Leathesia difformis (L.) Areschoug (L. difformis) is a species of littoral brown algae of the class Phaeophyceae. Only a few studies on the apoptotic, antiviral, and antioxidant properties of L. difformis have been reported, and its inhibitory effect on melanin synthesis has not been studied. The aim of this study was to investigate the anti-melanogenic effect of L. difformis extract on α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanocytes and its mechanism of action. L. difformis was extracted using 80% ethanol (LDE) and then fractioned between ethyl acetate (LDE-EA) and water (LDE-A). Our data demonstrated that LDE-EA significantly inhibited melanin level and cellular tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of genes associated with melanin synthesis, such as microphthalmia-associated transcription factor (Mitf), tyrosinase (Tyr), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (Dct), and melanocortin 1 receptor (Mc1r) was down-regulated by LDE-EA treatment. Moreover, LDE-EA decreased p-CREB levels, which suggests that the inhibition of the cAMP/PKA/CREB pathways may be involved in the anti-melanogenic effect of LDE-EA. Thus, this study revealed that LDE-EA is an effective inhibitor of hyperpigmentation through inhibition of CREB pathways and may be considered as a potential therapeutic agent for hyperpigmentation disorders.

Activated microglia interact with astrocytes and neuronal cells to induce neuroinflammation, which can contribute to the pathogenesis and progression of Alzheimer’s and Parkinson’s disease. To identify the most effective anti-neuroinflammatory agent, we designed and synthesized a family of 13 new azine derivatives and investigated their anti-neuroinflammatory activities in LPS-activated BV-2 microglial cells. Out of 13 derivatives, compound 3 [4,4′-(1E,1′E,3E,3′E)-3,3′-(hydrazine-1,2-diylidene) bis-(prop-1-ene-1-yl-3-ylidene) bis-(2-methoxyphenol)] exhibited excellent anti-neuroinflammatory activities (IC50 = 12.47 µM), which protected neurons from microglia-mediated neurotoxicity. Specifically, the anti-neuroinflammatory effects of compound 3 inhibited MAPK signaling pathways through the inhibition of p38 and JNK mediated signaling and the production of pro-inflammatory cytokines, and inflammatory mediators. Additionally, compound 3 strongly exhibited neuroprotective effect by inhibiting LPS-mediated necrosis and apoptosis. Preliminary SAR analysis suggests that the presence of methoxyphenol and the substitution pattern within hydrazine may influence the anti-neuroinflammatory activity. FACS analysis also strongly supports the neuroprotective effect of compound 3. Based on our results, the compound 3 exhibited excellent anti-neuroinflammatory activity against LPS-activated microglia, which resulted in the inhibition of neuronal apoptosis and neuronal degeneration.

Pyropia yezoensis, a red alga, is popular and harvested a lot in East Asia and is famous for its medicinal properties attributable to its bioactive compounds including amino acids (porphyra-334 and shinorine, etc.), polysaccharides, phytosterols, and pigments, but its anti-inflammatory effect and mechanism of anti-atopic dermatitis (AD) have not been elucidated. In this study, we investigate the anti-AD effect of P. yezoensis extract (PYE) on mRNA and protein levels of the pro-inflammatory chemokines, thymus, and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), in human HaCaT keratinocyte cells treated to interferon (IFN)-γ or tumor necrosis factor (TNF)-α (10 ng/mL each). The effect of the PYE on extracellular signal-regulated kinase (ERK) and other mitogen-activated protein kinases (MAPKs) was related to its suppression of TARC and MDC production by blocking NF-κB activation in HaCaT cells. Furthermore, astaxanthin and xanthophyll from P. yezoensis were identified as anti-AD candidate compounds. These results suggest that the PYE may improve AD and contained two carotenoids by regulating pro-inflammatory chemokines.

In this study, we investigated the inhibitory potential of 60 flavonoids from six distinct subgroups on the programmed cell death ligand 1 (PD-L1) dimer through molecular docking and dynamics simulations. Using AutoDock Vina for docking, the binding poses and affinities were evaluated, revealing an average binding affinity of −8.5 kcal/mol for the flavonoids. Among them, ginkgetin exhibited the highest binding free energy of −46.73 kcal/mol, indicating a strong interaction with PD-L1, while diosmin followed closely, with −44.96 kcal/mol. Molecular dynamics simulations were used to further elucidate the dynamic interactions and stability of the flavonoid–PD-L1 complexes, with the analyses showing minimal root mean square deviation (RMSD) and favorable root mean square fluctuation (RMSF) profiles for several compounds, particularly formononetin, idaein, and neohesperidin. Additionally, contact number and hydrogen bond analyses were performed, which highlighted ginkgetin and diosmin as key flavonoids with significant binding interactions, evidenced by their stable conformations and robust molecular interactions throughout the simulations. Ultimately, a cell-based assay confirmed their ability to inhibit the proliferation of cancer cells. These results, validated through cell-based assays, indicate that the strategy of identifying natural compounds with anticancer activity using computational modeling is highly effective.

Garrya flavescens S. Wats. (GF) has been traditionally used to treat gastrointestinal spasms, yet its bioactivity within the central nervous system remains unexplored. This study aimed to characterize the bioactive constituents of GF and evaluate its anti-inflammatory and metabolic regulatory effects in lipopolysaccharide-activated microglia. Phytochemical profiling using LC-HRMS and HPLC identified rutin as a primary bioactive component, present at an exceptionally high concentration (9309 μg/g). In BV-2 microglial and RAW 264.7 cells, GF treatment significantly suppressed the expression of pro-inflammatory cytokines and mediators in a dose-dependent manner. Mechanistic studies revealed that GF specifically modulated the ERK signaling pathway. Furthermore, Seahorse XF analysis demonstrated that GF restored mitochondrial homeostasis by reducing basal respiration and proton leak while significantly enhancing spare respiratory capacity. Finally, conditioned medium from GF-treated microglia improved the viability of N2A neuronal cells. These findings highlight GF as a potent botanical source with significant neuroprotective potential, offering a promising candidate for functional food or nutraceutical applications targeting neuroinflammatory disorders.