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HPLC-PDA and in vivo anti-inflammatory potential of isorhamnetin-3-O-β-D-glucoside from Zygophyllum simplex L. 单叶连翘中异鼠李素-3-O-β-D-葡萄糖苷的 HPLC-PDA 和体内抗炎潜力
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119089
Fatma M. Abdel Bar , Rana Alonazi , Engy Elekhnawy , Reham M. Samra , Mohammed H. Alqarni , Hussein Badreldin , Galal Magdy
<div><h3>Ethnopharmacological relevance</h3><div>Inflammation is a biological process in response to injury, resulting in altered blood flow, increased vascular permeability, tissue destruction, and the production of reactive oxygen species (ROS) and inflammatory mediators. <em>Zygophyllum simplex</em> L., a medicinal plant traditionally used in the Arabian Peninsula for inflammatory disorders, has demonstrated promising <em>in vitro</em> anti-inflammatory activity due to its phenolic content. Additionally, the ethyl acetate fraction has exhibited notable <em>in vivo</em> anti-inflammatory effects.</div></div><div><h3>Study objective</h3><div>This research aimed to evaluate the <em>in vivo</em> anti-inflammatory effects of a <em>Z. simplex</em> plant extract and its principal ethyl acetate isolate, isorhamnetin-3-<em>O</em>-β-D-glucoside (Isor-3-Glu). The study seeks to develop a straightforward and robust HPLC method for quantifying Isor-3-Glu within the total methanolic extract of <em>Z. simplex</em>.</div></div><div><h3>Materials and methods</h3><div>The total methanol extract of <em>Z. simplex</em> was successively partitioned with a variety of organic solvents and the ethyl acetate fraction was used to isolate Isor-3-Glu on a Sephadex LH-20 column. The <em>in vivo</em> anti-inflammatory activity was investigated using carrageenan-triggered inflammation in rats. Histological features and immunohistochemical expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) were analyzed, and the levels of interleukins (IL-1β and IL-6) as well as prostaglandin E2 (PGE2) of the paw tissues were examined by qRT-PCR and ELISA, respectively. Quantification of Isor-3-Glu was achieved using an HPLC-PDA method.</div></div><div><h3>Results</h3><div>Isor-3-Glu considerably (<em>p</em> < 0.05) lowered the weight of the paw edema. The histological abnormalities were improved, and the percentage of the COX-2 and TNF-α immunoreactive cells substantially decreased in the Isor-3-Glu-treated group in comparison with the positive control and <em>Z. simplex</em> extract group. Isor-3-Glu significantly ameliorated PGE2, IL-1β, and IL-6 levels. A straightforward and dependable HPLC technique was established for quantifying Isor-3-Glu in the total extract. The proposed methodology effectively determined Isor-3-Glu in less than 5 min. The calibration curve exhibited a linear relationship over the concentration range of 1.0–40.0 μg/mL, with a correlation coefficient (r) ≥ 0.9995. The developed method demonstrated a high level of sensitivity, with a detection limit as low as 0.139 μg/mL. The concentration of Isor-3-Glu in the total extract of <em>Z. simplex</em> was determined to be 0.05% w/w of dry extract.</div></div><div><h3>Conclusion</h3><div>Isor-3-Glu could be considered a promising anti-inflammatory compound that necessitates future clinical research. Isor-3-Glu was accurately quantified using a meticulously developed and optimized HPLC-PDA tec
民族药理学意义:炎症是对损伤做出反应的一个生物过程,会导致血流改变、血管通透性增加、组织破坏以及活性氧(ROS)和炎症介质的产生。单叶连翘(Zygophyllum simplex L.)是阿拉伯半岛传统上用于治疗炎症性疾病的药用植物,由于其酚类物质含量高,已在体外显示出良好的抗炎活性。此外,乙酸乙酯馏分也显示出显著的体内抗炎效果:本研究旨在评估单叶泽兰植物提取物及其主要乙酸乙酯分离物异鼠李素-3-O-β-D-葡萄糖苷(Isor-3-Glu)的体内抗炎作用。本研究旨在开发一种简单、稳健的高效液相色谱法,用于定量分析单叶泽兰甲醇总提取物中的 Isor-3-Glu:材料和方法:用多种有机溶剂对单叶泽兰的甲醇提取物进行分馏,然后用乙酸乙酯馏分在 Sephadex LH-20 柱上分离出 Isor-3-Glu。利用卡拉胶诱发的大鼠炎症对其体内抗炎活性进行了研究。通过 qRT-PCR 和 ELISA 分析了组织学特征以及环氧化酶-2 (COX-2) 和肿瘤坏死因子-α (TNF-α) 的免疫组化表达,并分别检测了爪组织中白细胞介素 (IL-1β 和 IL-6) 以及前列腺素 E2 (PGE2) 的水平。采用 HPLC-PDA 方法对 Isor-3-Glu 进行定量:结果:Isor-3-Glu(pConclusion:结论:Isor-3-Glu 是一种很有前景的抗炎化合物,需要在未来进行临床研究。采用精心开发和优化的 HPLC-PDA 技术对 Isor-3-Glu 进行了精确定量。
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引用次数: 0
Lancao decoction in the treatment of alzheimer's disease via activating PI3K/AKT signaling to promote ERK involving in enhancing neuronal activities in the hippocampus 兰草煎剂通过激活 PI3K/AKT 信号,促进 ERK 参与增强海马神经元的活动,从而治疗阿尔茨海默病。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119017
Lei Wu , Yan Sun , Ying Yin , Zhangjie Wu , Ruiyi Liu , Yuxin Liu , Yaping Zhu , Mengqi Shao , Hang Zhou , Chao Lu , Hailou Zhang
<div><h3>Ethnopharmacological relevance</h3><div>Previous study has demonstrated lancao decoction (LC), a traditional Chinese medicine (TCM) fomula and recorded in “Huangdineijing”, has a therapeutic effect on cognitive impairment (early clinical manifestations of alzheimer's disease (AD), which suggests that LC may have potential therapeutic advantages for AD. Whether LC has the therapeutic effect on AD and its potential mechanisms were still further indicated.</div></div><div><h3>Aim of the study</h3><div>In this study, we aimed to uncover the potential advantage and neuronal mechanisms of LC in the treatment of AD in APP/PS1 mice in the hippocampus.</div></div><div><h3>Methods and materials</h3><div>We chose APP/PS1 mice to combing with behavioral tests including morris water maze (MWM) or y-maze to determine the role of LC in the therapeutic actions of AD. Network pharmacology was used to screen potential targets and pathways involving in LC's treatments of AD. Western blot was used to detect the phosphorylated expressions of proteins in hippocampus in APP/PS1 mice in the hippocampus. Pharmacological interventions were used to elucidate the relationship between the role of LC in the treatment of AD and the pathway, as well as the upstream and downstream interactions with neuronal activities.</div></div><div><h3>Results</h3><div>According to our previous LC effective dose (2.5 g/kg), the dose was also able to significantly reduce the latency to the platform, and significantly increase the number of crossing times and time spend in the target quadrant in APP/PS1 mice in MWM, which was consistent with donepezil (DON) after 14 days chronic treatments. Network pharmacology showed that PI3K/AKT and MAPK pathways were closely associated with LC's treatments of AD, and protein autophosphorylation played a role in this process. The phosphorylated expressions of PI3K and AKT were obviously reduced in APP/PS1 mice in the hippocampus, which were both reversed by LC or DON. The phosphorylated expressions of MAPK including P38, JNK and ERK were also significantly reduced in APP/PS1 mice hippocampus, but only the phosphorylated expression of ERK was reversed by LC or DON. Inhibiting the activities of PI3K/AKT pathway by LY294002 blocked LC's improvement of behavioral deficits in APP/PS1 mice, including reducing latency to platform and increasing the number of crossings time in MWM in APP/PS1 mice, which also blunted LC's up-regulated phosphorylated expressions of PI3K, AKT and ERK in the hippocampus. Moreover, suppressing the activities of ERK by PD98059 also blocked LC's improvement of AD-related behavioral deficits including decreasing latency to new arm and increasing time in new arm in y-maze test, which also inhibited LC's enhancement of synaptic proteins (PSD95 and synapsin1) in the hippocampus and the number of EGR1-positive cells in the hippocampal dentate gyrus (DG).</div></div><div><h3>Conclusions</h3><div>Take together, our study revealed that LC
民族药理学意义:先前的研究表明,《黄帝内经》中记载的一种中药方剂--兰草煎(LC)对认知障碍(阿尔茨海默病(AD)的早期临床表现)有治疗作用,这表明兰草煎可能对AD有潜在的治疗优势。LC是否对AD有治疗作用及其潜在机制仍有待进一步研究:在本研究中,我们旨在揭示 LC 在 APP/PS1 小鼠海马中治疗 AD 的潜在优势和神经元机制:我们选择APP/PS1小鼠进行行为测试,包括莫里斯水迷宫(MWM)或y-迷宫,以确定LC在AD治疗中的作用。利用网络药理学筛选LC治疗AD的潜在靶点和通路。用Western印迹法检测APP/PS1小鼠海马中磷酸化蛋白的表达。药理干预用于阐明LC在治疗AD中的作用与途径之间的关系,以及与神经元活动的上下游相互作用:根据我们之前的LC有效剂量(2.5 g/kg),该剂量也能显著降低APP/PS1小鼠在MWM中的平台潜伏期,并显著增加穿越次数和在目标象限停留的时间,这与多奈哌齐(DON)在14天慢性治疗后的效果一致。网络药理学显示,PI3K/AKT和MAPK通路与LC对AD的治疗密切相关,而蛋白质自身磷酸化在这一过程中发挥了作用。在APP/PS1小鼠海马中,PI3K和AKT的磷酸化表达明显减少,而LC或DON均可逆转。包括P38、JNK和ERK在内的MAPK的磷酸化表达在APP/PS1小鼠海马中也明显减少,但只有ERK的磷酸化表达被LC或DON逆转。LY294002抑制PI3K/AKT通路的活性阻断了LC对APP/PS1小鼠行为缺陷的改善作用,包括减少APP/PS1小鼠平台潜伏期和增加MWM的穿越次数,这也减弱了LC对海马中PI3K、AKT和ERK磷酸化表达的上调作用。此外,PD98059抑制ERK的活性也阻碍了LC对AD相关行为缺陷的改善,包括在y-迷宫试验中减少新臂潜伏期和增加新臂时间,这也抑制了LC对海马突触蛋白(PSD95和synapsin1)和海马齿状回(DG)中EGR1阳性细胞数量的增强:综上所述,我们的研究揭示了LC通过激活PI3K/AKT通路来增强ERK活性,并进一步增强海马中神经元的活性,从而对AD具有治疗作用。
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引用次数: 0
Magnolol preserves the integrity of the intestinal epithelial barrier and mitigates intestinal injury through activation of PPAR γ in COPD rat 厚朴酚通过激活 PPAR γ 保护慢性阻塞性肺病大鼠肠上皮屏障的完整性并减轻肠道损伤。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119068
Liuying Tao , Qin Zhang , Lan Liu , Kun Wang , Xuefang Liu , Jiansheng Li , Peng Zhao

