Nworu and Akah Afr J Tradit Complement Altern Med. (2015) 12(Suppl.):52-61 http://dx.doi.org/10.4314/ajtcam.v12i6.3S ANTI-INFLAMMATORY MEDICINAL PLANTS AND THE MOLECULAR MECHANISMS UNDERLYING THEIR ACTIVITIES Chukwuemeka Sylvester Nworu & Peter Achunike Akah Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka Correspondence: peterakah@hotmail.com Abstract Background: Medicinal plant and plant products have shown tremendous potentials and are used beneficially in the treatment of inflammation and in the management of diseases with significant inflammatory components. Many medicinal plants employed as anti-inflammatory and anti- phlogistic remedies lack the gastro-erosive side effects of non-steroidal anti-inflammatory drugs (NSAID) or the plethora of unwanted side effects associated with steroidal anti-inflammatory drugs. In order to harness and optimise the applications of these herbs in inflammatory diseases, there is a need to understand how these herbs produce their anti-inflammatory actions. Materials and Methods: This paper is a review of some anti-inflammatory herbs and their molecular mechanisms of action. A literature search and analysis of published manuscript was employed to x-ray research findings that show how medicinal plants produce anti-inflammatory activities. Results: Many studies have shown that anti-inflammatory activities of herbal extracts and herb-derived compounds are mainly due to their inhibition of arachidonic acid (AA) metabolism, cyclo-oxygenase (COX), lipo-oxygenase (LOX), pro-inflammatory cytokines, inducible nitric oxide, and transcription activation factor (NF-κB). Some anti-inflammatory medicinal herbs are reported to stabilize lysosomal membrane and some cause the uncoupling of oxidative phosphorylation of intracellular signalling molecules. Many have also been shown to possess strong oxygen radical scavenging activities. Conclusion: Most of the mechanisms by which anti-inflammatory medicinal plants act are related and many herbal products have been shown to act through a combination of these molecular pathways. Key words: Medicinal plants, antiinflammatory, mechanism of action, molecular pathways. Introduction There are several proposed cellular actions or mechanisms explaining in vivo anti-inflammatory activity of medicinal plants. These mechanisms include antioxidative and radical scavenging activities, regulation of cellular activities of the inflammation-related cells: mast cells, macrophages, lymphocytes, and neutrophils (for instance, some inhibit histamine release from mast cells and others inhibit T-cell proliferation), modulation of the enzymatic activities of arachidonic acid (AA) metabolizing enzymes such as phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX) and the nitric oxide (NO) producing enzyme, nitric oxide synthase (NOS) (Vane and Botting, 1987; Chen, 2011). Inhibitions of these enzymes by anti-inflammatory medicinal plants products (AIMP) reduce the production of AA, prostaglandins (PG), leukotrienes (LT), and NO, which are crucial mediators of inflammation (Khanapure et al., 2007). Thus, the inhibition of these enzymes by AIMP is one of the important cellular mechanisms of anti-inflammation. In recent years, many lines of evidence support the idea that certain AIMP are the modulators of gene expression, especially the modulators of pro-inflammatory gene expression, thus leading to the attenuation of the inflammatory response. Here, we have highlighted the relevance of these mechanisms as they relate to the activities of herbal products used in the treatment of inflammation. 1.0 Inhibition of Phospholipase A2 During inflammatory response, arachidonic acid (AA), a precursor of eicosanoids, is released mostly from membrane lipids in cells. The enzyme responsible for this release is Phospholipase A2 (PLA2), although some portion is attributed to the combined action of phospholipase C and diacylglycerol lipase (Ito et al., 2002). AA mobilization by PLA2 and subsequent prostaglandins synthesis is considered to be a pivotal event in inflammation. Therefore, drugs that inhibit PLA2 thus block the cyclo-oxygenase (COX) and lipo-oxygenase (LOX) pathways in the AA cascade are effective in the treatment of inflammatory processes. PLA2 catalyses the hydrolysis of the acyl group attached to the 2-position of intracellular membrane phosphoglycerides which releases arachidonic acid from membrane phosphoglycerides. Arachidonic acid is the precursor of prostaglandins (PGs), thromboxanes, and leukotrienes. Some anti-inflammatory medicinal plants inhibit PLA2 (Figure 1) and this inhibition is mediated via lipocortine or by direct interaction with the enzyme itself. The former mechanism utilizes a protein known as lipocortine, the synthesis of which is induced by steroidal hormones and steroidal plant metabolite, triterpenoids (Barnes, 1998). The other mechanism involves a direct binding with the enzyme itself, a mechanism that is yet to be exploited in therapeutics but with great promise. It is known that betulinic acid, a triterpene act by direct binding to phospholipase A2 (Wiart, 2006). The inhibitory activity of several flavonoid derivatives against AA metabolizing enzymes was initially reported in 1980 (Bauman et al., 1980). Thereafter, investigators have studied the inhibitory effect of flavonoids on these enzymes (Kim et al., 2004). Up to date, many isoforms of PLA2 have been discovered (Murakami and Kudo, 2004). They are mainly classified into three large categories, secretory PLA2 (sPLA2), cytosolic PLA2 (cPLA2), and calcium independent PLA2 (iPLA2). These PLA2s are distributed in wide varieties of tissues and cells. In some conditions, they are coupled to COXs depending on the cells and agonists used (Murakami and Kudo, 2004). For instance, group IIA sPLA2 was found in arthritic synovial fluid, and group IV cPLA2 are coupled to COXs and 5-LOX to produce eicosanoids (Murakami and Kudo, 2004). Therefore, a modulation of sPLA2 and/or cPLA2 activity is important in the control of inflammatory processes. The first flavonoid inhibitor of PLA2 to be identified was quercetin, which inhibited PLA2 from human neutrophils (Lee et al., 1982). 52 brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by ATHMSI Journals