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Tanshinone IIA, a component of Salvia miltiorrhiza Bunge, attenuated sepsis-induced liver injury via the SIRT1/Sestrin2/HO-1 signaling pathway 丹参酮IIA通过SIRT1/Sestrin2/HO-1信号通路减轻脓毒症诱导的肝损伤
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119169
Wencong Tian , Peng Song , Junhao Zang , Jia Zhao , Yanhong Liu , Chuntao Wang , Hong Fang , Hongzhi Wang , Yongjie Zhao , Xingqiang Liu , Yang Gao , Lei Cao

Ethnopharmacological relevance

As a traditional Chinese medicine, Salvia miltiorrhiza Bunge has been widely used to treat ischemic and inflammation-related diseases for more than 2000 years. S. miltiorrhiza Bunge has hepatoprotective effects, but the underlying mechanism is not fully understood.

Objective

To verify the effect of tanshinone IIA (Tan IIA), the main fat-soluble component of S. miltiorrhiza Bunge, on liver damage induced by sepsis/LPS-induced inflammation and further explore the underlying mechanisms.

Materials and methods

Mice were administered Tan IIA 2 h before cecal ligation and puncture (CLP). Liver damage was evaluated by hematoxylin-eosin staining and changes in related serum factor levels. The expression of silent information regulator sirtuin 1 (SIRT1), Sestrin2, HO-1 and inflammatory cytokines was examined by immunohistochemistry or western blotting. LPS was used to induce the inflammatory response in vitro, and the activity of the related signaling pathway in response to Tan IIA was detected by western blotting. The SIRT1 inhibitor EX-527 and small interfering RNAs (siRNAs) were employed to determine the key roles of SIRT1 and Sestrin2 in Tan IIA's function.

Results

We found that Tan IIA significantly improved the pathological changes and function of the liver, and alleviated liver damage in CLP mice. Additionally, SIRT1, Sestrin2, and HO-1 expression was significantly elevated after Tan IIA treatment compared with that in the CLP group both in vivo and in vitro, and Tan IIA treatment additionally suppressed pro-inflammatory cytokine release. However, inhibition of either SIRT1 or Sestrin2 remarkably abrogated the protective effects of Tan IIA. Most importantly, Sestrin2 appeared to function downstream of SIRT1 based on their expression changes after EX-527 or siRNA treatment.

Conclusion

Tan IIA inhibited sepsis/LPS-induced inflammation through the SIRT1/Sestrin2/HO-1 pathway, thereby protecting against sepsis-induced liver injury (SLI). This study suggests that Tan IIA has therapeutic potential against SLI and that the SIRT1/Sestrin2/HO-1 signaling pathway might be a viable target for SLI treatment.
民族药理学相关性:丹参作为一种中药,被广泛用于治疗缺血性和炎症相关疾病已有2000多年的历史。丹参对肝脏有保护作用,但其作用机制尚不完全清楚。目的:验证丹参主要脂溶性成分丹参酮IIA (Tan IIA)对脓毒症/脂多糖诱导炎症所致肝损伤的影响,并进一步探讨其作用机制。材料和方法:小鼠在盲肠结扎穿刺(CLP)前2 h给予Tan IIA。采用苏木精-伊红染色及相关血清因子水平变化评价肝损害。免疫组化或western blotting检测沉默信息调节因子SIRT1 (SIRT1)、Sestrin2、HO-1及炎症因子的表达。采用LPS体外诱导炎症反应,western blotting检测Tan IIA相关信号通路的活性。使用SIRT1抑制剂EX-527和小干扰rna (sirna)来确定SIRT1和Sestrin2在Tan IIA功能中的关键作用。结果:我们发现Tan IIA能明显改善CLP小鼠肝脏的病理变化和功能,减轻肝损伤。此外,在体内和体外,与CLP组相比,Tan IIA治疗后SIRT1、Sestrin2和HO-1的表达均显著升高,并且Tan IIA治疗还抑制了促炎细胞因子的释放。然而,SIRT1或Sestrin2的抑制显著地取消了Tan IIA的保护作用。最重要的是,根据EX-527或siRNA处理后Sestrin2的表达变化,Sestrin2似乎在SIRT1的下游发挥作用。结论:Tan IIA通过SIRT1/Sestrin2 /HO-1通路抑制脓毒症/ lps诱导的炎症,从而对脓毒症诱导的肝损伤(SLI)具有保护作用。本研究提示Tan IIA具有治疗SLI的潜力,SIRT1/Sestrin2 /HO-1信号通路可能是治疗SLI的可行靶点。
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引用次数: 0
Modified Tou Nong Powder obstructs ulcerative colitis by regulating autophagy and mitochondrial function 头农散加味对溃疡性结肠炎自噬及线粒体功能的调节作用。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119220
Linzhen Li , Zhen Ye , Huanzhu Qian , Liulin Chen , Yu Hu , Xiaolan Liu , Jinyu Zhu , Taozhi Bao , Kumar Ganesan , Fating Lu , Juan Wang , Xudong Wen , Kaihua Qin , Qiaobo Ye

Ethnopharmacological relevance

Modified Tou Nong Powder (MTNP) is a traditional Chinese medicine formula widely used for treating body surface ulcers. Since colonic ulcers share similar pathological characteristics, MTNP has shown promising results in alleviating ulcerative colitis (UC) and has been safely used in clinical practice.

Aim of the study

This study aims to investigate how MTNP alleviates experimental colitis by inducing autophagy through the regulation of the AMP-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signaling pathway.

Materials and methods

In this study, UC rat models were created using 2,4,6-Trinitrobenzenesulfonic acid (TNBS). The therapeutic effects of MTNP on TNBS-induced colitis were evaluated through various methods such as disease activity index, visual examination, and histological examination of the colon. An inflammation model was also established in Caco-2 cells using H2O2. Western blot analysis was used to assess the expression of autophagy-related proteins, while immunofluorescence detection was employed for protein localization. Furthermore, quantitative real-time polymerase chain reaction (qPCR) was performed to analyze the expression of autophagy-related genes, confirming the role of MTNP in modulating the AMPK/PGC-1α signaling pathway.

Results

In vivo, oral administration of MTNP led to a remarkable reduction in colonic injury, inhibition of inflammatory infiltration, and improvement in the abnormal expression of inflammatory factors in colonic tissues. Furthermore, MTNP stimulated autophagy by activating the AMPK/PGC-1α signaling pathway, thereby mitigating mitochondrial dysfunction. In vitro, exposure to MTNP drug-containing serum (MTNP-DS) resulted in a reduction of reactive oxygen species levels, improvement in mitochondrial membrane potential, and activation of the AMPK/PGC-1α pathway, leading to the promotion of mitochondrial autophagy.