Ethnopharmacological relevance

Magnolia officinalis Rehder & E.H. Wilson is traditionally used in the treatment of gastrointestinal disorders, diarrhea, and cough. Its main active ingredient, magnolol, exhibits protective effects on the lungs and gastrointestinal tract, including the inhibition of inflammation in these organs.

Aim of the study

This work aims to explore the molecular mechanism by which magnolol suppressed Chronic obstructive pulmonary disease (COPD) intestinal damage by improving the intestinal epithelial barrier.

Materials and methods

The study focused on investigating the mitigation effect of magnolol on intestinal injury and epithelial barrier in a COPD rat. Caco-2 cells were induced with TNF-α or IL-1β to establish the barrier injury model in order to explore the direct protective effect of magnolol on the intestinal barrier and elucidate the molecular mechanism by which it activates peroxisome proliferators-activated receptors-γ (PPARγ).

Results

Magnolol significantly improves pulmonary function and tissue damage in COPD rats by inhibiting inflammation, protease imbalance, and oxidative stress. It also suppresses colon tissue damage and inflammation, and protects colon epithelial barrier function by suppressing the decline of tight junction proteins, reducing colon epithelial permeability. In Caco-2 cells, magnolol directly reduces monolayer permeability, increases TEER, and upregulates tight junction protein expression induced by TNF-α or IL-1β. Drug Affinity Responsive Target Stability (DARTS) and thermal shift assays show that magnolol effectively binds to SRC, activating PPARγ signaling in Caco-2 cells and colon tissues of COPD rats. Furthermore, magnolol enhances the binding of PPARγ and RXRα, promoting their activation and entry into the nucleus. The PPARγ inhibitor GW9662 can reverse the effects of magnolol on PPARγ activation and tight junction protein upregulation in IL-1β or TNF-α induced Caco-2 cells.

