A novel psoralen derivative-MPFC enhances melanogenesis via activation of p38 MAPK and PKA signaling pathways in B16 cells.

As an active compound, psoralen is present in various Chinese herbal medicines and has exhibited significant activity in skin disease treatment. Its derivative 8-methoxypsoralan (8-MOP) is the most commonly used drug to induce repigmentation of vitiligo. In our previous screening assays, 4-methyl-6-phenyl-2H-furo[3,2-g]chromen-2-one (MPFC), a psoralen derivative, was identified as more effective tyrosinase and melanin activator than the positive control 8-MOP in consideration of low doses, as well as low toxicity. The overall purpose of this study was to characterize the melanogenic effect and mechanisms of MPFC in B16 cells. The melanin biosynthesis effects of MPFC were determined by examination of cellular melanin contents, tyrosinase activity assay, cyclic adenosinemonophosphate (cAMP) assay, and western blotting of MPFC-stimulated B16 mouse melanoma cells. Our results showed that MPFC enhanced both melanin synthesis and tyrosinase activity in a concentration-dependent manner as well as significantly activated the expression of melanogenic proteins such as tyrosinase, tyrosinase-related protein-1 and tyrosinase-related protein-2. Western blot analysis showed that MPFC increased the phosphorylation of p38 mitogen-activated protein kinase and cAMP response element-binding protein (CREB) as well as the expression of microphthalmia-associated transcription factor (MITF). Moreover, MPFC stimulated intracellular cAMP levels and induced tyrosinase activity and melanin synthesis were attenuated by H89, a protein kinase A inhibitor. These results indicated that MPFC-mediated activation of the p38 MAPK and the protein kinase A (PKA) pathway may shed light on a novel approach for an effective therapy for vitiligo.

New coumarin from the roots of Prangos pabularia.

The new coumarin 1, yuganin A (7-methoxy-8-((1S,2S)-1,2,3-trihydroxy-3-methylbutyl)-2H-chromen-2-one) along with nine known coumarins, heraclenol 3'-O-ß-D-glucopyranoside (2), oxypeucedanin hydrate 3'-O-ß-D-glucopyranoside (3), heraclenol (4), oxypeucedanin hydrate (5), osthole (6), oxypeucedanin (7), heraclenin (8), isoimperatorin (9), imperatorin (10) and the disaccharide sucrose (11), have been isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by spectroscopic means, especially, UV, HR-ESIMS, and 1D and 2D NMR spectroscopy. Furthermore, the anti-melanogenic effect of yuganin A and its inhibitory effect on B16 cells were evaluated. Yuganin A may be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3ß/ß-Catenin Signaling Pathways.

Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one (PMPP) was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study. Further investigations revealed that Akt and GSK3ß were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents.

Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium collinum Root Extracts-Computational and Experimental Investigations.

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum. The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC50 values of 0.10 µg/mL and 0.09 µg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of G. collinum, led to the isolation of ten pure compounds identified as 3,3',4,4'-tetra-O-methylellagic acid (1), 3,3'-di-O-methylellagic acid (2), quercetin (3), caffeic acid (4), (+)-catechin (5), (-)-epicatechin (6), (-)-epigallocatechin (7), gallic acid (8), ß-sitosterol-3-O-ß-d-glucopyranoside (9), and corilagin (10). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC50 values below 0.9 µg/mL, more effective than the positive control (1.46 µg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and ß-sitosterol-3-O-ß-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of G. collinum is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from G. collinum shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of G. collinum.