11-keto-β-Boswellic Acid

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Background

IC50: 35.8 μM: inhibits MCF-7 (human breast adenocarcinoma) [1].
37.9 μM: blocks A2780 (cis-platin resistant ovarian cancer cells) [1].
11-keto-β-Boswellic Acid, known as KBA, is a naturally occurring pentacyclic triterpene isolated from the gum resin of the tree Boswellia serrata. KBA is non-redox, specific leukotriene synthesis inhibitors through the inhibition of 5-lipoxygenase (5-LOX) which has anti-arthritic and anti-inflammatory activities. 5-LOX catalyzes essential fatty acids substrates into leukotrienes and a variety of other biologically active products. KBA is a novel activator of nuclear factor erythroid-2-related factor 2 (Nrf2), which protects against cerebral ischemic injury.
In vitro: KBA, concentration dependently, decreased the formation of leukotriene B4 and the synthesis of all 5-LOX products from endogenous arachidonic acid in rat peritoneal neutrophils. In contrast, KBA exerted no remarkable effects on the 12-lipoxygenase and cyclooxygenase activities. [2].
In vivo: Adult male Sprague–Dawley rats were injected KAB intraperitoneally at a dose of 25 mg/kg for 48 hours. KAB remarkably decreased infarct volumes as well as apoptotic cells at 1 h, and then increased neurologic scores when applied 48 h. Moreover, posttreatment with KBA induced the decrease of malondialdehyde levels and the increase of protein Nrf2 and heme oxygenase-1 expression in brain tissues, indicating that the Nrf2/HO-1 pathway was involved in the neuroprotection of KBA against oxidative stress-induced ischemic injury [3].

[1]. Csuk, R., Barthel-Niesen, A., Barthel, A., Schffer, R., & Al-Harrasi, A. 11-Keto-boswellic acid derived amides and monodesmosidic saponins induce apoptosis in breast and cervical cancers cells. European Journal of Medicinal Chemistry. 2015; 100: 98-105.
[2]. Safayhi, H., Mack, T. H. O. M. A. S., Sabieraj, J. O. A. C. H. I. M., Anazodo, M. I., Subramanian, L. R., & Ammon, H. P. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. Journal of Pharmacology and Experimental Therapeutics. 1992; 261(3):1143-1146.
[3]. Ding, Y., Chen, M., Wang, M., Li, Y., & Wen, A. Posttreatment with 11-Keto-β-Boswellic Acid Ameliorates Cerebral Ischemia–Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism. Molecular Neurobiology. 2014; 52(3): 1430-1439.