RSC Advances
·
2026
·Vol. 16
·期 14
·12570-12578
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IF 6.1
Hang Yin,Lei Zhu,Xiaoyu Wang,Zhen Wang,Hecheng Wang,Yong Liu
As a natural plant active ingredient, sesamin has the following nutritional values: anti-inflammatory, antioxidant, anti-hypertension, liver protection, and cholesterol reduction, and has been developed for dietary supplements to assist clinical drug therapy. However, it is not known whether it inhibits the catalytic activities of drug-metabolizing enzymes. Hence, the objective of this research was to assess the inhibitory effects of sesamin on cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) and to predict the risk of inducing food–drug interactions (FDIs). The results indicated that sesamin had no significant inhibitory effects on UGTs. However, since people may take sesame in excessive amounts, the FDIs mediated by UGTs still cannot be ignored. Sesamin could increase the potential risk of FDIs by inhibiting the activities of CYP2C9 and CYP2C19. It is worth noting that for phenytoin, a CYP2C9 substrate with a narrow therapeutic window, sesamin can significantly inhibit the formation of its hydroxylation products and cause clinically significant FDIs. Therefore, when patients are being treated with CYP2C9 and CYP2C19 substrate drugs with narrow therapeutic windows, high doses of sesame or other sesamin-rich substances should be avoided.
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PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2018
·Vol. 75
·期 1
·204-214
·
IF 3.249
Ning Zhao,Yanyan Yan,Lu'an Ge,Baolin Zhu,Weitang Liu,Jinxin Wang
BACKGROUND Shortawn foxtail ( Alopecurus aequalis Sobol.) is a competitive grass weed infesting winter wheat- and canola-growing fields in China. In May 2016, a suspected A. aequalis resistant population AHTC-06 that survived fenoxaprop- P -ethyl and mesosulfuron-methyl applied at their field-recommended rates was collected from a wheat field in Jinji County, Anhui Province, China. This study aimed to determine the resistance profile of this AHTC-06 population to ACCase- and ALS-inhibitors, and to investigate its mechanisms of resistance to fenoxaprop- P -ethyl and mesosulfuron-methyl. RESULTS Two mutations, a common Ile-2041-Asn ( ACCase gene) and a very rare Pro-197-Tyr ( ALS1 gene), were both identified in resistant individual plants. The homozygous subpopulation AHTC-06F1 for the two mutations was generated, and it showed broad-spectrum resistance to APPs, DENs, and ALS-inhibiting herbicides of all five chemical families tested, with resistance index (RI) values that ranged from 2.2 to 36.5. In vitro ALS activity assays showed the ALS from the resistant population was insensitive to all the tested ALS inhibitors, with RI values ranging from 3.10 to 22.51. Pre-treatment with piperonyl butoxide (PBO) and malathion significantly ( P < 0.05) reversed the weed's resistance to fenoxaprop- P -ethyl and mesosulfuron-methyl, respectively. Two P450 genes, c21190_g1 and c43350_g3 , were constitutively overexpressed and mesosulfuron-methyl-induced upregulated in resistant plants, for which c43350_g3 was also fenoxaprop- P -ethyl-induced upregulated. CONCLUSION This study confirms the first case of a grass weed featuring broad-spectrum resistance to ALS-inhibiting herbicides due to a Pro-197-Tyr mutation in the ALS gene. Fenoxaprop- P -ethyl and mesosulfuron-methyl resistances in AHTC-06 plants were conferred by target site mutations and P450s-based metabolism. © 2018 Society of Chemical Industry
研究领域:
植物科学
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杂草科学
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分子生物学
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遗传学
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PubMed
高影响因子
CROP PROTECTION
·
2022
·
IF 3.036
Cuixia Wu,Min Song,Tiantian Zhang,Chao Zhou,Weitang Liu,Tao Jin,Ning Zhao
