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Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain 仙灵葛宝片引起的中草药肝损伤:使用更新的 RUCAM 和综合证据链评估一个病例的因果关系
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2023.10.005
Chunyu Li , Yingying Li , Zhaofang Bai , Jiabo Wang , Guohui Li , Xiaohe Xiao

Objective

A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory.

Methods

A patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines).

Results

Clinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient’s medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered “highly probable” (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.

Conclusion

In summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

目的 在临床和实验室系统研究一例典型的仙灵葛片诱发肝损伤病例。方法 以中草药肝损伤(HILI)患者为研究对象,根据《中草药肝损伤诊断和治疗指南》(HILI指南)推荐的最新Roussel Uclaf因果关系评估法(RUCAM)和综合证据链法(iEC)对病例进行诊断。结果通过临床病史、生化指标和影像学检查,排除了病毒性、酒精性和自身免疫性肝病等基础疾病和易混淆肝病对诊断的影响。根据对患者用药史的调查,由于患者仅口服 XLGB 片制剂,排除了其他药物对诊断的影响,因此怀疑其为 XLGB 片引起的 HILI。该患者的丙氨酸氨基转移酶(ALT)≥ 3 倍正常值上限(ULN),计算的 R 值为 6,因此被诊断为可能是急性药物性肝细胞损伤。根据 2016 年更新的 RUCAM,这种关系被视为 "高度可能"(9 分)。此外,患者服用的制剂与市售制剂之间的指纹相似度为 0.99,表明患者服用的是 XLGB 片而不是其他药物。利用 LC-MS 技术和 Agilent Fake TCM-Drugs 数据库对该药物进行了调查,未发现任何化学添加物。结论综上所述,XLGB 引起的肝损伤的最终诊断符合 HILI 的临床诊断,根据最新的 RUCAM 和 iEC,诊断为急性重症肝细胞损伤型。因此,本研究为中药复方制剂诱发肝损伤的因果关系评价提供了科学依据。
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引用次数: 0
Huangqi Guizhi Wuwu Decoction suppresses inflammation and bone destruction in collagen-induced arthritis mice 黄芪桂枝五味煎剂可抑制胶原诱导的关节炎小鼠的炎症和骨破坏
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2023.10.003
Jiamin Bao , Yongjia Song , Minghui Hang , Hao Xu , Qiang Li , Pengyu Wang , Tao Chen , Mengxiong Xia , Qi Shi , Yongjun Wang , Xiaoyun Wang , Qianqian Liang

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis, characterized by inflammatory infiltration and bone destruction. Huangqi Guizhi Wuwu Decoction (HGWD) is traditional Chinese medicine, which has been applied in the treatment of RA in clinical. The aim of this study was to investigate the therapeutic effect of HGWD on collagen-induced arthritis (CIA) mouse model.

Methods

DBA/1J female mice were used to establish the collagen-induced arthritis (CIA) model. HGWD was administered intragastrically once a day for four weeks starting on the 22nd day after the first immunization. The body weight, hind paw thickness and clinical score were measured every five days. Gait analysis, histopathological staining, enzyme-linked immunosorbent assay (ELISA), ultrasound imaging and micro-computed tomography imaging were performed to determine the effects of HGWD treatment on inflammation and bone structure in this model. Moreover, Real-time PCR and Western blot analysis were used to detect inflammatory factors mRNA and protein levels after HGWD intervention in RAW 264.7 cells.

Results

HGWD attenuated symptoms of arthritis, suppressed inflammatory synovium area and the serum levels of inflammatory factors, inhibited joint space enlargement in the knee and ankle joints, reduced numbers of osteoclasts, protected bone destruction, as well as improved motor function. HGWD decreased the expression of mRNA for inflammatory factors and the protein expression levels of p-NF-кB and IL-17.

Conclusion

These results suggested that HGWD suppresses inflammation, attenuates bone erosion and maintains motor function in collagen-induced arthritis mice.

