Forsythiae Fructus, Lonicerae Flos, and Scutellariae Radix are medicinal herbs that possess anti‐inflammatory and anti‐atopic effects. Hence, we investigated the effects of a mixture (ADM), containing arctigenin, hederagenin, and baicalein, which are the main compound from these herbs on atopic dermatitis (AD) skin lesions and the underlying molecular mechanisms. ADM was topically applied to dorsal skin lesions of 2,4‐dinitrochlorobenzene‐ (DNCB‐) induced ICR mice, and the expressions of proinflammatory mediators and HPA axis hormones were investigated. The topical application of 0.5% ADM significantly reduced the DNCB‐induced symptoms of AD in ICR mice. Histological analysis showed that ADM exerted antiatopic effects by reducing the epidermal thickness and mast cell infiltration into skin lesions. 0.5% ADM attenuated the levels of TNF‐α, IFN‐γ, IL‐4, and VEGF in skin lesions and serum IgE. The production of Th1‐/Th2‐related cytokines in splenic tissues, including TNF‐α, IFN‐γ, IL‐12, and IL‐4, were also decreased by ADM treatment. ADM diminished corticotropin‐releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosteroid (CORT) production in DNCB‐induced mice. In vitro, ADM reduced the productions of TARC/CCL17, MDC/CCL22, IL‐6, and ICAM‐1 in TNF‐α/IFN‐γ‐ (TI‐) stimulated HaCaT cells by suppressing the ERK and JNK signaling pathways. In addition, ADM inhibited corticotropin‐releasing hormone/substance P‐ (CRH/SP‐) induced VEGF production in HMC‐1 cells. These results suggest that ADM may have therapeutic potential in AD by reducing inflammation and attenuating HPA axis activation.

Gardeniae Fructus (GF) is the fruit of Gardenia jasminoides Ellis and is traditionally prescribed to treat pyogenic infections and skin ulcers. This study investigated the protective effects of GF and the underlying mechanism responsible for these effects on diesel exhaust particulate matter- (DEP-) induced skin damage. The protective effects of an ethanolic extract of GF (GFE) and its constituents (geniposidic acid, gardenoside, geniposide, chlorogenic acid, and genipin) were examined by analyzing reactive oxygen species (ROS) production, apoptosis, and tight junction (TJ) protein expression in HaCaT cells. Treatment with GFE dose-dependently inhibited intracellular ROS production and apoptosis by regulating the protein expressions of Bax, Bcl-2, and cytochrome C in DEP-stimulated (100μg/ml) HaCaT cells. Mechanistic studies revealed that the protective effects of GFE were related to its activation of Nrf2 and HO-1 signaling in HaCaT cells. Geniposide, a main constituent of GFE, enhanced the expression of occludin in DEP-stimulated HaCaT cells. Furthermore, topical application of geniposide reduced the expressions of 8-OHdG and Bax and increased the expression of occludin in the dorsal skin lesions of DEP-stimulated mice. Gardeniae Fructus and its main component geniposide are potential candidates for the repair of DEP-induced skin damage due to their antioxidant and antiapoptotic activities.

Huong Thi Nguyen, Sunghoon Hurh, Lan Phuong Nguyen, Thai Uy Nguyen, Hee-Kyung Park, Jae Young Seong, Cheol Soon Lee, Byung-Joo Ham, and Jong-Ik Hwang. Mol. Cells 2023;46:281-97. https://doi.org/10.14348/molcells.2023.2096

C-X-C motif chemokine ligand 12(CXCL12) is an essential chemokine for organ development and homeostasis in multiple tissues. Its receptor, C-X-C chemokine receptor type 4(CXCR4), is expressed on the surface of target cells. The chemokine and receptor are expressed almost ubiquitously in human tissues and cells throughout life, and abnormal expression of CXCL12 and CXCR4 is observed in pathological conditions, such as inflammation and cancer. CXCR4 is reportedly translated into five splicing variants of different lengths, which each have different amino acids in the N-terminus. As the N-terminus is the first recognition site for chemokines, CXCR4 variants may respond differently to CXCL12. Despite these differences, the molecular and functional properties of CXCR4 variants have not been thoroughly described or compared. Here, we explored the expression of CXCR4 variants in cell lines and analyzed their roles in cellular responses using biochemical approaches. RT-PCR revealed that most cell lines express more than one CXCR4 variant. When expressed in HEK293 cells, the CXCR4 variants differed in protein expression efficiency and cell surface localization. Although variant 2 demonstrated the strongest expression and cell surface localization, variants 1, 3, and 5 also mediated chemokine signaling and induced cellular responses. Our results demonstrate that the N-terminal sequences of each CXCR4 variant determine the expression of the receptor and affect ligand recognition. Functional analyses revealed that CXCR4 variants may also affect each other or interact during CXCL12-stimulated cellular responses. Altogether, our results suggest that CXCR4 variants may have distinct functional roles that warrant additional investigation and could contribute to future development of novel drug interventions.