Abstract
Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, anti-inflammatory, antiallergic, bone remodeling, neuroprotective, hair growth promoting, anticancer, and antidiabetic properties. Many of these bioactivities are supported by mechanistic details, such as the modulation of various intracellular signaling pathways involved in precipitating tissue inflammation, tumor growth and progression, bone loss, and neurodegeneration. The key molecular targets of costunolide include, but are not limited to, intracellular kinases, such as mitogen-activated protein kinases, Akt kinase, telomerase, cyclins and cyclin-dependent kinases, and redox-regulated transcription factors, such as nuclear factor-kappaB, signal transducer and activator of transcription, activator protein-1. The compound also diminished the production and/expression of proinflammatory mediators, such as cyclooxygenase-2, inducible nitric oxide synthase, nitric oxide, prostaglandins, and cytokines. This review provides an overview of the therapeutic potential of costunolide in the management of various diseases and their underlying mechanisms.
Highlights
Drug development from natural sources, from plants, has long been the mainstay in medical management of various human ailments
Pae and colleagues [21] have reported that the production of tumor necrosis factor alpha (TNF-α) and IL-6 in LPS-stimulated RAW264.7 cells was decreased by treatment with costunolide, which increased the expression and activity of Heme oxygenase-1 (HO-1) via enhanced nuclear accumulation of a redox-regulated transcription factor, nuclear factor erythroidrelated factor-2 (Nrf2)
Another study showed that costunolide-induced G2/M cell cycle arrest in MDA-MB-231 cells, which was mediated through the inhibition of cell division cycle protein 2 homolog (Cdc2) and cyclin B1, and the elevation of p21WAF1 expression was independent of p53 activation [56]
Summary
Drug development from natural sources, from plants, has long been the mainstay in medical management of various human ailments. One of the major classes of bioactive phytochemicals is the terpenoids, which are widely present in various plants and marine organisms, and are being examined for developing new antifungal, anticancer, anti-inflammatory, and antiviral agents [2]. The largest group of sesquiterpene lactones is germacranolides [3], which possesses a 10,5-ring structure and is present in several plant families. Costunolide, a colorless crystalline powder with a molecular formula of C15H20O2 and a molecular weight of 232.318 g/mol, is a well-known sesquiterpene lactone in the germacranolides series. Sci. 2018, 19, x FOR PEER REVIEW pfSbmtraamhbcbtfhrhueantnyriaeoorsoeoeotndlxdumeuaicrrandaeaearacnrtcohuttehbretpttychccucaayicey,eeovdaehecldrαuysripnrt[asatrbt5tu-torylwoluimdil]ooticgncyc.essioxis,eohoTtrphdpyfcht(islychoyheoSnelatcoidtviutdcysatgocshesettruelnrsntueedorloiostuaoonnetuncsgfccilnvpueotfaionyieurrdo-dirmsllosnaγoes,eitletlcdwiiauam-eeu.indheltdenniaPnlgilena,iaeocltovdsavue.ptcnfl(raioeioaiploFsstndarrnigaicsuiilmargmegeutoyelluC,funursi[eehnnwhet6ilrdesdhnaydoe]gyrh.rirgdaalodoakeiim1Tttrctdxtreeoe)heyhohsee)sndbelugiecdcfsrrahgmehaoitobolrntehnaarpaousimoxarnonlftruboamattuaiaecihlsphaunocrtaeemoenuyittgcnozinr[drtdhvsbsfia5eoonwrpio]pvoittcofd.gtnehyieaafsctcrcduerrthoTuaooihfibnstesouchfsgtieosttcthunicuii.uwxdsrsoeoscpnyeno[entshrc5pcoolivolet,yioia]erutleclcv.sianneotihlnddeitnnoStataeedoeeepdtltcwirib.rliniemnmiapufdydetsPrlsihrce,eooes,asotheancmiuuutrdiearahattslprnct.uiivtfeaymahahrmvdcrillo,lnyaleeeeyoyeshαsbrdgrdntpd,ily-yiroydmceiytdccaauihcaiolonrthtetlshrosegstgtyesotyetdhgrouuedurofdmyetimnrtnuhnrnludhoeoeoopegamsorcncllgriotoiiuohneiidedausnopfb-agnreteγgtnlvlnuiar,aez-hcaa(intfloniosFiarocnboiofmtisicetcogolgntsctluisusuolnudopfustnsndusreghoieletnoeapsneefcu[,lgrnir6ci1anewrowdte]r)ocesoi.tereoht.hcenladTiieiniisio[ftdncohcin5oeanthhsexae]ssrtl,,
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