目的类风湿性关节炎(RA)是一种慢性炎症性和破坏性关节炎,以炎症浸润和骨质破坏为特征。黄芪桂枝五物汤是一种传统中药,已应用于临床治疗类风湿性关节炎。本研究旨在探讨黄芪桂枝五味子汤对胶原诱导的关节炎(CIA)小鼠模型的治疗效果。从第一次免疫后的第 22 天开始,每天一次胃内注射 HGWD,连续注射四周。每五天测量一次体重、后爪厚度和临床评分。通过步态分析、组织病理学染色、酶联免疫吸附试验(ELISA)、超声波成像和显微计算机断层扫描成像来确定HGWD治疗对该模型炎症和骨结构的影响。结果 HGWD减轻了关节炎的症状,抑制了炎性滑膜面积和血清中炎性因子的水平,抑制了膝关节和踝关节的关节间隙扩大,减少了破骨细胞的数量,保护了骨破坏,并改善了运动功能。结论:这些结果表明,HGWD 可抑制炎症、减轻骨侵蚀并维持胶原蛋白诱导的关节炎小鼠的运动功能。
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引用次数: 0
Arbuscular mycorrhiza and plant growth promoting endophytes facilitates accumulation of saponin under moderate drought stress 在中度干旱胁迫下,丛枝菌根和促进植物生长的内生菌促进皂苷的积累
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2022.11.004
Shubiao Qian , Qing Zhang , Sha Li , Rui Shi , Xiahong He , Shuhui Zi , Tao Liu
<div><h3>Objective</h3><p><em>Paris polyphylla</em> var<em>. yunnanensis</em>, one of the important medicinal plant resources in Yunnan, China, usually takes 6–8 years to be harvested. Therefore, it is urgent to find a method that can not only shorten its growth years, but also improve its quality. In this study, we examined the effects of a combination treatment of arbuscular mycorrhizal fungi (AMF) and plant growth-promoting endophytes (PGPE) and drought stress on the accumulation of saponins in it<em>.</em></p></div><div><h3>Methods</h3><p><em>P. polyphylla</em> var<em>. yunnanensis</em> was infected with a mixture of AMF and PGPE under drought stress. The content of saponins, as well as morphological, physiological, and biochemical indicators, were all measured. The UGTs gene related to saponin synthesis was obtained from transcriptome data by homologous comparison, which were used for RT-PCR and phylogenetic analysis.</p></div><div><h3>Results</h3><p>Regardless of water, AMF treatment could infect the roots of <em>P. polyphylla</em> var<em>. yunnanensis</em>, however double inoculation with AMF and PGPE (AMF + PGPE) would reduce the infection rate of AMF. Plant height, aboveground and underground fresh weight did not differ significantly between the single inoculation AMF and the double inoculation treatment under different water conditions, but the inoculation treatment significantly increased the plant height of <em>P. polyphylla</em> var<em>. yunnanensis</em> compared to the non-inoculation treatment. Single inoculation with AMF considerably increased the net photosynthetic rate, stomatal conductance, and transpiration rate of <em>P. polyphylla</em> var<em>. yunnanensis</em> leaves under various water conditions, but