International Journal of Molecular Sciences Review An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases Nand Kishor Roy 1, Dey Parama 1, Kishore Banik 1, Devivasha Bordoloi 1, Amrita Khwairakpam Devi 1, Krishan Kumar Thakur 1, Ganesan Padmavathi 1, Mehdi Shakibaei 2, Lu Fan 3, Gautam Sethi 3,* and Ajaikumar B. Kunnumakkara 1,* 1 Cancer Biology Laboratory and DBT-AIST International Centre for Translational and Environmental Research(DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India 2 Musculoskeletal Research Group and Tumour Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Ludwig-Maximilian-University, 80336 Munich, Germany 3 Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore * Correspondence: [email protected] (G.S.); [email protected] or [email protected](A.B.K.); Tel.: +65-65163267 (G.S.); +91-361-258-2231 or +91-789-600-5326 (A.B.K.); Fax: +65-68737690 (G.S.); +91-361-258-2249 (A.B.K.) Received: 24 July 2019; Accepted: 16 August 2019; Published: 22 August 2019 Abstract: Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri. It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson’s disease, Alzheimer’s, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases. Keywords: boswellic acid; chronic diseases; molecular targets; pharmacokinetics; bioavailability 1. Introduction Chronic disease can be defined as a physical or psychological state that leads to functional limitations or requires constant observation or treatment for a long period. Worldwide, chronic diseases have hampered the health and living conditions of many [1]. Many of the universally used clinical drugs (especially the biologics) these days bear the shortcomings of side effects and high treatment cost [2]. Thus, numerous natural compounds, which have identified as potent modulators of signaling and epigenetic pathways leading to cancer, are under development presently [3]. Natural products have gained considerable attention as they are plentiful sources of diverse compounds, which can function as biologically active drugs against different chronic diseases [4–14]. These plant-derived molecules have significantly enhanced the existing medicinal system. For example, in a developing nation like India, around 65% of the country’s population gets benefitted by the use of phytomedicines that play an essential role in the health management system. satisfying. In developed nations like the USA, the sale of phytomedicines has registered a sharp incline in recent years. Around 80% of Int. J. Mol. Sci. 2019, 20, 4101; doi:10.3390/ijms20174101 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 2 of 27 nationsInt. J. 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Sources Sources and and Chemical Chemical Analogue Analoguess of of Boswellic Boswellic Acid Acid BABA comprises comprises of of a a series series of of pentacyclic pentacyclic triterpene triterpene molecules, molecules, generated generated by by the the trees trees in in the the genus genus BoswelliaBoswellia,, usually knownknown asas Indian Indian olibanum, olibanum, salai salai guggal, guggal, loban, loban, or kundur, or kundur and is, and found is tofound be eff toective be effectiveagainst manyagainst diseases. many diseases. Categorized Categorized under the under Burseraceae the Burseraceae family, these family, are moderatethese are tomoderate large-sized to largebranching-sized branching trees prevailing trees prevailing over the mountainous over the mountainous regions of India,regions Northern of India, Africa, Northern and Africa, the Middle and theEast. Middle The genus East. BoswelliaThe genusconsists Boswellia of roughlyconsists 25of speciesroughly widely 25 species dispersed widely in dispersed Arabia, the in Northeastern Arabia, the Ncoastortheastern of Africa, coast and of India Africa, [32 and,36] (FigureIndia [32,361). ] (Figure 1). (A) (B) FigureFigure 1. 1. (A(A) Boswellia) Boswellia (Pankaj (Pankaj Oudh Oudhiaia/www.discoverlife.org)/www.discoverlife.org )and and (B (B) )Boswellia Boswellia gum gum resin resin.. Int. J. Mol. Sci. 2019, 20, 4101 3 of 27 In India, Boswellia is mostly found in Andhra Pradesh, Gujarat, Madhya Pradesh, Jharkhand, and Chattisgarh. These are the most viable sources of Boswellia. The gum resin of B. serrata and B. carteri contain as many as 12 different types of BAs, but among these the six major acids identified are α and β-boswellic acids (BA), acetylated α and β-boswellic acids (ABA), 11-keto-β-boswellic acid (KBA), and 3-O-acetyl-11-keto-β-boswellic acid (AKBA), which