Conclusions

This work demonstrates that magnolol enhances lung and intestinal functions in COPD rats, and elucidates its mechanism of action in protecting the intestinal epithelial barrier by activating PPARγ.
民族药理学意义:厚朴(Magnolia officinalis Rehder & E.H. Wilson)传统上用于治疗胃肠道疾病、腹泻和咳嗽。其主要活性成分木兰醇对肺部和胃肠道具有保护作用,包括抑制这些器官的炎症:研究目的:本研究旨在探索麦格诺尔通过改善肠上皮屏障抑制慢性阻塞性肺病(COPD)肠道损伤的分子机制:研究重点是探讨马格诺尔对慢性阻塞性肺病大鼠肠道损伤和上皮屏障的缓解作用。用TNF-α或IL-1β诱导Caco-2细胞建立屏障损伤模型,以探讨马格诺尔对肠道屏障的直接保护作用,并阐明其激活过氧化物酶体增殖物激活受体-γ(PPARγ)的分子机制:结果:木酚醇通过抑制炎症、蛋白酶失衡和氧化应激,明显改善慢性阻塞性肺疾病大鼠的肺功能和组织损伤。它还能抑制结肠组织损伤和炎症,并通过抑制紧密连接蛋白的下降保护结肠上皮屏障功能,降低结肠上皮的通透性。在 Caco-2 细胞中,magnolol 可直接降低单层渗透性,增加 TEER,并上调 TNF-α 或 IL-1β 诱导的紧密连接蛋白表达。药物亲和力反应靶点稳定性(DARTS)和热转移试验表明,奥美洛尔能有效地与SRC结合,激活Caco-2细胞和慢性阻塞性肺病大鼠结肠组织中的PPARγ信号传导。此外,magnolol 还能增强 PPARγ 和 RXRα 的结合,促进其活化并进入细胞核。PPARγ抑制剂GW9662可逆转magnolol对IL-1β或TNF-α诱导的Caco-2细胞中PPARγ活化和紧密连接蛋白上调的影响:本研究表明,麦格诺尔能增强慢性阻塞性肺疾病大鼠的肺功能和肠功能,并阐明了其通过激活 PPARγ 保护肠上皮屏障的作用机制。
{"title":"Magnolol preserves the integrity of the intestinal epithelial barrier and mitigates intestinal injury through activation of PPAR γ in COPD rat","authors":"Liuying Tao ,&nbsp;Qin Zhang ,&nbsp;Lan Liu ,&nbsp;Kun Wang ,&nbsp;Xuefang Liu ,&nbsp;Jiansheng Li ,&nbsp;Peng Zhao","doi":"10.1016/j.jep.2024.119068","DOIUrl":"10.1016/j.jep.2024.119068","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Magnolia officinalis</em> Rehder &amp; E.H. Wilson is traditionally used in the treatment of gastrointestinal disorders, diarrhea, and cough. Its main active ingredient, magnolol, exhibits protective effects on the lungs and gastrointestinal tract, including the inhibition of inflammation in these organs.</div></div><div><h3>Aim of the study</h3><div>This work aims to explore the molecular mechanism by which magnolol suppressed Chronic obstructive pulmonary disease (COPD) intestinal damage by improving the intestinal epithelial barrier.</div></div><div><h3>Materials and methods</h3><div>The study focused on investigating the mitigation effect of magnolol on intestinal injury and epithelial barrier in a COPD rat. Caco-2 cells were induced with TNF-α or IL-1β to establish the barrier injury model in order to explore the direct protective effect of magnolol on the intestinal barrier and elucidate the molecular mechanism by which it activates peroxisome proliferators-activated receptors-γ (PPARγ).</div></div><div><h3>Results</h3><div>Magnolol significantly improves pulmonary function and tissue damage in COPD rats by inhibiting inflammation, protease imbalance, and oxidative stress. It also suppresses colon tissue damage and inflammation, and protects colon epithelial barrier function by suppressing the decline of tight junction proteins, reducing colon epithelial permeability. In Caco-2 cells, magnolol directly reduces monolayer permeability, increases TEER, and upregulates tight junction protein expression induced by TNF-α or IL-1β. Drug Affinity Responsive Target Stability (DARTS) and thermal shift assays show that magnolol effectively binds to SRC, activating PPARγ signaling in Caco-2 cells and colon tissues of COPD rats. Furthermore, magnolol enhances the binding of PPARγ and RXRα, promoting their activation and entry into the nucleus. The PPARγ inhibitor GW9662 can reverse the effects of magnolol on PPARγ activation and tight junction protein upregulation in IL-1β or TNF-α induced Caco-2 cells.</div></div><div><h3>Conclusions</h3><div>This work demonstrates that magnolol enhances lung and intestinal functions in COPD rats, and elucidates its mechanism of action in protecting the intestinal epithelial barrier by activating PPARγ.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119068"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic effects of Lianhuaqingwen in combination with Oseltamivir and Baloxavir against seasonal influenza virus: In vitro and in vivo assessment 联华青蒿素与奥司他韦和巴洛沙韦联用抗季节性流感病毒的协同作用:体外和体内评估。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119091
Cheng Zhang , Manhua Yuan , Wenwan Rong , Han Du , Xuanxuan Li , Tiannan Ji , Jianxiong Li , Bo Dai , Zhenghai Ma , Hui Qi , Ning Zhang , Jing Yang , Xuefeng Duan , Yuhai Bi

Ethnopharmacological relevance

Lianhuaqingwen (LH), a traditional Chinese medicine, presents a broad-spectrum antiviral effect and has been widely used to treat influenza. Given the potential rise of drug-resistant influenza viruses, it is necessary to develop new antiviral drugs and explore combination therapies involving LH in tandem with existing antivirals such as Oseltamivir acid (Osel) or Baloxavir (Bal). These multidrug combinations could help effectively control the seasonal influenza epidemics and reduce the disease burden.

Aim of the study

This study aimed to evaluate the antiviral effects of LH, alone and in combination with Osel or Bal, against human seasonal influenza viruses in vitro and in vivo models.

Materials and methods

The antiviral efficacy of LH alone and LH in combination with Osel/Bal against seasonal influenza A viruses (IAVs) (H1N1 and H3N2 subtypes) and influenza B viruses (IBVs) (BV- and BY-lineages) was assessed in vitro using MDCK cells. The median effective concentration (EC50) was determined, and the drug synergies were analyzed. Additionally, the antiviral activity of LH monotherapy and LH + Osel/Bal combination therapy were evaluated in vivo using an H1N1-infected BABL/c mouse model by monitoring changes in body weight, survival rate, lung viral titer, pathological damage, and inflammatory reaction.

