We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer’s disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC₅₀ of 29.6, 16.2 and 48.1 µM, respectively. The K_i values and binding energies (kcal/mol) between pterosins and BACE1, AChE, and BChE corresponded to the respective IC₅₀ values. (2R)-Pterosin B was a noncompetitive inhibitor against human BACE1 and BChE as well as a mixed-type inhibitor against AChE, binding to the active sites of the corresponding enzymes. Molecular docking simulation of mixed-type and noncompetitive inhibitors for BACE1, AChE, and BChE indicated novel binding site-directed inhibition of the enzymes by pterosins and the structure−activity relationship. (2R)-Pterosin B exhibited a strong BBB permeability with an effective permeability (P_e) of 60.3×10⁻⁶ cm/s on PAMPA-BBB. (2R)-Pterosin B and (2R,3 R)-pteroside C significantly decreased the secretion of Aβ peptides from neuroblastoma cells that overexpressed human β-amyloid precursor protein at 500 μM. Conclusively, our study suggested that several pterosins are potential scaffolds for multitarget-directed ligands (MTDLs) for AD therapeutics.

Atmospheric particulate matter (PM) is an important cause of skin damage, and an increasing number of studies have been conducted to discover safe, natural materials that can alleviate the oxidative stress and inflammation caused by PM. It has been previously shown that the extract of Ecklonia cava Kjellman, a perennial brown macroalga, can alleviate oxidative stress in epidermal keratinocytes exposed to PM less than 10 microns in diameter (PM10). The present study was undertaken to further examine the anti-inflammatory effects of E. cava extract and its major polyphenolic constituent, dieckol. HaCaT keratinocytes were exposed to PM10 in the presence or absence of E. cava extract or dieckol and analyzed for their viability, prostaglandin E₂ (PGE₂) release, and gene expression of cyclooxygenase (COX)-1, COX-2, microsomal prostaglandin E₂ synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E₂ synthase (cPGES). PM10 treatment decreased cell viability and increased the production of PGE₂, and these changes were partially abrogated by E. cava extract. E. cava extract also attenuated the expression of COX-1, COX-2, and mPGES-2 stimulated by PM10. Dieckol attenuated PGE₂ production and the gene expression of COX-1, COX-2, and mPGES-1 stimulated by PM10. This study demonstrates that E. cava extract and dieckol alleviate airborne PM10-induced PGE₂ production in keratinocytes through the inhibition of gene expression of COX-1, COX-2, mPGES-1, and/or mPGES-2. Thus, E. cava extract and dieckol are potentially useful natural cosmetic ingredients for counteracting the pro-inflammatory effects of airborne PM.

Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Hemp (Cannabis sativa L.) contains a variety of secondary metabolites, including cannabinoids, such as psychoactive (−)-trans-Δ⁹-tetrahydrocannabinol. The present study was conducted to identify the major phenolic components contained in hemp root, which has been relatively under-researched compared to other parts of hemp. The aqueous ethanol extract of hemp roots was fractionated into methylene chloride (MC), ethyl acetate (EA), and water (WT) fractions, and high-performance liquid chromatography with photodiode array detection (HPLC-DAD) analysis was performed. The main ultraviolet (UV)-absorbing phenolic compound contained in the EA fraction was identified as p-coumaric acid by comparing the retention time and UV absorption spectrum with a standard. Silica gel column chromatography was performed to isolate a hydrophobic derivative of p-coumaric acid contained in the MC fraction. Nuclear magnetic resonance (NMR) analysis identified the isolated compound as ethyl p-coumarate. For comparative purposes, ethyl p-coumarate was also chemically synthesized by the esterification reaction of p-coumaric acid. The content of p-coumaric acid and ethyl p-coumarate in the total extract of hemp root was estimated to be 2.61 mg g⁻¹ and 6.47 mg g⁻¹, respectively, by HPLC-DAD analysis. These values correspond to 84 mg Kg⁻¹ dry root and 216 mg Kg⁻¹ dry root, respectively. In conclusion, this study identified p-coumaric acid and ethyl p-coumarate as the main phenolic compounds contained in the hemp roots.