Inhibition of UVA Damage on Human Skin Dermis Fibroblasts by the Isoflavonoid Intermediate Deoxybenzoin-3A.

Ultraviolet rays are the main cause of skin aging. Isoflavone structures are good anti-ultraviolet natural compounds and have an especially strong anti-ultraviolet B (UVB) effect. However, the anti-ultraviolet A (UVA) effect of isoflavones is more controversial. Therefore, this study aims to discover which isoflavone analogue possesses a strong anti-ultraviolet A. We found the isoflavonoid intermediate deoxybenzoin-3A (DOB-3A) to be a similar isoflavone structural compound with strong anti-ultraviolet A effects. Ultraviolet rays with a wavelength of 350 nm are used to irradiate the fibroblasts of the human skin. Western blot, flow cytometry, and transmission electron microscope analyses were used to explore its anti-ultraviolet A mechanism. We established the results that DOB-3A (1) reduced the death of fibroblasts caused by ultraviolet A, (2) avoided the damage to the organelles and structures after UVA irradiation, (3) inhibited the generation of intracellular reactive oxygen species (ROS) and hydrogen peroxide-induced damage, and (4) decreased the phosphorylation of mitogen-activated protein kinases (MAPK) caused by UVA. Based on the above findings, DOB-3A is a very good anti-ultraviolet A isoflavone-related structure. Because it is simple to synthesize and has good effects, DOB-3A is a suitable anti-ultraviolet A product with an isoflavone structure. Moreover, DOB-3A's structure provides a reference for the synthesis of anti-UVA isoflavones.

A new anthraquinone glycoside from Rhamnus nakaharai and anti-tyrosinase effect of 6-methoxysorigenin.

In continual study on the heartwood of Rhamnus nakaharai, a new alaternin-8-O-glucoside, namely 1,2,6,8-tetrahydroxy-3-methylanthraquinone-8-O-ß-glucopyranoside (1), together with some known compounds were further isolated and characterised by 1-D, 2-D NMR and other spectral evidences. The free radical scavenging and antityrosinase activities of the isolates, including alaternin (1a), emodin (2a), emodin-8-O-ß-glucopyranoside (2), 6-methoxysorigenin-8-O-ß-glucopyranoside (3) and 6-methoxysorigenin (3a) were tested. Alaternin (1a) exhibited to be mild DPPH radical scavenger with half as potent as vitamin C, while both alaternin (1a) and emodin-8-O-ß-glucopyranoside (2) exhibited stronger SOD-like activity than that of BHA. 6-Methoxysorigenin (3a), a reported potential antioxidant, and its 8-O-glucoside (3) both performed significant inhibitory effect on mushroom tyrosinase with about twice as potent as kojic acid, the positive control.

Chemical constituents derived from Artocarpus xanthocarpus as inhibitors of melanin biosynthesis.

Twenty-four compounds, including the previously unknown artoxanthocarpuone A, artoxanthocarpuone B, hydroxylakoochin A, methoxylakoochin A, epoxylakoochin A, and artoxanthol, were isolated and characterized spectroscopically. Among them, artoxanthol is stilbene oligomer presumably constructed in a 5,11,12-triphenyl hexahydrochrysene scaffold by a Diels-Alder type of reaction, for which a biosynthetic pathway is proposed. Artoxanthol, alboctalol, steppogenin, norartocarpetin, resveratrol, oxyresveratrol, and chlorophorin potently inhibited mushroom tyrosinase activity with IC50 values from 0.9 to 5.7 µM that were all far stronger than the positive controls. Artoxanthocarpuone A, artoxanthocarpuone B, methoxylakoochin A, lakoochin A, cudraflavone C, artonin A, resveratrol, and chlorophorin reduced tyrosinase activity and inhibited α-melanocyte-stimulating hormone-induced melanin production in B16F10 melanoma cells without affecting cell proliferation. Collectively, the results suggest that the constituents of Artocarpus xanthocarpus have potential to be used as depigmentation agents.

Free-Radical-Scavenging, Antityrosinase, and Cellular Melanogenesis Inhibitory Activities of Synthetic Isoflavones.

