Abstract
This research is aimed towards the discovery of a novel skin whitening agent from sesquiterpene lactones. We screened nine sesquiterpene lactones from Saussurea lappa root extracts, costunolide (1), α-, β-, γ-cyclocostunolides (2, 3, 4), santamarine (5), reynosin (6), arbuscirin A (7), dehydrocostus lactone (8), and 11β, 13-dehydrocostus lactone (9), for their melanin inhibitory activity in B16 melanoma cells. This study was focused on the inhibition of the extracellular melanin content. The screening results revealed that only α-cyclocostunolide (2) showed notable inhibition of the melanin production, particularly the extracellular melanin content, with an IC50 value of 5.75 μM. In addition, structure-activity relationship (SAR) of 12 sesquiterpene lactone analogues with reference to their melanin inhibitory activity was also investigated. However, none of the analogues were found to show any significant melanin inhibitory activity. To the best of our knowledge the above study is the first SAR investigation involving the melanin inhibitory activity of sesquiterpene lactones. It established that eudesmanolide-type lactone having a double bond between C3 and C4 showed the most efficient melanin inhibition. Additionally, the presence of a hydroxyl, ketone or ester moiety as the C1-substituent markedly decreased the melanin inhibitory activity. Thus, these findings suggest that α-cyclocostunolide (2) might be useful in the therapy of skin disorders.
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References
Bae SJ, Ha YM, Park YJ et al. (2012) Design, synthesis, and evaluation of (E)-N-substituted benzylidene–aniline derivatives as tyrosinase inhibitors. Eur J Med Chem 57:383–390. https://doi.org/10.1016/j.ejmech.2012.09.026
Batubara I, Darusman LK, Mitsunaga T et al. (2010) Potency of Indonesian medicinal plants as tyrosinase inhibitor and antioxidant agent. J Biol Sci 10:138–144. https://doi.org/10.3923/jbs.2010.138.144
Briganti S, Camera E, Picardo M (2003) Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 16:101–110
Chadwick S, Heath R, Shah M (2012) Abnormal pigmentation within cutaneous scars: a complication of wound healing. Indian J Plast Surg 45:403–411. https://doi.org/10.4103/0970-0358.101328
Chang T-S (2012) Natural melanogenesis inhibitors acting through the down-regulation of tyrosinase activity. Materials 5:1661–1685. https://doi.org/10.3390/ma5091661
Choi JY, Choi EH, Jung HW et al. (2008) Melanogenesis inhibitory compounds from Saussureae Radix. Arch Pharm Res 31:294–299. https://doi.org/10.1007/s12272-001-1154-0
Choodej S, Pudhom K, Mitsunaga T (2018) Inhibition of TNF-α-induced inflammation by sesquiterpene lactones from Saussurea lappa and semi-synthetic analogues. Planta Med 84:329–335. https://doi.org/10.1055/s-0043-120115
Huang H-C, Hsieh W-Y, Niu Y-L, Chang T-M (2012) Inhibition of melanogenesis and antioxidant properties of Magnolia grandiflora L. flower extract. BMC Complement Altern Med 12:1041. https://doi.org/10.1186/1472-6882-12-72
Karioti A, Protopappa A, Megoulas N, Skaltsa H (2007) Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. Bioorg Med Chem 15:2708–2714. https://doi.org/10.1016/j.bmc.2007.01.035
Laskin JD, Piccinini L, Engelhardt DL, Weinstein IB (1982) Control of melanin synthesis and secretion by B16/C3 melanoma cells. J Cell Physiol 113:481–486. https://doi.org/10.1002/jcp.1041130318
Li Y, Xu C, Zhang Q et al. (2005) In vitro anti-Helicobacter pylori action of 30 Chinese herbal medicines used to treat ulcer diseases. J Ethnopharmacol 98:329–333. https://doi.org/10.1016/j.jep.2005.01.020
Ohguchi K, Tanaka T, Ito T et al. (2003) Inhibitory effects of resveratrol derivatives from dipterocarpaceae plants on tyrosinase activity. Biosci Biotechnol Biochem 67:1587–1589. https://doi.org/10.1271/bbb.67.1587
Pandey MM, Rastogi S, Rawat AKS (2007) Saussurea costus: botanical, chemical and pharmacological review of an ayurvedic medicinal plant. J Ethnopharmacol 110:379–390. https://doi.org/10.1016/j.jep.2006.12.033
Rao KS, Babu GV, Ramnareddy YV (2007) Acylated flavone glycosides from the roots of Saussurea lappa and their antifungal activity. Molecules 12:328–344
Rasul A, Parveen S, Ma T (2012) Costunolide: a novel anti-cancer sesquiterpene lactone. Bangladesh J Pharmacol 7:6–13. https://doi.org/10.3329/bjp.v7i1.10066
Riley PA (1997) Melanin. Int J Biochem Cell Biol 29:1235–1239
Thanigaimalai P, Rao EV, Lee K-C et al. (2012) Structure-activity relationship of naphthaldehydethiosemicarbazones in melanogenesis inhibition. Bioorg Med Chem Lett 22:886–889. https://doi.org/10.1016/j.bmcl.2011.12.035
Yamahara J, Kobayashi M, Miki K et al. (1985) Cholagogic and antiulcer effect of saussureae radix and its active components. Chem Pharm Bull 33:1285–1288
Yamauchi K, Mitsunaga T, Batubara I (2014) Synthesis of quercetin glycosides and their melanogenesis stimulatory activity in B16 melanoma cells. Bioorg Med Chem 22:937–944. https://doi.org/10.1016/j.bmc.2013.12.062
Yamauchi K, Mitsunaga T, Itakura Y, Batubara I (2015) Extracellular melanogenesis inhibitory activity and the structure-activity relationships of ugonins from Helminthostachys zeylanica roots. Fitoterapia 104:69–74. https://doi.org/10.1016/j.fitote.2015.05.006
Yang J-L, Wang R, Liu L-L, Shi Y-P (2010) Phytochemicals and biological activities of Saussurea species. J Asian Nat Prod Res 12:162–175. https://doi.org/10.1080/10286020903496455
Zhao F, Xu H, He E-Q et al. (2008) Inhibitory effects of sesquiterpenes from Saussurea lappa on the overproduction of nitric oxide and TNF-α release in LPS-activated macrophages. J Asian Nat Prod Res 10:1045–1053. https://doi.org/10.1080/10286020802274037
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SC greatly acknowledges the MEXT (MONBUKAGAKUSHO) scholarship provided by the Japanese Government for conducting research at the United Graduate School of Agricultural Science, Gifu University.
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Choodej, S., Pudhom, K., Yamauchi, K. et al. Inhibition of melanin production by sesquiterpene lactones from Saussurea lappa and their analogues. Med Chem Res 28, 857–862 (2019). https://doi.org/10.1007/s00044-019-02338-0
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DOI: https://doi.org/10.1007/s00044-019-02338-0