title: Glycyrrhizic acid (GA) inhibits reactive oxygen Species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts.
abstract: BACKGROUND
  Previously we have reported that generation of reactive oxygen species is the prime event responsible for calcium mediated activation of PERK-eIF2α-CHOP pathway and apoptosis in UV-B irradiated human skin fibroblasts (Hs68). We have also reported that glycyrrhizic acid (GA) mediates potent photoprotective activity against UV-B - irradiation-induced photodamage in human skin fibroblast.
  
  
  OBJECTIVE
  In the present study, we aimed to investigate the role of GA in preventing oxidative stress mediated unfolded protein response (UPR) and mitogen activated protein kinases (MAPK) pathway.
  
  
  METHODS
  Human skin fibroblast (Hs68) cells were exposed to UV-B radiations in lab conditions. Different parameters of UVB induced cellular and molecular changes were analysed using western-blotting, microscopy and flow cytometry.
  
  
  RESULTS
  Our results show that GA has strong photoprotective action against UV-B induced cellular damage. It was observed that: (a) Oxidative disturbances and intracellular Ca(2+) imbalance induced by UV-B irradiation was significantly restored by GA treatment; (b) activation of PERK-eIF2α-CHOP and MAPK pathway induced by UV-B was significantly blocked by GA; (c) Loss of mitochondrial membrane potential and apoptosis induced by UV-B were reduced by GA treatment.
  
  
  CONCLUSIONS
  Based on the above findings we conclude GA has a highly significant ROS quenching activity, thereby blocking the cascade of events including release of calcium from ER and subsequent ER stress, MAPK pathway and cellular demise. GA offers highly potent anti photodamage effect and can be exploited for cosmetic or therapeutic purposes.
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Mufti Rana
authors.initials: MR
authors.lastname: Farrukh
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Ul-Ashraf
authors.initials: UA
authors.lastname: Nissar
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, 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, Canal Road, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Quadri
authors.initials: Q
authors.lastname: Afnan
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Praduman R
authors.initials: PR
authors.lastname: Sharma
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), New Delhi, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: stabdullah@iiim.ac.in.
authors.forename: Sheikh A
authors.initials: SA
authors.lastname: Tasduq
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000528:radiation effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019695:Glycyrrhizic Acid / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019695:Glycyrrhizic Acid; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium
keywords: ER stress; Glycyrrhizic acid; MAPK; Oxidative stress; UV-B