JOURNAL OF PHARMACY AND PHARMACOLOGY
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2020
·Vol. 72
·期 12
·1854-1864
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IF 2.571
Zhao Huan,Tong Yongbin,Lu Danyi,Wu Baojian
ObjectivesWe aimed to determine the diurnal rhythm of Tripterygium wilfordii (TW) hepatotoxicity and to investigate a potential role of metabolism and pharmacokinetics in generating chronotoxicity.MethodsHepatotoxicity was determined based on assessment of liver injury after dosing mice with TW at different circadian time points. Circadian clock control of metabolism, pharmacokinetics and hepatotoxicity was investigated using Clock-deficient (Clock−/−) mice.Key findingsHepatotoxicity of TW displayed a significant circadian rhythm (the highest level of toxicity was observed at ZT2 and the lowest level at ZT14). Pharmacokinetic experiments showed that oral gavage of TW at ZT2 generated higher plasma concentrations (and systemic exposure) of triptolide (a toxic constituent) compared with ZT14 dosing. This was accompanied by reduced formation of triptolide metabolites at ZT2. Loss of Clock gene sensitized mice to TW-induced hepatotoxicity and abolished the time-dependency of toxicity that was well correlated with altered metabolism and pharmacokinetics of triptolide. Loss of Clock gene also decreased Cyp3a11 expression in mouse liver and blunted its diurnal rhythm.ConclusionsTripterygium wilfordii chronotoxicity was associated with diurnal variations in triptolide pharmacokinetics and circadian expression of hepatic Cyp3a11 regulated by circadian clock. Our findings may have implications for improving TW treatment outcome with a chronotherapeutic approach.
研究领域:
药理学
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毒理学
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时间生物学
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分子生物学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Yumei Sun,Jihong Wang,Peiyao Hu,Yi Tang,Yanwen Wang,Jianzhou Ye,Xuesong Yang,Junlin Yin
Tripterygium hypoglaucum (Lévl.) Hutch rhizome (THH) is mainly used in the clinical setting for the treatment of autoimmune diseases such as rheumatoid arthritis. In total, four active compounds were isolated from THH methanol extract （THH-MeOH）and identified. The HPLC results showed that the proportions of the active ingredients in THH-MeOH (i.e., celastrol, triptolide, and 3- O -acetyloleanolic acid) were 0.79 ‰, 0.46 ‰, and 0.76 ‰, respectively. THH-MeOH attenuated the M5-induced hyperproliferation of HaCaT cells, decreased the mRNA expression levels of inflammatory cytokines, and inhibited the phosphorylation of I κ B α , NF- κ B p65, MAPK, and STAT3/JAK2. Furthermore, THH-MeOH significantly reduced PASI scores in mice; reduced the level of Ki67 expression in skin tissues; decreased the expression of inflammatory cytokines in the skin lesions and serum; and ameliorated the IMQ-induced imbalance in the ROR γ t / Foxp3 ratio. The extract can attenuate psoriasis-like lesions by inhibiting cellular hyperproliferation, ameliorating inflammatory reactions, and modulating immune responses. Our work provides a theoretical basis to support the use of THH for treating psoriasis.
研究领域:
药理学
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免疫学
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皮肤科
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PubMed
高影响因子
JOURNAL OF INSECT PHYSIOLOGY
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2022
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IF 2.608
Junjun Zhang,Zhengwei Wang,Katrina Klett,Yufeng Qu,Ken Tan
The thunder god vine , Tripterygium hypoglaucum, is a toxic nectar plant distributed across China. A terpenoid, called triptolide (TRP), found in nectar can impair honeybees’ foraging responses, dance communication, and olfactory learning. In the present study, we tested the tolerances of the native honeybee Apis cerana and the introduced honeybee A. mellifera to short-term and long-term exposure to TRP. The results showed that introduced A. mellifera is more vulnerable in fatality to high concentrations of TRP sucrose solution (5 and 10 µg TRP mL −1 ) than A. cerana . We also compared the short-term and long-term exposure effects of TRP on olfactory learning and memory between the two honeybee species, and the olfactory learning and memory of both honey bee species showed impaired performance after both 2 h or 7 days of being fed with TRP sucrose solution. However, A. cerana showed a higher tolerance and resistance to TRP toxin than A. mellifera. Our results support a coevolution hypothesis in that the native species A. cerana has higher toxin tolerance than the introduced species A. mellifera .
