Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen-activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway

• Published in: Experimental dermatology 2016-06, Vol.25 (6), p.440-446
• Main Authors: Afnan, Quadri, Kaiser, Peerzada J., Rafiq, Rather A., Nazir, Lone A., Bhushan, Shashi, Bhardwaj, Subhash C., Sandhir, Rajat, Tasduq, Sheikh A.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; apoptosis; Apoptosis - drug effects; Cell Line; Dermatitis - etiology; Dermatitis - prevention & control; Drug Evaluation, Preclinical; glycyrrhizic acid; Glycyrrhizic Acid - pharmacology; Glycyrrhizic Acid - therapeutic use; Humans; Hyperplasia - etiology; Hyperplasia - prevention & control; inflammation; Methionine - analogs & derivatives; Mice, Inbred BALB C; mitogen-activated protein kinases; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; reactive oxygen species; Reactive Oxygen Species - metabolism; Skin - enzymology; Skin - radiation effects; Skin Aging - drug effects; Sulfoxides; Ultraviolet Rays - adverse effects; ultraviolet-B radiation
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.12964

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.