Italian ryegrass ( Lolium multiflorum Lam.) is a highly competitive grass weed capable of severely infesting wheat fields worldwide. In recent years, Chinese farmers are finding it increasingly difficult to control L. multiflorum when using acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. Accordingly, clarifying the resistance pattern of putative resistant populations of L. multiflorum is important for selecting alternative herbicides for effective weed control. In this study, a putative resistant L. multiflorum population, HN-03, which apparently has survived clodinafop-propargyl treatment under the recommended field application rate, was collected from a wheat field in Zhumadian, Henan, China. Whole-plant bioassay revealed that the HN-03 population had evolved high-level resistance to clodinafop-propargyl. Sequencing of the ACCase gene revealed a point mutation , of TGG to TGT, at codon position 1999, causing a Trp-to-Cys substitution in the resistant plants. The HN-03 population also exhibited cross-resistance to fenoxaprop- P -ethyl, clethodim, and pinoxaden and multiple-resistance to mesosulfuron-methyl and bixlozone, but it remained susceptible to cypyrafluone. Pre-treatment with piperonyl butoxide and malathion considerably increased the susceptibility of the HN-03 population to fenoxaprop- P -ethyl and mesosulfuron-methyl, by 25.3% and 36.6%, respectively. This study shows the L. multiflorum population HN-03 has evolved multiple herbicide resistance due to both a target-site mutation and P450s-mediated enhanced metabolism. Cypyrafluone can be used as an alternative herbicide to control resistant L. multiflorum , and it might be potentially helpful for improving the management of herbicide resistance in other aggressive weeds.
研究领域:
植物学
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遗传学
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农业科学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Chao Hu,Yu-Xi Liu,Shi-Pang Zhang,Ya-Qi Wang,Ping Gao,Yu-Ting Li,Xue-Qing Yang
Aryl hydrocarbon receptor (AhR) enhances insect resistance to insecticides by regulating the detoxification network. Our previous studies have confirmed that overexpressions of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are involved in lambda-cyhalothrin resistance in Cydia pomonella. Here, we report that CpAhR regulates the expression of GST and P450 genes, thus conferring resistance. Expression patterns indicated that the expression of CpAhR was highly induced by lambda-cyhalothrin exposure and upregulated in a lambda-cyhalothrin-resistant population. RNA interference (RNAi) of CpAhR decreases the expression of key resistance-related genes (CpGSTe3, CpCYP9A121, and CpCYP9A122) and the activity of the GST enzyme, reducing the tolerance to lambda-cyhalothrin. Furthermore, β-naphthoflavone, a novel agonist of AhR, was first proven to be effective in increasing CpAhR expression and larval tolerance to lambda-cyhalothrin. These results demonstrate that CpAhR regulates the expression of key detoxifying genes and GST activity, resulting in the development of resistance to lambda-cyhalothrin in C. pomonella.
研究领域:
昆虫学
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分子生物学
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毒理学
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PubMed
高影响因子
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
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2015
·
IF 3.45
Lulu Dai,Mingyuan Ma,Chunyan Wang,Qi Shi,Ranran Zhang,Hui Chen
Bark beetles oxidize the defensive allelochemicals from their host trees to both detoxify and convert these materials into components of their pheromone system. The ability of this insect to adapt to its chemical environment might be explained by the action of major detoxification enzymes such as cytochrome P450s (or CYPs). Sixty-four sequences coding for P450s were identified, and most of the transcripts were found to be expressed in the larvae, pupae and adults of Dendroctonus armandi . To gain information on how these genes help D. armandi overcome the host defense, differential transcript levels of the CYP genes were observed between sexes and within the sexes. Significant differences were observed among developmental stages, in feeding on the phloem of Pinus armandi and in exposure to stimuli ((±)-α-pinene, (S)-(−)-α-pinene, (S)-(−)-β-pinene, (+)-3-carene, (±)-limonene and turpentine oil) for 8 h. We investigated the effect of sex and generations on the survivorship of individual D. armandi that were exposed to host volatiles at concentrations comparable to constitutive and induced levels of defense using fumigant exposure to understand the ability of the beetles to tolerate host defensive chemicals. The differential transcript accumulation patterns of CYP genes of these bark beetle provided insight into the ecological interactions of D. armandi with its host pine.
