β-Boswellic Acid, A Safe and Clinically Effective Inhibitor of Prostaglandin E Synthase-1, Has Potential for Prevention of Cancer, Alzheimer’s Disease, and Vascular Disorders, and for Control of Inflammatory Pain

Boswellia serrata gum resin –a.k.a. frankincense – has traditionally been used as an anti-inflammatory agent in Ayurvedic medicine. More recently, extracts of this resin enriched in boswellic acids have demonstrated anti-inflammatory properties in rodents and beneficial clinical effects in arthritis, colitis, and brain edema, without notable side effects. Although initial reports suggested that the clinical utilty of boswellic acids might reflect inhibition of 5-lipoxygenase, more recent studies pinpoint microsomal prostaglandin E synthase-1 (mPGES-1) as their likely target. This raises the intriguing prospect that boswellic acids, by inhibiting PGE2 production at a distal level – so that production of protective prostacyclin is not blocked might provide many of the therapeutic and preventive benefits associated with cyclooxygenase inhibitors, without the toxic risks entailed by these drugs. Regular use of NSAIDs or aspirin has been associated with a modest reduction in risk for many cancers, and markedly lower risk for Alzheimers disease (albeit these agents are not therapeutically useful in the latter); there is reason to suspect that a suppression of mPGES-1-mediated PGE2 production may be largely responsible for these protective effects. mPGES-1 knockout mice appear to be less prone to atherosclerosis, experience less brain trauma following stroke, and do not develop the gastrointestinal or renal lesions associated with use of non-specific cyclooxygenase inhibitors; they are also protected in models of inflammatory hyperalgesia. If further studies confirm that boswellic acids can function clinically as mPGES-1 inhibitors, there will be reason to suspect that these safe natural agents will have utility in the prevention of Alzheimer’s disease and many cancers, without adverse consequences for the GI tract, kidneys, or vascular system, and will also be useful in the management of cancer and inflammatory hyperalgesia. Microsomal Prostaglandin E Synthase-1 May be the Key Target of Boswellic Acids The gum resin of Boswellia serrata – more popularly known as frankincense – have been used traditionally in Ayurvedic medicine for treatment of inflammatory disorders. More recently, extracts of this resin enriched in pentacyclic triterpenoids known as boswellic acids have been employed as antiinflammatory nutraceuticals. 1, 2 Pilot clinical studies do indeed suggest that such extracts can promote pain control and dampen inflammation in osteoarthritis and colitis, and help to control the brain edema associated with radiotherapy of cerebral tumors; anti-inflammatory effects in rodent models have also been demonstrated. 3-12 The most prominent of the boswellic acids in frankincense is beta-boswellic acid; the other boswellic acids are derived by addition of a ketone group and/or an acetyl group to betaboswellic acid. Initial attempts to clarify the molecular target of boswellic acids in inflammatory disorders determined that keto-boswellic acids can inhibit 5-lipoxygenase in low micromolar concentrations. 13-16 This suggested that boswellic acid preparations might dampen inflammation by blocking leukotriene synthesis,