Annona squamosa L. leaves inhibit alpha‐melanocyte‐stimulating hormone (α‐MSH) stimulated melanogenesis via p38 signaling pathway in B16F10 melanoma cells

Abstract

Background Annona squamosa L. is a branched shrub, which is believed to be originated from the America and West Indies. Fruits of this plant are commonly known as custard apple, sugar apple, or sweetsops. A number of studies have proven a range of biological activities associated with various parts of A. squamosa. Aims The main aim of the present investigation was to evaluate potential inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis and its underlying mechanisms in B16F10 murine melanoma cells. Methods Inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis were primarily assessed by determining melanin contents. Effects of ALE on tyrosinase activity and the expression of proteins associated with melanogenesis were then determined. GC–MS analysis was carried out to identify the phytochemical profile of A. squamosa leaf extract. Results Antimelanogenic effects of ALE were found to exert through the inhibition of melanocyte inducing transcription factor (MITF) and activation of p38. GC‐MS analysis identified ent‐kaur‐16‐en‐19‐ol, 18‐oxokauran‐17‐yl acetate, and β‐sitosterol as major phytochemicals. Conclusion To our knowledge, this is the first study on the antimelanogenic effects of A. squamosa leaves, rationalizing the use A. squamosa leaf extract as a natural depigmentation agent for the treatment of skin diseases and the development of cosmetic products with enhanced skin‐lightening capabilities.

The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds

“…Extracts derived from Artocarpus communis heartwood [ 145 ], Phyla nodiflora aerial part [ 146 ] and Oenothera laciniata [ 107 ] were found to modulate ERK and JNK phosphorylation, resulting in anti-melanogenic effects. Similar results were obtained for kaempferol-7-O-β-D-glucuronide and tilianin, a flavonoid glycoside isolated from the aerial parts of Cryptotaenia japonica [ 126 ]. Penthorum chinense whole plant extract [ 147 ], Kaempferia galanga whole plant extract [ 148 ] and Phragmites communis leaf extract [ 149 ] were found to modulate both p38 and JNK phosphorylation, followed by reduced melanin production, in B16 melanoma cells.…”

“…P38 positively regulates melanin synthesis in the B16 melanoma cell line [ 2 ]. In this line, Polygonum multiflorum root extract was found to up-regulate p38 phosphorylation, thus activating melanogenesis [ 124 ]; the same effects were observed for Vernonia anthelmintica seed extract [ 125 ] and Annona squamosa leaf extract [ 126 ]. In contrast, treatment with Cuscuta japonica seed extract [ 127 ], Morinda citrifolia fruit and leaf extract [ 128 ], Dendropanax morbiferus leaf extract [ 95 ] or Lotus seedpod extract [ 96 ] were found to downregulate p38 phosphorylation and thus inhibit melanogenesis.…”

Identification of Sitogluside as a Potential Skin-Pigmentation-Reducing Agent through Network Pharmacology

“…After the above screening process, we found that four TCMs in the top TCMs contained sitogluside and β -sitosterol. β -Sitosterol has been reported to inhibit alpha-melanocyte-stimulating hormone ( α -MSH), stimulating melanogenesis via the p38 signaling pathway in B16F10 melanoma cells [ 43 ]. However, the antipigmentation effects of sitogluside and its specific mechanism have not been reported.…”

Novel Antiviral Investigation of Annona squamosa Leaf Extract against the Dengue Virus Type-2: In vitro Study

“…Those compounds demonstrated the various therapeutic properties, such as an anticancer, antioxidant, antidiabetic, antimicrobial, antiviral, anti-inflammatory, and antimelanogenic activities. 6,10,12,13,14,15 However, there are no reports regarding Annona squamosa leaf extract (ASLE) activity as an antiviral effect against DENV. Therefore, we aimed to investigate the activity of ASLE against DENV-2 isolated from Surabaya, Indonesia in 2013.…”