title: Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.
abstract: Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur-NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products.
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 226001, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Chopra
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India.
authors.forename: Lipika
authors.initials: L
authors.lastname: Ray
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Dwivedi
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Shashi Kant
authors.initials: SK
authors.lastname: Tiwari
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Singh
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India.
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India.
authors.forename: Hari Narayan
authors.initials: HN
authors.lastname: Kushwaha
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Jahan
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Pandey
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India; Department of Systems Biology & Bioinformatics, University of Rostock, Rostock 18057, Germany.
authors.forename: Shailendra K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
authors.forename: Rajnish Kumar
authors.initials: RK
authors.lastname: Chaturvedi
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: abpant@iitr.res.in.
authors.forename: Aditya Bhushan
authors.initials: AB
authors.lastname: Pant
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: ratanray.2011@rediffmail.com.
authors.forename: Ratan Singh
authors.initials: RS
authors.lastname: Ray
authors.affiliation: CSIR-Indian Institute of Toxicology Research, P.O. Box No. 80, M.G. Marg, Lucknow 226001, India; CSIR-Institute of Genomics & Integrative Biology, Mall Road, Delhi 110007, India; Department of Biological Sciences and Bioengineering (BSBE) and Centre for Environmental Science and Engineering (CESE), Indian Institute of Technology, Kanpur 208016, India. Electronic address: kcgupta@iitk.ac.in.
authors.forename: Kailash Chand
authors.initials: KC
authors.lastname: Gupta
mesh_terms: D065638:Absorption, Radiation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects / Q000528:radiation effects; D053960:DNA Breaks / Q000187:drug effects / Q000528:radiation effects; D065546:Drug Liberation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects* / Q000648:ultrastructure; D019344:Lactic Acid / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D017319:Photosensitizing Agents; D020011:Protective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin
keywords: Apoptosis/necrosis; Curcumin; Nanoformulation; Photodegradation; Photoprotection; Phototoxicity