Diallyl Biphenyl-Type Neolignans Have a Pharmacophore of PPARα/γ Dual Modulators.

Adiponectin secretion-promoting compounds have therapeutic potentials in human metabolic diseases. Diallyl biphenyl-type neolignan compounds, magnolol, honokiol, and 4--methylhonokiol, from a extract were screened as adiponectin- secretion promoting compounds in the adipogenic differentiation model of human bone marrow mesenchymal stem cells (hBM-MSCs). In a target identification study, magnolol, honokiol, and 4--methylhonokiol were elucidated as PPARα and PPARγ dual modulators.

Benzophenone-3 and benzophenone-8 exhibit obesogenic activity via peroxisome proliferator-activated receptor γ pathway.

Benzophenone-3 (BP-3) and benzopenone-8 (BP-8) are commonly used ultraviolet (UV) filter ingredients in diverse sunscreen products. Recently, the obesogenic activity of avobenzone, a long wave UV A filter, was elucidated in the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs). In this study, the obesogenic potentials of BP-3 and BP-8 were investigated because of their chemical similarity to avobenzone.

Selenium bioisosteric replacement of adenosine derivatives promoting adiponectin secretion increases the binding affinity to peroxisome proliferator-activated receptor δ.

N-(3-Iodobenzyl)adenosine-5'-N-methyluronamide (1a, IB-MECA) exhibited polypharmacological characteristics targeting A adenosine receptor (AR), peroxisome proliferator-activated receptor (PPAR) γ, and PPARδ, simultaneously. The bioisosteric replacement of oxygen in 4'-oxoadenosines with selenium significantly increased the PPARδ-binding activity. 2-Chloro-N-(3-iodobenzyl)-4'-selenoadenosine-5'-N-methyluronamide (3e) and related 4'-selenoadenosine derivatives significantly enhanced adiponectin biosynthesis during adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs).

CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test.

To elucidate the roles of epidermal keratinocytes in the toxicological outcomes of chemically induced contact dermatitis, genome-scale transcriptional analyses were performed using normal human keratinocytes (NHKCs) treated with 10 μM sodium lauryl sulfate (SLS) or 5 μM urushiol. In Gene Ontology (GO) enrichment analyses, SLS- and urushiol-induced upregulated DEGs are commonly associated with the regulation of pro-inflammatory responses and epidermal differentiation processes in NHKCs whereas cellular protein metabolic process was also identified as a commonly downregulated DEG signature. Among the downregulated DEGs, CXCL14 was investigated as a potential biomarker for a new in vitro skin sensitization test using OECD TG429 reference chemicals.

Keratinocyte-derived IL-36γ plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes.

Chemical leukoderma is an acquired type of vitiligo that can be initiated by various exogenous chemicals such as hydroquinone (HQ), rhododendrol (RD), or 4-tertiary butyl phenol (4-TBP). Despite the importance of epidermal keratinocytes in diverse dermatological conditions, their toxicological role in chemical leukoderma is poorly understood. To elucidate their role in the pathogenesis of chemical leukoderma, genome-scale transcriptional analysis was performed in human epidermal keratinocytes (HEKs) treated with a sub-cytotoxic HQ concentration (10 µM).

Kojyl cinnamate esters are peroxisome proliferator-activated receptor α/γ dual agonists.

Adiponectin is an adipocytokine with insulin-sensitizing, anti-inflammatory, anti-atherosclerotic, and anti-aging properties. Compounds with the ability to promote adiponectin secretion are of interest for the development of anti-aging drugs to improve skin-aging phenotypes. In the phenotypic assay to measure adiponectin secretion during adipogenesis in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs), kojyl cinnamate ester derivatives increased adiponectin secretion.