title: Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen-activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway.
abstract: 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.
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.|Department of Biochemistry, Panjab University, Chandigarh, India.
authors.forename: Quadri
authors.initials: Q
authors.lastname: Afnan
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Peerzada J
authors.initials: PJ
authors.lastname: Kaiser
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Rather A
authors.initials: RA
authors.lastname: Rafiq
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Lone A
authors.initials: LA
authors.lastname: Nazir
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.|Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Department of Pathology, Government Medical College, Jammu, Jammu and Kashmir, India.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Bhardwaj
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, India.
authors.forename: Rajat
authors.initials: R
authors.lastname: Sandhir
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu Tawi, Jammu and Kashmir, India.|Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Sheikh A
authors.initials: SA
authors.lastname: Tasduq
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003872:Dermatitis / Q000209:etiology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D019695:Glycyrrhizic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D008715:Methionine / Q000031:analogs & derivatives; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects*; D013454:Sulfoxides; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013454:Sulfoxides; C000594507:buthionine sulfoxide; D019695:Glycyrrhizic Acid; D008715:Methionine; D020928:Mitogen-Activated Protein Kinases
keywords: apoptosis; glycyrrhizic acid; inflammation; mitogen-activated protein kinases; reactive oxygen species; ultraviolet-B radiation