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JOURNAL OF ETHNOPHARMACOLOGY · 2020 · IF 3.69

CYP3A4 inducer aggravates big flower Evodiae Fructus-induced hepatotoxicity whereas limonin attenuates its hepatotoxicity

Wei Zhang,Mengjiao Wang,Huijie Song,Chengfeng Gao,Dongmei Wang,Huiming Hua,Yingni Pan,Xiaoqiu Liu

Ethnopharmacological relevance Evodiae Fructus (EF), the traditional Chinese medicine , has been typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It is a mild toxicity herb-medicine listed in Sheng Nong's Herbal Classic . Recently, EF was reported to have toxicity or no toxicity in some investigations. Toxicity and approaches to reducing toxicity of EF are of great interest. Limonin (LIM), a major triterpenoid component of EF, also had various pharmacological activities such as anti-inflammatory, anticancer, and antioxidant effects. However, little attention was paid to the role of LIM in EF-induced hepatotoxicity. Aim of study The study aimed to address the problem of controversial hepatotoxicity of EF, evaluate the role of CYP3A4 inducer/inhibitor in EF-induced hepatotoxicity and disclose the effect of LIM in EF-induced hepatotoxicity. Materials and methods The chemical compositions and hepatotoxicity of small flower EF (SEF), medium flower EF (MEF), big flower EF (BEF) and the “organ knock-out” samples (the shell and seed part of BEF) were investigated. Simultaneously, C57BL-6 mice were randomly divided into four groups, which were given orally administered BEF, BEF in combination with dexamethasone (DEX), BEF in combination with ketoconazole (KTC), and BEF in combination with LIM, respectively. Results In this study, more alkaloids and less LIM were detected in BEF compared with the compounds in SEF and MEF. Furthermore, we found that BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in SEF and MEF groups. In addition, no LIM was detected in the shell part of BEF and five alkaloids were not detected in the seed part of BEF. Correspondingly, the shell part of BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in the seed part of BEF group. It was also found that the BEF-induced hepatotoxicity was remarkably exacerbated when the mice were pretreated with DEX whereas the BEF-induced hepatotoxicity could be reversed by pretreatment with KTC or LIM. Conclusions Based on the results in this study, the misuse of BEF but not SEF and MEF could produce hepatotoxicity. The hepatotoxicity difference of different categories of EF might be associated with the relative contents of alkaloids and LIM. In addition, the results demonstrated that CYP3A4 inducer aggravated BEF-induced hepatotoxicity and LIM attenuated its hepatotoxicity.

研究领域: 民族药理学 · 毒理学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF RARE EARTHS · 2020 · IF 3.104

Lanthanum: A novel inducer for enhancement of fungal laccase production by Shiraia bambusicola

Yue Wang,Xiang Zhang,Cansong Lu,Xinping Li,Jianqin Zhou,Jianwen Wang

Fungal laccases are industrially important inducible enzymes extensively used in the delignification of lignocellulosics, detoxification of environmental wastes and decolorization of textile dyes. The discovery of new inducers is crucial for laccase productivity by filamentous fungi. In this study, a novel laccase-producing strain S8 from a bambusicolous fungus Shiraia bambusicola was identified by using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) as laccase secretion indicator and native polyacrylamide gel electrophoresis . The corresponding full-length cDNA of laccase was cloned and characterized. The effect of lanthanum (LaCl 3 ) on extracellular laccase activity was tested at the concentration from 0.2 to 2.0 g/L and at different addition time (day 1–4) in the mycelium culture. In the presence of 1.0 g/L La 3+ at the beginning of the mycelium cultures, the highest laccase activity (2.7 × 10 4 U/L) is reached after 10 days of cultivation, about tenfold higher compared with non-induced cultures. La 3+ is shown to be a very strong inducer for fungal laccase activity with no inhibitory effect on fungal growth at the optimized concentration. In vivo , La 3+ added to the mycelium culture not only promotes a continuous and high expression of laccase gene ( lcc1 ), but also induces a rapid generation of signaling molecules including reactive oxygen species (ROS) and nitric oxygen (NO). Both the NO donor sodium nitroprusside (SNP) and exogenous hydrogen peroxide (H 2 O 2 ) potentiate La 3+ -induced laccase activity and increase membrane permeability of hyphal cells. Moreover, the scavengers such as 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) for NO and vitamin C for ROS suppress the induction. These results suggest that these signals can mediate La 3+ -induced laccase biosynthesis and its secretion. Our study provides a basis for understanding the induction mechanism of La 3+ on laccase and a practical strategy for enhanced fungal laccase production.