Results

In vitro, LH alone and in combination with Osel/Bal exhibited antiviral activity against both IAVs and IBVs. The addition of LH to Osel/Bal improved the therapeutic efficacy compared to Osel/Bal alone. In vivo, LH monotherapy reduced body weight loss and increased the survival rates of H1N1-infected mice. LH in combination with Osel/Bal resulted in lower virus titers, more effective relief of pathological damage, and comparable low expression of inflammatory factors in the lungs of H1N1-infected mice compared to the use of Osel/Bal alone. Transcriptomic analysis of the lungs revealed that LH + Osel/Bal significantly increased the expression of genes associated with antiviral and anti-inflammatory effects.

Conclusions

This study evaluated the antiviral effects of LH monotherapy and combination therapy with Osel/Bal against human seasonal influenza viruses in vitro and in vivo models. The results suggest that combining LH with Osel or Bal could enhance the antiviral efficiency for influenza viruses compared to the monotherapy using any of these three drugs.
民族药理学意义:传统中药莲花清心丸(LH)具有广谱抗病毒作用,被广泛用于治疗流感。鉴于抗药性流感病毒的潜在增加,有必要开发新的抗病毒药物,并探索 LH 与现有抗病毒药物(如奥司他韦酸(Osel)或巴洛沙韦(Bal))的联合疗法。这些多药联合疗法有助于有效控制季节性流感疫情,减轻疾病负担:本研究旨在评估 LH 单独或与 Osel 或 Bal 联合使用在体外和体内模型中对人类季节性流感病毒的抗病毒效果:使用 MDCK 细胞在体外评估了 LH 单独和 LH 与 Osel/Bal 联用对季节性甲型流感病毒(IAVs)(H1N1 和 H3N2 亚型)和乙型流感病毒(IBVs)(BV- 和 BY-系)的抗病毒效果。确定了中位有效浓度(EC50),并分析了药物的协同作用。此外,还使用 H1N1 感染的 BABL/c 小鼠模型,通过监测体重、存活率、肺部病毒滴度、病理损伤和炎症反应的变化,评估了 LH 单药疗法和 LH + Osel/Bal 联合疗法的体内抗病毒活性:结果:在体外,LH单独或与Osel/Bal联合使用均可对IAV和IBV产生抗病毒活性。与单独使用 Osel/Bal 相比,在 Osel/Bal 中添加 LH 可提高疗效。在体内,LH 单药治疗可减少 H1N1 感染小鼠的体重减轻,并提高其存活率。与单独使用奥赛/巴尔相比,LH与奥赛/巴尔联合使用可使H1N1感染小鼠肺部的病毒滴度更低,病理损伤得到更有效的缓解,炎症因子的表达也相当低。肺部转录组分析表明,LH+奥赛尔/巴尔可显著增加与抗病毒和抗炎作用相关的基因的表达:本研究在体外和体内模型中评估了 LH 单药治疗和与 Osel/Bal 联合治疗对人类季节性流感病毒的抗病毒效果。结果表明,与单药治疗相比,LH与奥赛尔或巴尔联合治疗可提高对流感病毒的抗病毒效率。
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引用次数: 0
Kerstinginone, a new flavanone derivative from Commiphora kerstingii Engl. (Burseraceae) with potent apoptosis-inducing activity and inhibition of AKT/mTOR signaling pathway in non-sensitive prostate cancer cells Kerstinginone 是一种新的黄烷酮衍生物,产自康美拉(Commiphora kerstingii Engl.)(Burseraceae),在非敏感性前列腺癌细胞中具有强大的凋亡诱导活性和 AKT/mTOR 信号通路抑制作用。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119073
Joël Abel Gbaweng Yaya , Stephane Zingue , Anne Offermann , Roméo Feunaing Toko , Duan Kang , Elisée Bapong , Céline Henoumont , Sophie Laurent , Verena-Wilbeth Sailer , Jutta Kirfef , Emmanuel Talla , Sven Perner

Ethnopharmacological relevance

Commiphora kerstingii Engl is a tree which is 20–30 m in height and commonly called “ararrabi” in Hausa. It is found in the Sahelian region (Cameroon, Chad, and Nigeria) where it is utilized for the treatment of several ailments including cancer.

Aim of the study

This study was aimed at investigating the chemical constituents and cytotoxic effect of extracts and isolates from the stem barks and leaves of C. kerstingii.

Materials and methods

Using classical chromatography technique coupled with spectroscopic analysis and literature information, ten (10) compounds were isolated from C. kerstingii stem barks and leaves, out of which two [kerstingilactone (3) and kerstinginone (10)] were new. To evaluate their potential cytotoxic effect, the impact on cell viability, growth, and proliferation was assessed using MTT and CCK-8 assays. Cell death mechanisms were analyzed via flow cytometry, and Western blotting was utilized to examine the expression of specific regulatory proteins. Furthermore, anti-metastatic properties were investigated through assays on cell migration, adhesion, and chemotaxis.

Results

Among the tested compounds, 2 (Masticadienonic Acid) and 10 (kerstinginone) exhibited significant dose-dependent inhibition of PC3 and LNCaP cell growth. Compound 2 displayed optimal inhibitory effects within a concentration range of 10–40 μg/mL, while compound 10 demonstrated potent growth inhibition at concentrations of 2.5–10 μg/mL. Both compounds suppressed cell proliferation and the formation of clones. Specifically, compound 2 induced apoptosis solely in the androgen-sensitive LNCaP prostate cancer cells, whereas compound 10 induced a stronger and concentration-dependent apoptotic response in both PC3 and LNCaP cells, resulting in approximately 50–70% apoptotic cells. It also induced potent cell migration/invasion arrest at concentrations ranging from 2.5 to 5 μg/mL and increased cell adhesion to the extracellular matrix.