研究领域:
昆虫学
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分子生物学
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高影响因子
ENVIRONMENTAL POLLUTION
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2024
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IF 7.6
Guangcai Ma,Kan Ma,Jing Zhang,Xianglong Zhao,Qiuyi Wang,Yewen Chen,Jiayu Lu,Xiaoxuan Wei,Xueyu Wang,Haiying Yu
The escalating focus on the environmental occurrence and toxicology of emerging pollutants underscores the imperative need for a profound exploration of their metabolic transformations mediated by human CYP450 enzymes. Such investigations have the potential to unravel the intricate metabolite profiles, substantially altering the toxicological outcomes. In this study, we integrated the computational simulations with in vitro metabolism experiments to investigate the metabolic activity and mechanism of an emerging pollutant, 1,3,5-tris(2,3-dibromopropyl)-1,3,5-triazinane-2,4,6-trione (TDBP-TAZTO), catalyzed by human CYP450s. The results highlight the important contributions of CYP2E1, 3A4 and 2C9 to the biotransformation of TDBP-TAZTO, leading to the identification of four distinct metabolites. The effective binding conformations governing biotransformation reactions of TDBP-TAZTO within active CYP450s are unveiled. Structural instability of primary hydroxyTDBP-TAZTO products suggests three potential outcomes: (1) generation of an alcohol metabolite through successive debromination and reduction reactions, (2) formation of a dihydroxylated metabolite through secondary hydroxylation by CYP450, and (3) production of an N-dealkylated metabolite via decomposition and isomerization reactions in the aqueous environment. The formation of a desaturated debrominated metabolite may arise from H-abstraction and barrier-free Br release during the primary oxidation, potentially competing with the generation of hydroxyTDBP-TAZTO. These findings provide detailed mechanistic insight into TDBP-TAZTO biotransformation by CYP450s, which can enrich our understanding of the metabolic fate and associated health risk of this chemical.
研究领域:
环境科学
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毒理学
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计算生物学
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PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2019
·Vol. 75
·期 12
·3175-3183
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IF 3.255
Ning Zhao,Lu'an Ge,Yanyan Yan,Shuang Bai,Dandan Wang,Weitang Liu,Jinxin Wang
BACKGROUND Asia minor bluegrass ( Polypogon fugax Nees ex Steud.) is an invasive grass species severely infesting wheat and canola fields in China. In May 2017, a suspected resistant P. fugax population AHHY that survived fenoxaprop- P -ethyl applied at its field-recommended rate was collected from a wheat field in Huaiyuan County, Anhui Province, China. This study aimed to determine the resistance profile of AHHY to acetyl-CoA carboxylase (ACCase) inhibitors and to investigate its mechanisms of resistance to fenoxaprop. RESULTS Single-dose testing indicated that the AHHY population had evolved resistance to fenoxaprop. The partial carboxyltransferase domain of ACCase in P. fugax was amplified and compared. Four loci encoding plastidic ACCase were isolated from both the resistant and sensitive individuals. Combining gene sequencing with the derived cleaved amplified polymorphic sequence assay, we found that 100% of the plants of AHHY carried Trp-1999-Ser mutation in their ACCase1,1–2 allele. Whole-plant dose–response bioassay indicated that AHHY was highly resistant to fenoxaprop and pinoxaden (resistance index (RI) ≥ 10) with low resistance to clodinafop-propargyl, sethoxydim, and clethodim (2 ≤ RI < 5). Pre-treatment with piperonyl butoxide largely reduced (55%) the weed's resistance to fenoxaprop. Both basal and fenoxaprop-induced glutathione S -transferases activities toward 1-chloro-2, 4-dinitrobenzene were significantly higher in resistant plants than in susceptible plants. CONCLUSION This study revealed that P. fugax had multiple alleles encoding plastidic ACCase, and reported for the first time the occurrence of Trp-1999-Ser mutation and non-target-site resistance in this species. Fenoxaprop resistance in AHHY plants was conferred by target-site mutation and P450s-involved enhanced metabolism. © 2019 Society of Chemical Industry
