Pub Date : 2024-11-09DOI: 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
{"title":"HPLC-PDA and in vivo anti-inflammatory potential of isorhamnetin-3-O-β-D-glucoside from Zygophyllum simplex L.","authors":"Fatma M. Abdel Bar , Rana Alonazi , Engy Elekhnawy , Reham M. Samra , Mohammed H. Alqarni , Hussein Badreldin , Galal Magdy","doi":"10.1016/j.jep.2024.119089","DOIUrl":"10.1016/j.jep.2024.119089","url":null,"abstract":"<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","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119089"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621531","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}
Pub Date : 2024-11-09DOI: 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。
{"title":"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","authors":"Lei Wu , Yan Sun , Ying Yin , Zhangjie Wu , Ruiyi Liu , Yuxin Liu , Yaping Zhu , Mengqi Shao , Hang Zhou , Chao Lu , Hailou Zhang","doi":"10.1016/j.jep.2024.119017","DOIUrl":"10.1016/j.jep.2024.119017","url":null,"abstract":"<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","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119017"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621537","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}
Pub Date : 2024-11-09DOI: 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.
{"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 , Qin Zhang , Lan Liu , Kun Wang , Xuefang Liu , Jiansheng Li , 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 & 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}
Pub Date : 2024-11-09DOI: 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.
{"title":"Synergistic effects of Lianhuaqingwen in combination with Oseltamivir and Baloxavir against seasonal influenza virus: In vitro and in vivo assessment","authors":"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","doi":"10.1016/j.jep.2024.119091","DOIUrl":"10.1016/j.jep.2024.119091","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>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.</div></div><div><h3>Aim of the study</h3><div>This study aimed to evaluate the antiviral effects of LH, alone and in combination with Osel or Bal, against human seasonal influenza viruses <em>in vitro</em> and <em>in vivo</em> models.</div></div><div><h3>Materials and methods</h3><div>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 <em>in vitro</em> using MDCK cells. The median effective concentration (EC<sub>50</sub>) was determined, and the drug synergies were analyzed. Additionally, the antiviral activity of LH monotherapy and LH + Osel/Bal combination therapy were evaluated <em>in vivo</em> using an H1N1-infected BABL/c mouse model by monitoring changes in body weight, survival rate, lung viral titer, pathological damage, and inflammatory reaction.</div></div><div><h3>Results</h3><div><em>In vitro</em>, 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. <em>In vivo</em>, 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.</div></div><div><h3>Conclusions</h3><div>This study evaluated the antiviral effects of LH monotherapy and combination therapy with Osel/Bal against human seasonal influenza viruses <em>in vitro</em> and <em>in vivo</em> 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.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119091"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621663","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}
Pub Date : 2024-11-09DOI: 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.
{"title":"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","authors":"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","doi":"10.1016/j.jep.2024.119073","DOIUrl":"10.1016/j.jep.2024.119073","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Commiphora kerstingii</em> 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.</div></div><div><h3>Aim of the study</h3><div>This study was aimed at investigating the chemical constituents and cytotoxic effect of extracts and isolates from the stem barks and leaves of <em>C. kerstingii.</em></div></div><div><h3>Materials and methods</h3><div>Using classical chromatography technique coupled with spectroscopic analysis and literature information, ten (10) compounds were isolated from <em>C. kerstingii</em> stem barks and leaves, out of which two [kerstingilactone (<strong>3</strong>) and kerstinginone (<strong>10</strong>)] 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.</div></div><div><h3>Results</h3><div>Among the tested compounds, <strong>2</strong> (Masticadienonic Acid) and <strong>10</strong> (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.</div></div><div><h3>Conclusion</h3><div>Kerstinginone exhibits potent cytotoxicity and apoptosis-inducing activity, making it a promising lead for discovering a new anticancer drug.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119073"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621536","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}
<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
{"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 , Angela Schröder , Gülaçtı Topçu , Thomas Efferth","doi":"10.1016/j.jep.2024.119074","DOIUrl":"10.1016/j.jep.2024.119074","url":null,"abstract":"<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","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}
Pub Date : 2024-11-09DOI: 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.