Conclusion

The results indicate that MTNP triggers autophagy and enhances mitochondrial function, leading to the alleviation of UC in both in vitro and in vivo. These benefits are strongly linked to the activation of the AMPK/PGC-1α signaling pathway.
民族药理学相关性:头农散加味是一种广泛用于治疗体表溃疡的中药方剂。由于结肠溃疡具有相似的病理特征,MTNP在缓解溃疡性结肠炎(UC)方面显示出良好的效果,并已安全用于临床实践。研究目的:本研究旨在探讨MTNP如何通过调节amp活化的蛋白激酶(AMPK)/过氧化物酶体增殖体活化受体γ辅助激活因子1- α (PGC-1α)信号通路诱导自噬,从而减轻实验性结肠炎。材料与方法:采用2,4,6-三硝基苯磺酸(TNBS)制备UC大鼠模型。通过疾病活动性指数、视觉检查、结肠组织学检查等多种方法评价MTNP对tnbs性结肠炎的治疗效果。用H2O2在Caco-2细胞中建立炎症模型。Western blot检测自噬相关蛋白的表达,免疫荧光检测检测蛋白定位。此外,通过实时定量聚合酶链反应(qPCR)分析自噬相关基因的表达,证实了MTNP在调节AMPK/PGC-1α信号通路中的作用。结果:在体内,口服MTNP可显著减轻结肠损伤,抑制炎症浸润,改善结肠组织中炎症因子的异常表达。此外,MTNP通过激活AMPK/PGC-1α信号通路刺激自噬,从而减轻线粒体功能障碍。在体外实验中,暴露于MTNP含药血清(MTNP- ds)导致活性氧水平降低,线粒体膜电位升高,AMPK/PGC-1α通路激活,从而促进线粒体自噬。结论:MTNP在体外和体内均可触发自噬,增强线粒体功能,减轻UC的发生。这些益处与AMPK/PGC-1α信号通路的激活密切相关。
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引用次数: 0
Angong Niuhuang Pill pretreatment alleviates cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through the SIRT1-H4K16ac axis 安宫牛黄丸预处理通过SIRT1-H4K16ac轴抑制过度自噬,减轻脑缺血再灌注损伤。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119214
Lihan Wang , Jingyi Hou , He Xu , Qingqing Cai , Liangliang Tian , Xueli Li , Jingjing Zhang , Hongjun Yang

Ethnopharmacological relevance

Cerebral ischemia-reperfusion injury (CIRI) is an important pathological process in stroke treatment. Angong Niuhuang Pill (ANP), originating from Wenbing Tiaobian, has been shown to have neuroprotective effects, but its mechanism in alleviating CIRI remains unclear.

Aim of the study

This study aimed to elucidate the mechanism by which ANP alleviates CIRI using acetylomics and proteomics.

Materials and methods

The CIRI model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scoring, TTC staining, regional cerebral blood flow (rCBF) measurement, and TUNEL staining were used to assess the neuroprotective effects of ANP pretreatment on CIRI. Acetylomics and proteomics analyses were performed to identify the potential mechanisms by which ANP reduces CIRI. Finally, the role of SIRT1-H4K16ac-mediated autophagy in the neuroprotective effects of ANP was validated by using a SIRT1 inhibitor, EX527.

Results

ANP pretreatment markedly lowered neurological deficit scores and cerebral infarct volumes, increased rCBF, and reduced apoptosis. Acetylomics and proteomics results suggested that ANP regulated autophagy at the transcriptional level by modulating H4K16ac. Immunofluorescence and Western blot analyses confirmed that ANP promoted the accumulation of sirtuin 1 (SIRT1). Specifically, ANP pretreatment reduced H4K16ac levels, decreased LC3B-II/I ratios, upregulated SQSTM1/p62, and suppressed the expression of ATG5 and ATG7. The ability of EX527 to counteract these effects underscored the importance of the SIRT1-H4K16ac pathway in mediating the protective action of ANP against CIRI.

