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Shenling Baizhu San improves spermatogenic dysfunction in hyperuricemia mice by regulating Sirt3/Nrf2 to inhibit testicular ferroptosis 参苓白珠散通过调节Sirt3/Nrf2抑制睾丸铁下垂改善高尿酸血症小鼠生精功能障碍。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119310
Xiaocui Jiang , Xiaoming Yu , Zhongyi Zhu , Yinjuan Lyu , Xingyu Jiang , Zihao Liu , Jigang Cao , Min Xiao

Ethnopharmacological relevance

The effect of hyperuricemia (HUA) on testicular spermatogenesis cannot be ignored. The classical Chinese medicine compound Shenling Baizhu San (SLBZS) can reduce uric acid and improve testicular spermatogenesis, while researchers have not well explored the related pathology and pharmacodynamic mechanism have.

Aims of study

To investigate whether the dysfunction of testicular spermatogenesis caused by HUA and the therapeutic effect of SLBZS are related to testicular cell ferroptosis.

Materials and methods

C57BL/6 mice and C57BL/6 background Sirt3−/− mice were induced by oxazinate potassium (OXO), and HUA spermatogenic dysfunction mice model were constructed and treated with SLBZS. Sperm quality detection and testicular histopathology served for evaluating the protective mechanism of SLBZS against testicular spermatogenesis in HUA mice. Biochemical detection, transmission electron microscopy, immunohistochemistry and immunofluorescence were used to evaluate ferroptosis level of testicular cells. Western blot analysis assisted in verifying the expression of the corresponding pathway proteins.

Results

The testes of mice with HUA spermatogenic dysfunction were subjected to OXO-induced oxidative stress and ferroptosis, and the Sirt3/Nrf2 pathway-related protein expressions were changed. SLBZS improved the testes of mice with HUA spermatogenic dysfunction in terms of their spermatogenic function, oxidative stress and ferroptosis, and promoted Sirt3/Nrf2 antioxidant pathway-related proteins to be expressed. The analysis of Sirt3−/− mice was modeled and dosed, and it was found that SLBZS could not improve the spermatogenic function, oxidative stress and ferroptosis of Sirt3-deficient model mice’ testes.

Conclusions

OXO-induced spermatogenic dysfunction in HUA is associated with ferroptosis of testicular cells. SLBZS can be used for treating spermatogenic dysfunction in HUA possibly by activating Sirt3/Nrf2 signaling pathway, which inhibits ferroptosis due to oxidative stress.
民族药理学相关性:高尿酸血症(HUA)对睾丸精子发生的影响不容忽视。中药复方参苓白珠散(SLBZS)具有降低尿酸、促进睾丸精子发生的作用,但其相关病理和药效学机制尚未得到很好的探讨。研究目的:探讨HUA所致的睾丸生精功能障碍及SLBZS的治疗效果是否与睾丸细胞铁下垂有关。材料与方法:采用恶嗪酸钾(OXO)诱导C57BL/6小鼠和C57BL/6背景Sirt3-/-小鼠,建立HUA生精功能障碍小鼠模型并给予SLBZS处理。通过精子质量检测和睾丸组织病理学来评价SLBZS对HUA小鼠睾丸精子发生的保护机制。采用生化检测、透射电镜、免疫组织化学、免疫荧光法检测睾丸细胞铁下垂程度。Western blot分析有助于验证相应途径蛋白的表达。结果:HUA生精功能障碍小鼠睾丸发生氧化应激和铁凋亡,Sirt3/Nrf2通路相关蛋白表达发生改变。SLBZS可改善HUA生精功能障碍小鼠睾丸的生精功能、氧化应激和铁凋亡,促进Sirt3/Nrf2抗氧化途径相关蛋白的表达。对Sirt3-/-小鼠进行建模和给药分析,发现SLBZS不能改善Sirt3缺失模型小鼠的睾丸生精功能、氧化应激和铁下沉。结论:氧合氧诱导的HUA患者生精功能障碍与睾丸细胞铁下垂有关。SLBZS可能通过激活Sirt3/Nrf2信号通路,抑制氧化应激引起的铁凋亡,从而治疗HUA的生精功能障碍。
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引用次数: 0
Corrigendum to "The extract from Hyssopus cuspidatus Boriss. Prevents bronchial airway remodeling by inhibiting mouse bronchial wall thickening and hASMC proliferation and migration" [J. Ethnopharmacol. 303 (2023) 116047]. “牛耳草提取物”的勘误表。通过抑制小鼠支气管壁增厚和hASMC增殖和迁移,防止支气管气道重塑”[J]。中国药理学杂志,2009(5):387 - 398。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 Epub Date: 2025-01-09 DOI: 10.1016/j.jep.2024.119280
Xiaocui Cai, Yan Mao, Xiaoli Shen, Haifang Li, Jinhua He, Mingjun Zhang
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引用次数: 0
Evaluation of the sedative-hypnotic effects of Menyanthes trifoliata L. extract in mice 三叶草提取物对小鼠镇静催眠作用的评价。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119227
Ranran Gong , Haizhou Jiang , Jin Hu , Guohua Liu , Lingxiao Gao , Qingwen Zhang , Yutong Wei , Changan Geng , Shanshan Wei

