ABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory effects of the Centella asiatica ethanol extract (CA) on an AD-like dermal disorder. Treatment with CA inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory stimulated HaCaT cells by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Eight-week-old BALB/c mice treated with 2,4-dinitrochlorobenzene (DNCB) were used as a mouse model of AD. In AD induce model, we had two types treatment of CA; skin local administration (80 µg/cm2, AD+CA-80) and oral administration (200 mg/kg/d, AD+CA-200). Interestingly, the CA-treated groups exhibited considerably decreased mast cell infiltration in the ear tissue. In addition, the expression of IL-6 in mast cells, as well as the expression of various pathogenic cytokines, such as TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9, was reduced in both AD+CA-80 and AD+CA-200 groups. Collectively, our data demonstrate the pharmacological role and signaling mechanism of CA in the regulation of allergic inflammation of the skin, which supports our hypothesis that CA could potentially be developed as a therapeutic agent for AD.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Dermatitis, Atopic/drug therapy , Immunomodulation/drug effects , Triterpenes/pharmacology , Administration, Oral , Administration, Topical , Animals , Centella , Cytokines/blood , Dermatitis, Atopic/chemically induced , Dinitrochlorobenzene , Disease Models, Animal , Inflammation , Mast Cells , Mice , Mice, Inbred BALB C , Plant Extracts , Skin/drug effectsABSTRACT
This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomorphometrical analysis revealed improvements in the number of osteoblasts, osteoclasts, and osteocytes; the osteoblast and osteoclast surface per bone surface; and bone volume in vitamin C-treated OVX rats. The vitamin C-treated group additionally displayed an increase in the expression of osteoblast differentiation genes, including bone morphogenetic protein-2, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin, and type I collagen. Vitamin C reduced the expression of osteoclast differentiation genes, such as receptor activator of nuclear factor kappa-B, receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase, and cathepsin K. This study is the first to show that vitamin C can inhibit osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through the activation of wingless-type MMTV integration site family/ß-catenin/activating transcription factor 4 signaling, which is achieved through the serine/threonine kinase and mitogen-activated protein kinase signaling pathways. Therefore, our results suggest that vitamin C improves bone regeneration.
Subject(s)
Activating Transcription Factor 4/metabolism , Ascorbic Acid/pharmacology , Osteoblasts/drug effects , Osteoclasts/drug effects , Wnt Proteins/metabolism , beta Catenin/metabolism , Activating Transcription Factor 4/genetics , Animal Feed , Animals , Bone Density , Diet , Female , Gene Expression Regulation/drug effects , Osteoporosis/prevention & control , Ovariectomy , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Wnt Proteins/genetics , beta Catenin/geneticsABSTRACT
BACKGROUND: We aimed to elucidate the preventive effects of taurine against osteopenia in ovariectomized (OVX) rats and the mechanisms by which taurine regulates osteoblastogenesis in vitro and in vivo. METHODS: The effects of the taurine on human osteoblast MG-63 cell differentiation and osteoblastogenesis effect in OVX rat were examined Konkuk University in 2018 by evaluating osteoblast differentiation, and expression of osteoblast-specific factors by western blotting analysis. RESULTS: Taurine supplementation significantly improved alkaline phosphatase (ALP) activity and mineralization in a concentration-dependent manner. Further, taurine induced the expression of osteogenic growth factors such as bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX2), small mothers against decapentaplegic 1/5/8 (SMAD1/5/8), wingless-type MMTV integration site family member 3A (Wnt3a), and collagen type 1 (COL-1) via mitogen-activated protein kinase (MAPK) and serine/threonine protein kinase (Akt). Moreover, the RUNX2 activity of the taurine-treated group was enhanced by protein-protein interactions such as Wnt3a-induced p-AKT/RUNX2 and BMP-mediated SMADs/MAPK/RUNX2 interactions. CONCLUSION: Our in vitro and in vivo results suggested that taurine can be considered as a potential therapeutic candidate agent for preventing bone loss in postmenopausal osteoporosis.
