Antioxidant Potential of Artemisia capillaris, Portulaca oleracea, and Prunella vulgaris Extracts for Biofabrication of Gold Nanoparticles and Cytotoxicity Assessment.

Three aqueous plant extracts (Artemisia capillaris, Portulaca oleracea, and Prunella vulgaris) were selected for the biofabrication of gold nanoparticles. The antioxidant activities (i.e., free radical scavenging activity, total phenolic content, and reducing power) of the extracts and how these activities affected the biofabrication of gold nanoparticles were investigated. P. vulgaris exerted the highest antioxidant activity, followed by A. capillaris and then P. oleracea. P. vulgaris was the most efficient reducing agent in the biofabrication process. Gold nanoparticles biofabricated by P. vulgaris (PV-AuNPs) had a maximum surface plasmon resonance of 530 nm with diverse shapes. High-resolution X-ray diffraction analysis showed that the PV-AuNPs had a face-centered cubic structure. The reaction yield was estimated to be 99.3% by inductively coupled plasma optical emission spectroscopy. The hydrodynamic size was determined to be 45 ± 2 nm with a zeta potential of - 13.99 mV. The PV-AuNPs exerted a dose-dependent antioxidant activity. Remarkably, the highest cytotoxicity of the PV-AuNPs was observed against human colorectal adenocarcinoma cells in the absence of fetal bovine serum, while for human pancreas ductal adenocarcinoma cells, the highest cytotoxicity was observed in the presence of fetal bovine serum. This result demonstrates that P. vulgaris extract was an efficient reducing agent for biofabrication of gold nanoparticles exerting cytotoxicity against cancer cells.

Evaluation of Antimelanogenic Activity and Mechanism of Galangin in Silico and in Vivo.

Abnormal pigmentation owing to excessive melanin synthesis can result in serious problems such as freckles, age-spots, and melanoma. Tyrosinase inhibitors have been an interesting target for the treatment of hyperpigmentation because tyrosinase is the rate-limiting enzyme in melanin synthesis. The screening for strong tyrosinase inhibitors led to the finding of the flavonoid galangin, which showed notable inhibitory effects on mushroom tyrosinase. The IC50 value of galangin (3.55±0.39 µM) was lower than that of kojic acid (48.55±1.79 µM), which was used as a positive control. In silico docking simulation and mechanistic studies demonstrated that galangin interacted with the catalytic sites of tyrosinase and competed with tyrosine. In B16F10 melanoma cells stimulated with α-melanocyte stimulating hormone, galangin inhibited tyrosinase activity as well as melanin production. Although high doses of galangin were cytotoxic, no cytotoxic effects were observed at low doses. In addition, the in vivo efficacy of galangin was evaluated in HRM2 melanin-possessing hairless mice. As measured by the skin-whitening index and melanin staining, repeated UVB exposure increased skin melanin synthesis. Galangin application significantly reduced melanogenesis induced by UVB exposure. Collectively, our data indicates that galangin shows strong tyrosinase inhibition activity, which suggests that it may be an effective skin-whitening agent.

Synthesis of novel azo-resveratrol, azo-oxyresveratrol and their derivatives as potent tyrosinase inhibitors.

Ten azo compounds including azo-resveratrol (5) and azo-oxyresveratrol (9) were synthesized using a modified Curtius rearrangement and diazotization followed by coupling reactions with various phenolic analogs. All synthesized compounds were evaluated for their mushroom tyrosinase inhibitory activity. Compounds 4 and 5 exhibited high tyrosinase inhibitory activity (56.25% and 72.75% at 50 µM, respectively). The results of mushroom tyrosinase inhibition assays indicate that the 4-hydroxyphenyl moiety is essential for high inhibition and that 3,5-dihydroxyphenyl and 3,5-dimethoxyphenyl derivatives are better for tyrosinase inhibition than 2,5-dimethoxyphenyl derivatives. Particularly, introduction of hydroxyl or methoxy group into the 4-hydroxyphenyl moiety diminished or significantly reduced mushroom tryosinase inhibition. Among the synthesized azo compounds, azo-resveratrol (5) showed the most potent mushroom tyrosinase inhibition with an IC(50) value of IC(50)=36.28 ± 0.72 µM, comparable to that of resveratrol, a well-known tyrosinase inhibitor.

Anticancer effects of the MHY218 novel hydroxamic acid-derived histone deacetylase inhibitor in human ovarian cancer cells.

To investigate the anticancer effects of the novel hydroxamic acid-derived histone deacetylase (HDAC) inhibitor MHY218, its efficacy was compared to that of suberoylanilide hydroxamic acid (SAHA) in human ovarian cancer cells. The anticancer effects of MHY218 on cell viability, cell cycle regulation and apoptosis were investigated. In addition, MHY218 or SAHA was administered for 28 days in a tumor carcinomatosis model with SKOV-3 cells. MHY218 significantly reduced the expression of HDAC4 and HDAC7 in SKOV-3 cells. Similarly, MHY218 also inhibited total HDAC, HDAC1, HDAC4 and HDAC7 enzyme activity in a concentration-dependent manner. The anticancer effect of MHY218 (IC50, 3.2 microM) was more potent than SAHA (IC50, 3.9 microM) in suppressing the SKOV-3 cell viability. Moreover, MHY218 markedly increased expression of p21WAF1/CIP1, which acts as a cell cycle inhibitor. Cell cycle analysis showed that the high dose (5 microM) of MHY218 significantly increased the proportion of cells in the G2/M phase. In particular, MHY218 and SAHA significantly increased the sub-G1 population and the number of TUNEL-positive apoptotic cells compared with those in the untreated control. These results were confirmed by analysis of poly-ADP ribose polymerase (PARP), where MHY218 and SAHA increased the level of an 85-kDa fragment resulting from PARP cleavage as well as caspase-3 activity. Likewise, MHY218-induced apoptosis through caspase-3 activation was confirmed by the increase in the release of cytochrome c and Bax/Bcl-2 ratio. In an in vivo tumor carcinomatosis model, the growth of transplanted SKOV-3 cells was inhibited by 71% after treatment with MHY218 (10 mg/kg), whereas SAHA (25 mg/kg) suppressed growth by 48%. These results indicate that MHY218 is a potent HDAC inhibitor that targets regulating multiple aspects of cancer cell death and might have preclinical value in ovarian cancer chemotherapy, warranting further investigation.