double inoculation with AMF + PGPE greatly increased the intercellular CO<sub>2</sub> concentration and chlorophyll fluorescence parameter (Fv/Fm). Under diverse water treatments, single inoculation AMF had the highest proline content, whereas double inoculation AMF + PGPE may greatly improve the amount of abscisic acid (ABA) and indoleacetic acid (IAA) compared to normal water under moderate drought. Double inoculation AMF + PGPE treatment improved the proportion of N, P, and K in the rhizome of <em>P. polyphylla</em> var<em>. yunnanensis</em> under various water conditions. Under moderate drought stress, AMF + PGPE significantly enhanced the contents of <em>P. polyphylla</em> var<em>. yunnanensis</em> saponins I, II, VII, and total saponins as compared to normal water circumstances. Farnesyl diphosphate synthase (<em>FPPS</em>), Geranyl pyrophosphate synthase (<em>GPPS</em>), Cycloartenol synthase (<em>CAS</em>), and Squalene epoxidase (<em>SE1</em>) were the genes that were significantly up-regulated at the same time. The amount of saponins was favorably linked with the expression of CAS, GPPS, and SE1. Saponin VI content and glycosyl transferase (UGT) 010922 gene expression were found to be substantially associated, as wa
目的云南白药是中国云南重要的药用植物资源之一,通常需要 6-8 年才能采收。因此,迫切需要找到一种既能缩短其生长年限,又能提高其品质的方法。本研究考察了丛枝菌根真菌(AMF)和植物生长促进内生菌(PGPE)联合处理以及干旱胁迫对其皂苷积累的影响。测定了皂苷的含量以及形态、生理和生化指标。结果无论水质如何,AMF 都能侵染云南斑潜蝇的根部,但 AMF 和 PGPE(AMF + PGPE)的双重接种会降低 AMF 的侵染率。在不同水质条件下,单一接种 AMF 和双重接种处理的植株高度、地上部和地下部鲜重没有显著差异,但接种处理比不接种处理显著增加了云南斑潜蝇的植株高度。在不同水分条件下,AMF的单一接种显著提高了云南红豆杉叶片的净光合速率、气孔导度和蒸腾速率,但AMF+PGPE的双重接种则大大提高了细胞间CO2浓度和叶绿素荧光参数(Fv/Fm)。在不同的水处理条件下,单接种AMF的脯氨酸含量最高,而在中度干旱条件下,与普通水相比,双接种AMF + PGPE可大大提高脱落酸(ABA)和吲哚乙酸(IAA)的含量。双接种 AMF + PGPE 处理可提高云南白药在各种水分条件下根茎中氮、磷、钾的比例。在中度干旱胁迫下,与正常水条件相比,AMF + PGPE 显著提高了云南白药皂苷 I、II、VII 和总皂苷的含量。同时,二磷酸法尼酯合成酶(FPPS)、焦磷酸香叶酯合成酶(GPPS)、环木菠萝烯醇合成酶(CAS)和角鲨烯环氧化物酶(SE1)等基因被显著上调。皂苷的含量与 CAS、GPPS 和 SE1 的表达密切相关。结论 在中度干旱条件下,AMF + PGPE 更有利于增加云南红豆杉的激素含量、养分吸收和总皂苷含量。结论 在中度干旱条件下,AMF + PGPE 更有利于云南红豆杉激素含量、养分吸收和总皂苷含量的增加,AMF + PGPE 能不同程度地调控一个或多个甾体皂苷合成途径中的关键基因和 UGTs 基因的表达,从而刺激云南红豆杉根茎中甾体皂苷的合成和积累。结合接种 AMF 和 PGPE 以及适当的土壤干旱,可减少云南白药皂苷的积累并提高其品质。
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引用次数: 0
Rhizosphere microbial markers (micro-markers): A new physical examination indicator for traditional Chinese medicines 根圈微生物标记(微标记):一种新的中药体检指标
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2023.11.003
Kailin Yang , Yaping Zheng , Kangmeng Sun , Xinyan Wu , Zheng Zhang , Chunnian He , Peigen Xiao