Conclusions

ANP provides neuroprotection by modulating the SIRT1-H4K16ac pathway, thereby preventing the excessive autophagy triggered by CIRI.
民族药理学相关性:脑缺血再灌注损伤(CIRI)是脑卒中治疗的重要病理过程。安宫牛黄丸(ANP)源于温冰条,具有神经保护作用,但其缓解CIRI的机制尚不清楚。研究目的:本研究旨在通过乙酰组学和蛋白质组学研究ANP减轻CIRI的机制。材料和方法:采用大脑中动脉闭塞法(MCAO)建立CIRI模型。采用神经功能缺损评分、TTC染色、区域脑血流量(rCBF)测定和TUNEL染色评估ANP预处理对CIRI的神经保护作用。进行了乙酰组学和蛋白质组学分析,以确定ANP降低CIRI的潜在机制。最后,使用SIRT1抑制剂EX527验证了SIRT1- h4k16ac介导的自噬在ANP神经保护作用中的作用。结果:ANP预处理显著降低神经功能缺损评分和脑梗死体积,增加rCBF,减少细胞凋亡。乙酰组学和蛋白质组学结果表明,ANP通过调控H4K16ac在转录水平上调控自噬。免疫荧光和western blot分析证实ANP促进sirtuin 1 (SIRT1)的积累。ANP预处理降低H4K16ac水平,降低LC3B-II/I比值,上调SQSTM1/p62,抑制ATG5和ATG7的表达。EX527抵消这些影响的能力强调了SIRT1-H4K16ac通路在介导ANP对CIRI的保护作用中的重要性。结论:ANP通过调节SIRT1-H4K16ac通路发挥神经保护作用,从而阻止CIRI引发的过度自噬。
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引用次数: 0
Nephroprotective and diuretic effect of Alternanthera brasiliana (L.) Kuntze leaf extract; acute and sub-acute toxicity assessment 巴西莲子的肾保护和利尿作用昆参叶提取物;急性和亚急性毒性评估。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119225
Muhammad Hassan Bilal, Iram Bibi
<div><h3>Ethnopharmacological relevance</h3><div>Alternanthera brasiliana (L.) Kuntze of the family Amaranthaceae has been extensively used in traditional medicinal practices in Brazil and India for its reputed efficacy in promoting diuresis, as well as treating wounds, inflammation, postnatal symptoms, diarrhea, and cough. Its selection for this study was driven not only by its ethnomedicinal significance but also by its rich phytochemical composition, including bioactive compounds such as flavonoids, saponins, and alkaloids, which are known to exhibit nephroprotective and diuretic effects. Additionally, while many species from the Amaranthaceae family have demonstrated similar therapeutic properties, <em>A. brasiliana</em> remains underexplored in this context. Therefore, this research aimed to scientifically evaluate its potential nephroprotective and diuretic activities, providing a pharmacological basis for its traditional uses.</div></div><div><h3>Aim of study</h3><div>This experiment was designed to determine nephroprotective effect against cisplatin-induced kidney injury and diuretic effect of <em>Alternanthera brasiliana</em> (L.) in rats. This study also aimed to evaluate the toxicity of plant's extract by performing acute and sub-acute toxicity trials.</div></div><div><h3>Material and methods</h3><div>In current study, the nephroprotective effect of aqueous-ethanol extract of <em>A. brasiliana</em> was evaluated after induction of kidney injury with cisplatin. Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A diuretic activity was also performed by comparing results with control and standard (furosemide). Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A 14 day trial for acute toxicity assessment was performed at doses 2000 mg/kg and 3000 mg/kg, whereas a 28 day trial for sub-acute toxicity assessment was performed at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. The biological active ingredients were identified and determined using HPLC technique.</div></div><div><h3>Results</h3><div>The aqueous-ethanol extract of <em>A. brasiliana</em> (ABAE) safeguarded the rats from toxic effects of cisplatin. This extract also enhanced urine output. The protective effect of ABAE increased with increasing dose and produced maximum nephroprotective effect and diuresis at a dose 300 mg/kg. The outcomes from acute toxicity trials suggested that LD<sub>50</sub> lied beyond 3000 mg/kg, and no antagonizing effects occurred in sub-acute toxicity trials at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. ABAE posed no toxicities on kidney, liver, and heart tissues as evident from histopathological, hematological, and serum biochemical analysis. HPLC-DAD analysis of ABAE indicated the presence of betanin, kaempherol, gallic acid, <em>p</em>-coumaric acid and oxalic acid.</div></div><div><h3>Conclusions</h3><div>These results demonstrate an abundant supply of bioactive chemicals found in <em>A. brasiliana</em> (L.) extrac
民族药理学相关性:巴西莲藕(L.)紫红科的紫子在巴西和印度的传统医学实践中被广泛使用,因为它具有促进利尿的功效,以及治疗伤口、炎症、产后症状、腹泻和咳嗽。选择它作为本研究的对象不仅是因为它的民族医学意义,还因为它丰富的植物化学成分,包括黄酮类化合物、皂苷和生物碱等生物活性化合物,已知它们具有保护肾脏和利尿的作用。此外,虽然苋菜科的许多物种都表现出类似的治疗特性,但在这方面,巴西苋仍未得到充分的研究。因此,本研究旨在科学评价其潜在的肾保护和利尿作用,为其传统应用提供药理学依据。研究目的:研究巴西莲子对顺铂所致大鼠肾损伤的保护作用和利尿作用。本研究还通过急性和亚急性毒性试验来评价植物提取物的毒性。材料与方法:本研究采用顺铂诱导大鼠肾损伤后,评价巴西木水乙醇提取物对肾脏的保护作用。提取物分75 mg/kg、150 mg/kg和300 mg/kg三种剂量给药。通过与对照和标准品(速尿)的比较,还进行了利尿活性测定。提取物分75 mg/kg、150 mg/kg和300 mg/kg三种剂量给药。在2000 mg/kg和3000 mg/kg剂量下进行了为期14天的急性毒性评估试验,在250 mg/kg、500 mg/kg和1000 mg/kg剂量下进行了为期28天的亚急性毒性评估试验。采用高效液相色谱法对其生物活性成分进行了鉴定和测定。结果:巴西木水乙醇提取物(ABAE)对大鼠顺铂毒性作用有保护作用。这种提取物还能增加尿量。ABAE的保护作用随着剂量的增加而增强,在剂量为300 mg/kg时肾保护作用和利尿作用最大。急性毒性试验结果表明,LD50大于3000 mg/kg,在亚急性毒性试验中,250 mg/kg、500 mg/kg和1000 mg/kg剂量均未发生拮抗作用。从组织病理学、血液学和血清生化分析可以看出,ABAE对肾、肝和心脏组织没有毒性。ABAE的HPLC-DAD分析表明,ABAE中含有甜菜素、山酚、没食子酸、对香豆酸和草酸。结论:巴西木提取物中含有丰富的生物活性物质,在改善肾功能的同时减少不良反应应予以考虑。
{"title":"Nephroprotective and diuretic effect of Alternanthera brasiliana (L.) Kuntze leaf extract; acute and sub-acute toxicity assessment","authors":"Muhammad Hassan Bilal,&nbsp;Iram Bibi","doi":"10.1016/j.jep.2024.119225","DOIUrl":"10.1016/j.jep.2024.119225","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Alternanthera brasiliana (L.) Kuntze of the family Amaranthaceae has been extensively used in traditional medicinal practices in Brazil and India for its reputed efficacy in promoting diuresis, as well as treating wounds, inflammation, postnatal symptoms, diarrhea, and cough. Its selection for this study was driven not only by its ethnomedicinal significance but also by its rich phytochemical composition, including bioactive compounds such as flavonoids, saponins, and alkaloids, which are known to exhibit nephroprotective and diuretic effects. Additionally, while many species from the Amaranthaceae family have demonstrated similar therapeutic properties, &lt;em&gt;A. brasiliana&lt;/em&gt; remains underexplored in this context. Therefore, this research aimed to scientifically evaluate its potential nephroprotective and diuretic activities, providing a pharmacological basis for its traditional uses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of study&lt;/h3&gt;&lt;div&gt;This experiment was designed to determine nephroprotective effect against cisplatin-induced kidney injury and diuretic effect of &lt;em&gt;Alternanthera brasiliana&lt;/em&gt; (L.) in rats. This study also aimed to evaluate the toxicity of plant's extract by performing acute and sub-acute toxicity trials.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Material and methods&lt;/h3&gt;&lt;div&gt;In current study, the nephroprotective effect of aqueous-ethanol extract of &lt;em&gt;A. brasiliana&lt;/em&gt; was evaluated after induction of kidney injury with cisplatin. Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A diuretic activity was also performed by comparing results with control and standard (furosemide). Extract was given in three doses as 75 mg/kg, 150 mg/kg and 300 mg/kg. A 14 day trial for acute toxicity assessment was performed at doses 2000 mg/kg and 3000 mg/kg, whereas a 28 day trial for sub-acute toxicity assessment was performed at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. The biological active ingredients were identified and determined using HPLC technique.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The aqueous-ethanol extract of &lt;em&gt;A. brasiliana&lt;/em&gt; (ABAE) safeguarded the rats from toxic effects of cisplatin. This extract also enhanced urine output. The protective effect of ABAE increased with increasing dose and produced maximum nephroprotective effect and diuresis at a dose 300 mg/kg. The outcomes from acute toxicity trials suggested that LD&lt;sub&gt;50&lt;/sub&gt; lied beyond 3000 mg/kg, and no antagonizing effects occurred in sub-acute toxicity trials at doses 250 mg/kg, 500 mg/kg and 1000 mg/kg. ABAE posed no toxicities on kidney, liver, and heart tissues as evident from histopathological, hematological, and serum biochemical analysis. HPLC-DAD analysis of ABAE indicated the presence of betanin, kaempherol, gallic acid, &lt;em&gt;p&lt;/em&gt;-coumaric acid and oxalic acid.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;These results demonstrate an abundant supply of bioactive chemicals found in &lt;em&gt;A. brasiliana&lt;/em&gt; (L.) extrac","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119225"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801078","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
Panax quinquefolium saponins protects neuronal activity by promoting mitophagy in both in vitro and in vivo models of Alzheimer's disease 在阿尔茨海默病的体外和体内模型中,三七皂苷能通过促进有丝分裂来保护神经元活性。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119250
Wei Zhao , Rui Yang , Xin Meng , Shi-qi Xu , Meng-meng Li , Zhi-chao Hao , Si-yi Wang , Yi-Kai Jiang , Anam Naseem , Qing-shan Chen , Li-li Zhang , Hai-xue Kuang , Bing-you Yang , Yan Liu

