Anti-oxidative, anti-apoptotic, and anti-inflammatory activities of Connarus semidecandrus Jack ethanol extract in UVB-irradiated human keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Connarus semidecandrus Jack (Family: connaraceae) is a medicinal plant known for its wide distribution throughout Southeast Asia. Renowned for its diverse therapeutic properties, it has been traditionally used for treating fever, skin irritation, and colic. AIM OF THE STUDY: Numerous individuals suffer from skin issues, including wrinkles, hyperpigmentation, and inflammation, due to environmental factors. Although many drugs are available to treat skin problems, chemical drugs have many shortcomings and side effects. Therefore, natural products are attractive potential medicines for alleviating skin troubles. We recently showed that Connarus semidecandrus Jack ethanol extract (Cs-EE) has anti-alopecia potential. This paper aims to explore the potential skin-protective effects and underlying molecular mechanisms of Connarus semidecandrus Jack in UVB-induced human keratinocytes (HaCaT). MATERIALS AND METHODS: Before utilization, Cs-EE was dissolved in dimethyl sulfoxide (DMSO) and was preserved at a temperature of -20 °C. The phytochemical constituents of Cs-EE were detected by gas chromatography-mass spectrometry analysis (GC-MS). Sequentially, HaCaT cells were exposed to varying concentrations of Cs-EE prior to ultraviolet B (UVB) irradiation. Evaluations of cellular responses in HaCaT cells, including assessments of cell viability, deoxyribonucleic acid (DNA) damage, and gene and protein expressions, were carried out. To explore the specific signaling pathway involved, we conducted a luciferase assay in addition to validating these pathways using Western blot analysis. RESULTS: Nitric oxide (NO) and intracellular reactive oxygen species were decreased. Melanin production through the activation of melanocytes by α-melanocyte-stimulating hormone (MSH) was also inhibited by Cs-EE. Furthermore, the mRNA expression levels of key factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), MMP-1, MMP-3, and MMP-9 exhibited a remarkable decrease. In addition, the phosphorylation of TAK1 within the signaling cascade exhibited a decline, and the activities of the transcription factor AP-1 were decreased according to a luciferase reporter assay. CONCLUSIONS: Taken together, these findings suggest that the anti-inflammatory, anti-aging, and anti-apoptotic effects of Cs-EE indicate the compound's potential usefulness as a natural component in pharmaceutical and cosmetic products.

Connarus semidecandrus Jack Exerts Anti-Alopecia Effects by Targeting 5α-Reductase Activity and an Intrinsic Apoptotic Pathway.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair-skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Trigonostemon reidioides modulates endothelial cell proliferation, migration and tube formation via downregulation of the Akt signaling pathway.

Trigonostemon reidi`oides (TR) is used as a Thai traditional medicine for the treatment of drug addiction, asthma, food poisoning, constipation and snake bites. The present study investigated the effects and molecular mechanisms of the ethanolic extract of TR (ETR) on mitogen-induced human umbilical vein endothelial cells (HUVECs) responses, proliferation, adhesion, migration and tube formation. ETR treatment inhibited mitogen-induced HUVEC proliferation by downregulation of cell cycle-associated proteins, including cyclins and cyclin-dependent kinases, which induced retinoblastoma protein hypophosphorylation. The present study also demonstrated that ETR treatment suppressed mitogen-induced HUVEC adhesion, migration, invasion and tube formation, and that these anti-angiogenic activities were mediated by inactivation of mitogen-induced Akt and matrix metalloproteinase (MMP)-2, but not of extracellular signal-regulated kinase, p70 ribosomal S6 kinase or MMP-9. Collectively, the results of the present study suggested pharmacological functions and molecular mechanisms of ETR in regulating endothelial cell fates, and supported further evaluation and development of ETR as a potential therapeutic agent for the treatment and prevention of angiogenesis-associated diseases, including cancer.

Regulatory effects and molecular mechanism of Trigonostemon reidioides on lipopolysaccharide­induced inflammatory responses in RAW264.7 cells.

Trigonostemon reidioides (Kurz) Craib has been traditionally used for the treatment of vomiting and asthma in Cambodia. However, the underlying molecular mechanisms of the anti­inflammatory effect of T. reidioides extract remains unknown. The present study investigated the anti­inflammatory activity and molecular action of an ethanol extract of T. reidioides (ETR) in lipopolysaccharide (LPS)­induced RAW264.7 macrophage cells. Nitric oxide assays, ELISA, reverse transcription­quantitative polymerase chain reaction and western blot analysis were used. ETR treatment inhibited the production of nitric oxide by downregulating inducible nitric oxide synthase expression, while exhibiting no significant cytotoxicity compared with macrophages treated with LPS­alone. Consequently, ETR decreased the production of certain proinflammatory cytokines, including interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α. Additionally, ETR inhibited the activation of mitogen­activated protein kinases (MAPKs), including extracellular signal­regulated kinase, c­Jun N­terminal kinase and p38 MAPK, as well as the phosphatidylinositol 3­kinase (PI3K)/Akt signaling pathway. These effects were mediated by inhibition of the nuclear localization of nuclear factor κ­B (NF­κB). Taken together, the results of the present study demonstrate that ETR may exert an anti­inflammatory effect by inhibiting the expression of inflammatory mediators and cytokines via downregulation of the NF­κB, PI3K/Akt and the MAPK signaling pathways in LPS­stimulated macrophages. Based on these results, we hypothesize that ETR may be a potential therapeutic agent for the treatment of inflammatory disorders.