Rhizosphere microorganisms, as one of the most important components of the soil microbiota and plant holobiont, play a key role in the medicinal plant-soil ecosystem, which are closely related to the growth, adaptability, nutrient absorption, stress tolerance and pathogen resistance of host plants. In recent years, with the wide application of molecular biology and omics technologies, the outcomes of rhizosphere microorganisms on the health, biomass production and secondary metabolite biosynthesis of medicinal plants have received extensive attention. However, whether or to what extent rhizosphere microorganisms can contribute to the construction of the quality evaluation system of Chinese medicinal materials is still elusive. Based on the significant role of rhizosphere microbes in the survival and quality formation of medicinal plants, this paper proposed a new concept of rhizosphere microbial markers (micro-markers), expounded the relevant research methods and ideas of applying the new concept, highlighted the importance of micro-markers in the quality evaluation and control system of traditional Chinese medicines (TCMs), and introduced the potential value in soil environmental assessment, plant pest control and quality assessment of TCMs. It provides reference for developing ecological planting of TCMs and ensuring the production of high quality TCMs by regulating rhizosphere microbial communities.

根瘤微生物作为土壤微生物群和植物全生物体最重要的组成部分之一,在药用植物-土壤生态系统中发挥着关键作用,与寄主植物的生长、适应性、养分吸收、抗逆性和抗病性等密切相关。近年来,随着分子生物学和全息技术的广泛应用,根瘤微生物对药用植物健康、生物量生产和次生代谢物生物合成的影响受到广泛关注。然而,根瘤微生物能否或在多大程度上促进中药材质量评价体系的构建仍是一个未知数。基于根圈微生物在药用植物生存和质量形成过程中的重要作用,本文提出了根圈微生物标志物(微标志物)的新概念,阐述了应用新概念的相关研究方法和思路,强调了微标志物在中药质量评价与控制体系中的重要性,介绍了其在土壤环境评价、植物病虫害防治和中药质量评价中的潜在价值。它为发展中药生态种植、通过调控根瘤菌群落确保优质中药的生产提供了参考。
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引用次数: 0
Protective role of fruits of Rosa odorata var. gigantea against WIRS-induced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis 蔷薇果实通过调节炎症、氧化应激和细胞凋亡相关途径,对 WIRS 诱导的大鼠胃黏膜损伤具有保护作用
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2023.10.006
Xinnan Liu , Zhen Yuan , Lifei Luo , Teng Wang , Feng Zhao , Jingze Zhang , Dailin Liu

Objective

Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved.

Methods

A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot.

Results

Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival.

Conclusion

The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

目的 罗萨果是一种常用的药用植物。一些研究表明,臭腥草果实的乙醇提取物(FOE)具有胃保护特性。本研究旨在探讨 FOE 对水浸应激(WIRS)诱导的大鼠胃黏膜损伤的胃保护活性,并阐明其中可能涉及的分子机制。大鼠口服 FOE 7 d 后,用苏木精和伊红(H&E)染色法分析 FOE 治疗的效果,用 ELISA 法检测大鼠血液和胃组织中炎症因子、氧化应激因子、胃特异性调节因子和胃蛋白酶的变化。结果与 WIRS 组相比,FOE 能减轻胃黏膜的宏观和微观病理形态。FOE 能明显保护抗氧化剂谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的含量;抗炎细胞因子白细胞介素-10(IL-10)和前列腺素 E2(PGE2)的含量,以及调节因子肿瘤坏死因子-α(TGF-α)和体生长抑素(SS)的含量、同时降低丙二醛(MDA)、一氧化氮合酶(iNOS)、肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、胃泌素(GAS)和内皮素(ET)的水平。此外,FOE 还明显上调了 Nrf2、HO-1、Bcl2 和增殖细胞核抗原(PCNA)的表达。此外,FOE 还能激活 p-EGFR 的表达,下调 NF-κB、Bax、Cleaved-caspase-3、Cyto-C 和 Cleaved-PARP1 的表达,从而促进胃黏膜细胞的存活。其潜在机制可能与抗炎、抗氧化和抗细胞凋亡系统的改善有关。
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引用次数: 0
Microbial interactions within Chinese traditional medicinal plants 中国传统药用植物中的微生物相互作用
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2024.03.002
Juan Chen, Luping Qin
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引用次数: 0
Chemical profiling of principle active and toxic constituents in herbs containing aristolochic acids 含马兜铃酸草药中主要活性成分和毒性成分的化学分析
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2023.02.008
Lijun Yue , Kaijun Yang , Feng Jiang , Shuai Dong , Kang Yang , Dan Zhu

Objective

To clear the amounts of the principal active/toxic components in herbs containing aristolochic acids (HCAAs), which are still used as medicine and/or seasoning in many ethnic minority areas of China.