Conclusion

Kerstinginone exhibits potent cytotoxicity and apoptosis-inducing activity, making it a promising lead for discovering a new anticancer drug.
民族药理学意义:Commiphora kerstingii Engl 是一种树,高 20-30 米,在豪萨语中通常被称为 "ararrabi"。它分布在萨赫勒地区(喀麦隆、乍得和尼日利亚),可用于治疗包括癌症在内的多种疾病:本研究旨在调查 C. kerstingii 茎皮和叶中提取物和分离物的化学成分和细胞毒性作用:采用经典色谱技术,结合光谱分析和文献信息,从 C. kerstingii 茎皮和叶中分离出十(10)种化合物,其中两种 [kerstingilactone (3) 和 kerstinginone (10)]是新化合物。为了评估它们潜在的细胞毒性作用,使用 MTT 和 CCK-8 试验评估了它们对细胞活力、生长和增殖的影响。通过流式细胞术分析了细胞死亡机制,并利用 Western 印迹法检测了特定调控蛋白的表达。此外,还通过细胞迁移、粘附和趋化试验研究了抗转移特性:在测试的化合物中,2(Masticadienonic Acid)和 10(kerstinginone)对 PC3 和 LNCaP 细胞的生长具有显著的剂量依赖性抑制作用。化合物 2 在 10 至 40 μg/mL 的浓度范围内显示出最佳抑制效果,而化合物 10 在 2.5-10 μg/mL 的浓度范围内显示出有效的生长抑制作用。这两种化合物都能抑制细胞增殖和克隆的形成。具体来说,化合物 2 只诱导对雄激素敏感的 LNCaP 前列腺癌细胞凋亡,而化合物 10 则诱导 PC3 和 LNCaP 细胞产生更强的浓度依赖性凋亡反应,导致约 50-70% 的细胞凋亡。在 2.5 至 5 μg/ml 的浓度范围内,它还能有效阻止细胞迁移/侵袭,并增加细胞与细胞外基质的粘附性:结论:Kerstinginone 具有很强的细胞毒性和细胞凋亡诱导活性,是一种很有前景的抗癌新药。
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引用次数: 0
Identification of anti-inflammatory and anti-cancer compounds targeting the NF-κB-NLRP3 inflammasome pathway from a phytochemical library of the Sideritis genus 从蛛网膜属植物化学文库中鉴定靶向 NF-κB-NLRP3 炎症组通路的抗炎和抗癌化合物
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119074
Rümeysa Yücer , Angela Schröder , Gülaçtı Topçu , Thomas Efferth
<div><h3>Ethnobotanical relevance</h3><div>For centuries, the aerial parts of <em>Sideritis</em> species have been known for their medicinal properties as herbal teas. Although the antioxidant and anti-inflammatory properties of the genus have been widely documented, the underlying mechanisms are yet to be sufficiently clarified.</div></div><div><h3>Aim of the study</h3><div>We investigated the anti-inflammatory and anticancer activities of phytochemicals of the <em>Sideritis</em> genus.</div></div><div><h3>Material and methods</h3><div>Through literature mining, a chemical library containing 657 components of the <em>Sideritis</em> genus was formed. We studied these compounds for binding to NLRP3 and NF-κB proteins <em>in silico</em> by virtual drug screening and molecular docking, and <em>in vitro</em> by microscale thermophoresis (MST). Liquid chromatography-high-resolution mass spectrometry analysis (LC-HRMS) was performed in the <em>Sideritis</em> extracts. One of the identified compounds, verbascoside, was investigated for its cytotoxic activity by mining a panel of 49 tumor cell lines in the data repository of the National Cancer Institute (NCI, USA).</div></div><div><h3>Results</h3><div>Virtual screening and molecular docking results highlighted two compounds targeting both proteins of interest, <em>i.e</em>., verbascoside (acteoside) and apigenin 7,4′-bis(trans-<em>p</em>-coumarate), as both had lowest binding energies of less than −10 kcal/mol. Using MST, we then verified that both compounds bound to the target proteins. Verbascoside bound to NLRP3 and NF-κB with K<sub>d</sub> values of 0.67 ± 0.18 μM and 0.01 ± 0.08 μM, while apigenin 7,4′-bis(trans-<em>p</em>-coumarate) had K<sub>d</sub> values of 4.60 ± 1.66 μM and 0.27 ± 0.75 μM, respectively. Verbascoside was abundant in the <em>Sideritis</em> extracts, according to LC-HRMS analysis. Since inflammation is strongly related to carcinogenesis, we investigated the anticancer activity of verbascoside in the second part of this study. We investigated the activity of verbascoside in 49 tumor cell lines of the NCI. Comparing its activity with 81 standard anticancer drugs revealed numerous interactions with DNA-damaging agents (alkylators, topoisomerase I/II inhibitors, antimetabolites), indicating that verbascoside may also affect the DNA of tumor cells. We further investigated the involvement of verbascoside in several main drug resistance mechanisms, <em>i.e</em>., ABC transporters, oncogenes, tumor suppressors, cellular proliferation rates, and other parameters. Except for the correlation to the mutational status of NRAS, no other significant relationships were found, indicating that verbascoside is not involved in most of the common drug resistance mechanisms. Two-dimensional cluster analysis-based heatmap generation of a proteomic profile from 40 out of 3171 proteins revealed a significant correlation between the expression of these proteins in 49 tumor cell lines, and the cellular re
民族植物学意义:几个世纪以来,凫翁属植物的气生部分一直以其作为草药茶的药用特性而闻名。虽然该属植物的抗氧化和抗炎特性已被广泛记载,但其潜在机制仍有待充分阐明:研究目的:我们研究了凫翁属植物化学物质的抗炎和抗癌活性:通过文献挖掘,我们建立了一个包含 657 种梭梭菌属成分的化学库。我们通过虚拟药物筛选和分子对接对这些化合物与 NLRP3 和 NF-κB 蛋白的结合进行了研究,并通过微尺度热泳(MST)对其进行了体外研究。对梭菌提取物进行了液相色谱-高分辨质谱分析(LC-HRMS)。通过挖掘美国国家癌症研究所(NCI,美国)数据储存库中的 49 种肿瘤细胞系,对其中一种已鉴定化合物马鞭草苷的细胞毒性活性进行了研究:虚拟筛选和分子对接结果表明,有两种化合物能同时靶向两种相关蛋白,即马鞭草苷(肌动蛋白苷)和芹菜素-7,4'-双(反式-对香豆酸酯),因为这两种化合物的最低结合能均小于-10 kcal/mol。然后,我们利用 MST 验证了这两种化合物与目标蛋白质的结合。马鞭草苷与 NLRP3 和 NF-κB 的 Kd 值分别为 0.67 ± 0.18 μM 和 0.01 ± 0.08 μM,而芹菜素 7,4'-双(反式-对香豆酸酯)的 Kd 值分别为 4.60 ± 1.66 μM 和 0.27 ± 0.75 μM。根据 LC-HRMS 分析,蛛网膜炎提取物中含有丰富的马鞭草甙。由于炎症与癌变密切相关,我们在本研究的第二部分对马鞭草苷的抗癌活性进行了研究。我们研究了马鞭草苷在 NCI 49 种肿瘤细胞系中的活性。将其活性与 81 种标准抗癌药物进行比较后发现,马鞭草苷与 DNA 破坏剂(烷化剂、拓扑异构酶 I/II 抑制剂、抗代谢物)之间存在许多相互作用,这表明马鞭草苷也可能影响肿瘤细胞的 DNA。我们进一步研究了马鞭草苷参与几种主要耐药机制的情况,即ABC转运体、癌基因、肿瘤抑制因子、细胞增殖率和其他参数。除与 NRAS 突变状态相关外,未发现其他显著关系,表明马鞭草苷未参与大多数常见的耐药机制。基于二维聚类分析的热图生成蛋白质组图谱,从 3171 个蛋白质中筛选出 40 个,发现这些蛋白质在 49 种肿瘤细胞系中的表达与细胞对马鞭草苷的反应之间存在显著相关性。这表明,这些蛋白质的存在决定了对这种天然产品的敏感性或抗性:本文建立的数据库是筛选蛛网膜属生物活性物质的宝贵资源。对所选化合物抗炎和细胞毒性活性的实验验证证明,虚拟药物筛选和分子对接是鉴定候选药物的合适工具。马鞭草苷是与 NLRP3 和 NF-kB 这两种关键抗炎蛋白结合的前 10 种化合物之一。此外,NCI 的数据表明,马鞭草苷与主要的耐药机制无关。
{"title":"Identification of anti-inflammatory and anti-cancer compounds targeting the NF-κB-NLRP3 inflammasome pathway from a phytochemical library of the Sideritis genus","authors":"Rümeysa Yücer ,&nbsp;Angela Schröder ,&nbsp;Gülaçtı Topçu ,&nbsp;Thomas Efferth","doi":"10.1016/j.jep.2024.119074","DOIUrl":"10.1016/j.jep.2024.119074","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnobotanical relevance&lt;/h3&gt;&lt;div&gt;For centuries, the aerial parts of &lt;em&gt;Sideritis&lt;/em&gt; species have been known for their medicinal properties as herbal teas. Although the antioxidant and anti-inflammatory properties of the genus have been widely documented, the underlying mechanisms are yet to be sufficiently clarified.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;We investigated the anti-inflammatory and anticancer activities of phytochemicals of the &lt;em&gt;Sideritis&lt;/em&gt; genus.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material and methods&lt;/h3&gt;&lt;div&gt;Through literature mining, a chemical library containing 657 components of the &lt;em&gt;Sideritis&lt;/em&gt; genus was formed. We studied these compounds for binding to NLRP3 and NF-κB proteins &lt;em&gt;in silico&lt;/em&gt; by virtual drug screening and molecular docking, and &lt;em&gt;in vitro&lt;/em&gt; by microscale thermophoresis (MST). Liquid chromatography-high-resolution mass spectrometry analysis (LC-HRMS) was performed in the &lt;em&gt;Sideritis&lt;/em&gt; extracts. One of the identified compounds, verbascoside, was investigated for its cytotoxic activity by mining a panel of 49 tumor cell lines in the data repository of the National Cancer Institute (NCI, USA).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Virtual screening and molecular docking results highlighted two compounds targeting both proteins of interest, &lt;em&gt;i.e&lt;/em&gt;., verbascoside (acteoside) and apigenin 7,4′-bis(trans-&lt;em&gt;p&lt;/em&gt;-coumarate), as both had lowest binding energies of less than −10 kcal/mol. Using MST, we then verified that both compounds bound to the target proteins. Verbascoside bound to NLRP3 and NF-κB with K&lt;sub&gt;d&lt;/sub&gt; values of 0.67 ± 0.18 μM and 0.01 ± 0.08 μM, while apigenin 7,4′-bis(trans-&lt;em&gt;p&lt;/em&gt;-coumarate) had K&lt;sub&gt;d&lt;/sub&gt; values of 4.60 ± 1.66 μM and 0.27 ± 0.75 μM, respectively. Verbascoside was abundant in the &lt;em&gt;Sideritis&lt;/em&gt; extracts, according to LC-HRMS analysis. Since inflammation is strongly related to carcinogenesis, we investigated the anticancer activity of verbascoside in the second part of this study. We investigated the activity of verbascoside in 49 tumor cell lines of the NCI. Comparing its activity with 81 standard anticancer drugs revealed numerous interactions with DNA-damaging agents (alkylators, topoisomerase I/II inhibitors, antimetabolites), indicating that verbascoside may also affect the DNA of tumor cells. We further investigated the involvement of verbascoside in several main drug resistance mechanisms, &lt;em&gt;i.e&lt;/em&gt;., ABC transporters, oncogenes, tumor suppressors, cellular proliferation rates, and other parameters. Except for the correlation to the mutational status of NRAS, no other significant relationships were found, indicating that verbascoside is not involved in most of the common drug resistance mechanisms. Two-dimensional cluster analysis-based heatmap generation of a proteomic profile from 40 out of 3171 proteins revealed a significant correlation between the expression of these proteins in 49 tumor cell lines, and the cellular re","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119074"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Anti-inflammatory effects and mechanism of Plantago asiatica L. and Lonicera japonica Thunb. extracts based on canine and feline kidney cell models 基于犬和猫肾细胞模型的车前子和忍冬提取物的抗炎作用及其机制
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119069
Tong Liu , Huasong Bai , Hengyan Wang , Yunliang Li , Zhanzhong Wang

