UVB exposure causes DNA mutation and ROS generation, which lead to skin photoaging, skin wrinkling, skin sagging, and uneven skin pigmentation. ROS activate the NF-κB and MAPK signaling pathways leading to production of inflammatory molecules such as COX-2, collagen-degrading proteins such as matrix metalloproteinases (MMPs), and moisture-deficiency-related proteins such as hyaluronidases (HYALs). UVB exposure also induces irregular skin pigmentation though melanin overproduction, related to CREB transcription factor activity and transcription of melanogenesis genes. Here, we demonstrate that Chrysophyllum lucentifolium methanol extract (Cl-ME) has antioxidant activity; it dose-dependently decreased the expression of COX-2, MMP-1, MMP-9, HYAL-1, and HYAL-4 by downregulating the NF-κB (IKKα/β, IκBα) and MAPK (ERK, JNK, and p38) pathways and increased the expression of Col1a1, which encodes a protein important for maintaining skin elasticity. Cl-ME also showed promising antimelanogenic activity by decreasing the expression of CREB, a transcription factor, which in turn inhibited the expression of genes encoding tyrosinase, MITF, TYRP1, and TYRP2. In summary, a methanol extract of C. lucentifolium exhibited antiphotoaging and antimelanogenic activity and could be useful in the cosmeceutical industry.

Ultraviolet (UV) irradiation induces ROS production, which activates activator protein (AP)-1 and nuclear factor (NF)-κB signaling and downstream molecules, ultimately triggering the generation of matrix metalloproteinases (MMPs) and degradation of collagen. The aim of this study was to investigate the protective effect of methanol extract from Malus baccata (L.) Borkh (Mb-ME) against aging. DPPH and ABTS assays showed that Mb-ME had a significant antioxidant capacity. Flow cytometry results indicated that Mb-ME attenuated UVB and H₂O₂-stimulated apoptosis and reactive oxygen species (ROS) generation. RT-PCR analysis in HaCaT and HDF cells suggested that Mb-ME treatment blocked the expression of MMPs, COX-2, IL-1β, IL-6, HYALs, and p53 while promoting the levels of TGM1, FLG, HASs, Sirt1, and Col1A1. Mechanically, Mb-ME inhibited the phosphorylation of MAP kinases and NF-κB signaling. Overall, these results strongly suggest that Mb-ME can be developed as an antiaging therapy.

Possessing a variety of medicinal functions, Olea europaea L. is widely cultivated across the world. However, the anti-inflammatory mechanism of Olea europaea is not yet fully elucidated. In this study, how the methanol extract of the leaves of Olea europaea (Oe-ME) can suppress in vitro inflammatory responses was examined in terms of the identification of the target protein. RAW264.7 and HEK293T cells were used to study macrophage-mediated inflammatory responses and to validate the target protein using PCR, immunoblotting, nuclear fraction, overexpression, and cellular thermal shift assay (CETSA) under fixed conditions. Oe-ME treatment inhibited the mRNA expression levels of cyclooxygenase (COX)-2, matrix metallopeptidase (MMP)-9, and intercellular adhesion molecule-1 (ICAM-1) in activated RAW264.7 cells. Oe-ME diminished the activation of activator protein (AP)-1 and the phosphorylation of its upstream signaling cascades, including extracellular signal regulated kinase (ERK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 3/6 (MKK3/6), p38, MKK7, and transforming growth factor-β-activated kinase 1 (TAK1), in stimulated-RAW264.7 cells. Overexpression and CETSA were carried out to verify that TAK1 is the target of Oe-ME. Our results suggest that the anti-inflammatory effect of Oe-ME could be attributed to its control of posttranslational modification and transcription of TAK1.

Malus baccata (L.) Borkh. is a widely used medical plant in Asia. Since the anti-inflammatory mechanism of this plant is not fully understood, the aim of this study was to explore the anti-inflammatory function and mechanism of Malus baccata (L.) Borkh. methanol extract (Mb-ME). For in vitro experiments, nitric oxide production assay, PCR, overexpression strategy, immunoblotting, luciferase reporter assay, and immunoprecipitation were employed to explore the molecular mechanism and the target proteins of Mb-ME. For in vivo experiments, an HCl/EtOH-induced gastritis mouse model was used to confirm the anti-inflammatory function. Mb-ME showed a strong ability to inhibit the production of nitric oxide and the expression of inflammatory genes. Mb-ME decreased NF-κB luciferase activity mediated by MyD88 and TRIF. Moreover, Mb-ME blocked the activation of Src, Syk, p85, Akt, p50, p60, IKKα/β, and IκBα in LPS-induced RAW264.7 cells. Overexpression and immunoprecipitation analyses suggested Syk and Src as the target enzymes of Mb-ME. In vitro results showed that Mb-ME could alleviate gastritis and relieve the protein expression of p-Src, p-Syk, and COX-2, as well as the gene expression of COX-2 and TNF-α. In summary, this study implied that Mb-ME performs an anti-inflammatory role by suppressing Syk and Src in the NF-κB signaling pathway, both in vivo and in vitro.