Ethnopharmacological relevance

Insomnia is a pervasive and prominent problem worldwide, afflicting approximately one-third of the population and profoundly affecting patients' quality of life. Efficient and safe sedative-hypnotic medications are required. Menyanthes trifoliata L. (Mt), a sleeping herb in China, is used as a hypnotic remedy in ethnomedicines; however, there are few studies on this herb.

Aim of the study

We systematically evaluated the potential of Mt as a sedative-hypnotic candidate.

Materials and methods

The chemical constituents of the Mt extract were analyzed by lLiquid chromatography with photodiode array detection and mass spectrometry (LC-PDA-MS). The sedative-hypnotic effects of Mt extract (0.5, 2, and 4 g/kg) were investigated using the pentobarbital-induced sleep test (PIST), the caffeine-induced insomnia model (CIIM), and the open field test (OFT). Furthermore, the effect of Mt on sleep architecture was ‌investigated using electroencephalography/electromyography (EEG/EMG). The safety of the Mt extract was evaluated using the maximum tolerated dose method.

Results

Fifteen phenolic compounds were identified based on their UV absorption and MS fragmentation using LC-PDA-MS analysis. In the CIIM, PIST, and OFT, Mt extract exhibited a dose-dependent reduction in sleep latency, an extension of total sleep duration, and a decrease in locomotor activity. Moreover, it increased the duration of non-rapid eye movement (NREM) sleep and reduced wakefulness after one day's administration, according to EEG/EMG. Additionally, no signs of toxicity were observed at a dose of 30 g/kg (equivalent to 316.46 g/kg of crude drugs).

Conclusion

This study supports the potential medicinal use of Mt extract for sleep promotion.
民族药理学相关性:失眠是世界范围内普遍存在的突出问题,折磨着大约三分之一的人口,深刻地影响着患者的生活质量。需要有效和安全的镇静催眠药物。三叶Menyanthes trifoliata L (Mt)是中国的一种睡眠草本植物,在民族医学中被用作催眠药物;然而,关于这种草药的研究很少。研究目的:我们系统地评估了Mt作为镇静催眠候选药物的潜力。材料与方法:采用液相色谱-光电二极管阵列检测-质谱法(LC-PDA-MS)对Mt提取物的化学成分进行分析。采用戊巴比妥诱导睡眠实验(PIST)、咖啡因诱导失眠模型(CIIM)和开放场实验(OFT)研究了Mt提取物(0.5、2和4 g/kg)的镇静催眠作用。此外,利用脑电图/肌电图(EEG/EMG)研究了Mt对睡眠结构的影响。采用最大耐受剂量法评价Mt提取物的安全性。结果:采用LC-PDA-MS分析,通过紫外吸收和质谱破碎鉴定出15种酚类化合物。在CIIM, ist和OFT中,Mt提取物显示出剂量依赖性的睡眠潜伏期减少,总睡眠时间延长,运动活动减少。此外,根据脑电图/肌电图,服用一天后,它增加了非快速眼动睡眠(NREM)的持续时间,减少了清醒时间。此外,在剂量为30 g/kg(相当于316.46 g/kg生药)时未观察到毒性迹象。结论:本研究支持山麻提取物促进睡眠的潜在药用价值。
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引用次数: 0
6-Shogaol attenuates cisplatin induced emesis by inhibiting the mtDNA-cGAS-STING signaling pathway in a rat pica model 6-shogaol通过抑制异食癖大鼠mtDNA-cGAS-STING信号通路减轻顺铂诱导的呕吐。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119251
Shaojun Kan , Binbin Ye , Yusu Wang, Ziyao Mo, Weijian Chen, Jingrui Zheng, Yarong Zhai, Ke Nie

Ethnopharmacological relevance

Ginger (Zingiber officinale Rosc.) is a traditional anti-emetic herb. 6-shogaol, the main active compound of ginger, is reported to possess a variety of bioactivities.

Aims of the study

This study aimed to investigate the anti-emetic effect of 6-shogaol in a cisplatin-induced pica rat model and explore its underlying mechanism.