研究领域:
植物学
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植物生理学
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分子生物学
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杂草科学
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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2023
·Vol. 396
·期 8
·1759-1771
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IF 3.6
Liu Fei,Xu Yanjun,Wang Li,Ma Xifeng,Zhang Zhen,Zhuang Xiaomei
Anaprazole, a new proton pump inhibitor (PPI), is designed for the treatment of acid-related diseases, such as gastric ulcers and gastroesophageal reflux. This study explored the in vitro metabolic transformation of anaprazole. The metabolic stabilities of anaprazole in human plasma and human liver microsomes (HLM) were analyzed by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Then, the contribution (%) of non-enzymatic and cytochrome P450s (CYPs) enzyme-mediated anaprazole metabolism was assessed. To obtain the metabolic pathways of anaprazole, the metabolites generated in HLM, thermal deactivated HLM, and cDNA-expressed recombinant CYPs incubation systems were identified by ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF–MS). Results showed that anaprazole was very stable in human plasma and unstable in HLM. The contribution (%) of non-enzymatic vs . CYPs enzyme-mediated metabolism was 49% vs . 51%. CYP3A4 was the major enzyme (48.3%), followed by CYP2C9 (17.7%) and CYP2C8 (12.3%), in responsible for the metabolism of anaprazole. Specific chemical inhibitors targeting CYP enzymes notably blocked the metabolic transformation of anaprazole. Six metabolites of anaprazole were identified in the non-enzymatic system, whereas 17 metabolites were generated in HLM. The biotransformation reactions mainly included sulfoxide reduction to thioether, sulfoxide oxidation to sulfone, deoxidation, dehydrogenation, O-dealkylation or O-demethylation of thioether, O-demethylation and dehydrogenation of thioether, O-dealkylation and dehydrogenation of thioether, thioether O-dealkylation and dehydrogenation of thioether, and O-dealkylation of sulfone. Both enzymatic and non-enzymatic metabolisms contribute to the clearance of anaprazole in human. Anaprazole is less likely to develop drug-drug interactions in clinical use compared to other PPIs.
研究领域:
药理学
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药物代谢
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PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2022
·
IF 4.966
Ming-yang Li,Chang-wei Gong,Yun-zheng Zhang,Xia Zhao,Yan Jia,Jian Pu,Xue-mei Liu,Xiang Xu,Xue-gui Wang
Chilo suppressalis Walker (Lepidoptera: Crambidae) is one of the most destructive pests occurring in the rice-growing regions of Asia. Parasitoids , mainly egg parasitoids , have been of interest for several years even with practical used cases. Therefore, the potential impact of insecticides on natural enemies needs great attention. In this study, chlorantraniliprole was evaluated for its impact on C. suppressalis and two dominant parasitic wasps . Bioassays showed that chlorantraniliprole had negligible toxicity to Eriborus terebrans but was significantly toxic to Chelonus munakatae ; the mortality exceeded 50% when the concentration reached 46.83 ng/cm 2 . Enzyme assays suggested that the significantly different carboxylesterase activity may be involved in the high-level detoxification metabolism of E. terebrans . According to the results of enzyme gene correlation analysis, P450s may be the dominant factor in the detoxification metabolism of C. munakatae . In addition, the ryanodine receptor C-terminus of C. suppressalis (CsRyR), C. munakatae (CmRyR) and E. terebrans (EtRyR) were successfully cloned. Different amino acids at resistance mutation I4758 M between susceptible C. suppressalis (I) and parasitic wasps (M) may be related to susceptibility differences. Simulated docking showed that CsRyR and CmRyR can interact with chlorantraniliprole but not EtRyR. More interaction forces were formed between CsRyR and chlorantraniliprole than CmRyR. Furthermore, a Pi-Pi T-shape formed between 73PHE in CsRyR and the benzene ring in chlorantraniliprole. These results indicated that both detoxification metabolism and the target site could mediate the susceptibility difference between C. suppressalis and its parasitic wasps.
