Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation

Abstract

Human skin is constructed with many proteins such as collagen and elastin. Collagen and elastin play a key role in providing strength and elasticity to the human skin and body. However, damage to collagen causes various symptoms such as wrinkles and freckles, which suggests that they are important to maintain skin condition. Extrinsic or intrinsic skin aging produces an excess of skin destructive factors such as tumor necrosis factor (TNF)-α, which is a major mediator of the aging process. In aged skin, TNF-α provokes the generation of intracellular ROS (reactive oxygen species). It triggers the excessive secretion of MMP-1, which is a collagen-degrading enzyme that causes the collapse of skin collagen. Therefore, we aimed to search for a natural-product-derived candidate that inhibits the skin damage caused by TNF-α in human dermal fibroblasts. In this study, the protective effect of withagenin A diglucoside (WAD) identified from Withania somnifera against TNF-α-stimulated human dermal fibroblasts is investigated. W. somnifera (Solanaceae), well-known as ‘ashwagandha’, is an Ayurvedic medicinal plant useful for promoting health and longevity. Our experimental results reveal that WAD from W. somnifera suppresses the generation of intercellular ROS. Suppressing intracellular ROS generation inhibits MMP-1 secretion and the collapse of type 1 collagen. The effect of WAD is shown to depend on the inhibition of MAPK phosphorylation, Akt phosphorylation, c-Jun phosphorylation, COX-2 expression, and NF-κB phosphorylation. Further, WAD-depressed expression of the pro-inflammatory cytokines IL-6 and IL-8 triggers various inflammatory reactions in human skin. These findings suggest that WAD has protective effects against skin damage. Accordingly, our study provides experimental evidence that WAD can be a potential agent that can be applied in various industrial fields, such as cosmetics and pharmaceuticals related to skin aging.

Effects of Bacterial Lysates and Metabolites on Collagen Homeostasis in TNF-α-Challenged Human Dermal Fibroblasts

“…Furthermore, it inhibited TGF-β1 control-induced type I pro-collagen synthesis (Figures 2 and 3a). In separate studies with HDFs, a 15 min challenge with TNF-α at 20 ng/mL (comparable concentration with our study) already led to 1.5-to 2.5-fold increases in intracellular ROS and raised phosphorylation of several mitogen-activated protein kinases and nuclear factor kappa B [23][24][25]. Similar effects have been noticed to be the result of UV-B challenge [26].…”

“…Stimulation of dermal fibroblasts with TNF-α increases the production of MMP-1 and the proinflammatory cytokines IL-6 and IL-8, as well as degrades type I collagen and decreases its synthesis [ 22 , 23 ]. Furthermore, long-term presence of TNF-α upregulates ROS levels and induces premature senescence in human dermal fibroblasts [ 6 ].…”

Gallium-modified gelatin nanoparticles loaded with quercetin promote skin wound healing via the regulation of bacterial proliferation and macrophage polarization

“…However, the difference between the QCT@GNP group and the QCT@GNP-Ga group was insignificant ( Figures 2C, D ). Human skin is constructed with many proteins, among which Type I collagen (COL1) and elastin (ELN) that are derived from fibroblasts and constitute extracellular matrix (ECM) play a key role in providing strength and elasticity to the human skin and body ( Lee et al, 2022 ). The expressions of COL1 and ELN can well reflect the ability of fibroblast to produce ECM that is related to process of wound healing and scar formation ( Bui et al, 2022 ).…”

Extracellular vesicles derived from mesenchymal stem cells: the wine in Hebe's hands to treat skin aging

“…Located beneath the epidermis, the dermis serves as its foundational support and is connected to the epidermis through the dermal–epidermal junction. The dermis primarily consists of fibroblasts and their ECM, encompassing collagen, elastin, and various proteins responsible for the skin's mechanical strength and elasticity [ 113 ]. With advancing age, both the epidermis and dermis gradually thin, accompanied by a decline in the self-renewal capacity of skin stem cells, ultimately leading to compromised skin barrier function.…”