Title:Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases
Volume: 24
Issue: 16
Author(s): Sadaf Jahan, Dipak Kumar, Swati Chaturvedi, Mamunur Rashid, Muhammad Wahajuddin, Yasir A. Khan, Sameer N. Goyal, C. R. Patil, Rajesh Mohanraj, Sandeep Subramanya and Shreesh Ojha*
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
Keywords:
Herbs, inflammasome, inflammation, interleukins-1β, NLRP3, phytochemicals, medicinal plants,
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.