研究领域:
昆虫学
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毒理学
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生物化学
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分子生物学
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PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 12
·1865-1878
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IF 2.571
Xing Han,Yang Jing,Ren Kaidi,Qin Zifei,Wang Peile,Zhang Xiaojian,Yao Zhihong,Gonzalez Frank J,Yao Xinsheng
ObjectivesIsobavachin is a phenolic with anti-osteoporosis activity. This study aimed to explore its metabolic fates in vivo and in vitro, and to investigate the potential drug–drug interactions involving CYPs and UGTs.MethodsMetabolites of isobavachin in mice were first identified and characterized. Oxidation and glucuronidation study were performed using liver and intestine microsomes. Reaction phenotyping, activity correlation analysis and relative activity factor approaches were employed to identify the main CYPs and UGTs involved in isobavachin metabolism. Through kinetic modelling, inhibition mechanisms towards CYPs and UGTs were also explored.Key findingsTwo glucuronides (G1 - G2) and three oxidated metabolites (M1 - M3) were identified in mice. Additionally, isobavachin underwent efficient oxidation and glucuronidation by human liver microsomes and HIM with CLint values from 5.53 to 148.79 μl/min per mg. CYP1A2, 2C19 contributed 11.3% and 17.1% to hepatic metabolism of isobavachin, respectively, with CLint values from 8.75 to 77.33 μl/min per mg. UGT1As displayed CLint values from 10.73 to 202.62 μl/min per mg for glucuronidation. Besides, significant correlation analysis also proved that CYP1A2, 2C19 and UGT1A1, 1A9 were main contributors for the metabolism of isobavachin. Furthermore, mice may be the appropriate animal model for predicting its metabolism in human. Moreover, isobavachin exhibited broad inhibition against CYP2B6, 2C9, 2C19, UGT1A1, 1A9, 2B7 with Ki values from 0.05 to 3.05 μm.ConclusionsCYP1A2, 2C19 and UGT1As play an important role in isobavachin metabolism. Isobavachin demonstrated broad-spectrum inhibition of CYPs and UGTs.
研究领域:
药理学
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代谢组学
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中药学
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PubMed
高影响因子
JOURNAL OF PEST SCIENCE
·
2024
·
IF 4.3
Zheng Qun,Yan Wenjuan,Zhu Shiqi,Miao Xiaoran,Wu Jian,Lin Zewei,Huang Suqing,Cheng Dongmei,Xu Hanhong,Zhang Zhixiang,Zhang Peiwen
Gelsemium elegans Benth. ( Loganiaceae ), also known as heartbreak herb, can be used in the manufacture of herbal medicines. Insecticidal activity has also been found and can be used to develop botanical insecticides. This study aimed to reveal the insecticidal mechanism of its extracts against red fire ants and provide strategies for the development of biopesticides and the promotion of green and sustainable agriculture. 16s rRNA, pathohistological, behavioral, and enzyme activity assays were performed to reveal its biological effects, including the effects on non-target organisms. Our results showed that red fire ants exposed to G. elegans extracts exhibited slowed growth, reduced feeding, and decreased aggressiveness. The midgut and its peritrophic membrane of red fire ant were significantly disrupted, the diversity of gut microbial community was reduced, and the balance of microbial composition was disturbed. Significant increases in functional abundance of xenobiotics biodegradation and metabolism pathway and P450s enzyme activity confirmed the toxic stress of G. elegans extract. Functional prediction of Kyoto Encyclopedia of Genes and Genomes pathway showed that the functional abundance of novobiocin biosynthesis, flavonoid biosynthesis, lysosome, proteasome, and wingless/integrated signaling pathways were significantly inhibited in the gut. Besides, G. elegans extracts induced an increase in acetylcholinesterase activity. These results revealed dysregulation of immune system and metabolic functions in red fire ants, as well as toxic effects of G. elegans extracts on physiological functions and nerves. These findings revealed the insecticidal mechanism of G. elegans and supported the development of eco-friendly insecticides for red fire ants.
研究领域:
昆虫学
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微生物学
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药理学
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农业科学
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分子生物学
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高影响因子
危险品化学品经营许可证（带存储）