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Biotransformation of Monoterpenoids by Microorganisms, Insects, and Mammals
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Yoshiaki Noma, Yoshinori Asakawa
The metabolic pathway of (+)-camphor (37) by microorganisms is shown in Figure 22.189. (+)-Camphor (37) is metabolized to 3-hydroxy- (243), 5-hydroxy- (235), 6-hydroxy- (228), and 9-hydroxycamphor (225) and 1,2-campholide (237). 6-Hydroxycamphor (228) is degradatively metabolized to 6-oxocamphor (229) and 4-carboxymethyl-2,3,3-trimethylcyclopentanone (230), 4-carboxymethyl-3,5,5-trimethyltetrahydro-2-pyrone (231), isohydroxycamphoric acid (232), isoketocamphoric acid (233), and 3,4,4-trimethyl-5-oxo-trans-2-hexenoic acid (234), whereas 1,2-campholide (237) is also degradatively metabolized to 6-hydroxy-1,2-campholide (238), 6-oxo-1,2-campholide (239), and 5-carboxymethyl-3,4,4-trimethyl-2-cyclopentenone (240), 6-carboxymethyl-4,5,5-trimethyl-5,6-dihydro-2-pyrone (241), and 5-carboxymethyl-3,4,4-trimethyl-2-heptene-1,7-dioic acid (242). 5-Hydroxycamphor (235) is metabolized to 6-hydroxy-1,2-campholide (238), 5-oxocamphor (236), and 6-oxo-1,2-campholide (239). 3-Hydroxycamphor (243) is also metabolized to camphorquinone (244) and 2-hydroxyepicamphor (245) (Bradshaw et al., 1959; Conrad et al., 1961, 1965a,b; Gunsalus et al., 1965; Chapman et al., 1966; Hartline and Gunsalus, 1971; Oritani and Yamashita, 1974) (Figure 22.189).
Molecular docking study of britannin binding to PD-L1 and related anticancer pseudoguaianolide sesquiterpene lactones
Published in Journal of Receptors and Signal Transduction, 2022
Gérard Vergoten, Christian Bailly
The compound structure/PD-L1 binding relationships in this short series of SLs are apparently complex. There is no simple rule to promote protein binding. The curvature of the tricyclic core is not essential. A compound like coronopilin, with a lactone ring annelated to the seven-membered ring via the 6,7-positions, is a relatively good PD-L1 binder (the third best in our series) whereas the close analogue damsin appears as a much weaker binder. The comparison of the pseudoguaianolides damsin and coronopilin (both isolated from the medicinal plant Ambrosia arborescens) is easy because they only differ by a C1–OH group. This hydroxyl on coronopilin is largely implicated in the interaction with PD-L1 (Figure 6), mimicking the C2 oxygen atom found in BRT and CHM. Coronopilin has been characterized as an anti-leukemic agent [36]. The potential contribution of PD-L1 inhibition to the anticancer activity of warrants further investigation. Finally, we noted that the presence of an α,β-unsaturated cyclopentenone moiety (as in helenalin, mexicanin I, bigelovin) is apparently not a favorable or necessary element for PD-L1 binding.
New insights into human prefrontal cortex aging with a lipidomics approach
Published in Expert Review of Proteomics, 2021
Mariona Jové, Natalia Mota-Martorell, Pascual Torres, Manuel Portero-Otin, Isidre Ferrer, Reinald Pamplona
Polyunsaturated fatty acids (PUFAs), profusely present in cell membranes, are very vulnerable to oxidation, and this vulnerability increases in function of the number of double bonds per fatty acid molecule [55,56]. The result of this sensitivity of PUFAs to diverse oxidation reactions and radical reactions, as part of the so-called lipid peroxidation process [55–58], is the formation of electrophilic lipid products, also called reactive carbonyl compounds (RCS). RCSs have signaling properties, but they can also be cytotoxic [19,59]. It is estimated that over a hundred different RCS can be generated, each with a wide range of reactivity, abundance, and half-life. Specifically, α,β-unsaturated aldehydes (acrolein and 4-hydroxy-2-nonenal (HNE)), di-aldehydes (glyoxal, and malondialdehyde (MDA)), and keto-aldehydes (neuroketals, and 4-oxo-2-nonenal (ONE)) are the most reactive RCS [60–62]. Additional significant lipid peroxidation-derived compounds are cyclopentenone prostaglandins, 2-hydroxyheptanal, 4-hydroxyhexenal, levuglandins, and oxidized phospholipids. The relatively long half-life (from seconds to minutes) of these compounds and their non-charged structure are features that allow them to react with cellular components both near and distant such as proteins, lipid membranes (specially aminophospholipids), and DNA [58,59].
Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and Inflammation Related to Cancer
Published in Nutrition and Cancer, 2018
Shreena J. Desai, Ben Prickril, Avraham Rasooly
The NF-κB family of transcription factors is a key regulator of immune development, immune responses, inflammation, and cancer. The promoter regions of COX-2 contain consensus sequences for NF-κB (53) and the NF-κB signaling system, including those governing interactions between NF-κB dimers and IκB regulators. These play key roles in COX-2 transcription and inflammation activated by external stimuli including lipopolysaccharide (LPS), infectious agents, free radicals, and cytokine stimuli such as trauma, viruses, UV radiation, free radicals, TNF-α, and IL-1β. These signals, along with PPAR-γ, turn on specific genes that lead to the production of inflammatory cytokines (54). The NF-κB binds to the IκB kinase forming the NF-κB-IκB complex. Pro-inflammatory stimuli activate the complex containing the NF-κB essential modulator (NEMO) and IκB kinase (IKK)1/2. IKK1/2 phosphorylates IκBs by IKK signalosome complex. After IκB has been phosphorylated it is ubiquitinated and degraded by 26S proteosome (55–57) and the resulting free NF-κB translocates to the nucleus where it binds to the promoter κB sites of pro-inflammatory genes. These include inducible nitric oxide synthase (iNOS), COX-2, IL-1β, IL-6, and TNF-α (58–60), and activate gene expression (61,62) to induce expression (63). A negative feedback prevents overproduction of cyclopentenone prostaglandins (cyPG) which can directly inhibit NF-κB activity by preventing phosphorylation and degradation of the NF-κB inhibitor IκBα (64). Alternatively, the cyPG metabolite PGA1 inhibits TNF-α-induced phosphorylation of ΙκBα-NF-κB DNA binding and prevents NF-κB transactivation and continued nuclear accumulation of NF-κB (65)