Mufti Rana Farrukh1, Ul-Ashraf Nissar2, Peerzada J Kaiser1, Quadri Afnan1, Praduman R Sharma3, Shashi Bhushan4, Sheikh A Tasduq5. 1. PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India. 2. 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. 3. Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India. 4. 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. 5. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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.