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.

Many species in the genus Guettarda are known to exert anti-inflammatory effects and are used as traditional medicinal plants to treat various inflammatory symptoms. However, no studies on the inflammatory activities of Guettarda crispiflora Vahl have been reported. The aim of the study was to investigate in vitro and in vivo the anti-inflammatory effects of a methanol extract of Guettarda crispiflora Vahl (Gc-ME). To determine the anti-inflammatory activity of Gc-ME, lipopolysaccharide (LPS)-, poly(I:C)-, or Pam3CSK4-treated RAW264.7 cells, HCl/EtOH- and LPS-treated mice were employed for in vitro and in vivo tests. LPS-induced nitric oxide production in RAW264.7 cells was determined by Griess assays and cytokine gene expression in LPS-activated RAW264.7 cells, confirmed by RT- and real-time PCR. Transcriptional activation was evaluated by luciferase reporter gene assay. Target protein validation was assessed by Western blot analysis and cellular thermal shift assays (CETSA) with LPS-treated RAW264.7 and gene-transfected HEK293 cells. Using both a HCl/EtOH-induced gastritis model and an LPS-induced lung injury model, inflammatory states were checked by scoring or evaluating gastric lesions, lung edema, and lung histology. Phytochemical fingerprinting of Gc-ME was observed by using liquid chromatography–mass spectrometry. Nitric oxide production induced by LPS and Pam3CSK4 in RAW264.7 cells was revealed to be reduced by Gc-ME. The LPS-induced upregulation of iNOS, COX-2, IL-6, and IL-1β was also suppressed by Gc-ME treatment. Gc-ME downregulated the promotor activities of AP-1 and NF-κB triggered by MyD88- and TRIF induction. Upstream signaling proteins for NF-κB activation, namely, p-p50, p-p65, p-IκBα, and p-Src were all downregulated by Ch-EE. Moreover, Src was revealed to be directly targeted by Gc-ME. This extract, orally treated strongly, attenuated the inflammatory symptoms in HCl/EtOH-treated stomachs and LPS-treated lungs. Therefore, these results strongly imply that Guettarda crispiflora can be developed as a promising anti-inflammatory remedy with Src-suppressive properties.