Ethnopharmacological relevance

Stone symptoms are one of the most common health problems in pets. Inflammation in the kidneys causes the pet's urine to form a hard substance that blocks the urinary tract. Plantago asiatica L. and Lonicera japonica Thunb., as traditional Chinese diuretics, have remarkable effects on anti-inflammatory and analgesia. However, their mechanism of action remains unclear.

Purpose

The alleviating effect of Plantago asiatica and Lonicera japonica extracts upon lipopolysaccharide (LPS)-induced inflammation in canine and feline kidney cells was investigated in this work.

Materials and methods

Inflammatory factor concentrations and oxidative stress indicators were used to evaluate the inflammatory response. The mechanism by which two extracts reduced inflammation was explored using quantitative real-time polymerase chain reaction (RT-qPCR) and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) metabolome assay.

Results

The results demonstrated that Plantago asiatica or Lonicera japonica extract at safe concentration (25–200 μg/mL for canine kidney cell and 1–20 μg/mL for feline kidney cell, respectively) could significantly reduce the release of nitric oxide (p < 0.05) and oxidative damage (p < 0.05) after LPS stimulation, inhibit the production of inflammatory factors (p < 0.05), and improve cell migration ability (p < 0.05). The RT-qPCR results confirmed that Plantago asiatica and Lonicera japonica extracts significantly reduced the mRNA expressions of TLR4, MyD88, NF-kB, Caspase9 and Bax (p < 0.05), and enhanced the mRNA expression of Bcl-2 (p < 0.05). Non-targeted metabolomics results indicated that the cells treated with two extracts raised the contents of allopurinol, further inhibited uric acid and gout and lowered the contents of adenosine and adenine. Moreover, it was revealed that the Plantago asiatica and Lonicera japonica participated in purine metabolism, glycerophospholipid metabolism, protein digestion and absorption, nucleotide metabolism pathways to alleviate kidney cell inflammation.

