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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
Dictamine, skimmianine, psoralen, chalepensin, clausidine, and graveolinine isolated from a member of the genus Ruta L. at a concentration of 100 μM inhibited the aggregation of rabbit platelets challenged with arachidonic acid by more than 80%.205 Dictamine, chalepensin, and graveolinine a concentration of 100 μM inhibited the aggregation of rabbit platelets challenged with collagen by more than 80%.205 Methanol extract of a member of the genus Ruta given orally at a dose of 20 mg/kg/day to Sprague–Dawley rats on cholesterol-enriched diet for 90 days lowered the activity of alanine transaminase and aspartate transaminase. This Regimen decreased total cholesterol from 107.4 to 87.6 mg/dL (normal diet: 73.9 mg/dL), lowered low-density lipoprotein–cholesterol from 72.3 to 51.6 mg/dL (normal diet: 34.8 mg/dL), increased high-density lipoprotein–cholesterol from 17.5 to 22.6 mg/dL (normal diet: 26.1 mg/dL), and lowered atherogenic index from 4.2 to 2.2 (normal diet: 1.3).206 This treatment increased the activities of superoxide dismutase, catalase and glutathione peroxidase, and increased glutathione in liver and heart of treated animals.206 In monocytes, this extract lowered the enzymatic activity of cyclo-oxygenase and 15-lipoxygenase by about 35% and 50%, respectively. It also decreased serum myeloperoxidase activity, decreased serum C-reactive protein as well as white blood cell count.206 Histological observation of aorta of treated animals revealed a preventive effect on early atherogenesis.206 It would be of interest to explore the effect of Ruta angustifolia Pers. (Figure 5.17) on high-fat diet in rodent.
Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions
Published in Drug Metabolism Reviews, 2020
Kai Wang, Qing Gao, Tingting Zhang, Jinqiu Rao, Liqin Ding, Feng Qiu
The phenylpropanoid family mainly contains coumarins, lignans and phenylpropionic acids, many of which are possible inhibitors of CYP2C9. Many furanocoumarins have been reported to have inhibitory effects on different CYP enzymes, so they are also known as “natural toxins”. Exposure to furanocoumarins is extremely common for people, due to their wide distribution in numerous herbs, fruits and foods (Hung et al. 2017; Chen et al. 2018). The best-known example are the furocoumarins in grapefruit juice, which have been shown to interact with many prescription medications, such as ethinylestradiol, cyclosporin, midazolam, triazolam, and terfenadine (Guo and Yamazoe 2004). Bergamottin, bergaptol, dihydroxybergamottin, paradisin A, and paradisin B (Table 2) have been identified as the main furocoumarins and show strong inhibitory potency toward CYP enzymes, especially CYP3A4 and CYP2C9, with a lower IC50 for the latter. They are characterized as mechanism-based inactivators of CYP3A4, whereas the CYP2C9 inhibition mode is unclear. Obviously, the dimer form of paradisin A showed much stronger inhibitory effect than the monomer (Tassaneeyakul et al. 2000; Girennavar et al. 2007). Epoxidation metabolism of the furan moiety may be the crucial factor for CYP inhibition induced by furanocoumarins, including chalepensin, which is another furanocoumarin present in herbs of the Rutaceae family (Ueng et al. 2013; Row et al. 2006).
“Not tonight zebrafish”: the effects of Ruta graveolens on reproduction
Published in Pharmaceutical Biology, 2018
Mohammad Navid Forsatkar, Maryam HedayatiRad, Ana Carolina Luchiari
One of the most widely used plants for medical purposes is rue, a perennial shrub native to the Mediterranean region, which is grown in many parts of the world (Asgarpanah and Khoshkam 2012). Of the two species of rue used for medical purposes, Ruta graveolens L. (Rutaceae), an odoriferous herb, is more important (Ratheesh and Helen 2007). Herbal medicines derived from R. graveolens extracts are increasingly used to treat a variety of clinical diseases; this plant has been shown to act as an antibiotic, cytotoxic (Ivanova et al. 2005), anti-inflammatory (Raghav et al. 2006), fungicide (Oliva et al. 2003; Meepagala et al. 2005), pain killer for rheumatism, and hypotensive (Chiu and Fung 1997). However, one of its most ancient prescriptions is related to its contraceptive and abortive effects (Gutiérrez-Pajares et al. 2003; Maurya et al. 2004; De Freitas et al. 2005). A number of phytochemical compounds have been identified in R. graveolens, including acridone alkaloids, coumarins, volatile substances, terpenoids, flavonoids, furoquinolines, saponins, tannins, glycosides and chalepensins (Kuzovkina et al. 2004; Hashemi et al. 2011). The last substance (chalepensin) has been suggested as the active component of the abortifacient (De Freitas et al. 2005). However, relatively little knowledge about rue’s mode of action is available, and while there is growing interest in the pharmacological evaluation of the plant, no attention has been given to excretion and disposal. Indeed, many pharmaceutical products are present in detectable levels in aquatic systems worldwide, some with endocrine disrupting effects on organisms (Kolpin et al. 2002; Blair et al. 2013).