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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Matrine (Figure 12.23) is a tetracyclo-quinolizidine, and the predominant alkaloid in Sophora plants. It has a structure based on four saturated six-membered rings with two ring-junction nitrogen atoms, making it rich in stereochemistry. Matrine is reported to have both in vitro and in vivo antitumor activity, and is the main bioactive compound in Kushen at a concentration of 1 g/10 kg. It is also a constituent of the herb Sophora flavescens used in Chinese medicine. Structure of the alkaloid matrine.
Hyperthermia in oncology and nontoxic integrative treatments
Published in Clifford L. K. Pang, Kaiman Lee, Hyperthermia in Oncology, 2015
Clifford L. K. Pang, Kaiman Lee
Some non-chemotherapeutic drugs can be used in combination with hyperthermia to treat cancer. These drugs have no or little anticancer effect. But if they are heated, they can develop strong anticancer activities. Thus, they have great development prospects. They exceed the anticancer effect of even the combination of heating with chemotherapeutic drugs. In this respect, herbal medicine has great potential and we have found its sound clinical prospects. Through the comparisons of thermal synergistic actions of seven drugs totaling five types, some researchers have found that some Chinese herbal medicines can induce apoptosis of more cells. For example, matrine can improve the therapeutic effect of MA737 on small breast cancer. Therefore, the combination of cancer hyperthermia with herbal drugs has wide development prospects and requires our further research.
Inhibiting Low-Density Lipoproteins Intimal Deposition and Preserving Nitric Oxide Function in the Vascular System
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Matrine given orally at a dose of 200 mg/kg daily for 10 days protected rodents against myocardial infarction induced by isoproterenol as evidenced by reduced serum lactate dehydrogenase and creatine kinase from.165 Besides, this alkaloid at 200 mg/kg corrected LVSP, mean blood pressure, and heart rate.165 This quinolizidinie alkaloid increased the enzymatic activity of superoxide dismutase, catalase and glutathione peroxidase in cardiac tissues.165 Furthermore, histological observation of cardiac tissues revealed that matrine protected cardiac tissues against necrosis, inflammation and interstitial edema.165 Oxymatrine given parenterally to Wistar rats 10 minutes before experimental myocardial infarction decreased the infarct size of the left ventricle by about 10%.166 Myocytes from the ischemic zone from treated rats exhibited milder apoptosis, had lower fatty acid synthetase and higher Bcl-2 expression and reduced cytosolic calcium contents compared with untreated animals.166 In a subsequent study, oxymatrine given intravenously at a dose of 20 mg/kg to Wistar rats 10 minutes before left anterior coronary descending artery occlusion reduced the duration of ventricular arrhythmia and the scores of arrhythmia from 6.7 to 4.8 minutes and 4.7 to 3.3, respectively. This alkaloid delayed the onset of arrhythmia by 1 minute.167 Oxymatrine given orally at a dose of 60 mg/kg daily for 21 weeks to hypertensive rodents reduced the mean arterial pressure from about 150 to 120 mmHg.168 Histological observation revealed a decrease of collagen accumulation in the interstitial and perivascular space of left ventricle.168 The myocardium of hypertensive rodents receiving this alkaloid orally at a dose of 60 mg/kg daily for 21 weeks presented reduced amounts type I and type III collagen fibres.168 Besides, oxymatrine given orally at a dose of 60 mg/kg daily for 21 weeks reduced serum norepinephrine from about 0.3 to 0.1 ng/mL in hypertensive rodents.168 In addition, myocardium angiotensin II concentration was decreased from about 160 pg/mg.prot to 80 pg/mg.prot in hypertensive rodents receiving oxymatrine. Furthermore, the phosphorylation of extracellular signal-regulated kinase-1/2, in hypertensive rodents was decreased as well as the phosphorylation of JNK and p38 mitogen-activated protein kinase.168
Preparation and cytotoxicity evaluation of folic acid-modified YF8-OA self-assembled lipid prodrug nanoparticles
Published in Pharmaceutical Development and Technology, 2023
Fu Li, Fangfang Yang, Chenxi Guan, Pengcheng Wei, Dongqiong He, Qingwen Li, Lisheng Wang, Mingqing Yuan
In this study, we successfully synthesized the lipophilic prodrug YF8-OA by connecting the matrine derivative YF8 to oleic acid by using an ester bond. The resulting U-shaped particles formed without any carriers in water and were flocculated easily, but with the addition of 10% DSPE-mPEG2000 or DSPE-mPEG2000-FA, uniform spherical particles were formed in aqueous solution due to hydrophobic forces. These particles remained stable at 4 °C in a refrigerator or at 37 °C in a culture medium. In vitro release experiments showed that the release was faster and more complete in the presence of esterase compared to blank controls. Cell viability tests showed that the FA-modified PEGylated YF8-OA/LPs exhibited significantly higher cytotoxicity than the PEGylated YF8-OA/LPs in HeLa cells, while showing no significant difference in A549 and HepG2 cells, which have fewer FA receptors. In conclusion, adopting the LPs strategy appears to be a promising approach to enhance the pharmacological activity of matrine analogs.
Matrine attenuates cardiomyocyte ischemia–reperfusion injury through activating AMPK/Sirt3 signaling pathway
Published in Journal of Receptors and Signal Transduction, 2021
Qiubei Lu, Xiangyu Lin, Jing Wu, Binhao Wang
Matrine is an alkaloid found in plants from the genus sophora [10]. Numerous studies have reported the protective effects exerted by matrine on cell death. For example, myocardial fibrosis could be attenuated by matrine through the RPS5/p38 signaling pathway [11]. In cerebral ischemia reperfusion injury, delivery matrine has been found to attenuate neural death through modulation of cellular energy metabolism [11]. In colon cancer cell, matrine is reported to regulate the Warburg effect through affecting the stability of HIF1α [12]. Besides, matrine also shows anti-oxidative property through affecting the NRf2-related antioxidant response [13]. In human myeloid leukemia cell, matrine is associated with cell death through the HK2 [14]. In doxorubicin-induced cardiotoxicity, matrine alleviates oxidative stress and cardiomyocyte apoptosis in a manner involving AMPK/UCP2 signaling pathway [15]. However, the role of matrine in cardiomyocyte ischemia–reperfusion injury has not been fully understood. In the present study, we conducted experiments to shape the influence of matrine on cardiomyocyte hypoxia-reoxygenation damage with a focus on mitochondrial homeostasis.
Matrine protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via upregulation of miR-9
Published in Pharmaceutical Biology, 2020
Matrine is a main alkaloid component in a traditional Chinese herb, derived from leguminous plant Sophora flavescens Ait (Leguminosae) (Cai et al. 2018). It has been found to possess a wide range of pharmacological effects, including immunity-regulation (Kan et al. 2013), anti-arrhythmia (Zhou et al. 2014), antibacterial (Feng et al. 2018), analgesic (Haiyan et al. 2013), antihepatic fibrosis (Yu et al. 2014), and antitumor activities (Rashid et al. 2019). Due to these pharmacological activities, matrine has been considered as a promising candidate for the management of various diseases, like acute lung injury (Liou et al. 2016), non-alcoholic steatohepatitis (Mahzari et al. 2019), acute lymphoblastic leukaemia (Aghvami et al. 2018), etc. More recently, it was found that matrine possessed neuroprotective functions, for example, matrine had promise in treating Parkinson’s disease (Meng et al. 2017). Moreover, matrine was able to promote the growth of axon and the recovery of spinal cord following SCI (Tanabe et al. 2018). Nonetheless, the impact of matrine on SCI is still incompletely disclosed.