Methods

In this study, six major active and toxic components in HCAAs were extracted with ultrasonic extraction. With 6-O-methyl guanosine as internal standard, the target compounds were analyzed qualitatively and quantitatively by using ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) with multiple reaction monitoring-information dependent acquisition-enhanced production ion scanning mode (MRM-IDA-EPI) combined with dynamic background subtraction (DBS) function.

Results

The method showed good linearity in the linear range of the six analytes. The limit range of detection was from 0.01 ng/mL to 0.27 ng/mL. All of the detection repeatability, extraction repeatability and accuracy of the method were good. After extraction, the samples remained stable at 15 °C within 24 h. Six analytes were all found in samples except aristolactam (AL) in sample 2, and the contents varied greatly. The contents of these compounds decreased in fruits, leaves and stems of Aristolochia delavayi successively.

Conclusion

This method has the advantages of less sample dosage, simple operation, short analysis cycle, high sensitivity, specificity and accuracy. It laid a good foundation for guiding the safety of HCAAs, the in-depth study of pharmacological and toxicological effects and the scientific and standardized processing and compatibility of HCAAs.

方法 用超声波提取法提取含马兜铃酸中草药中的六种主要活性成分和毒性成分,以6-O-甲基鸟苷为内标物,采用超高效液相色谱-电喷雾串联质谱对目标化合物进行定性和定量分析。以6-O-甲基鸟苷为内标物,采用超高效液相色谱-电喷雾串联质谱(UPLC-ESI-MS/MS)的多反应监测-信息依赖采集-增强产离子扫描模式(MRM-IDA-EPI)结合动态背景减除(DBS)功能对目标化合物进行定性和定量分析。检测限范围为 0.01 ng/mL 至 0.27 ng/mL。该方法的检测重复性、萃取重复性和准确性均良好。除样品 2 中的马兜铃内酰胺(AL)外,其他 6 种分析物在样品中均有检出,且含量差异较大。该方法具有样品用量少、操作简单、分析周期短、灵敏度高、特异性强、准确度高等优点。该方法具有样品用量少、操作简便、分析周期短、灵敏度高、特异性强、准确度高等优点,为指导马兜铃属植物的安全性研究、药理毒理作用的深入研究以及马兜铃属植物的科学规范加工和相容性研究奠定了良好的基础。
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引用次数: 0
Pleiotropic attenuating effect of Ginkgo biloba against isoprenaline-induced myocardial infarction via improving Bcl-2/mTOR/ERK1/2/Na+, K+-ATPase activities 银杏叶通过改善 Bcl-2/mTOR/ERK1/2/Na+、K+-ATPase 活性,对异丙肾上腺素诱发的心肌梗死具有多效减轻作用
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-01 DOI: 10.1016/j.chmed.2023.11.001
Jerome Ndudi Asiwe , Abodunrin Adebayo Ojetola , Nwoke Enekabokom Ekene , Esthinsheen Osirim , Anthony Chibuzor Nnamudi , Benjamin Oritsemuelebi , Jackson Erozueme Onuelu , Nicholas Asiwe , Harrison Ogheneochuko Eruotor , Saviour Inegbenehi

Objective

Myocardial infarction (MI) is linked to an imbalance in the supply and demand of blood oxygen in the heart muscles. Beta-blockers and calcium antagonists are just two of the common medications used to treat MI. However, these have reportedly been shown to be either ineffective or to have undesirable side effects. Extract of Ginkgo biloba leaves (GBE), a Chinese herbal product offers special compatibility benefits in therapeutic settings relating to inflammatory diseases and oxidative stress. In order to better understand how GBE affects MI in rats insulted by isoprenaline (ISO), the current study was designed.

Methods

The heart weight index, serum lipid profile, cardiac marker enzymes, endogenous antioxidants [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), nitrites and malondialdehyde (MDA)], inflammatory mediators [tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)], immunohistochemical expressions of B-cell lymphoma factor-2 (Bcl-2), extracellular signal-regulated kinase (ERK1/2), and mammalian target of rapamycin (mTOR) and histopathological analysis were used to assess the cardioprotective properties of GBE.