Ethnopharmacological relevance

In the realm of traditional Chinese medicine, Panax quinquefolius L. has garnered significant attention for its potential to treat various ailments associated with deficiencies, including qi, blood, and kidneys. As its primary bioactive constituent, Panax quinquefolius saponins (PQS) have the potential therapeutic role of Alzheimer's disease (AD) treatment, but with unclear mechanisms of action. Meanwhile, AD is considered as a common dementia disease with kidney insufficiency and deficiency by traditional medicine, and often accompanied by autophagy in modern medical research.

Aim of the study

This study aimed to investigate the therapeutic effects of PQS on AD through the regulation of mitophagy.

Materials and methods

The chemical constituents of PQS were characterized using the UPLC-QTOF-MS technique. After that, the HT22 cell line was used to establish the D-galactose-induced cell model, and the SAMP8 mice model of AD was also employed. Cell viability was assessed using the CCK-8 assay, ROS detection, JC-1 staining, Mito-tracker Red and LC3 staining, and Mito-tracker Green and Lyso-tracker Red staining were used to assess levels of mitophagy. The Morris Water Maze (MWM) was used for the experimental evaluation of learning and memory abilities in mice. Subsequently, the mechanism was studied by pathological staining and western blotting.

Results

Fifty-eight triterpenoid saponins were identified from PQS, and PQS alleviated D-galactose-induced HT22 cell death and increased intracellular levels of mitochondrial autophagy-related factors. In vivo, PQS significantly improved cognitive deficits and mitigated AD-like pathological features by activating the mitophagy mechanism. Furthermore, PQS may promote Pink1/Parkin-mediated mitophagy by activating the AMPK/mTOR/ULK1/DRP1 and SIRT1/PGC-1α pathways.

Conclusion

In conclusion, PQS have demonstrated the potential to mitigate mitochondrial dysfunction and enhance cognitive function in AD through the activation of mitophagy. This promising strategy holds great promise for the treatment of AD.
民族药理学相关性:在传统中医领域,西洋参因其治疗与气、血、肾等缺陷相关的各种疾病的潜力而引起了极大的关注。西洋参皂苷(PQS)作为其主要生物活性成分,具有治疗阿尔茨海默病(AD)的潜在作用,但作用机制尚不清楚。同时,传统医学认为AD是一种常见的伴有肾虚、肾功能不全的痴呆病,现代医学研究常伴有自噬。研究目的:本研究旨在探讨PQS通过调节线粒体自噬对AD的治疗作用。材料与方法:采用UPLC-QTOF-MS技术对PQS的化学成分进行表征。之后,采用HT22细胞系建立d -半乳糖诱导的细胞模型,并采用SAMP8小鼠AD模型。采用CCK-8法评估细胞活力,采用ROS检测、JC-1染色、Mito-tracker Red和LC3染色,采用Mito-tracker Green和Lyso-tracker Red染色评估细胞自噬水平。采用Morris水迷宫(Morris Water Maze, MWM)对小鼠学习记忆能力进行了实验评价。随后采用病理染色和免疫印迹法研究其作用机制。结果:从PQS中鉴定出58种三萜皂苷,PQS可减轻d -半乳糖诱导的HT22细胞死亡,提高细胞内线粒体自噬相关因子水平。在体内,PQS通过激活线粒体自噬机制,显著改善认知缺陷,减轻ad样病理特征。此外,PQS可能通过激活AMPK/mTOR/ULK1/DRP1和SIRT1/PGC-1α途径促进Pink1/ parkin介导的有丝分裂。结论:PQS可能通过激活线粒体自噬来减轻AD患者的线粒体功能障碍和增强认知功能。这种有希望的策略为治疗阿尔茨海默病带来了巨大的希望。
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引用次数: 0
Guben Kechuan granule attenuates bronchial asthma by inhibiting NF-κB/STAT3 signaling pathway-mediated apoptosis 固本咳喘颗粒通过抑制NF-κB/STAT3信号通路介导的细胞凋亡减轻支气管哮喘。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119124
Chuanhao Dai , Dewen Liu , Cuiying Qin , Jingya Fang , Guangqing Cheng , Chunhong Xu , Qixin Wang , Tianming Lu , Zuchang Guo , Jigang Wang , Tianyu Zhong , Qiuyan Guo

Ethnopharmacological relevance

Chronic asthma caused by allergies is a lung illness marked by airway remodeling and hyperresponsiveness. Guben Kechuan (GK) granule is a clinically proven formula for treating lung disease. It relieves cough and helps to clear phlegm, but the mechanisms underlying its treatment for asthma are not clear.

