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      Googling the Guggul (Commiphora and Boswellia) for Prevention of Chronic Diseases

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          Abstract

          Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug discovery which is based on thinking that most chronic diseases are caused by alteration of a single gene and thus most therapies are single gene-targeted therapies. However, extensive research has revealed that most chronic diseases are caused by multiple gene products. Although most drugs designed by man are mono-targeted therapies, however, those designed by “mother nature” and have been used for thousands of years, are “multi-targeted” therapies. In this review, we examine two agents that have been around for thousands of years, namely “guggul” from Commiphora and Boswellia. Although we are all familiar with the search engine “google,” this is another type of “guggul” that has been used for centuries and being explored for its various biological activities. The current review summarizes the traditional uses, chemistry, in vitro and in vivo biological activities, molecular targets, and clinical trials performed with these agents.

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          Most cited references215

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          Cells of the synovium in rheumatoid arthritis. Macrophages

          The multitude and abundance of macrophage-derived mediators in rheumatoid arthritis and their paracrine/autocrine effects identify macrophages as local and systemic amplifiers of disease. Although uncovering the etiology of rheumatoid arthritis remains the ultimate means to silence the pathogenetic process, efforts in understanding how activated macrophages influence disease have led to optimization strategies to selectively target macrophages by agents tailored to specific features of macrophage activation. This approach has two advantages: (a) striking the cell population that mediates/amplifies most of the irreversible tissue destruction and (b) sparing other cells that have no (or only marginal) effects on joint damage.
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            Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

            Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings.
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              A natural product that lowers cholesterol as an antagonist ligand for FXR.

              Extracts of the resin of the guggul tree (Commiphora mukul) lower LDL (low-density lipoprotein) cholesterol levels in humans. The plant sterol guggulsterone [4,17(20)-pregnadiene-3,16-dione] is the active agent in this extract. We show that guggulsterone is a highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is activated by bile acids. Guggulsterone treatment decreases hepatic cholesterol in wild-type mice fed a high-cholesterol diet but is not effective in FXR-null mice. Thus, we propose that inhibition of FXR activation is the basis for the cholesterol-lowering activity of guggulsterone. Other natural products with specific biologic effects may modulate the activity of FXR or other relatively promiscuous nuclear hormone receptors.
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                Author and article information

                Contributors
                URI : http://loop.frontiersin.org/people/363056/overview
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                06 August 2018
                2018
                : 9
                : 686
                Affiliations
                [1] 1Cancer Biology Laboratory, DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati , Assam, India
                [2] 2Department of Biochemistry, Institute of Science, Banaras Hindu University , Varanasi, India
                [3] 3Inflammation Research Center , San Diego, CA, United States
                Author notes

                Edited by: Atanas G. Atanasov, Institute of Genetics and Animal Breeding (PAS), Poland

                Reviewed by: Gokhan Zengin, Selçuk University, Turkey; Ajay Bommareddy, Wilkes University, United States

                *Correspondence: Ajaikumar B. Kunnumakkara kunnumakkara@ 123456iitg.ac.in
                Bharat B. Aggarwal bbaggarwal@ 123456gmail.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.00686
                6087759
                30127736
                babe80de-e0cc-41f3-bb6f-7badd24495bd
                Copyright © 2018 Kunnumakkara, Banik, Bordoloi, Harsha, Sailo, Padmavathi, Roy, Gupta and Aggarwal.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 January 2018
                : 06 June 2018
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 221, Pages: 19, Words: 15499
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                guggul,guggulsterone,boswellia,boswellic acid,cancer,commiphora,chronic diseases

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