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Anti-Cancer Agents from Natural Sources
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Felipe Gonzalez
As mentioned before, while NSCLC accounts for about 85% of all lung cancers but there are limited drugs/effective treatments against NSCLC due to its stagnancy in advance lung cancer stages. Severalcoumarin derivatives are under preclinical exploration to validate their antineoplastic efficacyin NSCLC. For instance, Osthole (7-methoxy-8-(3- methyl-2-butenyl) coumarin), daphnetin (7,8-dihydroxycoumarin), and umbelliprenin are notable antineoplastic coumarin derivatives, capable of treating NSCLC. Osthole an anticancer agent from Cnidium monnieri plant is capable to stop lung cancer growth. It helps to arrest G2/M and speeds upapoptosis (Xu et al., 2011). Daphnetin (7,8-dihydroxycoumarin), suppresses Akt/NF-κB signaling pathways causing apoptosis in lung cancer. Umbelliprenin is a natural compound isolated from the plant genus Ferula (Wang et al., 2013). It adopts apoptosis in QU-DB (large lung tumor cells) and A549 adenocarcinoma (Khanghanzadeh et al., 2012) cells.
Phytotherapeutic Agents in Epilepsy
Published in Vikas Kumar, Addepalli Veeranjaneyulu, Herbs for Diabetes and Neurological Disease Management, 2018
Osthole is a natural coumarin derivative [7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one] found in plants such as Cnidium monnieri, Angelica archangelica and Angelica pubescens. Osthole has demonstrated good suppression of seizure activity in the MES model in mice160 which is comparable to imperatorin.156
Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Osthol from the fruits of Cnidium monnieri (L.) Cusson given to spontaneously hypertensive rats at 0.05% of diet for 4 weeks lowered systolic blood pressure by approximately 15%.367 This supplementation increased hepatic expression of 3-hydroxy-3-methylglutaryl-CoA reductase, acyl CoA oxidase, liver X receptor α and decreased hepatic apolipoprotein C-II and apolipoprotein C-III.367 This prenylated coumarin from given to Kunming mice on high-fat diet, orally at a dose of 40 mg/kg/day for 6 weeks evoked a reduction of body weight from 47.1 to 45.2 g, lowered hepatic cholesterol, hepatic triglycerides, and hepatic free fatty acids.368 In the serum of treated animals, osthol (Figure 3.27) reduced total cholesterol from 2.2 to 1.7 mmol/L (normal value: 1.8 mmol/L), triglycerides from 1.2 to 0.9 mmol/L, and free fatty acids from 6543 to 3373 µmol/L (below normal value: 5699 µmol/L). This coumarin evoked a reduction of hepatic expression of sterol regulatory element-binding protein-1c by about 45% and its target fatty acid synthetase.368 This coumarin evoked a reduction of sterol regulatory element-binding protein-2 by 80% hence decreased low-density lipoprotein expression. This coumarin increased the expression of CYP7A1.368 One could infer that osthol antagonizes liver X receptor hence repression of sterol regulatory element-binding protein-1c and CYP7A1.
Osthole exhibits an antitumor effect in retinoblastoma through inhibiting the PI3K/AKT/mTOR pathway via regulating the hsa_circ_0007534/miR-214-3p axis
Published in Pharmaceutical Biology, 2022
Xiufang Lv, Haojiang Yang, Hui Zhong, Li He, Li Wang
Natural products, containing bioactive secondary metabolites, have beneficial effects on human health. Osthole [7-methoxy-8-(3-methyl-2-butenyl) coumarin, Figure 1A] is a natural coumarin first derived from Cnidium plant. Osthole frequently presents in the mature fruit of Cnidium monnieri Cusson ex Juss (Fructus Cnidii) of the Apiaceae family. Osthole is known to exert anti-inflammatory, antimicrobial, and anti-allergic activities (Matsuda et al. 2002; Shokoohinia et al. 2018). In addition, osthole is also known to exert therapeutic effects against several cancer types including breast (Park et al. 2019), gastric (Xu et al. 2018), gallbladder (Le Zou et al. 2019) and ovarian cancers (Bae et al. 2021). It has been reported that osthole exerts antitumor effects by inhibiting cell proliferation, inducing cell cycle arrest and apoptosis, and inhibiting the epithelial-mesenchymal transition (EMT) process (Wen et al. 2015; Xu et al. 2018; Zhu et al. 2018). The signalling pathways, such as PI3K/AKT and JAK/STAT3, have been reported to be involved in the antitumor process of osthole (Zhu et al. 2018; Le Zou et al. 2019). Although many cancer types were reported to be inhibited by osthole, the effect of osthole on RB still remains unclear.