Aim of the study

We aimed to elucidate the efficacy and potential mechanisms by which GK ameliorates allergic asthma.

Materials and methods

Ultra-performance liquid chromatography (UHPLC-LTQ-Orbitrap-MS) identified the main chemical components of GK. The efficacy of GK was studied in an ovalbumin/alum (OVA)/AL(OH)3-sensitized rat model of bronchial asthma by measuring cytokine concentrations in serum and alveolar lavage samples, examining tissue pathology, and performing leukocyte counts. The mechanisms underlying its effectiveness in asthma were investigated by both transcriptomic and proteomic analyses.

Results

GK relieved asthma-induced airway inflammation and remodeling, reduced inflammatory cell infiltration, and decreased the levels of the inflammatory cytokines TNF-α, IL-4, IL-5, IL-6, and IL-10. Analysis of the transcriptomic and proteomic results found that asthma activated the transcription factors STAT3 and NF-κB and induced oxidative-stress damage and apoptosis. GK was found to reduce Bax and caspase-3 expression, increase Bcl-2 expression, and inhibit asthma-induced apoptosis. GK downregulated the expression of the transcription factors STAT3 and NF-kB, which decreased the inflammatory response. Decreases in CAT, SOD, and GSH reduced asthma-induced oxidative-stress damage.

Conclusions

Our findings provide evidence that GK alleviates bronchial asthma by inhibiting apoptosis and oxidative stress damage mediated by the NF-κB/STAT3 signaling pathway.
民族药理学相关性:由过敏引起的慢性哮喘是一种以气道重塑和高反应性为特征的肺部疾病。固本咳喘颗粒是临床证实的治疗肺部疾病的方剂。它能止咳、清痰,但其治疗哮喘的机制尚不清楚。研究目的:我们旨在阐明GK改善过敏性哮喘的疗效及其潜在机制。材料与方法:超高效液相色谱法(UHPLC-LTQ-Orbitrap-MS)鉴定了GK的主要化学成分。通过测定血清和肺泡灌洗液中细胞因子的浓度、组织病理学检查和白细胞计数,研究GK在卵白蛋白/明矾(OVA)/AL(OH)3致敏大鼠支气管哮喘模型中的作用。通过转录组学和蛋白质组学分析研究了其对哮喘有效的机制。结果:GK可缓解哮喘气道炎症和重塑,减少炎症细胞浸润,降低炎症因子TNF-α、IL-4、IL-5、IL-6、IL-10水平。转录组学和蛋白质组学分析发现,哮喘激活转录因子STAT3和NF-κB,诱导氧化应激损伤和细胞凋亡。发现GK可降低Bax和caspase-3表达,增加Bcl-2表达,抑制哮喘诱导的细胞凋亡。GK下调转录因子STAT3和NF-kB的表达,降低炎症反应。CAT、SOD和GSH的降低降低了哮喘引起的氧化应激损伤。结论:GK可通过抑制NF-κB/STAT3信号通路介导的支气管哮喘细胞凋亡和氧化应激损伤,从而减轻支气管哮喘的发病。
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引用次数: 0
Pharmacological effects and mechanisms of danlong oral liquid in asthma airway remodeling: Insights from serum medicinal chemistry, network pharmacology, and experimental validation 丹龙口服液对哮喘气道重塑的药理作用及机制:来自血清药物化学、网络药理学和实验验证的见解。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119259
Bowen Liu , Min Xiang , Mengqi Zhou , Chunxiao Li , Hou Xin , Shuwen Zhang , Jiangtao Lin

Ethnopharmacological relevance

Danlong oral liquid (DLOL) is a traditional Chinese proprietary medicine commonly used to treat chronic respiratory diseases, including bronchial asthma and chronic obstructive pulmonary disease. However, the therapeutic effects and pharmacological mechanisms of DLOL in improving airway remodeling remain unclear.

Aims of the study

This study utilizes in vivo and in vitro experiments, serum pharmacological analysis, and network-based pharmacology approaches to investigate the effects and mechanisms of DLOL on airway remodeling and epithelial-mesenchymal transition (EMT) in asthma.

Methods

An asthma model was established through ovalbumins (OVA) sensitization and challenge in BALB/c mice to observe the effects of DLOL on airway hyperresponsiveness (AHR), inflammation, remodeling, and molecular markers of EMT. The absorbed chemical prototype constituents of DLOL were analyzed using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and targets for asthma and airway remodeling were predicted using a network pharmacology approach. Key biological processes and signaling pathways were analyzed. Additionally, TGF-β1 was used to induce EMT in BEAS-2B cells. TGF-β1 and DLOL-containing serum were screened to determine the optimal time and concentration in BEAS-2B cells using CCK8 assays. The cell scratch assay was used to assess cell migration, while immunofluorescence and immunohistochemistry were employed to evaluate protein expression levels.

Results

DLOL improved AHR in asthmatic mice, reduced inflammatory cell infiltration in lung tissue, decreased airway wall and smooth muscle thickness, and reduced collagen deposition. It also down-regulated mesenchymal markers (N-cadherin, vimentin, α-SMA) and key remodeling factors (TGF-β1, MMP9), while up-regulating the epithelial marker E-cadherin. A total of 17 absorbed chemical prototype constituents were identified, predicting 54 core targets involved in airway remodeling. Following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the key targets were found to be associated with the regulation of cell migration, cell-cell adhesion, and cell adhesion molecular processes, with the PI3K-Akt signaling pathway likely playing a critical role. Cellular experiments confirmed that DLOL-containing serum inhibited TGF-β1-induced EMT in BEAS-2B cells and suppressed the phosphorylation of Akt and GSK-3β.