Conclusions

The interaction mechanism was revealed to reduce the content of inflammatory factors by inhibiting TLR4-MyD88-NF-kB signaling pathway, and participate in purine metabolism to reduce the inflammation of kidney cells. These findings could provide significant insight into alleviating nephritis in canine and feline, and strategies for preventing urinary tract and kidney stones using Plantago asiatica and Lonicera japonica extracts.
民族药理学意义:结石症状是宠物最常见的健康问题之一。肾脏发炎会导致宠物的尿液形成硬物,堵塞尿路。车前草和忍冬作为传统的中药利尿剂,具有显著的消炎和镇痛作用。目的:本文研究了车前草和忍冬藤提取物对脂多糖(LPS)诱导的犬和猫肾细胞炎症的缓解作用:材料和方法:炎症因子浓度和氧化应激指标用于评估炎症反应。采用实时定量聚合酶链式反应(RT-qPCR)和高效液相色谱-串联质谱(HPLC-MS/MS)代谢组分析法探讨了两种提取物减轻炎症反应的机制:结果表明,在安全浓度下(犬肾细胞为25-200 μg/mL,猫肾细胞为1-20 μg/mL),车前草或忍冬藤提取物能显著降低一氧化氮的释放(p 结论):该相互作用机制通过抑制 TLR4-MyD88-NF-kB 信号通路来减少炎症因子的含量,并参与嘌呤代谢以减轻肾细胞的炎症反应。这些发现为缓解犬科和猫科动物的肾炎以及使用车前子和忍冬提取物预防尿路和肾结石提供了重要启示。
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引用次数: 0
New idea of Fuke Qianjin capsule in treating sequelae of pelvic inflammatory disease: Anti-inflammatory in the early stage and reparative in the later stage. 福克千金胶囊治疗盆腔炎后遗症的新思路:前期抗炎,后期修复。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-09 DOI: 10.1016/j.jep.2024.119066
Chunfang Xu, Meijin Yi, Zhikui Xiao, Feng Xiang, Mengyao Wu, Zhimin Zhang, Yuanqing Zheng, Yun Gong, Yamei Li, Liang Su, Yingyan Liao, Peng Zhang, Bohou Xia, Duanfang Liao, Limei Lin

Ethnopharmacological relevance: Sequelae of pelvic inflammatory disease (SPID) occurs in female internal genitalia and surrounding connective tissue. Recent clinical studies have shown that the traditional Chinese medicine Fuke Qianjin capsule (FKQ) can shorten the course of this disease, but its pharmacological effects and potential mechanism have not been fully elucidated.

Aim of the study: This study aimed to investigate the efficacy and underlying mechanisms of FKQ in the treatment of SPID.

Methods: In this study, we first established a mixed infection model to explore the protective effect of FKQ on common pathogens of SPID. Afterwards, mixed bacterial infection and mechanical injury were used in a SPID rat model to explore the protective mechanism of FKQ on SPID rats. Inflammation, repair and immune cells were tested.

Results: FKQ has a protective effect against infections caused by SPID pathogenic bacterial and may reduce mortality from mixed infections. In the SPID model, FKQ improved pathological damage to the uterus, reduced the area of uterine fibrosis, and inhibited the levels of cytokines (TNF-α, IL-6, IL-1β, IL-18, TGF-β1 and VEGF) caused by pathogenic bacteria. Moreover, FKQ treatment reduced the accumulation of NLRP3, Caspase-1, GSDMD Vimentin, and Cytokeratin 18 in the uterus and suppressed the expression of TGF-β1 and VEGF in the fallopian tubes, thereby reducing inflammation and promoting mucosal repair. In addition, FKQ can restore the immune function balance of SPID rats by increasing the proportion of Treg cells in the spleen and thymus in a rat model of SPID, reducing the proportion of Th17 lymphocytes, and promoting an immunological balance of Treg/Th17 cells, thereby regulating the immune system of the body.

Conclusion: In summary, FKQ treatment for SPID is the result of a fourfold combination of antibacterial, anti-inflammatory, reparative and immune-enhancing activities.

民族药理学意义:盆腔炎(SPID)的后遗症发生在女性内生殖器和周围结缔组织。最近的临床研究表明,中药复方千金胶囊(FKQ)可缩短该病的病程,但其药理作用和潜在机制尚未完全阐明:本研究旨在探讨复方千金胶囊治疗SPID的疗效及其潜在机制:本研究首先建立了混合感染模型,探讨FKQ对SPID常见病原体的保护作用。方法:本研究首先建立了混合感染模型,探讨FKQ对SPID大鼠常见病原体的保护作用,然后在SPID大鼠模型中使用细菌混合感染和机械损伤,探讨FKQ对SPID大鼠的保护机制。结果显示:FKQ对SPID大鼠的炎症、修复和免疫细胞具有保护作用:结果:FKQ对SPID致病菌引起的感染具有保护作用,并可降低混合感染的死亡率。在 SPID 模型中,FKQ 改善了子宫的病理损伤,减少了子宫纤维化的面积,抑制了病原菌引起的细胞因子(TNF-α、IL-6、IL-1β、IL-18、TGF-β1 和 VEGF)水平。此外,FKQ 还能减少子宫中 NLRP3、Caspase-1、GSDMD Vimentin 和 Cytokeratin 18 的积累,抑制输卵管中 TGF-β1 和 VEGF 的表达,从而减轻炎症,促进粘膜修复。此外,FKQ还能恢复SPID大鼠的免疫功能平衡,增加SPID大鼠脾脏和胸腺中Treg细胞的比例,降低Th17淋巴细胞的比例,促进Treg/Th17细胞的免疫平衡,从而调节机体的免疫系统:总之,FKQ治疗SPID是抗菌、抗炎、修复和免疫增强四重作用相结合的结果。
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引用次数: 0
Ganoderma lucidum polysaccharide alleviates cognitive dysfunction by inhibiting neuroinflammation via NLRP3/NF-κB signaling pathway 灵芝多糖通过NLRP3/NF-κB信号通路抑制神经炎症,缓解认知功能障碍
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-08 DOI: 10.1016/j.jep.2024.119065
Yudi Jiang , Zhe Wang , Wanshuai Wang , Yang Liu , Yang Meng , Yaozhong Wang , Minghao Fan , Chao Cai

Ethnopharmacological relevance

Ganoderma lucidum (G. lucidum), a traditional Chinese medicinal herb, is commonly recommended for its potential to promote mental relaxation and alleviate memory impairment. Recently, there have been reports suggesting that it exhibits anti-neuroinflammatory activity through the gut-brain axis. Cognitive dysfunction is among the most prevalent neurodegenerative diseases.