CAS / MDL: 10025-84-0
研究领域: 微生物学 · 酶学 · 环境生物技术
✓ 已验证 产品关联 DOI 高影响因子
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CHEMICO-BIOLOGICAL INTERACTIONS · 2020 · IF 3.723

Effect of CYP3A inducer/inhibitor on pharmacokinetics of five alkaloids in Evodiae Fructus

Wei Zhang,Jingyan Guo,Dongmei Wang,Shumeng Ren,Huiming Hua,Toshio Morikawa,Yingni Pan,Xiaoqiu Liu

Evodiae Fructus (EF), the dried nearly mature scented fruit of Tetradium ruticarpum (A.Juss.) T.G.Hartley, was typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It had been reported to be a mild toxic herb through metabolic activation mainly by CYP3A but was barely explained from pharmacokinetic interaction. The aim of the study was to investigate the role of CYP3A inducer/inhibitor in pharmacokinetics of five alkaloids (evodiamine (EVOD), rutaecarpine (RUTA), 1-methyl-2-undecyl-4(1 H )-quinolone (MUDQ), 1-methyl-2-nonyl-4(1 H )-quinolone (MNNQ) and evocarpine (EVOC)) associated with hepatotoxicity of EF in Sprague Dawley (SD) rats. The results demonstrated that the metabolism of the five alkaloids of EF were inhibited in presence of CYP3A inhibitor whereas the metabolism of the five alkaloids of EF were promoted in presence of CYP3A inducer . Therefore, the dose is required attention when EF is taken in conjunction with CYP3A inducer as there is an enhancement in drug metabolism, which might lead to toxicity.

CAS / MDL: 298-46-4 65277-42-1
研究领域: 中药学 · 药理学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Horticulturae · 2022 ·Vol. 8 ·期 12 ·1208 · IF 2.923

Preharvest Elicitors Spray Improves Antioxidant Activity, Alleviates Chilling Injury, and Maintains Quality in Harvested Fruit

Di Gong,Yang Bi,Yongcai Li,Yi Wang,Dov Prusky,Noam Alkan

Antioxidant activity is an important feature for evaluating fruit quality and tolerance to biotic or abiotic stresses. Moreover, antioxidant activity is involved in chilling injury (CI) response and postharvest quality in fruit. Chemical elicitors can induce systemic acquired resistance in fruit against pathogens, which could partially replace synthetic fungicides. Recently, researchers have found that preharvest sprays with chemical elicitors can improve antioxidant activity, reduce CI, and maintain quality in harvested fruit. In this review, we summarize that preharvest elicitors spray improve antioxidant activity in harvested fruit by promoting antioxidant components biosynthesis as well as antioxidant ability in vitro. Moreover, preharvest elicitors spray alleviates CI in fruit by regulation of membrane lipid metabolism and reactive oxygen species metabolism. In addition, preharvest elicitors spray maintains fruit quality by modulation of respiration and ethylene release. Finally, this review points out the issues existing and proposes an outlook on preharvest elicitors spray to maintain postharvest fruit quality.Keywords:fruit;preharvest elicitor spray;antioxidant activity;chilling injury;postharvest quality

CAS / MDL: 119-36-8
研究领域: 植物学 · 食品科学
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JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY · 2023 · IF 2.2

TPGS/soluplus® blended micelles: an effective strategy for improving loading capacity of ferroptosis inducer erastin