Results

The findings showed that GBE effectively attenuated myocardial infarction by boosting the body’s natural antioxidant defense system and reducing the release of inflammatory cytokines as well as heart injury marker enzymes. The expression of Bcl-2, ERK1/2 and mTOR was increased while the histomorphological alterations were reversed.

Conclusion

The cardioprotective effects of GBE may be due to a mechanism involving increased Bcl-2/mTOR/ERK1/2/Na+, K+-ATPase activity.

目标心肌梗死(MI)与心肌血氧供需失衡有关。β-受体阻滞剂和钙拮抗剂是治疗心肌梗塞的两种常用药物。但据报道,这些药物要么无效,要么有不良副作用。银杏叶提取物(GBE)是一种中草药产品,在治疗炎症性疾病和氧化应激方面具有特殊的兼容性优势。为了更好地了解 GBE 如何影响异丙肾上腺素(ISO)损伤大鼠的心肌梗死,本研究进行了设计。方法心脏重量指数、血清脂质概况、心脏标志酶、内源性抗氧化剂[过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、亚硝酸盐和丙二醛(MDA)]、炎症介质[肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)]、采用 B 细胞淋巴瘤因子-2(Bcl-2)、细胞外信号调节激酶(ERK1/2)和哺乳动物雷帕霉素靶标(mTOR)的免疫组化表达以及组织病理学分析来评估 GBE 的心脏保护特性。结果研究结果表明,GBE能增强机体的天然抗氧化防御系统,减少炎性细胞因子和心脏损伤标志酶的释放,从而有效减轻心肌梗死。结论GBE对心脏的保护作用可能是由于其增加了Bcl-2/mTOR/ERK1/2/Na+、K+-ATPase活性的机制。
{"title":"Pleiotropic attenuating effect of Ginkgo biloba against isoprenaline-induced myocardial infarction via improving Bcl-2/mTOR/ERK1/2/Na+, K+-ATPase activities","authors":"Jerome Ndudi Asiwe ,&nbsp;Abodunrin Adebayo Ojetola ,&nbsp;Nwoke Enekabokom Ekene ,&nbsp;Esthinsheen Osirim ,&nbsp;Anthony Chibuzor Nnamudi ,&nbsp;Benjamin Oritsemuelebi ,&nbsp;Jackson Erozueme Onuelu ,&nbsp;Nicholas Asiwe ,&nbsp;Harrison Ogheneochuko Eruotor ,&nbsp;Saviour Inegbenehi","doi":"10.1016/j.chmed.2023.11.001","DOIUrl":"10.1016/j.chmed.2023.11.001","url":null,"abstract":"<div><h3>Objective</h3><p>Myocardial infarction (MI) is linked to an imbalance in the supply and demand of blood oxygen in the heart muscles. Beta-blockers and calcium antagonists are just two of the common medications used to treat MI. However, these have reportedly been shown to be either ineffective or to have undesirable side effects. Extract of <em>Ginkgo biloba</em> leaves (GBE), a Chinese herbal product offers special compatibility benefits in therapeutic settings relating to inflammatory diseases and oxidative stress. In order to better understand how GBE affects MI in rats insulted by isoprenaline (ISO), the current study was designed.</p></div><div><h3>Methods</h3><p>The heart weight index, serum lipid profile, cardiac marker enzymes, endogenous antioxidants [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), nitrites and malondialdehyde (MDA)], inflammatory mediators [tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)], immunohistochemical expressions of B-cell lymphoma factor-2 (Bcl-2), extracellular signal-regulated kinase (ERK1/2), and mammalian target of rapamycin (mTOR) and histopathological analysis were used to assess the cardioprotective properties of GBE.</p></div><div><h3>Results</h3><p>The findings showed that GBE effectively attenuated myocardial infarction by boosting the body’s natural antioxidant defense system and reducing the release of inflammatory cytokines as well as heart injury marker enzymes. The expression of Bcl-2, ERK1/2 and mTOR was increased while the histomorphological alterations were reversed.</p></div><div><h3>Conclusion</h3><p>The cardioprotective effects of GBE may be due to a mechanism involving increased Bcl-2/mTOR/ERK1/2/Na<sup>+</sup>, K<sup>+</sup>-ATPase activity.</p></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"16 2","pages":"Pages 282-292"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1674638423001041/pdfft?md5=301e510167e9a1ab4d4debda425ca60a&pid=1-s2.0-S1674638423001041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139305043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways 厚朴酚和5-氟尿嘧啶协同抑制子宫颈癌细胞转移的PI3K/AKT/mTOR和EMT通路
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.1016/j.chmed.2023.01.004
Yuanyuan Chen , Shanshan Chen , Kaiting Chen , Lanfang Ji , Shuna Cui

