Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen-activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway
| Autor: | Sheikh A. Tasduq, Subhash Bhardwaj, Shashi Bhushan, Peerzada Kaiser, Rather A. Rafiq, Quadri Afnan, Lone A. Nazir, Rajat Sandhir |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Ultraviolet Rays p38 mitogen-activated protein kinases Anti-Inflammatory Agents Drug Evaluation Preclinical Apoptosis Dermatitis Dermatology Mitochondrion Biology medicine.disease_cause Biochemistry Cell Line 03 medical and health sciences Methionine medicine Animals Humans Molecular Biology Skin Mice Inbred BALB C Hyperplasia Kinase NF-kappa B Glycyrrhizic Acid Skin Aging Cell biology HaCaT 030104 developmental biology Sulfoxides Tumor necrosis factor alpha Mitogen-Activated Protein Kinases Reactive Oxygen Species Oxidative stress |
| Zdroj: | Experimental Dermatology. 25:440-446 |
| ISSN: | 0906-6705 |
| DOI: | 10.1111/exd.12964 |
| Popis: | Glycyrrhizic acid (GA), a natural triterpene, has received attention as an agent that has protective effects against chronic diseases including ultraviolet UV-B-induced skin photodamage. However, the mechanism of its protective effect remains elusive. Here, we used an immortalized human keratinocyte cell line (HaCaT) and a small animal model (BALB/c mice), to investigate the protective effects of GA against UV-B-induced oxidative damage, and additionally, delineated the molecular mechanisms involved in the UV-B-mediated inflammatory and apoptotic response. In the HaCaT cells, GA inhibited the UV-B-mediated increase in intracellular reactive oxygen species (ROS) and down-regulated the release of pro-inflammatory cytokines interleukin (IL)-1α, -1β and -6, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2). GA inhibited UV-B-mediated activation of p38 and JNK MAP kinases, COX-2 expression and nuclear translocation of NF-κB. Furthermore, GA inhibited UV-B-mediated apoptosis by attenuating translocation of Bax from the cytosol to mitochondria, thus preserving mitochondrial integrity. GA-treated HaCaT cells also exhibited elevated antiapoptotic Bcl-2 protein, concomitant with reduced caspase-3 cleavage and decreased PARP-1 protein. In BALB/c mice, topical application of GA on dorsal skin exposed to UV-B irradiation protected against epidermal hyperplasia, lymphocyte infiltration and expression of several inflammatory proteins, p38, JNK, COX-2, NF-κB and ICAM-1. Based on the above findings, we conclude that GA protects against UV-B-mediated photodamage by inhibiting the signalling cascades triggered by oxidative stress, including MAPK/NF-κB activation, as well as apoptosis. Thus, GA has strong potential to be used as a therapeutic/cosmeceutical agent against photodamage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|