Conclusion

This study identifies, for the first time, the serum medicinal chemistry of DLOL using UPLC-MS. Combining network pharmacology, in vivo and in vitro experiments, it elucidates the effects and potential mechanisms of the drug on airway remodeling and EMT. DLOL may offer a novel therapeutic approach for asthma-related airway remodeling.
民族药理学相关性:丹龙口服液是一种常用的中成药,用于治疗慢性呼吸系统疾病,包括支气管哮喘和慢性阻塞性肺疾病。然而,DLOL在改善气道重塑方面的治疗效果和药理机制尚不清楚。研究目的:本研究通过体内外实验、血清药理学分析和基于网络的药理学方法,探讨DLOL对哮喘气道重塑和上皮-间质转化(EMT)的影响及其机制。方法:通过卵清蛋白(OVA)致敏和激发建立BALB/c小鼠哮喘模型,观察DLOL对气道高反应性(AHR)、炎症、重塑及EMT分子标志物的影响。利用超高效液相色谱-质谱(UPLC-MS)分析了DLOL的吸收化学原型成分,并利用网络药理学方法预测了其治疗哮喘和气道重塑的靶点。分析了关键的生物学过程和信号通路。另外,利用TGF-β1诱导BEAS-2B细胞EMT。筛选含TGF-β1和dloll的血清,采用CCK8法确定在BEAS-2B细胞中的最佳时间和浓度。采用细胞划痕法评估细胞迁移,免疫荧光和免疫组织化学评估蛋白表达水平。结果:DLOL改善哮喘小鼠AHR,减少肺组织炎症细胞浸润,降低气道壁和平滑肌厚度,减少胶原沉积。下调间质标志物(N-cadherin、vimentin、α-SMA)和关键重塑因子(TGF-β1、MMP9),上调上皮标志物E-cadherin。共鉴定了17种吸收的化学原型成分,预测了54个参与气道重塑的核心靶点。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析,发现关键靶点与细胞迁移、细胞-细胞粘附和细胞粘附分子过程的调控有关,其中PI3K-Akt信号通路可能起关键作用。细胞实验证实,含dloll的血清抑制TGF-β1诱导的BEAS-2B细胞EMT,抑制Akt和GSK-3β的磷酸化。结论:本研究首次利用超高效液相色谱-质谱法鉴定了盐酸多洛尔的血清药物化学。结合网络药理学、体内和体外实验,阐明该药对气道重塑和EMT的作用及其潜在机制。dll可能为哮喘相关气道重构提供一种新的治疗方法。
{"title":"Pharmacological effects and mechanisms of danlong oral liquid in asthma airway remodeling: Insights from serum medicinal chemistry, network pharmacology, and experimental validation","authors":"Bowen Liu ,&nbsp;Min Xiang ,&nbsp;Mengqi Zhou ,&nbsp;Chunxiao Li ,&nbsp;Hou Xin ,&nbsp;Shuwen Zhang ,&nbsp;Jiangtao Lin","doi":"10.1016/j.jep.2024.119259","DOIUrl":"10.1016/j.jep.2024.119259","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Danlong oral liquid (DLOL) is a traditional Chinese proprietary medicine commonly used to treat chronic respiratory diseases, including bronchial asthma and chronic obstructive pulmonary disease. However, the therapeutic effects and pharmacological mechanisms of DLOL in improving airway remodeling remain unclear.</div></div><div><h3>Aims of the study</h3><div>This study utilizes <em>in vivo</em> and <em>in vitro</em> experiments, serum pharmacological analysis, and network-based pharmacology approaches to investigate the effects and mechanisms of DLOL on airway remodeling and epithelial-mesenchymal transition (EMT) in asthma.</div></div><div><h3>Methods</h3><div>An asthma model was established through ovalbumins (OVA) sensitization and challenge in BALB/c mice to observe the effects of DLOL on airway hyperresponsiveness (AHR), inflammation, remodeling, and molecular markers of EMT. The absorbed chemical prototype constituents of DLOL were analyzed using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS), and targets for asthma and airway remodeling were predicted using a network pharmacology approach. Key biological processes and signaling pathways were analyzed. Additionally, TGF-β1 was used to induce EMT in BEAS-2B cells. TGF-β1 and DLOL-containing serum were screened to determine the optimal time and concentration in BEAS-2B cells using CCK8 assays. The cell scratch assay was used to assess cell migration, while immunofluorescence and immunohistochemistry were employed to evaluate protein expression levels.</div></div><div><h3>Results</h3><div>DLOL improved AHR in asthmatic mice, reduced inflammatory cell infiltration in lung tissue, decreased airway wall and smooth muscle thickness, and reduced collagen deposition. It also down-regulated mesenchymal markers (N-cadherin, vimentin, α-SMA) and key remodeling factors (TGF-β1, MMP9), while up-regulating the epithelial marker E-cadherin. A total of 17 absorbed chemical prototype constituents were identified, predicting 54 core targets involved in airway remodeling. Following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the key targets were found to be associated with the regulation of cell migration, cell-cell adhesion, and cell adhesion molecular processes, with the PI3K-Akt signaling pathway likely playing a critical role. Cellular experiments confirmed that DLOL-containing serum inhibited TGF-β1-induced EMT in BEAS-2B cells and suppressed the phosphorylation of Akt and GSK-3β.</div></div><div><h3>Conclusion</h3><div>This study identifies, for the first time, the serum medicinal chemistry of DLOL using UPLC-MS. Combining network pharmacology, <em>in vivo</em> and <em>in vitro</em> experiments, it elucidates the effects and potential mechanisms of the drug on airway remodeling and EMT. DLOL may offer a novel therapeutic approach for asthma-related airway remodeling.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119259"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854250","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
Antiviral activity of HuaganJiedu decoction (HGJDD) against hepatitis B virus (HBV) through FOXO4/ERK/HNF4α signal pathway 花肝解毒汤(HGJDD)通过FOXO4/ERK/HNF4α信号通路对乙型肝炎病毒(HBV)的抗病毒活性
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119238
Hongxuan Tong , Jiale Zhang , Lijie Jiang , Rendong Qu , Tao Lu , Jingqing Hu

Ethnopharmacological relevance

Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.

Aim of the study

This study aims to explore the therapeutic mechanism of HuaganJiedu Decoction (HGJDD) in HBV.

Materials and methods

We investigated the therapeutic potential of HGJDD, and LC-MS analysis characterized the chemical profile of HGJDD. In vitro, we utilized HepG2.2.15 cell line to assess cytotoxicity and treatment efficacy of HGJDD compared to Entecavir controls. In vivo, assessments included monitoring HBV-related biomarkers and viral load. Network pharmacology and RNA-seq analyses identified molecular pathways and targets influenced by HGJDD treatment. Immunofluorescence and Western blotting provided further insights into the therapeutic mechanisms underlying HGJDD for HBV.