In this study, we examined the potential of synthetic isoflavones for application in cosmeceuticals. Twenty-five isoflavones were synthesized and their capacities of free-radical-scavenging and mushroom tyrosinase inhibition, as well as their impact on cell viability of B16F10 murine melanoma cells and HaCaT human keratinocytes were evaluated. Isoflavones that showed significant mushroom tyrosinase inhibitory activities were further studied on reduction of cellular melanin formation and antityrosinase activities in B16F10 melanocytes in vitro. Among the isoflavones tested, 6-hydroxydaidzein (2) was the strongest scavenger of both ABTS(.+) and DPPH(.) radicals with SC50 values of 11.3 ± 0.3 and 9.4 ± 0.1 µM, respectively. Texasin (20) exhibited the most potent inhibition of mushroom tyrosinase (IC50 14.9 ± 4.5 µM), whereas retusin (17) showed the most efficient inhibition both of cellular melanin formation and antityrosinase activity in B16F10 melanocytes, respectively. In summary, both retusin (17) and texasin (20) exhibited potent free-radical-scavenging capacities as well as efficient inhibition of cellular melanogenesis, suggesting that they are valuable hit compounds with potential for advanced cosmeceutical development.

Effects of Grifola frondosa non-polar bioactive components on high-fat diet fed and streptozotocin-induced hyperglycemic mice.

CONTEXT: Consumption of medicinal mushrooms for disease prevention and maintaining health has a very long history in Asia. Grifola frondosa (Fr) S.F. Gray (GF) (Meripilaceae) is a medicinal fungus popularly used for enhancing immune systems, lowering blood glucose, and improving spleen, stomach, and nerve functions. OBJECTIVE: This study examines the hypoglycemic effects of GF in vitro and in vivo, and analyzes the chemical profiles of its bioactive components. MATERIALS AND METHODS: In vitro hypoglycemic effects of GF was evaluated enzymatically using α-amylase and α-glucosidase inhibition assays, whereas in vivo study was conducted on high-fat diet fed and streptozotocin (HFD + STZ)-induced hyperglycemic mice. GC-MS was used to determine the chemical profiles of bioactive components. RESULTS: The non-polar fraction of GF exhibited a stronger anti-α-glucosidase activity (IC50: 0.0332 mg/ml) than acarbose, but its anti-α-amylase activity (IC50: 0.671 mg/ml) was weaker. Oral administration of GF at 600 mg/kg (GF600) significantly lowered the blood glucose, HbA1c, average blood glucose, and serum total cholesterol levels in hyperglycemic mice. Although GF was found to contain mainly oleic acid and linoleic acid, their levels in the fungus were low, suggesting that the effects of GF on HFD + STZ-induced hyperglycemic mice could be due to factors other than these fatty acids. CONCLUSION: These results conclude that GF possesses anti-α-glucosidase activity, and hypoglycemic effect in HFD + STZ-induced hyperglycemic mice.

Inhibitory potential of Grifola frondosa bioactive fractions on α-amylase and α-glucosidase for management of hyperglycemia.

This study examined the inhibitory effects of Grifola frondosa (GF), a medicinal mushroom popularly consumed in traditional medicine and health food, on digestive enzymes related to type 2 diabetes; chemical profiles and inhibitory kinetics of its bioactive fractions were also analyzed. Results showed that all GF extracts showed weak anti-α-amylase activity; however, strong anti-α-glucosidase activity was noted on GF n-hexane extract (GF-H). Further fractionation confirmed that compared with acarbose (a commercial α-glucosidase inhibitor), the nonpolar fraction of GF possessed a stronger anti-α-glucosidase activity but a weaker anti-α-amylase activity. These activities were not derived from ergosterol and ergosterol peroxide, two major compounds of this fraction. The inhibitory kinetics of GF-H on α-glucosidase was competitive inhibition. GF-H was as good as acarbose in inhibiting the starch digestion in vitro. Oleic acid and linoleic acid could be the major active constituents that have contributed to the potency of GF in inhibiting α-glucosidase activity.

A novel monoterpene-stilbene adduct with a 4,4-dimethyl-2,3-diphenylchromane skeleton from Artocarpus xanthocarpus.

