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia. Brain Research 1017(1), 98-107.

[38] Breuer, C., Wolf, G., Andrabi, S.A., Lorenz, P., Horn, T.F.W., 2006. Blood-brain barrier permeability to the neuroprotectant oxyresveratrol. Neuroscience Letters 393(2-3), 113-118.

[39] Lorenz, P., Roychowdhury, S., Engelmann, M., Wolf, G., Horn, T.F., 2003. Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 9(2), 64-76.

[40] Qiu, F., Komatsu, K.I., Saito, K.I., Kawasaki K., Yao, X.S., Kano, Y., 1996. Pharmacological properties of traditional medicines. xxii. pharmacokinetic study of mulberroside a and its metabolites in rat. Biological and Pharmaceutical Bulletin 19(11), 1463-1467.

[41] Venkataraman K., 1972. Wood phenolics in the chemotaxonomy of the moraceae. Phytochemistry 11, 1571-1586.

[42] Povichit, N., Phrutivorapongkul, A., Suttajit, M., Leelapornpisid, P., 2010. Antiglycation and antioxidant activities of oxyresveratrol extracted from the heartwood of Artocarpus lakoocha Roxb. Maejo international journal of science and technology 4(3), 454-461.

[43] Likhitwitayawuid, K., Chaiwiriya, S., Sritularak, B., Lipipun, V., 2006. Antiherpetic flavones from the heartwood of Artocarpus gomezianus. Chemistry & Biodiversity 3(10), 1138-1143.

[44] Fang, S.C., Hsu, C.L., Yen, G.C., 2008. Anti-inflammatory effects of phenolic compounds isolated from the fruits of Artocarpus heterophyllus. Journal of Agricultural and Food Chemistry 56, 4463–4468.

[45] Lee, K.T., Lee, K.S., Jeong, J.H., Jo, B.K., Heo, M.Y., Kim, H.P., 2003. Inhibitory effects of Ramulus mori extracts on melanogenesis. Journal of Cosmetic Science 54, 133-142.

[46] Suwannalert, P., Povichit, N., Puchadapirom, P., Junking M., 2012. Anti-aging activity and non-toxic dose of phytooxyresveratrol from Artocarpus lakoocha Roxb. Tropical Journal of Pharmaceutical Research 11(1): 69-74.