研究领域:
昆虫学
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毒理学
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生态学
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PubMed
高影响因子
Computational and Mathematical Methods in Medicine
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2022
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IF 2.809
Song Wang,Jiali Cui,Gaoqiong Zhao,Hongbin Liu,Jingkun Wang
Background. Chinese Materia Medica and Jiangsu New Medical College record that Radix Veratri root is Liliaceae Veratrum taliense Loses. f. and the root of Veratrum stenophyllum Diels. According to traditional Chinese medicine (TCM) example, Radix Veratri is a Liliaceae plant Veratrum taliense. Another literature pointed out that the aliases of Veratrum taliense and Veratrum angustifolia are both Radix Veratri, and their effects are basically the same. The main active ingredient of Veratrum is veratramine, of which veratramine and Jervine are higher in content, reaching 24.60% and 21.28% of the total alkaloids, respectively. Veratrum alkaloids are both toxic and effective ingredients. In addition to its good clinical efficacy, attention should also be paid to its pharmacokinetic characteristics in vivo. It is particularly important to study the pharmacokinetic characteristics of veratramine and Jervine in vivo. Objective. The goal of this study was to develop a simple and effective method for measuring veratramine and Jervine in rat plasma at the same time. This method was used to study the pharmacokinetic characteristics of veratramine and Jervine in the alcohol extract of Radix Veratri in rats, to provide a reasonable basis for the clinical use of Radix Veratri. Methods. Eighteen SD rats were randomly assigned into three groups, half male and half female, and were given 0.04 g/kg, 0.08g/kg, and 0.16 g/kg Radix Veratri alcohol extract, respectively. Blood samples were collected at different time points and were analyzed by LC-MS/MS after protein precipitation. Bullatine was set as the internal standard; the plasma samples were extracted with ethyl acetate. After the sample was processed, acetonitrile-10 mM ammonium acetate, whose pH was adjusted to 8.8 with ammonia water, was taken as the mobile phase. Veratramine quantitative ion pair was , Jervine quantitative ion pair was , and Bullatine B (IS) quantitative ion pair was . In the positive ion mode, the multireaction monitoring (MRM) mode was used to determine the blood concentration of veratramine and Jervine. DAS 3.3.0 was used to calculate the relevant pharmacokinetic parameters. Results. Veratramine had a good linear relationship in the concentration range of 0.0745~18.2 ng/mL, and that of Jervine was 1.11~108 ng/mL. The correlation coefficient of three consecutive batches of the standard curve was greater than 0.995. Veratramine’s lower quantification limit was 0.745 ng/mL, Jervine’s was 1.11 ng/mL, and precision and accuracy were both less than 15%. The accuracy of veratramine was between 88.96% and 101.85%, and the accuracy of Jervine was between 92.96% and 104.50%. This method was adopted for the pharmacokinetic study of alcohol extracts of Radix Veratri. The results showed that only of veratramine female rats did not show linear kinetic characteristics in the dose range of Radix Veratri alcohol extract from 0.04 g/kg to 0.16 g/kg. For and of veratramine and Jervine, it could not determine whether the Radix Veratri alcohol extract showed linear kinetic characteristics within the dosage range of 0.04 g/kg~0.16 g/kg. Veratramine and Jervine showed obvious gender differences in the absorption and elimination stages. The absorption rate of veratramine and Jervine by male mice was about 10 times higher than that of female mice, and the elimination rate of male mice is about 20 times lower than that of female mice. It was suggested that the clinical application of the steroidal alkaloids veratramine and Jervine in Radix Veratri required rational use of drugs based on gender. Conclusion. An LC-MS/MS analysis method suitable for the pharmacokinetic study of veratramine and Jervine in Radix Veratri in SD rats was established to provide a basis for in vivo pharmacokinetic studies. The pharmacokinetic characteristics of veratramine and Jervine in the alcohol extract of Radix Veratri were significantly different in female and male rats. During the clinical use of Radix Veratri, it should pay close attention to the obvious gender differences that may occur after the medication.
