The pleiotropic anti-inflammtory effects of boswellic acids can be discussed as follows:
- Inhibition of leukotrienes biosynthesis
- Inhibition of human leukocyte elastase (HLE)
- Higher terpenoids, including boswellic acids (25 – 35%)
- By cathespin G (catG) inhibition
- By anticholinesterase (AChE) inhibition
Leukotrienes, which are fatty acids derived from arachidonic acid through the action of the enzyme 5-lipoxygenase (5-LO), play a role in the body’s natural inflammatory and immune responses (Majeed et al., 1996; Henderson, 1994; Ford-Hutchinson et al., 1993). These compounds are involved in managing the body’s response to various physiological challenges and can influence the maintenance of healthy inflammatory processes. Research highlights the involvement of leukotrienes in the complex mechanisms behind the body’s response to inflammation and allergens (Mogana et al., 2013). Understanding these processes is crucial for exploring how natural substances might support the body in maintaining normal, healthy responses to environmental and internal triggers
Boswellic acids are reported to possess non-redox, non-competitive inhibitory actions on 5-LO enzyme via allosteric regulation. It has been suggested that the pentacyclic triterpene ring system is crucial for binding to the highly selective effector site, whereas functional groups (especially the 11-keto function in addition to a hydrophilic group on C-4 of the ring A) are essential for 5-LO inhibitory activity.
- Interacting with the 5-lipoxygenase-activating protein (FLAP) (Safayhi et al., 1992)
Based on IC50 values, acetyl-11-keto-β-boswellic acid (AKBBA) provides the most potent inhibitory action due to its optimal structure (Safayhi et al., 1992, Sailer et al., 1996).
Inhibition of human leukocyte elastase (HLE)
Human Leukocyte Elastase (HLE) is a serine protease enzyme present in neutrophil leukocytes, playing a role in the body’s natural processes related to inflammation (Lee and Downey, 2001). HLE’s activity is part of the complex mechanisms the body uses to respond to various physiological challenges. Research has explored the involvement of HLE in the body’s inflammatory responses, highlighting its significance in maintaining normal immune and inflammatory functions (Shah et al., 2009). Understanding these natural processes is key to exploring how nutritional and herbal supplements might support the body in maintaining healthy immune and inflammatory responses
Boswellic acids, especially AKBBA showed HLE inhibition with an IC50 of 15 μM
Inhibition of cathepsin G (catG)
CatG is also a serine protease enzyme found in the neutrophils. Its role has been implicated in various pathophysiological processes, though controversially discussed, viz digestion of extracellular matrix and damaging local connective tissues, chemoinvasion of T cells and leukocytes, and stimulation of platelet aggregation Tausch et al., 2019.
Boswellic acids directly bind, competitively interact and reversibly inhibit catG at submicromolar IC50 ranges. They suppressed the catG activity ex vivo after oral administration to human subjects (Tausch et al., 2019).
Inhibition of acetylcholinesterase (AChE)
AChE is a specific enzyme that is involved in the hydrolysis of cholinergic neurotransmitter acetylcholine (ACh) into choline and acetate (Ota abd Houghton, 2007).Inhibitors of Acetylcholinesterase (AChE) have been studied for their role in supporting the body’s natural regulatory processes, including modulation of inflammation. Research suggests that these inhibitors can influence the body’s response to inflammation by affecting the release of cytokines, which are part of the immune system’s communication network. Such insights highlight the potential for certain nutrients or compounds to support the body in maintaining a balanced inflammatory response as part of overall health and wellness. (Mogana et al., 2013).
Ota and Houghton, 2007, reported that boswellic acids viz 11α-hydroxy-βboswellic acid and 11-keto-β-boswellic acid inhibit AChE activity. Their AChE inhibitory activity was associated to the presence of either the free hydroxyl group or keto group at C-11 and free hydroxyl group at C-3 in the ursane skeleton.