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Mitochondrial Redox Regulation in Adaptation to Exercise
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Christopher P. Hedges, Troy L. Merry
The main producers of ROS during exercise are thought to be enzymes external to mitochondria, such as xanthine oxidase and different NADPH oxidase (NOX) isoforms (Powers et al., 2011b; Powers and Jackson, 2008). NOX enzymes are located in many places in skeletal muscle – including mitochondrial membranes (Sakellariou et al., 2013; Ago et al., 2010; Ferreira and Laitano, 2016), and mice that express a kinase-dead form of NOX2, a cytosolic NOX isoform, show no change in cell redox state or phosphorylation of p38 MAPK in response to exercise (Henriquez-Olguin et al., 2019a). Furthermore, inhibition of NOX2 prevents exercise-induced changes in muscle mitochondrial and antioxidant mRNA expression (Henriquez-Olguin et al., 2016). However, some caution should be taken attributing the effects seen by Henriquez-Olguin et al. (2016) solely to NOX2, as the inhibitor used (apocynin) can act as a general antioxidant rather than specifically as a NOX inhibitor (Ferreira and Laitano, 2016; Heumuller et al., 2008). Xanthine oxidase is another prominent candidate for ROS production during exercise, as it is present in skeletal muscle (Wajner and Harkness, 1989; Hellsten-Westing, 1993), and use of the xanthine oxidase inhibitor allopurinol attenuates oxidative stress and muscle damage in both humans and rodents (Gomez-Cabrera et al., 2003; Vina et al., 2000). It is therefore likely that these non-mitochondrial sources play a key role in cell signalling in response to exercise.
Phytolacca dodecandra (African Soapberry) and Picrorhiza kurroa (Kutki)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
K. Meenakshi, Mansi Shah, Indu Anna George
Cucurbitacin glycosides B, D, and E are reported from P. kurroa (Mallick et al., 2015). The phenolic compounds phenol glycoside picein, apocynin, androsin, and vanillic acid are also reported from the P. kurroa (Dorsch et al., 1991; Engels et al., 1992; Krupashree et al., 2014). Carbohydrates such as D mannitol and aromatic compounds cinnamic acid, vanillic acid, and ferulic acid are present in the plant (Masood et al., 2015).
Cardiovascular Disease and Oxidative Stress
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marco Fernandes, Alisha Patel, Holger Husi
Apocynin a NADPHox agonist exerts its mode of action by binding to the p47phox subunit (Stolk et al., 1994). Experimental studies with animal models using this inhibitor have shown reduction of ROS and an overall enhancement of the hypertensive state in rats (Baumer et al., 2007), and it could also be demonstrated to lead to an inhibition of both NADPHox expression and activation in streptozotocin (STZ)-diabetes (Olukman et al., 2010) and high fructose-fed mice (Shinozaki et al., 2004). Additionally, apocynin seems to reduce, in a dose-dependent mode, the number of cell adhesion molecules, such as of P-selectin and VCAM1, and also reduce platelet adhesion and monocyte accumulation (Liu et al., 2013). Other promising NOX4 inhibitors such as the recently designed novel tertiary sulphonylureas (23–25) are being discovered using computational approaches, but those need further scientific scrutiny of functional classification and characterization of their pharmacological profile (Xu et al., 2018).
Pharmacology of apocynin: a natural acetophenone
Published in Drug Metabolism Reviews, 2021
Shreya R. Savla, Ankit P. Laddha, Yogesh A. Kulkarni
Growing evidence and research on apocynin has highlighted its potential as a therapeutic agent for many disorders. A number of chemical and pharmaceutical modifications have significantly improved the pharmacokinetic profile of apocynin, making it potentially more druggable. Many in vitro and in vivo studies have reported significant activity of apocynin against diabetic complications, Parkinson’s disease, cardiovascular disorders, and cancer. The major mechanism of action of apocynin is its ability to limit ROS production by inhibiting the NOX enzyme by inhibiting the translocation of its p47phox subunit, which was reported in neurodegeneration and hypertension. Additionally, apocynin has shown inhibition of eNOS-dependent superoxide production in diabetic cardiomyopathy, reduction of NLRP3 activation and TGFβ/Smad signaling in diabetic nephropathy, diminished VEGF expression and retinal NF-κB activation in diabetic retinopathy, inhibition of P38/MAPK/Caspase3 pathway in pheochromocytoma, inhibition of AKT-GSK3β and ERK1/2 pathways in pancreatic cancer, and decreased FAK/PI3K/Akt signaling in hepatocellular cancer. Summarizing the available literature, it can be concluded that apocynin is an important phytochemical having low toxicity, easily modifiable and improved pharmacokinetic profile, and wide therapeutic applicability. Thus, further studies are warranted to confirm the pharmacological activity of apocynin in many serious disorders along with testing for a combination of apocynin with other drugs to facilitate the extrapolation of its preclinical data into clinical studies.
Apocynin protects retina cells from ultraviolet radiation damage via inducing sirtuin 1
Published in Journal of Drug Targeting, 2020
Feng Liu, Chen Lin, Jinsheng Hong, Chuanshu Cai, Weijian Zhang, Jianrong Zhang, Lihong Guo
Apocynin is one of the main bioactives found in the roots of Canadian hemp (Apocynum cannabinum), which was used to treat heart problems and dropsy. It is a naturally occurring methoxy-substituted catechol with a molecular weight of 166.17 Da (Figure 1(A)). It is wildly recognised as a specific inhibitor of nicotinamide-adenine dinucleotide phosphate (NADPH)-oxidase complex in many cell types including both non-phagocytic and phagocytic cells [7]. Though its inhibitory mechanism is not fully understood, Apocynin has been shown to reduce both the membrane translocation and the expression level of neutrophil cytosol factor 1 (p47phox), a cytosolic component of NADPH complex [8]. The membrane translocation of p47phox is required for the activation of NAPDH-oxidase, which functions as a transmembrane electrogenic enzyme that catalyses the production of reactive oxygen species (ROS) [9,10]. The inhibition of NADPH-oxidase activation by Apocynin leads to the decreased production of ROS in the cells. For example, Apocynin can reduce ROS production in activated neutrophils with a half maximal inhibitory concentration (IC50) of 10 µM, though it has no impact on phagocytosis or other intracellular defensive mechanisms [11].
Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease
Published in Renal Failure, 2018
Jorge Osvaldo Montes-Rivera, Feliciano Tamay-Cach, Julio César Quintana-Pérez, Juan Alberto Guevara-Salazar, José Guadalupe Trujillo-Ferrara, Leonardo Del Valle-Mondragón, Mónica Griselda Arellano-Mendoza
In the 5/6 nephrectomy group with drug treatment, captopril and losartan displayed antihypertensive activity by blocking the effects of Ang II, as mentioned by Feldstein et al., where ACE and ARA II achieve a significant blockade of the RAAS. Consequently, there is a reversal of the remodeling generated by profibrotic and inflammatory processes at the vascular and renal levels, which in turn has the beneficial hemodynamic effect of regulating blood pressure in the inferior renal capsule (IRC) [31]. However, the lack of effect of apocynin on blood pressure could possibly be overcome by administering it with a coadjuvant for the treatment of CKD.