title: Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases.
abstract: Inflammasomes are multiprotein complexes having nucleotide-binding domain and leucine-rich repeat consisting members along with pyrin and HIN domain family. An inflammasome mainly consists of cytoplasmic sensor molecule, such as NLRP3, the adaptor apoptosisassociated speck-like protein containing caspase recruitment domain) protein along with effector procaspase-1. The inflammasome regulates caspase-1 activation, resulting in secretion of interleukin- 1β and interleukin-18. The inflammasome activation is linked with infection, stress, or other immunological signals involved in inflammation. The pathophysiological role of NLRP3 inflammasome in immune regulation, inflammatory receptor-ligand interactions, microbial-associated molecular patterns, danger as well as pathogen associated molecular patterns has been demonstrated in last few years. Furthermore, the role of the inflammasome in peripheral and central nervous system involved with cytokine and chemokine inflammatory responses has been demonstrated in preclinical and clinical studies. The understanding of molecular regulation of inflammasome associated pathways is crucial for drug design and delivery. The use of natural product as an alternate therapy is gaining focus because of easy access and cost effectiveness. A number of herbal extracts and its bioactive constituents known as phytochemicals have shown to be effective in inflammatory response mediated by NLRP3 inflammasomes pathways. To understand the interaction of phytochemicals and inflammasome at the molecular level, it is vital to develop effective drugs that can be evaluated further in the clinical settings. Therefore, this review renders an extensive account of all the phytochemicals which are evaluated either in inflammatory experimental animal models or in immortalized human/animal cell lines that modulate NLRP3 inflammasome mediated pathways to mitigate inflammatory responses with the hope that this pathway modulation by phytochemicals may provide a another class of drugs in the armamentarium as well as novel molecular mechanism of natural products targeting NLRP3 inflammasome.
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow-226001, India.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Jahan
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Lucknow-226001, India.
authors.forename: Dipak
authors.initials: D
authors.lastname: Kumar
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow-226001, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow-226001, India.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow-226001, India.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wahajuddin
authors.affiliation: Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India.
authors.forename: Yasir A
authors.initials: YA
authors.lastname: Khan
authors.affiliation: Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharastra, India.
authors.forename: Sameer N
authors.initials: SN
authors.lastname: Goyal
authors.affiliation: Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharastra, India.
authors.forename: C R
authors.initials: CR
authors.lastname: Patil
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Science, United Arab Emirates University, PO Box - 17666, Al Ain. United Arab Emirates.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Mohanraj
authors.affiliation: Department of Physiology, College of Medicine and Health Science, United Arab Emirates University, PO Box - 17666, Al Ain. United Arab Emirates.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Subramanya
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Science, UAE University, P.O. Box 17666; Al Ain, Abu Dhabi. United Arab Emirates.
authors.forename: Shreesh
authors.initials: S
authors.lastname: Ojha
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D064209:Phytochemicals / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D010946:Plants, Medicinal / Q000737:chemistry / Q000378:metabolism
chemical_list: D001688:Biological Products; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D064209:Phytochemicals
keywords: Herbs; NLRP3; inflammasome; inflammation; inflammatory diseases; interleukins-1β; medicinal plants; phytochemicals