Results

HGJDD showed no toxicity on HepG2.2.15 cells at 10%, 20%, 40%, and 80% serum concentrations. In vitro, HGJDD reduced HBsAg, HBeAg, and HBV DNA levels by dose-dependently and time-dependently. HGJDD can decrease the levels of HBsAg, HBeAg, and HBV DNA in serum and liver levels, meanwhile the therapeutic effect of high-dose HGJDD approach to EVT’s in HBV Tg mice. According to intersection of network pharmacology and transcriptome, FOXO signal pathway was highlighted as potential targets and Immunofluorescence find that FOXO4D protein expression lever was increased in three HGJDD group, especially in high-dose HGJDD group. Western blotting confirmed increased level of FOXO4, ERK, and p-ERK and decreased levels of HNF4α, which reflected that the therapeutic effect was closely to FOXO4/ERK/HNF4α signal pathway.

Conclusions

Traditional Chinese medicine (TCM) offers diverse herbal treatments for HBV, with HGJDD showing efficacy in reducing HBsAg, HBeAg, and HBV DNA levels at cellular and animal levels. This study identified that FOXO4/ERK/HNF4α signal pathway played an important role in HGJDD’s therapeutic effects. These findings support HGJDD’s potential in HBV treatment, providing a scientific basis for clinical use.
民族药理学相关性:慢性乙型肝炎病毒(HBV)感染仍然是一个广泛的全球健康问题。化肝解毒汤(HGJDD)是国内治疗HBV的常用方剂,具有增强抗病毒疗效,提高临床疗效的作用。然而,其确切的作用机制尚不清楚,需要进一步研究以阐明其治疗潜力并将其纳入标准医疗实践。研究目的:探讨化肝解毒汤(HGJDD)治疗HBV的作用机制。材料和方法:我们研究了HGJDD的治疗潜力,并通过LC-MS分析表征了HGJDD的化学特征。在体外,我们利用HepG2.2.15细胞系来评估HGJDD与恩替卡韦对照的细胞毒性和治疗效果。在体内,评估包括监测hbv相关生物标志物和病毒载量。网络药理学和RNA-seq分析确定了受HGJDD治疗影响的分子途径和靶点。免疫荧光和Western blotting进一步揭示了HGJDD治疗HBV的机制。结果:HGJDD在10%、20%、40%、80%血清浓度下对HepG2.2.15细胞无毒性作用。在体外,HGJDD降低HBsAg、HBeAg和HBV DNA水平呈剂量依赖性和时间依赖性。HGJDD可降低血清和肝脏中HBsAg、HBeAg、HBV DNA水平,同时观察大剂量HGJDD对HBV Tg小鼠EVT的治疗作用。通过网络药理学和转录组交叉分析,FOXO信号通路作为潜在靶点被突出,免疫荧光发现FOXO4D蛋白表达水平在三个HGJDD组中升高,特别是在高剂量HGJDD组。Western blotting证实FOXO4、ERK、p-ERK水平升高,HNF4α水平降低,提示治疗效果与FOXO4/ERK/HNF4α信号通路密切相关。结论:中药为HBV提供了多种草药治疗方法,HGJDD在细胞和动物水平上显示出降低HBsAg、HBeAg和HBV DNA水平的疗效。本研究发现FOXO4/ERK/HNF4α信号通路在HGJDD的治疗效果中发挥重要作用。这些发现支持了HGJDD治疗HBV的潜力,为临床应用提供了科学依据。
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引用次数: 0
Saffron extract alleviates D-gal-induced late-onset hypogonadism by activating the PI3K-Akt-Nrf2 signaling pathway 藏红花提取物通过激活PI3K-Akt-Nrf2信号通路减轻d -gal诱导的晚发性性腺功能减退。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119273
Hao Liu , Zhongkai Guo , Zhenjie Zang , Bin Jia , Yuhang Zhou , Hui Zhang , Qiang Fu

Ethnopharmacological relevance

Late-onset hypogonadism (LOH) is a common age-related condition in men, characterized by a decline in serum testosterone and a range of associated signs and symptoms, and is classified as impotence in traditional medicine. Saffron is the dried stigma of Crocus sativus L., which is used in traditional medicine as an aphrodisiac.

Aim of the study

This study aimed to investigate the effects of saffron extract (SE) on LOH using an aging mouse model and Leydig cells.

Methods

The potential mechanisms and therapeutic targets of SE for the treatment of LOH were first identified using network pharmacology. An aging model was induced in mice by administration of D-galactose, followed by treatment with varying concentrations of SE. Subsequent assessments of serum testosterone levels, semen quality, testicular aging, oxidative stress, and apoptotic markers were performed to assess the impact of SE and to elucidate its mechanisms. In addition, in vitro experiments assessed the effect of SE on Leydig cell viability, oxidative stress, and apoptosis.

Results

The results showed that SE could modulate the PI3K-Akt-Nrf2 signaling pathway, enhancing Leydig cell resistance to oxidative stress and reducing Leydig cell apoptosis, thereby improving Leydig cell function and alleviating the decrease in serum testosterone associated with aging.

Conclusion

Saffron is a promising strategy for the treatment of LOH and provides an effective approach to alleviate serum testosterone decline in older men.
民族药理学相关性:迟发性性腺功能减退(LOH)是男性中一种常见的与年龄有关的疾病,其特征是血清睾酮水平下降以及一系列相关体征和症状,在传统医学中被归类为阳痿。藏红花是藏红花(Crocus sativus L.)的干柱头,在传统医学中用作壮阳药。研究目的:采用衰老小鼠模型和间质细胞,探讨藏红花提取物(SE)对LOH的影响。方法:首次利用网络药理学方法确定SE治疗LOH的潜在机制和治疗靶点。通过给药d -半乳糖诱导小鼠衰老模型,然后用不同浓度的SE治疗。随后对血清睾酮水平、精液质量、睾丸老化、氧化应激和凋亡标志物进行评估,以评估SE的影响并阐明其机制。此外,体外实验评估了SE对间质细胞活力、氧化应激和凋亡的影响。结果:结果显示,SE可调节PI3K-Akt-Nrf2信号通路,增强间质细胞抗氧化应激能力,减少间质细胞凋亡,从而改善间质细胞功能,缓解血清睾酮与衰老相关的下降。结论:藏红花是治疗LOH的有效方法,可有效缓解老年男性血清睾酮水平下降。
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引用次数: 0
n-butanol extract of Pulsatilla decoction alleviates vulvovaginal candidiasis via the regulation of mitochondria-associated Type I interferon signaling pathways 白头草汤正丁醇提取物通过调节线粒体相关的I型干扰素信号通路缓解外阴阴道念珠菌病。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119292
Ziyi Li , Hui Wu , Can Li , Yemei Wang , Jing Shao , Daqiang Wu , Tianming Wang , Changzhong Wang

Ethnopharmacological relevance

Vulvovaginal candidiasis (VVC) is a relatively common fungal infectious disease in the female reproductive tract. The pathogenesis of VVC not only involves Candida albicans (C. albicans) infection, but also the improper immune response of the vaginal mucosal immune system to the fungus. As a classical formula, Pulsatilla decoction has been proven to exert protective effect in both clinical and experimental research in VVC. However, the specific mechanism of Pulsatilla decoction in VVC remains elusive. This study investigated the mechanism of n-butanol extract of Pulsatilla decoction (BEPD) in treating VVC from the perspective of type I interferon signaling and related mitochondrial function.

