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Cytochromes P450, Cardiovascular Homeostasis and Disease
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Chin Eng Ong, Amelia Dong, Boon Hooi Tan, Yan Pan
All eicosanoid metabolites are derived from arachidonic acid (AA), a 20-carbon, omega-6 polyunsaturated fatty acid (PUFA) released from the cell membrane phospholipids by the cytosolic enzyme phospholipase A2 (Sudhahar et al., 2010). Cell injury, shear stress, and hormones such as bradykinin, acetylcholine, angiotensin II, and adenosine are among the phospholipase activators that initiate eicosanoid synthesis. Figure 15.1 depicts three major pathways involved in eicosanoid synthesis: the cyclooxygenase (COX) pathway, which generates prostanoids; lipoxygenase (LOX) pathway, which produces leukotrienes and HETEs; and lastly, CYP pathways (CYP epoxygenase and CYP ω-hydroxylase) that generate EETs (Oni-Orisan et al., 2014; Wang and Dubois, 2012). Two CYP isoforms, CYP5A1 and CYP8A1, are involved in generation of prostanoids in the COX pathway. More popularly known as thromboxane A2 synthase (Wang and Kulmacz, 2002), CYP5A1 is involved in platelet aggregation, whereas CYP8A1, also called prostacyclin (PGI2) synthase (Ullrich and Hecker, 1990), participates in platelet disaggregation. Thus, CYP5A1 and CYP8A1 provide a Yin-Yang mechanism for regulation of blood coagulation. CYP epoxygenases are involved in production of EETs (Spector et al., 2004) through olefin epoxidation with both CYP2J and CYP2C epoxygenases generating four EET regioisomers defined by the location of the appended oxygen atom (5,6-, 8,9-, 11,12-, and 14,15-EETs). Each regioisomer consists of a mixture of S/R and R/S enantiomers. CYP2J2, CYP2C8, and CYP2C9 are constitutively and abundantly expressed in the human heart tissue (DeLozier et al., 2007). All EETs are subsequently hydrolyzed by soluble epoxide hydrolase (sEH) (Wang and Dubois, 2012) to form the less active dihydroxyeicosatrienoic acids (DHETs) with a shorter half-life, effectively terminating their biological effects. This makes sEH a target for increasing and prolonging the actions of EETs (Harris and Hammock, 2013). CYP ω-hydroxylases catalyze ω-terminal hydroxylation to form C16–C20 alcohols of AA (16-, 17-, 18-, 19-, and 20-HETEs). Among the different ω-hydroxylases available, CYP4A and CYP4F enzymes are involved in generating 20-HETE, a vasoactive and natriuretic eicosanoid important for vascular function (Fan et al., 2016).
Isolation of bioactive components with soluble epoxide hydrolase inhibitory activity from Stachys sieboldii MiQ. by ultrasonic-assisted extraction optimized using response surface methodology
Published in Preparative Biochemistry & Biotechnology, 2021
Dan Gao, Vinh Le Ba, Rustamov Rustam, Chong Woon Cho, Seo Young Yang, Xiang Dong Su, Young Ho Kim, Jong Seong Kang
Stachys sieboldii MiQ. (Labiatae), Korean name Cho Seok jam, is a well-known food and herbal medicine widely distributed in China, South Korea, and Japan.[1]Stachys sieboldii MiQ (SSM) is also used in Chinese folk medicine for the treatment of cerebral infarction, dementia, gastrointestinal related diseases, and cardiovascular disease.[2,3] SSM is used in Korea as a food additive to improve the taste and nutritional value of traditional porridge, noodles, rice cake, and bread.[4–6] Modern pharmacological studies demonstrate that SSM can benefit nephritis, hypoxia, learning and memory dysfunction, oxidative stress, and diabetes.[6–9] However, to the best of our knowledge, soluble epoxide hydrolase (sEH) inhibition by SSM has not be investigated.