Junwei Liu,Meihong Zhang,Chuanbin Wu,Xin Pan,Zhengwei Huang

Erastin is the most classical small molecular ferroptosis inducer but its clinical application is hindered due to its poor solubility. Nanotechnology has been used to improve ferroptosis inducer erastin’s solubility. The recently reported erastin-incorporated nanosystems (e.g., nanoparticulate ferritin, poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (mPEG-PLGA) nanoparticle, exosome, and liposome) could to some degree elevate its solubility, but were still poor in loading capacity. To be specific, the maximum entrapment efficiency and drug loading in previous studies were approximately 36% and 3.7%, respectively. In order to improve drug loading capacity, we constructed a novel carrier based on Vitamin E d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) blended micelles. The erastin@TPGS/Soluplus® micelles were prepared by thin film hydration method, and formulation details including dosage of Soluplus®, the weight ratio of TPGS to Soluplus®, the weight ratio of erastin to TPGS/Soluplus® were optimized. The physicochemical properties of the erastin micelles were measured by DLS, TEM, FTIR, and TG-DSC analysis. The products exhibited a nanoscale and uniform particle size (78.11 ± 0.54 nm) and neutral surface charge (-0.43 ± 0.32 mV). Significantly improved entrapment efficiency (89.63 ± 1.81%) and drug loading rate (10.03 ± 0.14%) were obtained, which was over 2-fold of current reports. The in vitro release study demonstrated that erastin could release in a sustained yet complete manner, and the drug release might be governed by multiple mechanisms including anomalous diffusion of non-Fickian diffusion, matrix erosion and sustained release. In summary, this proposed erastin nanosystem provides a new strategy for improving loading capacity, and may probably augment ferroptosis-inducing therapy for cancer treatment.

CAS / MDL: 64-19-7 571203-78-6
研究领域: 药学 · 肿瘤学 · 生物医学工程
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ENVIRONMENTAL POLLUTION · 2020 · IF 6.793

Tributyltin triggers lipogenesis in macrophages via modifying PPARγ pathway

Jiapeng Jie,Ling Ling,Yuguo Yi,Liang Tao,Xin Liao,Pingshi Gao,Qian Xu,Weigao Zhang,Yuxin Chen,Jianfa Zhang,Dan Weng

Tributyltin (TBT), a bioaccumulative and persistent environmental pollutant, has been proposed as a metabolism disruptor and obesogen through targeting peroxisome proliferator-activated receptor gamma (PPARγ) receptor pathway. However, it remains unknown whether this biological effect occurs in macrophage, a cell type which cooperates closely with hepatocytes and adipocytes to regulate lipid metabolism . This study for the first time investigated the effect of TBT on PPARγ pathway in macrophages. Our results indicated that nanomolar levels of TBT was able to strongly activate PPARγ in human macrophages. TBT treatment also markedly increased the intracellular lipid accumulation, and enhanced the expression of lipid metabolism-related genes in macrophages, while these effects were all significantly down-regulated in PPARγ-deficient macrophages, confirming the involvement of PPARγ in TBT-induced lipogenesis. Next, a mouse model that C57BL/6 mice were orally exposed to TBT with the doses (250 and 500 μg/kg body weight) lower than NOAEL (no observed adverse effect level) was used to further investigate the in vivo mechanisms. And the in vivo results were consistent with cellular assays, confirming the induction of PPARγ and the increased expression of lipogenesis-regulating and lipid metabolism-related genes by TBT in vivo. In conclusion, this study not only provided the first evidence that TBT stimulated lipogenesis, activated PPARγ and related genes in human macrophages, but also provided insight into the mechanism of TBT-induced metabolism disturbance and obesity through targeting PPARγ via both in vitro cellular assays and in vivo animal models.

CAS / MDL: 8001-30-7
研究领域: 毒理学 · 分子生物学 · 细胞生物学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CHROMATOGRAPHY A · 2014 · IF 4.258

Determination of autoinducer-2 in biological samples by high-performance liquid chromatography with fluorescence detection using pre-column derivatization

Xiang-Ning Song,Hai-Bin Qiu,Xiang Xiao,Yuan-Yuan Cheng,Wen-Wei Li,Guo-Ping Sheng,Xiao-Yan Li,Han-Qing Yu

Autoinducer-2 (AI-2), as a small-molecular-weight organic molecule secreted and perceived by various bacteria, enables intra- and inter-species communications. Quantitative determination of AI-2 is essential for exploring the bacterial AI-2-related physiological and biochemical processes. However, current strategies for sensitive detection of AI-2 require sophisticated instruments and complicated procedures. In this work, on the basis of the derivatization of AI-2 with 2,3-diaminonaphthalene, a simple, sensitive and cost-effective high-performance liquid chromatography with fluorescence detector (HPLC–FLD) method is developed for the quantitative detection of AI-2. Under the optimized conditions, this method had a broad linear range of 10–14,000   ng/ml ( R 2   =   0.9999), and a low detection limit of 1.0   ng/ml. Furthermore, the effectiveness of this approach was further validated through measuring the AI-2 concentrations in the cell-free culture supernatants of both Escherichia coli and Vibrio harveyi .

