Cedrol Enhances Extracellular Matrix Production in Dermal Fibroblasts in a MAPK-Dependent Manner

Abstract

BackgroundThe extracellular matrix (ECM) produced by dermal fibroblasts supports skin structure, and degradation and/or reduced production of ECM are the main causes of wrinkle formation.ObjectiveThe aim of this study was to identify the active ingredient that enhances ECM production in dermal fibroblasts.MethodsPolarity-based fractionation was used to isolate the active ingredient from natural extracts, and the effects of cedrol (isolated from Pterocarpus indicusirginia) on ECM production in cultured human dermal fibroblasts was investigated by reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay, and Western blot analysis.ResultsCedrol accelerated fibroblast growth in a dose-dependent manner and increased the production of type 1 collagen and elastin. Phosphorylation of p42/44 extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and Akt was markedly increased by cedrol, indicating that enhanced ECM production is linked to activation of intracellular signaling cascades.ConclusionThese results indicate that cedrol stimulates ECM production, with possible applications to the maintenance of skin texture.

Inhibitory effect of a new orally active cedrol-loaded nanostructured lipid carrier on compound 48/80-induced mast cell degranulation and anaphylactic shock in mice

“…25 Later, Hori et al found that cedrol not only modulates autonomic activity via central nervous system 26 but also causes an increase in the extracellular matrix in dermal cells which may be useful for clinical skin care. 27 Now cedrol is mostly used as positive control in different experiments for comparing the PAF antagonist activity. 28,29 In the present study, we showed that (+) cedrol had a strong inhibitory effect on mast cell degranulation and anaphylactic shock in mice.…”

Anti‑apoptotic effects of glycosaminoglycans via inhibition of ERK/AP‑1 signaling in TNF‑α‑stimulated human dermal fibroblasts

“…The present study also assessed the upstream signal transduction pathways of collagen synthesis via the regulation of MMP-1 and TIMP-1. Previous studies have demonstrated that MAPK signaling pathways serve pivotal roles in controlling various cellular functions, including cell growth, MMP expression and collagen synthesis (26,(30)(31)(32). In addition, several studies have revealed that MMP-1 expression is enhanced by activated MAPK in dermal fibroblasts following stimulation with particular stimuli (70,71).…”

“…GAGs inhibit MMP-1 expression via suppression of the ERK signaling pathway. Previous studies have indicated that MAPK pathways, specifically those induced by TNF-α, serve an important role in the regulation of procollagen synthesis (26,(30)(31)(32)35,44). Thus, the present study assessed TNF-α induced MAPK signaling.…”

“…In addition to aging, the stimulation of various cytoplasmic signal transduction pathways, including transforming growth factor (TGF)-β/Smad, mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, cause fibroblasts to lose their proliferative potential. Fibroblasts then synthesize reduced levels of ECM, meaning that the secretion of type I collagen is also reduced (24)(25)(26)(27)(28). Impairments in dermal fibroblast functions during aging contribute to skin thinning, as they cause reductions in the quantity of collagen in aged human skin (29).…”

“…Impairments in dermal fibroblast functions during aging contribute to skin thinning, as they cause reductions in the quantity of collagen in aged human skin (29). Previous studies have demonstrated that various MAPKs, including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK) and p38, are associated with skin aging (26,(30)(31)(32). The phosphorylation of ERK 1/2 mediates the inhibition of type I collagen synthesis in human skin fibroblasts (32,33).…”