Boswellic acid, the major constituent of boswellia, is thought to contribute to most of the herb's pharmacological activities. In vitro studies and animal models show that boswellic acid inhibits 5-lipoxygenase selectively (1) (3) and has anti-inflammatory (13), antiarthritic, and anti-proliferative effects (2). It also inhibits the signaling pathways of the transcription factor, nuclear factor (NF-KappaB), in macrophages in mouse model of psoriasis, markedly decreasing the production of the pro-inflammatory key cytokine tumor necrosis factor (TNF-alpha) (17). Unlike other non-steroidal anti-inflammatory drugs, however, boswellic acid fails to show analgesic or antipyretic effects (16); it does not cause gastric ulcers in animals. This suggests that it acts through other mechanisms and not by inhibiting prostaglandin synthesis.
Research on the cytotoxic effects of boswellic acid indicates that it induces p21 expression through a p53-independent pathway and causes apoptosis in glioma (4) (6) and leukemia (5) cell lines. In addition, a Boswellia extract induced apoptosis in a cervical cancer cell line by inducing endoplasmic reticulum (ER) stress (18); another apoptotic mechanism exhibited by Boswellia is via oxidative stress by early generation of nitric oxide and reactive oxygen species that up regulate time-dependent expression of p53/p21/PUMA (19).
A semisynthetic analog of boswellic acid, 3-alpha-Butyryloxy-beta-boswellic acid, demonstrated significant growth inhibition in Ehrlich Ascitic Tumour (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma- 180 tumour models, via down-regulation of NF-KappaB and by induction of poly (ADP-ribose) polymerase (PARP) cleavage (27).
In other studies, acetyl-boswellic acids was shown to inhibit topoisomerases by competing with DNA for binding sites (20). Whereas acetyl-11-keto-beta-boswellic acid (AKBA) inhibited the activation of signal transducers and activators of transcription-3 (STAT-3), which has been linked with survival, proliferation, chemoresistance, and angiogenesis of tumor cells (21). Conversely, AKBA was found to inhibit human prostate tumor growth via inhibition of angiogenesis induced by VEGFR2 signaling pathways (22). Further research is needed to resolve this discrepancy and to clarify the role of AKBA.