Aim of the study

This study aimed to investigate the efficacy of polysaccharides extracted from G. lucidum in alleviating cognitive dysfunction.

Methods and materials

A polysaccharide was extracted through the process of alkali extraction followed by alcohol precipitation. Comprehensive analysis was conducted to characterize the total sugar content, amino acid composition, and sugar chain structure. The levels of inflammatory related factors were assessed using griess reagent, qPCR and western blotting assay in vitro. The efficacy of alleviating cognitive dysfunction was evaluated through a series of behavioral studies in mice model induced by the high-fat high-sugar diet combined with chronic unpredictable mild stress (HFFD/CUMS) in vivo. The mechanism was investigated by 16S rRNA sequence, immunohistochemistry, flow cytometry and short-chain fatty acid detection.

Results

Ganoderma lucidum polysaccharide (GLP) is a polysaccharide identified as β-glucan. Bioactivity experiments have demonstrated that GLP possesses the potential to ameliorate cognitive dysfunction. The mechanism study revealed that GLP can modulate the composition of gut microbiota and suppress the activation of inflammasomes via NLRP3/NF-κB signaling pathway, thereby attenuating neuroinflammatory. Furthermore, GLP may enhance the peripheral immunity response of the body, leading to a comprehensive regulatory effect.

Conclusion

A polysaccharide alleviates cognitive dysfunction via inhibiting neuroinflammation.
民族药理学意义:灵芝(Ganoderma lucidum)是一种传统的中药材,因其具有促进精神放松和缓解记忆障碍的潜力而被广泛推荐。最近有报告表明,灵芝通过肠道-大脑轴具有抗神经炎活性。认知功能障碍是最常见的神经退行性疾病之一:本研究旨在探讨从鹿角胶中提取的多糖在缓解认知功能障碍方面的功效:方法:采用碱提取、酒精沉淀的方法提取一种多糖。对多糖的总糖含量、氨基酸组成和糖链结构进行了综合分析。在体外使用 griess 试剂、qPCR 和 Western 印迹法评估了炎症相关因子的水平。通过对高脂高糖饮食结合慢性不可预测轻度应激(HFFD/CUMS)诱导的小鼠模型进行一系列行为研究,评估了其缓解认知功能障碍的功效。通过16S rRNA序列、免疫组织化学、流式细胞术和短链脂肪酸检测等方法对其机制进行了研究:灵芝多糖(GLP)是一种被鉴定为β-葡聚糖的多糖。生物活性实验证明,GLP 具有改善认知功能障碍的潜力。机理研究发现,GLP 可调节肠道微生物群的组成,通过 NLRP3/NF-κB 信号通路抑制炎性体的活化,从而减轻神经炎症。此外,GLP 还可增强机体外周免疫反应,从而产生综合调节作用:结论:一种多糖可通过抑制神经炎症缓解认知功能障碍。
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引用次数: 0
Danggui Buxue Decoction and its components dilate coronary artery through activating the inward rectification K+ channels pathway 当归附子汤及其成分通过激活内向整流 K+ 通道途径扩张冠状动脉。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-11-08 DOI: 10.1016/j.jep.2024.119064
Wenqiao An , Qianqian Tian , Pengmei Guo , Mingzhu Chen , Ting Zhang , Peng Yang , Sanyin Zhang

Ethnopharmacological relevance

Danggui Buxue Decoction (DBD), a classic representative prescription of invigorating Qi and producing blood, is used to treat coronary heart disease angina pectoris and vascular injury diseases. Abnormal coronary artery is an important cause of cardiovascular disease. However, the mechanism of DBD dilates coronary arteries is still unclear.

Aim of the study

This study aimed to elucidate the impacts and distinctions among DBD, Astragalus, Angelica sinensis, and identified active components on pre-constricted coronary arteries, as well as to delve deeper into their respective mechanisms.

Materials and methods

After the preconstriction of a rat isolated coronary artery ring with either 30 mM KCl or 200 nM U46619, the vascular tension was observed following the addition of DBD, and other components. Subsequently, the impact of these active components on coronary blood flow (CBF) was confirmed through in vivo testing. Further investigation into the underlying mechanism was carried out using a combination of blockers, molecular docking, surface plasmon resonance (SPR), cell heat transfer analysis (CETSA), and patch-clamp techniques.

Results

In vitro experiments showed that DBD and its components butylidenephthalide, ligustilide, calycosin, and quercetin could dilate coronary artery preconstricted with either 30 mM KCl or 200 nM U46619. In addition, the active ingredient was found to significantly increase CBF. Mechanistically, BaCl2 was found to reduce the relaxation effect of the drug by adding a blocker. Molecular docking, SPR and CETSA results showed that the active ingredients had a strong binding potential with inward rectification K+ channels (KIR) channel protein. Patch clamp studies demonstrate that quercetin can increase KIR current, and BaCl2 can significantly reduce its current.

Conclusions

The active components of DBD, butylidenephthalide, ligustilide, calycosin, and quercetin, activate KIR channels to relax coronary artery and increase CBF.
民族药理学意义:当归附子汤(Danggui Buxue Decoction,DBD)是活气生血的经典代表方剂,用于治疗冠心病心绞痛和血管损伤疾病。冠状动脉异常是导致心血管疾病的重要原因。然而,DBD 扩张冠状动脉的机制仍不清楚:本研究旨在阐明 DBD、黄芪、当归和已鉴定的活性成分对预收缩冠状动脉的影响和区别,并深入研究它们各自的机制:用 30 mM KCl 或 200 nM U46619 对大鼠离体冠状动脉环进行预收缩后,观察加入 DBD 和其他成分后的血管张力。随后,通过体内测试证实了这些活性成分对冠状动脉血流量(CBF)的影响。通过结合使用阻滞剂、分子对接、表面等离子体共振(SPR)、细胞热传导分析(CETSA)和贴片钳技术,对其基本机制进行了进一步研究:体外实验表明,DBD及其成分丁烯基苯酞、藁本内酯、钙黄苷和槲皮素能扩张30 mM KCl或200 nM U46619预收缩的冠状动脉。此外,还发现活性成分能显著增加 CBF。从机理上讲,BaCl2 通过添加阻滞剂降低了药物的松弛效应。分子对接、SPR 和 CETSA 结果表明,活性成分与内向整流 K+ 通道(KIR)通道蛋白有很强的结合潜力。膜片钳研究表明,槲皮素能增加 KIR 电流,而 BaCl2 能显著降低其电流:结论:DBD 的活性成分丁烯基苯酞、女贞苷、萼苷和槲皮素可激活 KIR 通道,从而舒张冠状动脉并增加 CBF。
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引用次数: 0
期刊
Journal of ethnopharmacology
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