Osthole inhibited the activity of CYP2C9 in human liver microsomes and influenced indomethacin pharmacokinetics in rats
Published in Xenobiotica, 2020
Hui He, Yuandong Zhang, Dezhang Zhao, Junhao Jiang, Baogang Xie, Limei Ma, Xueqing Liu, Chao Yu
Osthole is a pharmacologically active ingredient found in many traditional Chinese medicines (Zoungas et al., 2010). It is the highest content in Chinese medicinal materials, such as Angelica, Duhuo, and Snake Bed (Yang et al., 2010). It is clinically applicable to the treatment of various surgical and medical diseases (Kirchheiner et al., 2002). Traditional Chinese medicines containing osthole active ingredients are frequently used in clinical practice and are easy to co-administration with other drugs (Garcia-Martin et al., 2006). Yang Yuan demonstrated that CYP2C9 is involved in the metabolism of osthole in human liver microsomes (HLMs) in vitro (Sachse-Seeboth et al., 2009). However, it is unclear whether osthole will affect the activity of CYP2C9 enzyme, and whether it will interact with other drugs. Emerged evidence proved that osthole could increase the mRNA expression of CYP7A (Du et al., 2011; Sun et al., 2010) or CYP11B1 in a dose-dependent manner (Pan et al., 2015), and decrease the mRNA expression of CYP 2E1 (Zhang et al., 2011). It is indicated that osthole could impact on the metabolic elimination of other drugs and cause toxic side effects via inhibiting or inducing some of CYP450 enzyme expression. At present, there are more researches on the pharmacological and pharmacodynamic effects of osthole at home and abroad, but few studies on the pharmacokinetics of osthole (Jarząb et al., 2017; Jiang et al., 2016; Wang et al., 2018).
Characterization of osthenol metabolism in vivo and its pharmacokinetics
Published in Xenobiotica, 2020
Piljoung Cho, Su Min Choi, Younah Kim, Doo Hyun Lee, Yeeun Noh, Sujeong Kim, Ju-Hyun Kim, Taeho Lee, Sangkyu Lee
Although the diverse pharmacological effects of osthenol have already been reported, very few studies have been reported on its pharmacokinetic (PK) profiling. Following osthenol is known to be a major metabolite of osthole in rats, it is suggested that osthenol may be involved in the pharmacological action of osthole (Cho et al., 2018b). In our previous studies, we investigated the metabolic pathway of osthenol in HLMs after incubation in presence of uridine diphosphate glucuronic acid (UDPGA) and beta-nicotinamide adenine dinucleotide phosphate (β-NADPH) and identified five hydroxylated metabolites formed by cytochrome P450s (CYPs) and two glucuronide conjugates of osthenol by uridine diphosphate-glucuronosyltransferases (UGTs) enzyme (Cho et al., 2018b). We also found that glucuronidation is the principal metabolic pathway of osthenol in human liver microsomes (HLMs) compared to hydroxylation by CYPs. In addition to this, we observed strong and selective inhibitory effect of osthenol on CYP2C8-catalyzed paclitaxel hydroxylation in HLMs suggesting a potential herb–drug interaction between osthenol and CYP2C8 substrate drugs (Cho et al., 2018a).