研究领域:
中药学
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药理学
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分析化学
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PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2024
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IF 4.1
Mengmeng Chen,Mingyang Xue,Yong Zhou,Chen Xu,Nan Jiang,Yuding Fan,Yan Meng
Largemouth bass ranavirus (LMBRaV), also known as largemouth bass virus (LMBV), is a highly damaging viral pathogen that causes widespread mortality in cultured largemouth bass and poses a significant threat to the farming industry in China. However, there is a paucity of effective preventive methods for this disease by LMBRaV. Research has established that herbal extracts possess antiviral activity, potentially exerting a controlling effect on viruses in aquaculture. Therefore, the identification of simple and structurally safe herbal extract immunomodulators is critical for largemouth bass health and development. Rhein, an herbal compound, exhibits a broad spectrum of pharmacological effects in herbal medicine. This study aimed to evaluate the properties and effects of rhein against LMBRaV in epithelioma papilloma cyprinid (EPC) and largemouth bass. In vitro CCK-8 assays were performed to determine the highest safe concentrations. Significantly, 50 mg/L rhein effectively inhibited cytopathic effects (CPE) in EPC induced by LMBRaV, resulting in a 97 % reduction in viral replication rates. Furthermore, a six-point dose-response experiment revealed that rhein doses as low as 6.4 mg/L inhibited LMBRaV and suppressed LMBRaV infection with a dose-dependent manner. Subsequent experiments demonstrated that sustained rhein activity effectively alleviated CPE and nuclear damage caused by LMBRaV infection. Additionally, rhein exerted protective effects against declines in LMBRaV-induced mitochondrial membrane potential. In vivo experiments validated that largemouth bass diets supplemented with 0.075 % rhein exerted a protective effect against LMBRaV infection. Moreover, LMBRaV MCP gene expression levels were lower in several organs of fish in the rhein supplementation group. Immunogene analysis determined that rhein upregulated relevant gene expression levels in multiple organs of largemouth bass, with higher activities observed for the Mx, INF-γ, and IRF3 genes. Histopathological results displayed that a supplemental dosage of 0.075 % rhein significantly mitigated LMBRaV infection-induced pathological damage in the liver, spleen, and kidney. Taken together, these in vivo and in vitro results support the effective use of rhein as a promising candidate for the development of antiviral treatment against LMBRaV infection, highlighting its role in aquatic animal husbandry as a wide-spectrum antiviral and immune response booster.
研究领域:
水产养殖学
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病毒学
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药理学
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2020
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IF 3.594
Yaping Duan,Congmin Liu,Xiaowen Dou,Liu Wu,Hao Liu,Linan Shan,Shihai Yang,Jiaoyang Luo,Meihua Yang
Triptolide is a characteristic chemical component and quality marker of Tripterygium wilfordii Hook. F., a widely used traditional Chinese medicine with various pharmacological activities. Triptolide-14-succinate is a derivative of triptolide that can be combined with bovine serum albumin and ovalbumin to form an immunogen and coating antigen. Monoclonal antibody specific to triptolide-14-succinate conjugated with ovalbumin was produced and named mAb 2D10 1H8. An indirect competitive enzyme-linked immunosorbent assay (icELISA) was established by using mAb 2D10 1H8. The 50% inhibition concentration and working range of triptolide for the icELISA were 0.28 and 0.09–0.87 μg mL −1 , (based on 20–80% binding inhibition of mAb 2D10 1H8 to triptolide, R 2 = 0.9997, y = -0.571Logx + 0.246), respectively. The icELISA displayed crossreactivity values of 48.6, 20.5, 3.27, and < 1.00% for triptonide, triptophenolide, tripterifordin, and other analogs of triptolide, respectively. The average recovery of triptolide from the Tripterygium wilfordii samples as determined by icELISA ranged from 90.05 to 106.6%. Triptolide was detected in 38 batches of Tripterygium wilfordii samples by icELISA, which was validated by ultra-fast liquid chromatography combined with electrospray ionization tandem-mass spectrometry. In conclusion, the icELISA method established in the present study is applicable for rapid authentication of Tripterygium wilfordii and related products.