CAS / MDL: 771-97-1
研究领域: 微生物学 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2025 · IF 6.1

Development of an Indirect Competitive Enzyme Immunoassay for Detection of a Plant Elicitor Methiadinil

Yue Zhang,Rongyan Shen,Yuting Huang,Zhihong Wang,Liangfu Tang,Zhijin Fan

Plant elicitors with distinctive benefits including low toxicity, small application dosages and an innovative mode of action are considered as green agrochemicals by stimulating the host plant immunity. Several new plant elicitors have been developed for tobacco protection against virus attack. Among them, as a milestone in Chinese plant elicitor development, methiadinil (IUPAC: 4-methyl- N -(5-methylthiazol-2-yl)-1,2,3-thiadiazole-5-carboxamide) shows broad application prospects. Because of its low application dosage, its residue determination requires diverse highly sensitive method. Here we developed an indirect enzyme-linked immunosorbent assay (ELISA) method for methiadinil residue determination with the lowest detection limit of 10.69 ng/mL and a linear detection range between 21.84 ng/mL of IC 20 and 1513.81 ng/mL of IC 80 by a rational hapten designation. Meanwhile, this indirect ELISA method showed good specificity with low cross-reactivity for methiadinil analogue determination and a good correlation with the HPLC method for tobacco sample measurement. This sensitive, rapid and accurate methiadinil residue determination method in tobacco leaves is of great significance for the monitoring of methiadinil in tobacco and guidance for other environmental sample determination and the rational application of methidadinil.

研究领域: 植物保护 · 农业化学 · 免疫学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF PLANT PHYSIOLOGY · 2023 · IF 4.3

Evaluation of inducing activity of CIP elicitors from diverse sources based on monosaccharide composition and physiological indicators

Guofu Luo,Yirui Shen,Kun Wu,Huining Yang,Chuntao Wu,Xiangbing Chang,Wei Tian

Application of elicitors can greatly enhance plant immune resistance against pathogens. However, it is still obscure whether elicitor activity is influenced by diverse sources. This study investigated the effect of foliar spraying of 19 batches of Chrysanthemum indicum polysaccharides (CIPs) on the disease resistance of Atractylodes macrocephala Koidz. ( A. macrocephala ) and explored the main reasons for the differences of inducing activity of CIP elicitors. PCA, OPLS-DA, grey relational analysis and entropy weight method had good predictability for the activity evaluation of CIP elicitors and other plant-derived elicitors. The results showed that 19 batches of CIPs had definite regional differences in inducing activity and monosaccharide content. CIP elicitors with high inducing activity could significantly increase the accumulation of Atractylenolide Ⅱ and Atractylenolide Ⅲ, the mRNA relative transcription level of CAT , POD , PAL genes, the amount of pH change in the medium and effectively reduce the disease index of A. macrocephala . Furthermore, CIP with high inducing activity exhibited the high contents of Rha, Ara and GalA, which might be the main contributor to their high activity. The evaluation procedure developed in this work can be applied for screening CIP elicitors with high inducing activity, and it lays a foundation for identifying more functional elicitors related to plant immune resistance.

CAS / MDL: 89-25-8
研究领域: 植物科学 · 药用植物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOORGANIC CHEMISTRY · 2025 · IF 4.7

Unusual chaetoglobosins and a new type of ferroptosis inducer from an endophytic fungus Chaetomium sp. UJN-EF006

Yin-Yin Wang,Yu-Song Wang,Jun-Jiang Li,Ze-Yi Wan,Hua Zhang

Seven unreported chaetoglobosin-type alkaloids, namely brachaetoglobosin A ( 1 ), chaetochalasins B F ( 2 – 6 ) and armochaeglobine C ( 7 ), together with the formerly described cytoglobosin C ( 8 ) and chaetoglobosin E ( 9 ), were obtained from an endophytic fungus Chaetomium sp. UJN-EF006 isolated from the leaves of Vaccinium bracteatum . Their structures were characterized through various spectral techniques including MS, NMR, X-ray crystallography and electronic circular dichroism. Also, this is only the second record of novel chaetochalasin and armochaeglobine skeletons of the cytochalasin super family, after 27 and 10 years of the first report, respectively. Compound 9 showed significant cytotoxic effect against two human tumor cell lines (MDA-MB231 and A549) and was identified as a new type of ferroptosis inducer (toward A549 cells) that could be used as a molecular tool in future related research.