{"title":"Anti-inflammatory effects and mechanism of Plantago asiatica L. and Lonicera japonica Thunb. extracts based on canine and feline kidney cell models","authors":"Tong Liu , Huasong Bai , Hengyan Wang , Yunliang Li , Zhanzhong Wang","doi":"10.1016/j.jep.2024.119069","DOIUrl":"10.1016/j.jep.2024.119069","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>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. <em>Plantago asiatica</em> L. and <em>Lonicera japonica</em> Thunb., as traditional Chinese diuretics, have remarkable effects on anti-inflammatory and analgesia. However, their mechanism of action remains unclear.</div></div><div><h3>Purpose</h3><div>The alleviating effect of <em>Plantago asiatica</em> and <em>Lonicera japonica</em> extracts upon lipopolysaccharide (LPS)-induced inflammation in canine and feline kidney cells was investigated in this work.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>The results demonstrated that <em>Plantago asiatica</em> or <em>Lonicera japonica</em> 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 (<em>p</em> < 0.05) and oxidative damage (<em>p</em> < 0.05) after LPS stimulation, inhibit the production of inflammatory factors (<em>p</em> < 0.05), and improve cell migration ability (<em>p</em> < 0.05). The RT-qPCR results confirmed that <em>Plantago asiatica</em> and <em>Lonicera japonica</em> extracts significantly reduced the mRNA expressions of <em>TLR4</em>, <em>MyD88</em>, <em>NF-kB</em>, <em>Caspase9</em> and <em>Bax</em> (<em>p</em> < 0.05), and enhanced the mRNA expression of <em>Bcl-2</em> (<em>p</em> < 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 <em>Plantago asiatica</em> and <em>Lonicera japonica</em> participated in purine metabolism, glycerophospholipid metabolism, protein digestion and absorption, nucleotide metabolism pathways to alleviate kidney cell inflammation.</div></div><div><h3>Conclusions</h3><div>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 <em>Plantago asiatica</em> and <em>Lonicera japonica</em> extracts.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119069"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621782","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}
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.
{"title":"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.","authors":"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","doi":"10.1016/j.jep.2024.119066","DOIUrl":"10.1016/j.jep.2024.119066","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>This study aimed to investigate the efficacy and underlying mechanisms of FKQ in the treatment of SPID.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>In summary, FKQ treatment for SPID is the result of a fourfold combination of antibacterial, anti-inflammatory, reparative and immune-enhancing activities.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119066"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621539","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}
Pub Date : 2024-11-08DOI: 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.
{"title":"Ganoderma lucidum polysaccharide alleviates cognitive dysfunction by inhibiting neuroinflammation via NLRP3/NF-κB signaling pathway","authors":"Yudi Jiang , Zhe Wang , Wanshuai Wang , Yang Liu , Yang Meng , Yaozhong Wang , Minghao Fan , Chao Cai","doi":"10.1016/j.jep.2024.119065","DOIUrl":"10.1016/j.jep.2024.119065","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ganoderma lucidum</em> (<em>G. lucidum</em>), 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.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the efficacy of polysaccharides extracted from <em>G. lucidum</em> in alleviating cognitive dysfunction.</div></div><div><h3>Methods and materials</h3><div>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 <em>in vitro</em>. 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) <em>in vivo</em>. The mechanism was investigated by 16S rRNA sequence, immunohistochemistry, flow cytometry and short-chain fatty acid detection.</div></div><div><h3>Results</h3><div><em>Ganoderma lucidum</em> 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 <em>via</em> 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.</div></div><div><h3>Conclusion</h3><div>A polysaccharide alleviates cognitive dysfunction <em>via</em> inhibiting neuroinflammation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119065"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621783","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}
Pub Date : 2024-11-08DOI: 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。
{"title":"Danggui Buxue Decoction and its components dilate coronary artery through activating the inward rectification K+ channels pathway","authors":"Wenqiao An , Qianqian Tian , Pengmei Guo , Mingzhu Chen , Ting Zhang , Peng Yang , Sanyin Zhang","doi":"10.1016/j.jep.2024.119064","DOIUrl":"10.1016/j.jep.2024.119064","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>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.</div></div><div><h3>Aim of the study</h3><div>This study aimed to elucidate the impacts and distinctions among DBD, <em>Astragalus</em>, <em>Angelica sinensis</em>, and identified active components on pre-constricted coronary arteries, as well as to delve deeper into their respective mechanisms.</div></div><div><h3>Materials and methods</h3><div>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 <em>in vivo</em> 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.</div></div><div><h3>Results</h3><div><em>In vitro</em> 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, BaCl<sub>2</sub> 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<sup>+</sup> channels (K<sub>IR</sub>) channel protein. Patch clamp studies demonstrate that quercetin can increase K<sub>IR</sub> current, and BaCl<sub>2</sub> can significantly reduce its current.</div></div><div><h3>Conclusions</h3><div>The active components of DBD, butylidenephthalide, ligustilide, calycosin, and quercetin, activate K<sub>IR</sub> channels to relax coronary artery and increase CBF.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119064"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621507","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}