研究领域:
中药学
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免疫学
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分析化学
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DOI
高影响因子
Journal of Pharmaceutical Analysis
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2025
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IF 8.9
Jia Guo,Yuqing Song,Mengru Sun,Jun Qian,Dihang See,Tian Tian,Yunqing Song,Wei Liu,Hongping Deng,Yao Sun,Guangbo Ge,Yongfang Zhao
Osteoporosis, a severe systemic skeletal disorder characterized by decreased bone mineral density, leads to increased risks of bone fragility and fracture. Although some herbal medicines are clinically used for treating osteoporosis, the crucial anti-osteoporotic constituents and their mechanisms have not been well-elucidated. Notum, a negative regulator of Wnt/β-catenin signaling, has been validated as a druggable target for enhancing cortical bone thickness and alleviating osteoporosis. Herein, we showcase an efficient strategy for uncovering the key anti-Notum constituents from herbal medicines via integrating biochemical, phytochemical, computational, and cellular assays. Following screening the anti-Notum potentials of herbal medicines, Polygonum multiflorum Thunb. (PM), a commonly used anti-osteoporosis herb , showed potent and competitive inhibition against Notum. Phytochemical profiling coupling with docking-based virtual screening suggested that three anthraquinones, including rhein, emodin, and chrysophanol, showed high binding-potency towards Notum. Biochemical assays validated that three anthraquinones were strong competitive inhibitors of Notum, while rhein was the most potent one (IC 50 = 9.98 nM). Cellular investigations demonstrated that rhein markedly promoted osteoblast differentiation in dexamethasone-challenged MC3T3-E1 osteoblasts, while RNA sequencing showed that rhein remarkably regulated Wnt signaling-related and osteogenic differentiation-related genes. In vivo tests showed that rhein displayed favorable safety profiles in healthy mice and this agent significantly elevated bone mineral density, augmented trabecula and cortical bone thickness in dexamethasone-induced osteoporotic mice. Collectively, this study showcases an efficient strategy for uncovering the key anti-Notum constituents from herbal medicines, while rhein was identified as a naturally occurring Notum inhibitor that shows favorable safety profiles and impressive anti-osteoporosis effects.
研究领域:
药理学
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生物化学
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计算生物学
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高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2014
·Vol. 131
·期 20
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IF 1.64
Guoxiang Li,Daichan Lu,Xindan Shi,Mingyue Cai
By blending chitin with rectorite and organic rectorite in an 8 wt % NaOH/4 wt % urea aqueous solution, we successfully fabricated millimeter-scale chitin/rectorite composite beads (BCRs) and chitin/organic rectorite beads (BCO), respectively, via an optimal dropping technology. The adsorption of the organic dyes on the BCRs and BCOs were investigated to evaluate the selective removal of methylene blue (MB) and methyl orange (MO) of different charges. Adsorption kinetics experiments were carried out, and the data fit a pseudo-second-order equation well. The results reveal that the BCR and BCO sorbents efficiently and selectively adsorbed MO and MB, respectively, from wastewater. The adsorption capacity ( Q e ) and removed percentage of MB by BCR were 0.1978 mg/g and 98.90%. The Q e and R values of MO by BCO were 0.3988 mg/g and 99.70%. Therefore, in this study, we dealt with the development of a clean and safe process for water pollution remediation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40905.
研究领域:
环境科学
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材料科学
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化学工程
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DOI
高影响因子
Nature Communications
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2020
·Vol. 11
·期 1
·1-12
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IF 12.121
Tu Lichan,Su Ping,Zhang Zhongren,Gao Linhui,Wang Jiadian,Hu Tianyuan,Zhou Jiawei,Zhang Yifeng,Zhao Yujun,Liu Yuan,Song Yadi,Tong Yuru,Lu Yun,Yang Jian,Xu Cao,Jia Meirong,Peters Reuben J.,Huang Luqi,Gao Wei
Triptolide is a trace natural product of Tripterygium wilfordii . It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
研究领域:
植物生物学
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基因组学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Li Lin,Longxin Guo,Minjuan Long,Ming Niu,Yuming Guo,Shengkai Zhu,Zhaofang Bai,Xu Zhao,Huaqiang Zhai,Xiaohe Xiao
