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The Role of Plant-Based Natural Compounds in Inflammation
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Marcela Dvorakova, Premysl Landa, Lenka Langhansova
Arachidonic acid (AA) is released from membrane phospholipids by the action of phospholipases A2 (PLA2), which include about 30 different enzymes. Particularly, the cytosolic PLA2α enzyme regulates the AA release for a massive eicosanoid production in response to cytokines, growth factors and hormones, and is activated by intracellular Ca2+-influx and phosphorylation (Koeberle and Werz, 2018). The biosynthesis of eicosanoids occurs in all mammalian tissues and is regulated by an immune system. Eicosanoids are formed from AA via three systems (Figure 22.1): (i) by cyclooxygenases (COXs) and microsomal prostaglandin E synthase-1 (mPGES-1) to prostanoids that include prostaglandins (PGs) and thromboxane; (ii) by lipoxygenases (LOXs) to hydroperoxyeicosatetraenoic acids (HPETEs), leukotrienes (LTs), lipoxins (LXs) and monohydroxyeicosatetraenoic acids (HETEs); and (iii) by cytochrome P450 epoxygenase (CYP450) to epoxyeicosatrienoic acids (EETs). While PGs and LTs trigger inflammation processes, EETs are anti-inflammatory; however, they are rapidly degraded by soluble epoxide hydrolase (sEH) to corresponding diols-dihydroxyeicosatrienoic acids (DiHETrEs), thus losing their anti-inflammatory effect (Garscha et al., 2017).
Macronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
The cyclooxygenase pathways (COX 1 and 2) initiate the metabolism of omega-6 fatty acids (arachidonic acid, dihomo-gamma-linoleic acid) and omega-3 fatty acids like eicosapentaenoic acid (EPA) to prostanoids, including different prostaglandins, prostacyclins, and thromboxanes (98–102). The lipoxygenase pathways (5-LOX, 12-LOX, 15-LOXa, 15-LOXb) initiate the oxidation of arachidonic acid (AA) of omega-6 fatty acids as well as eicosapentaenoic acid (EPA) of omega-3 fatty acids to different leukotrienes and lipoxins in leukocytes (98–102). The cytochrome P450 pathways comprise a large number of enzymes that contain a heme iron, and are found in the liver and other tissues where they inactivate and eliminate toxins and metabolites and form various epoxy, hydroxy and dihydroxy derivatives. Near hundreds of distinct eicosanoid species are produced from omega-6 and omega-3 metabolism (98–100). Because they are rapidly catabolized (destroyed), eicosanoids mainly act locally to the site of their production. Many eicosanoids have multiple, sometimes pleiotropic, effects on immunity and inflammation (98). They also have roles in the regulation of the vascular, renal, gastrointestinal and female reproductive systems (98). They are also formed when cells are attacked by microbes, viruses, parasites, and so on. The most widely studied is prostaglandin PGE2. Although eicosanoids are most frequently associated with inflammation, they also have homeostatic functions (99).
Defences Against Infection
Published in Jeremy R. Jass, Understanding Pathology, 2020
These do not exist as preformed chemicals but are synthesised by activated inflammatory cells from the fatty acid arachidonic acid. The latter is released from cell membrane phospholipids by the action of phospholipase A2. There are two main families of eicosanoids: prostaglandins and leukotrienes. The prostaglandins have multiple biological effects, both stimulating and inhibiting inflammation. The ability of aspirin and other non-steroidal antiinflammatory drugs to suppress inflammation is explained in part by their inhibition of the enzyme cyclo-oxygenase (which converts arachidonic acid to prostaglandin G2). Leukotrienes are powerful inflammatory mediators serving as neutrophil chemotaxins and causing increased vascular permeability.
Antinociceptive activity of doliroside B
Published in Pharmaceutical Biology, 2023
Xishan Bai, Yanhong Li, Yuxiao Li, Min Li, Ming Luo, Kai Tian, Mengyuan Jiang, Yong Xiong, Ya Lu, Yukui Li, Haibo Yu, Xiangzhong Huang
The acetic acid-induced writhing model has been widely utilized as a standard assay to explore compounds with peripheral antinociceptive activity from natural sources (Ayumi et al. 2020). It was widely employed to evaluate the antinociceptive activity of triterpenoid saponins (Wang et al. 2006; Speroni et al. 2007; Yang et al. 2008; Chen et al. 2018). The injection of acetic acid stimulates peripheral tissue damage, which further promotes the synthesis of eicosanoids – an important mediator in pain and inflammation, and then results in the release of various inflammatory mediators and prostaglandins – a main substance sensitizing the nociceptive neuron and inducing hyperalgesia – which plays a key role in the writhing behaviors in this test (Berkenkopf and Weichman 1988). Therefore, we used the acetic acid-induced writhing model to evaluate the antinociceptive activity of D. trilobus-related compounds. Among them, DBDS showed the highest antinociceptive activity. The observed high antinociceptive activity of DBDS in the acetic acid-induced writhing test suggested that it could produce peripheral antinociception might related to the mechanism like peripherally acting drugs such as NSAIDs.
What can we learn from the platelet lipidome?
Published in Platelets, 2023
Gaëtan Chicanne, Jean Darcourt, Justine Bertrand-Michel, Cédric Garcia, Agnès Ribes, Bernard Payrastre
Another important pathway in platelets involves PLA2. Among the fatty acyls generated by PLA2, arachidonic acid is a major precursor for oxidative transformation to eicosanoids by lipoxygenase and cyclooxygenase pathways. Following stimulation, platelets produce a number of eicosanoids, including thromboxane A2 (TXA2), a proaggregatory lipid. T×A2 released by activated platelets acts as an auto- and paracrine molecule through the G-protein coupled receptor TP-receptor [7,8]. The calcium-sensitive cytosolic PLA2α isoform (cPLA2α) has a major role in human platelets as demonstrated in a rare inherited human deficiency of this enzyme leading to impaired platelet eicosanoid generation associated with platelet dysfunction [21]. A platelet lipidomic profiling study has highlighted the importance of PLA2α (cPLA2α) in platelet activation and clarified the substrates of this PLA2 isoform [22]. Moreover, the lysophospholipids generated by cPLA2 were identified but their role in platelet remains poorly understood. This study also suggested the involvement of cPLA2 in the production of a unique eicosanoid downstream of PAR4 and GPVI triggering.
Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy
Published in Drug Metabolism Reviews, 2023
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
AA is a polyunsaturated ω-6 fatty acid containing 20 carbons which are present in the phospholipids of the cell membrane and are liberated upon the action of cytosolic phospholipase A2 (cPLA2) (Sudhahar et al. 2010). The liberated intracellular AA is enzymatically metabolized into a vast array of biologically active metabolites known as ‘eicosanoids’ (Imig 2012). Eicosanoids encompass prostaglandins (PGs) and leukotrienes (LTs) synthesized from AA by cyclooxygenases (COXs) and lipoxygenases (LOXs), respectively (Kuehl and Egan 1980; Zordoky and El-Kadi 2010). Also, the CYP-mediated pathway generate hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) through CYP ω-hydroxylases and CYP epoxygenases, respectively (Figure 1) (Alsaad et al. 2013; Shoieb et al. 2020).