Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities.

The skin containing melanin pigment acts as a protective barrier and counteracts the UVR and other environmental stressors to maintain or restore disrupted cutaneous homeostasis. The production of melanin pigment is dependent on tyrosine levels. L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) can serve both as a substrates and intermediates of melanin synthetic pathway and as inducers and positive regulators of melanogenesis. The biosynthesis of melanin is stimulated upon exposure to UVR, which can also stimulate local production of hormonal factors, which can stimulate melanoma development by altering the chemical properties of eu- and pheomelanin. The process of melanogenesis can be altered by several pathways. One involves activation of POMC, with the production of POMC peptides including MSH and ACTH, which increase intracellular cAMP levels, which activates the MITF, and helps to stimulate tyrosinase (TYR) expression and activity. Defects in OCA1 to 4 affects melanogenic activity via posttranslational modifications resulting in proteasomal degradation and reducing pigmentation. Further, altering, the MITF factor, helps to regulate the expression of MRGE in melanoma, and helps to increase the TYR glycosylation in ER. CRH stimulates POMC peptides that regulate melanogenesis and also by itself can stimulate melanogenesis. The POMC, P53, ACTH, MSH, MC1R, MITF, and 6-BH4 are found to be important regulators for pigmentation. Melanogenesis can affect melanoma behaviour and inhibit immune responses. Therefore, we reviewed natural products that would alter melanin production. Our special focus was on targeting melanin synthesis and TYR enzyme activity to inhibit melanogenesis as an adjuvant therapy of melanotic melanoma. Furthermore, this review also outlines the current updated pharmacological studies targeting the TYR enzyme from natural sources and its consequential effects on melanin production.

Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues.

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca2+ -dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca2+ -dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety.

Traditional uses, phytochemistry, and pharmacology of genus Vitex (Lamiaceae).

Vitex, the genus of the family Lamiaceae, comprises of about 230 species mostly distributed in the warm regions of Europe and temperate regions of Asia. Several Vitex species have been used as folk medicine in different countries for the treatment of various kinds of diseases and ailments. The main aim of this review is to collect and analyze the scientific information available about the Vitex species regarding their chemical constituents and pharmacological activities. The phytochemical investigation of various Vitex species has resulted in the isolation of about 556 chemical constituents belong to various chemical category viz. iridoids, diterpenoids, triterpenoids, flavonoids, lignans, sesquiterpenoids, monoterpenoids, ecdysteroids, and others. The crude extracts of different Vitex species as well as pure phytochemicals exhibited a wide spectrum of in-vitro and in-vivo pharmacological activities. In the present review, the scientific literature data on the ethnopharmacological, phytochemical, and pharmacological investigations on the genus Vitex are summarized. More attention should be given in future research to evaluate the pharmacological potential with detailed mechanism of actions for the pure compounds, extracts of plants from this genus. Moreover, their clinical study is needed to justify their use in modern medicine and to further exploring this genus for new drug discovery.