Materials and methods

A VVC-rat model was developed using an estrogen-based method to evaluate the effectiveness of BEPD in treating VVC, and the therapeutic efficacy of BEPD against VVC was comprehensively evaluated by fungal morphology and burden, neutrophil numbers, histopathology, pro-inflammatory and anti-inflammatory cytokines production, and LDH level. Immunohistochemistry (IHC), immune fluorescence (IF), Western Blot (WB) and RT-qPCR assays were conducted to assess type I interferon signaling and mitochondria functions. Candidalysin-induced vaginal epithelial inflammation in vitro, as cellular models, was employed to detect the changes in type I interferon signaling and mitochondria function before and after BEPD-containing serum intervention.

Results

BEPD could significantly improve the inflammation, reduce fungal loads and inhibit fungal growth, balance pro-inflammatory and anti-inflammatory cytokine levels in VVC model rats. The findings from IHC, IF, WB and RT-qPCR revealed that BEPD could promote type I interferon signaling and alleviate mitochondrial functional damage in VVC model rats, and BEPD-containing serum could play the same role in vitro.

Conclusion

The study findings generally demonstrated that BEPD could improve the inflammation and correct the immune imbalance in VVC through regulation of type I interferon signaling and mitochondrial function.
民族药理学相关性:外阴阴道念珠菌病(VVC)是一种相对常见的女性生殖道真菌感染性疾病。VVC的发病机制不仅与白色念珠菌(C. albicans)感染有关,还与阴道黏膜免疫系统对真菌的免疫反应不当有关。白头翁汤作为经典方剂,在临床和实验研究中均被证明对VVC有保护作用。白头草汤治疗VVC的具体机制尚不清楚。本研究从I型干扰素信号通路及相关线粒体功能角度探讨白头翁汤正丁醇提取物(BEPD)治疗VVC的作用机制。材料与方法:采用基于雌激素的方法建立VVC大鼠模型,评价BEPD对VVC的治疗效果,并从真菌形态和负荷、中性粒细胞数量、组织病理学、促炎和抗炎细胞因子产生、LDH水平等方面综合评价BEPD对VVC的治疗效果。采用免疫组化(IHC)、免疫荧光(IF)、Western Blot (WB)和RT-qPCR检测ⅰ型干扰素信号传导和线粒体功能。以体外假丝酵素诱导的阴道上皮炎症为细胞模型,检测含bepd血清干预前后I型干扰素信号和线粒体功能的变化。结果:BEPD能显著改善VVC模型大鼠的炎症反应,减轻真菌负荷,抑制真菌生长,平衡促炎和抗炎细胞因子水平。IHC、IF、WB和RT-qPCR结果显示,BEPD能促进VVC模型大鼠I型干扰素信号传导,减轻线粒体功能损伤,体外实验中含BEPD血清也能起到同样的作用。结论:研究结果普遍表明,BEPD可通过调节I型干扰素信号和线粒体功能,改善VVC炎症,纠正免疫失衡。
{"title":"n-butanol extract of Pulsatilla decoction alleviates vulvovaginal candidiasis via the regulation of mitochondria-associated Type I interferon signaling pathways","authors":"Ziyi Li ,&nbsp;Hui Wu ,&nbsp;Can Li ,&nbsp;Yemei Wang ,&nbsp;Jing Shao ,&nbsp;Daqiang Wu ,&nbsp;Tianming Wang ,&nbsp;Changzhong Wang","doi":"10.1016/j.jep.2024.119292","DOIUrl":"10.1016/j.jep.2024.119292","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Vulvovaginal candidiasis (VVC) is a relatively common fungal infectious disease in the female reproductive tract. The pathogenesis of VVC not only involves <em>Candida albicans</em> (<em>C. albicans</em>) infection, but also the improper immune response of the vaginal mucosal immune system to the fungus. As a classical formula, <em>Pulsatilla</em> decoction has been proven to exert protective effect in both clinical and experimental research in VVC. However, the specific mechanism of <em>Pulsatilla</em> decoction in VVC remains elusive. This study investigated the mechanism of n-butanol extract of <em>Pulsatilla</em> decoction (BEPD) in treating VVC from the perspective of type I interferon signaling and related mitochondrial function.</div></div><div><h3>Materials and methods</h3><div>A VVC-rat model was developed using an estrogen-based method to evaluate the effectiveness of BEPD in treating VVC, and the therapeutic efficacy of BEPD against VVC was comprehensively evaluated by fungal morphology and burden, neutrophil numbers, histopathology, pro-inflammatory and anti-inflammatory cytokines production, and LDH level. Immunohistochemistry (IHC), immune fluorescence (IF), Western Blot (WB) and RT-qPCR assays were conducted to assess type I interferon signaling and mitochondria functions. Candidalysin-induced vaginal epithelial inflammation in vitro, as cellular models, was employed to detect the changes in type I interferon signaling and mitochondria function before and after BEPD-containing serum intervention.</div></div><div><h3>Results</h3><div>BEPD could significantly improve the inflammation, reduce fungal loads and inhibit fungal growth, balance pro-inflammatory and anti-inflammatory cytokine levels in VVC model rats. The findings from IHC, IF, WB and RT-qPCR revealed that BEPD could promote type I interferon signaling and alleviate mitochondrial functional damage in VVC model rats, and BEPD-containing serum could play the same role in vitro.</div></div><div><h3>Conclusion</h3><div>The study findings generally demonstrated that BEPD could improve the inflammation and correct the immune imbalance in VVC through regulation of type I interferon signaling and mitochondrial function.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119292"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895002","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}
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Journal of ethnopharmacology
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