Anti-wrinkle effect of magnesium lithospermate B from Salvia miltiorrhiza BUNGE: inhibition of MMPs via NF-kB signaling

• Published in: PloS one 2014-08, Vol.9 (8), p.e102689
• Main Authors: Jung, Yu Ri, Kim, Dae Hyun, Kim, So Ra, An, Hye Jin, Lee, Eun Kyeong, Tanaka, Takashi, Kim, Nam Deuk, Yokozawa, Takako, Park, Jin Nam, Chung, Hae Young
• Format: Article
• Language: English
• Subjects: Acids; Activator protein 1; Aging; Aging (artificial); Animals; Antioxidants; Biology and life sciences; Collagen; Collagen Type II - metabolism; Collagenases - metabolism; Cosmetics - chemistry; Cosmetics - pharmacology; Cyclooxygenase-2; Dermatologic agents; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Fibroblasts; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Humans; Inflammation; Inflammatory response; Kinases; Magnesium; Male; MAP kinase; Medicine and Health Sciences; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Oral administration; Oxidative stress; Oxygen; Pharmacy; Physical Sciences; Physiology; Procollagen; Protein kinase; Proteins; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Research and Analysis Methods; Rodents; Salvia miltiorrhiza; Salvia miltiorrhiza - chemistry; Signal transduction; Signal Transduction - drug effects; Signal Transduction - radiation effects; Signaling; Skin; Skin Aging - drug effects; Skin Aging - pathology; Skin Aging - radiation effects; Skin care; Transcription Factor AP-1 - metabolism; Transcription factors; Ultraviolet Rays - adverse effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102689

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.