Ethnopharmacological relevance Compound preparations of traditional Chinese medicines (TCMs) have gained considerable interest. However, ensuring their safety is difficult because of ingredient complexity. Reynoutria multiflora (Thunb.) Moldenke (PM), commonly used in tonic preparations for clinical use, has been frequently reported to cause drug-induced liver injury (DILI). Liver injury caused by PM is idiosyncratic and its underlying mechanisms have been elucidated. However, a systematic evaluation of the safety of PM compound formulations is lacking. Our preliminary research predicted a potential compatibility risk between PM and Cullen corylifolium (Linnaeus) Medikus (PF); however, the specific effects and mechanisms of their combined action on the liver have not been fully studied. Aim of the study To determine the effects of the PM and PF combination on the liver and its mechanisms. Materials and methods This study used a lipopolysaccharide-induced idiosyncratic (IDILI) model. Kits were employed to measure the liver function indices and ELISA was used to detect inflammatory factor content. The histopathological changes of the liver were observed using H&E and TUNEL staining. Serum metabolomics and liver transcriptomics were performed simultaneously to detect overall differences in metabolite and gene expression. Network pharmacology and molecular docking were used to screen hepatotoxic components and their potential pathways. Results Liver function indicators and pathological results demonstrated that the combined treatment with PM and PF may exacerbate immune-mediated liver injury compared to treatment with either herb alone. Inflammatory factor levels indicated that the combination had an immuno-amplifying effect, further increasing inflammatory cytokine levels. Integrated metabolomic and transcriptomic analysis revealed that the combination primarily affected the primary bile acid synthesis and glycerophospholipid metabolism. This exacerbated hepatocyte apoptosis and liver injury by down-regulating the expression of key genes ( BAAT and ALB ) for bile acid metabolism. Network pharmacology and molecular docking identified 2,3,5,4'-Tetrahydroxy stilbene-2-Ο-β-D-glucoside and psoralidin as potential toxic components of PM and PF, respectively. These two ingredients specifically targeted the cytosolic DNA-sensing pathway and NOD-like receptor signalling pathway. When combined, PM and PF triggered immune hyperactivation via dual-pathway cross-regulation, leading to immuno-metabolic disorders, increased hepatocyte apoptosis and enhanced inflammatory cascade responses. Conclusions The PM and PF combination represents a newly identified incompatible pair that can aggravate IDILI under specific conditions. Our findings provide a critical reference for the safe use of compound medication, enriching the TCM combination theory.
研究领域:
民族药理学
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肝脏病学
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中药学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
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IF 3.4
Shu Chen,Li Liu,Hong-Xia Jiang,Qun Sun,Liang Zhang,Jian-Qun Liu,Li-Fang Liu
Tripterygium wilfordii (TW), a well-known traditional Chinese medicine , was widely used in the treatment of autoimmune disorders and inflammatory diseases . However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity . Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.
研究领域:
中药学
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毒理学
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代谢组学
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DOI
PubMed
高影响因子
Frontiers in Oncology
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2025
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IF 3.3
Wei Zhang,Jiping Li,Xiuli Gao,Likun Liu,Hong Liang,Liling Yue
Background/Objectives Breast cancer treatment remains challenged by the non-specific distribution and systemic toxicity of conventional chemotherapeutics. Celastrol (CEL), a natural compound with antitumor efficacy, faces clinical limitations due to its toxicity and poor solubility. Glycyrrhizic acid (GA), known for tumor-suppressive and membrane-modifying properties, offers potential to enhance targeted drug delivery. This study aimed to develop GA-modified liposomes (GA/LIP-CEL) to synergistically improve CEL’s therapeutic specificity and safety. Methods GA/LIP-CEL nanoparticles were engineered via thin-film hydration, replacing cholesterol with GA. Physicochemical properties were characterized using TEM, DLS, and HPLC. In vitro evaluations included stability assays, cellular uptake (flow cytometry), cytotoxicity (MTT assay), mitochondrial membrane potential (JC-1 staining), apoptosis (Annexin V/PI), DNA damage (γ-H2AX immunofluorescence), and cell cycle analysis in BT549 breast cancer and MCF-10A normal cells. Results GA/LIP-CEL exhibited uniform spherical morphology (122.48 ± 5.37 nm), high drug loading (87.75 ± 2.61%), sustained release (70.13% cumulative release at 24 h), and colloidal stability (negligible size variation over 14 days). Compared to LIP-CEL, GA/LIP-CEL reduced IC50 in BT549 cells while lowering cytotoxicity in MCF-10A cells. Compared with the LIP-CEL group, GA/LIP-CEL treatment demonstrated a statistically significant increase in apoptotic cell proportion (P < 0.05). Enhanced mitochondrial dysfunction (P < 0.05) and DNA (P < 0.05) damage were observed. GA modification improved cellular uptake potentially via regulating membrane fluidity and receptor-mediated endocytosis effects, and induced S-phase arrest (31.66 ± 1.70% cells). Conclusions GA/LIP-CEL combines GA’s membrane-targeting capabilities with CEL’s therapeutic effects, improving stability, specificity, and safety. This platform represents a novel strategy for precision drug delivery, addressing limitations of conventional systems through natural component integration. Further validation of in vivo performance and pharmacokinetics is warranted to advance clinical translation.
研究领域:
药学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）