研究领域: 真菌学 · 天然产物化学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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MOLECULES · 2018 ·Vol. 23 ·期 12 ·3276 · IF 3.098

Effect of Aspergillus flavus Fungal Elicitor on the Production of Terpenoid Indole Alkaloids in Catharanthus roseus Cambial Meristematic Cells

Chuxin Liang,Chang Chen,Pengfei Zhou,Lv Xu,Jianhua Zhu,Jincai Liang,Jiachen Zi,Rongmin Yu

This study reported the inducing effect ofAspergillus flavusfungal elicitor on biosynthesis of terpenoid indole alkaloids (TIAs) inCatharanthus roseuscambial meristematic cells (CMCs) and its inducing mechanism. According to the results determined by HPLC and HPLC-MS/MS, the optimal condition of theA. flavuselicitor was as follows: after suspension culture ofC. roseusCMCs for 6 day, 25 mg/LA. flavusmycelium elicitor were added, and the CMC suspensions were further cultured for another 48 h. In this condition, the contents of vindoline, catharanthine, and ajmaline were 1.45-, 3.29-, and 2.14-times as high as those of the control group, respectively. Transcriptome analysis showed thatD4H,G10H,GES,IRS,LAMT,SGD,STR,TDC, andORCA3were involved in the regulation of this induction process. The results of qRT-PCR indicated that the increasing accumulations of vindoline, catharanthine, and ajmaline inC. roseusCMCs were correlated with the increasing expression of the above genes. Therefore,A. flavusfungal elicitor could enhance the TIA production ofC. roseusCMCs, which might be used as an alternative biotechnological resource for obtaining bioactive alkaloids.Keywords:Catharanthus roseus;cambial meristematic cells;Aspergillus flavus;terpenoid indole alkaloids;biosynthesis

研究领域: 植物生物技术 · 植物化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 21 ·15722 · IF 5.6

Four-Chlorophenoxyacetic Acid Treatment Induces the Defense Resistance of Rice to White-Backed Planthopper Sogatella furcifera

Wanwan Wang,Haiyun Rui,Lei Yu,Nuo Jin,Wan Liu,Chen Guo,Yumeng Cheng,Yonggen Lou

Chemical elicitors can increase plant defense against herbivorous insects and pathogens. The use of synthetic chemical elicitors is likely to be an alternative to traditional pesticides for crop pest control. However, only a few synthetic chemicals are reported to protect plants by regulating signaling pathways, increasing the levels of defense metabolites and interfering with insect feeding. Here, we found that the exogenous application of a phenoxycarboxylic compound, 4-chlorophenoxyacetic acid (4-CPA), can induce chemical defenses to protect rice plants from white-backed planthoppers (WBPH,Sogatella furcifera). Four-CPA was rapidly taken up by plant roots and degraded to 4-chlorophenol (4-CP). Four-CPA treatment modulated the activity of peroxidase (POD) and directly induced the deposition of lignin-like polymers using hydrogen peroxide (H2O2) as the electron acceptor. The polymers, which are thought to prevent the planthopper’s stylet from reaching the phloem, were broken down by WBPH nymphs. Meanwhile, 4-CPA increased the levels of flavonoids and phenolamines (PAs). The increased flavonoids and PAs, together with the degradation product of the polymers, avoided nymphal feeding and prolonged the nymphal period for 1 day. These results indicate that 4-CPA has the potential to be used as a chemical elicitor to protect rice from planthoppers. Moreover, these findings also open a pathway for molecule structure design of phenoxycarboxylic compounds as chemical elicitors.Keywords:chemical elicitor;4-chlorophenoxyacetic acid;lignin-like polymers;white-backed planthoppers;rice;chemical defense

CAS / MDL: 122-88-3 106-48-9
研究领域: 植物科学 · 昆虫学 · 农业化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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