Objective

This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil (5-FU) and magnolol against cervical cancer.

Methods

Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study.

Results

Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of α-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.

Conclusion

Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition (EMT) signaling pathways.

本研究旨在探讨 5-氟尿嘧啶(5-FU)与马格诺洛尔(magnolol)对宫颈癌的协同作用模式。方法应用网络药理学方法预测 5-FU 与马格诺洛尔联合治疗宫颈癌的分子机制。方法应用网络药理学方法预测 5-FU 联合马格诺洛尔治疗宫颈癌的分子机制,并通过 CCK-8 试验、菌落形成试验、免疫荧光染色、粘附试验、伤口愈合迁移率试验、细胞迁移和侵袭试验以及 Western 印迹分析来验证硅学研究的结果。实验结果表明,5-FU联合magnolol能强烈抑制宫颈癌细胞的增殖,并通过下调α-肌动蛋白、tensin-2和vinculin的表达诱导HeLa细胞的形态变化。此外,magnolol 还能增强 5-FU 对细胞粘附、迁移和侵袭的抑制作用。5-FU 和 magnolol 的联合作用强烈抑制了 AKT 和 PI3K 的磷酸化以及 mTOR 的表达。结论综上所述,本研究表明,5-FU 联合 magnolol 可通过调节 PI3K/AKT/mTOR 和上皮-间质转化(EMT)信号通路,发挥协同抗宫颈癌作用。
{"title":"Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways","authors":"Yuanyuan Chen ,&nbsp;Shanshan Chen ,&nbsp;Kaiting Chen ,&nbsp;Lanfang Ji ,&nbsp;Shuna Cui","doi":"10.1016/j.chmed.2023.01.004","DOIUrl":"10.1016/j.chmed.2023.01.004","url":null,"abstract":"<div><h3>Objective</h3><p>This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil (5-FU) and magnolol against cervical cancer.</p></div><div><h3>Methods</h3><p>Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of <em>in silico</em> study.</p></div><div><h3>Results</h3><p>Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was identified as the key pathway <em>in silico</em> study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of <em>α</em>-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and <em>β</em>-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.</p></div><div><h3>Conclusion</h3><p>Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition (EMT) signaling pathways.</p></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"16 1","pages":"Pages 94-105"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1674638423000540/pdfft?md5=fb223695f3b17d7b14f4aff34742d7b6&pid=1-s2.0-S1674638423000540-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43979249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biosynthesis of natural products from medicinal plants: Challenges, progress and prospects 药用植物天然产品的生物合成:挑战、进展与前景
IF 3.8 4区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.1016/j.chmed.2024.01.001
Shilin Chen (Associate Editor-in-Chief)
{"title":"Biosynthesis of natural products from medicinal plants: Challenges, progress and prospects","authors":"Shilin Chen (Associate Editor-in-Chief)","doi":"10.1016/j.chmed.2024.01.001","DOIUrl":"https://doi.org/10.1016/j.chmed.2024.01.001","url":null,"abstract":"","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"16 1","pages":"Pages 1-2"},"PeriodicalIF":3.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1674638424000029/pdfft?md5=ce46f7400b6d872f3560075c67d14c47&pid=1-s2.0-S1674638424000029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Chinese Herbal Medicines
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