Artoxanthochromane (1), a DielsAlder-type conjugation product of 4-isopropenylresorcinol and oxyresveratrol, was isolated from the heartwood of Artocarpus xanthocarpus and characterized. The structure of 1 was elucidated as 2-(2,4-dihydroxyphenyl)-3-(3,5-dihydroxyphenyl)-7-hydroxy-4,4-dimethylchromane by 1D- and 2D-NMR spectroscopy, and other spectral evidences. A plausible metabolic mechanism was proposed to illustrate the biosynthetic pathway of artoxanthochromane. This compound exhibited mild mushroom tyrosinase inhibitory, and weak free radical-scavenging activities on ABTS(+.) and superoxide anion (O$\rm{{_{2}^{-{^\cdot} }}}$) free radicals.

Immunomodulatory activities of medicinal mushroom Grifola frondosa extract and its bioactive constituent.

Grifola frondosa (GF), a high value medicinal mushroom in China and Japan, is popularly consumed as traditional medicines and health foods, especially for enhancing immune functions. In this study, our aim was to examine the immunomodulatory activities of GF and its bioactive compound ergosterol peroxide (EPO) in lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. At low concentrations, EPO but not other extracts showed a full protection against LPS-induced cell toxicity. EPO significantly blocked MyD88 and VCAM-1 expression, and cytokine (IL-1ß, IL-6 and TNF-α) production in LPS-stimulated cells. It also effectively inhibited NF-κB activation, which was further confirmed with siRNA treatment. These results conclude that EPO may play an important role in the immunomodulatory activity of GF through inhibiting the production of pro-inflammatory mediators and activation of NF-κB signaling pathway.

Synthesis and structure-activity relationship study of deoxybenzoins on relaxing effects of porcine coronary artery.

Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to be developed as food preservatives and cosmetic ingredients. To explore the potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary arterial contraction. The results revealed deoxybenzoins are significant inhibitors of KCl-induced arterial contraction. Among those synthesized, two-thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing contracted artery including 2,4-dihydroxydeoxybenzoin with EC50=3.30 µM (Emax=100%, n=7) and 2,4-dihydroxy-4'-methoxydeoxybenzoin EC50=3.70 µM (Emax=100%, n=5). Deoxybenzoins displayed an endothelium-dependent relaxing manner on the contracted artery; the contractile responses of neither endothelium denuded nor L-NAME deactivated rings were inhibited. The structure-activity relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4-dihydroxylated deoxybenzoins presented a potential vascular relaxing pharmacophore, with favoring substitution on ring B in the order of H≥p-OMe>p-OH>o-OMe>m,p-diOMe≥m-OMe.

Potential antioxidants and tyrosinase inhibitors from synthetic polyphenolic deoxybenzoins.

Deoxybenzoins (DOBs) are one-pot synthetic precursors of isoflavones with feature analogous to those beneficial polyphenols such as resveratrol (stilbene) and phloretin (dihydrochalcone). In this study, seventeen polyphenolic DOBs were synthesized and evaluated by various antioxidant assays and tyrosinase inhibitory effect in vitro. Results displayed that these DOBs are powerful antioxidants; for example, 2,3,4-trihydroxy-3',4'-dimethoxydeoxybenzoin possesses an excellent anti-lipid peroxidation activity (IC(50)=0.72+/-0.16 microM), whilst 2,4,4',5-tetrahydroxydeoxybenzoin showed good DPPH radical scavenging activity (IC(50)=0.69+/-0.04 microM), which were better than Trolox and vitamin C. Besides exhibiting a weak metal chelating effect, these DOBs were effective in scavenging ABTS(+) and superoxide anion (O2-) radicals. DOBs also exhibited potent mushroom tyrosinase inhibitory activity; for example 2,3,4'-trihydroxy-4-methoxydeoxybenzoin displayed stable and significant inhibitory effect on tyrosinase activity, with IC(50) values 43.37, 43.10 and 46.10 microM at incubation intervals of 0.5, 1.5, and 2.5h, respectively. These results suggest that, with the advantage of being readily synthesizable small molecules, DOBs can be potentially developed into clinical and industrial antioxidants.