Abstract
Skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmentally induce damage. Wrinkle formation is a striking feature of intrinsic and photo-induced skin aging, which are both associated with oxidative stress and inflammatory response. The present study was undertaken to identify the mechanisms responsible for the anti-wrinkle effects of MLB, and thus, we investigated whether magnesium lithospermate B (MLB) from Salvia miltiorrhiza BUNGE associated with wrinkle formation caused by intrinsic and extrinsic skin aging using Sprague-Dawley rats aged 5 and 20 months and ultraviolet B (UVB)-irradiated human skin fibroblasts cells, respectively. The results obtained showed that the oral administration of MLB significantly upregulated the level of type I procollagen and downregulated the activities and expressions of matrix-metalloproteinases (MMPs) in rat skin. In fibroblasts, MLB suppressed the transactivation of nuclear factor-kB (NF-kB) and activator protein 1(AP-1), which are the two transcription factors responsible for MMP expression, by suppressing oxidative stress and the mitogen activated protein kinase (MAPK) pathway. Our results show that the antioxidant effect of MLB is due to the direct scavenging of reactive oxygen species (ROS) and its inhibitory effects on NF-kB-dependent inflammation genes, such as, cyclooxygenase-2 and inducible nitric oxide synthase. MLB was found to reverse both age- and UVB-related reductions in skin procollagen levels by suppressing the expressions and activities of NF-kB and AP-1-dependent MMPs by modulating ROS generation and the MAPK signaling pathway. We suggest that MLB potentially has anti-wrinkle and anti-skin aging effects.
Highlights
Aging is characterized by progressive loss of structural integrity and physiological function caused by intrinsic and extrinsic determinants [1]
ELISA analysis showed that procollagen production was dose-dependently increased in fibroblasts pretreated with magnesium lithospermate B (MLB) as compared with cells exposed to ultraviolet B (UVB) only (Fig. 2C)
Photoaging refers to the damage caused by repeated exposure to UV radiation from the sun, whereas intrinsic aging concerns the damage caused by the passage of time
Summary
Aging is characterized by progressive loss of structural integrity and physiological function caused by intrinsic and extrinsic determinants [1]. Intrinsic aging of skin is a natural consequence of physiological change and extrinsic factors, such as, ultraviolet (UV) exposure, environment pollution, and nicotine. Wrinkle formation is representative of skin aging and is characterized by reduced skin elasticity and degeneration of the extracellular matrix (ECM), which in the dermis is produced by fibroblasts and is composed of a mesh of fibrous proteins, such as, collagen and elastic fibers, and glycosaminoglycans that influence the outer appearance of skin [2]. Type I collagen is the major structural component of the ECM and the most abundant protein in skin connective tissue. It has been reported that reductions in the age-induced expressions of MMP-2, MMP-3, MMP-9, and MMP-13 via the suppressions of the activities of cJun and c-Fos are associated with reduced wrinkle formation [7]
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