In vitro and in silico studies of 7'',8''-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors.

Excessive macrophage activation induces the release of high levels of inflammatory mediators which not only amplify chronic inflammation and degenerative diseases but also exacerbate fever and retard wound healing. To identify anti-inflammatory molecules, we examined Carallia brachiata-a medicinal terrestrial plant from Rhizophoraceae. Furofuran lignans [(-)-(7''R,8''S)-buddlenol D (1) and (-)-(7''S,8''S)-buddlenol D (2)] isolated from the stem and bark inhibited nitric oxide (half maximal inhibitory concentration (IC50): 9.25 ± 2.69 and 8.43 ± 1.20 micromolar for 1 and 2, respectively) and prostaglandin E2 (IC50: 6.15 ± 0.39 and 5.70 ± 0.97 micromolar for 1 and 2, respectively) productions in lipopolysaccharide-induced RAW264.7 cells. From western blotting, 1 and 2 suppressed LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner (0.3-30 micromolar). Moreover, analysis of the mitogen-activated protein kinase (MAPK) signaling pathway showed decreased p38 phosphorylation levels in 1- and 2-treated cells, while phosphorylated ERK1/2 and JNK levels were unaffected. This discovery agreed with in silico studies which suggested 1 and 2 bound to the ATP-binding site in p38-alpha MAPK based on predicted binding affinity and intermolecular interaction docking. In summary, 7'',8''-buddlenol D epimers demonstrated anti-inflammatory activities via p38 MAPK inhibition and may be used as viable anti-inflammatory therapies.

Bioactivities of Karanda (Carissa carandas Linn.) fruit extracts for novel cosmeceutical applications.

The aim of this research was to determine the total phenolic content (TPC), antioxidation, antiaging, and antibacterial activities of Carissa carandas Linn., and aims at the novel plant sources which is utilized for their cosmeceutical applications. The two conditions (fresh and dried) and three stages (unripe, ripe, and fully ripe) of C. carandas were extracted by ethanolic maceration. Folin-Ciocalteu assay was used for determining the TPC. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays were used for estimating antioxidant activity. The inhibitory tyrosinase activities were measured using the modified dopachrome assay. Antiaging was evaluated by inhibition of collagenase and elastase, and antibacterial activities. The result of six extracts from C. carandas showed that the highest phenolic content and elastase inhibition of the fresh fruit in fully ripe stage were 100.31 ± 2.64 mg GAE/g extract and 14.11% ± 0.95%, respectively. The fresh fruit in the unripe stage showed that the strongest percentage of DPPH IC50 and collagenase inhibitory activity were 29.11 ± 0.23 µg/mL and 85.94% ± 2.21%, respectively. The ethanolic extract of unripe dried fruit exhibited the highest antioxidant activity in the of ABTS assay, with an IC50 of 0.17 ± 0.01 µg/mL. The MBC displayed the dried fruit ripe stage anti Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus strains were 25.0, 25.0, and 16.25 mg/mL, respectively. The fresh fruit in the ripe stage showed that the strongest inhibition tyrosinase was 93.88% ± 5.64%. The conclusion of this research indicates that the fresh fruit of C. carandas fruit extracts has high potential as a novel cosmeceuticals' applications to antiaging and skin whitening. The dried fruit in ripe stage extract has the most effective ingredient for antiacne products.