Materials and methods

The rat pica model was established by intraperitoneal injection of cisplatin. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum 8-Hydroxy-desoxyguanosine (8-OHdG) were detected by ELISA. The expression of ZO1 tight junction protein (TJP-1) and occludin in ileum were determined by IHC. The levels of 8-oxo G DNA glycosylase 1 (OGG1), flap endonuclease 1 (FEN1), cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), phospho-STING (p-STING), TANK binding kinase 1 (TBK1), phospho-TBK1 (pTBK1), nuclear factor kappa-B (NF-κB) and phospho-NF-κB (p-NF-κB) in gastric antrum and ileum were assayed by western blotting.

Results

We found that 6-shogaol significantly improved pica behavior in rats by downregulating NF-κB and IL-1β level, and ameliorating inflammatory damage in gastric antrum and ileum. Mechanistically, cGAS-STING axis activated by mtDNA is responsible for the cisplatin-induced gastrointestinal inflammatory responses. 6-Shogaol inhibited the mtDNA-cGAS-STING signaling pathway by increasing the level of base-excision repair enzyme OGG1 and decreasing the level of endonuclease FEN1.

Conclusions

This study indicates that 6-shogaol has a therapeutic effect against chemotherapy-induced nausea and vomiting (CINV), potentially attributable to the suppression of the mtDNA-cGAS-STING signaling pathway.
民族药理学相关性:生姜(Zingiber officinale Rosc.)是一种传统的止吐草药。6-酚是生姜的主要活性成分,具有多种生物活性。研究目的:本研究旨在观察6-shogaol对顺铂诱导异食癖大鼠模型的止吐作用,并探讨其机制。材料与方法:采用顺铂腹腔注射法建立大鼠异食癖模型。苏木精-伊红染色观察大鼠胃窦和回肠的病理损伤。ELISA法检测血清8-羟基去氧鸟苷(8-OHdG)水平。采用免疫组化法检测回肠ZO1紧密连接蛋白(TJP-1)和occludin的表达。western blotting检测胃窦和回肠组织中8-oxo G DNA糖基酶1 (OGG1)、皮瓣核酸内切酶1 (FEN1)、环GMP-AMP合成酶(cGAS)、干扰素基因刺激因子(STING)、磷酸化-STING (p-STING)、TANK结合激酶1 (TBK1)、磷酸化-TBK1 (pTBK1)、核因子κ b (NF-κB)和磷酸化-NF-κB (p-NF-κB)的水平。结果:我们发现6-shogaol通过下调NF-κB和IL-1β水平,改善胃窦和回肠炎症损伤,显著改善异食癖大鼠行为。机制上,由mtDNA激活的cGAS-STING轴负责顺铂诱导的胃肠道炎症反应。6-Shogaol通过提高碱基切除修复酶OGG1水平和降低内切酶FEN1水平抑制mtDNA-cGAS-STING信号通路。结论:本研究提示6-shogaol对化疗诱导的恶心呕吐(CINV)具有治疗作用,可能与抑制mtDNA-cGAS-STING信号通路有关。
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引用次数: 0
Centipeda minima extracts and the active sesquiterpene lactones have therapeutic efficacy in non-small cell lung cancer by suppressing Skp2/p27 signaling pathway 蜈蚣草提取物及其活性倍半萜内酯通过抑制Skp2/p27信号通路对非小细胞肺癌有治疗作用。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119277
Han-Chen Wang , Pei-En Wu , Wen-Da He , Chu-Ying Chen , Rou-Qiao Zheng , Yan-Chun Pang , Li-Chuan Wu , Yong-Xian Cheng , Yong-Qiang Liu

Ethnophamacological relevance

Centipeda minima (L.) A. Braun & Asch (C. minima) was applied to treat nasal allergy, headache, cough, and even nasopharyngeal carcinoma in traditional Chinese medicine. However, the underlying anticancer mechanisms of C. minima and its active components have not been systematically illustrated.

Aim of the study

The study aims to examine the therapeutic efficacy of the ethanol extract of C. minima (ECM) and its active components in non-small cell lung cancer (NSCLC) and illustrate the underlying mechanisms.

Materials and methods

The main chemical components in the ethanol extract of C. minima (ECM) and the supercritical CO2 fluid extract of C. minima (CM-SFE) were determined by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The antitumor effects of ECM and CM-SFE were examined by using NSCLC cell xenografts. The flow cytometry, cell colony formation, wound-healing, transwell assay, and Western blotting were conducted to investigate the anticancer properties of ECM, CM-SFE, and these sesquiterpene lactones that abundantly distributed in these extracts.

Results

We first determined that ECM contains high levels of sesquiterpene lactones. ECM can markedly induce cell cycle arrest and suppress migration and invasion of NSCLC cells. Mechanistically, ECM promoted proteasome-dependent degradation of Skp2 protein and induced the accumulation of its substrates p27; whereas Skp2 overexpression can attenuate the inhibitory effects of ECM on NSCLC proliferation and migration. Moreover, ECM at 200–600 mg/kg can significantly inhibit tumor growth and metastasis in A549-luciferase cell orthotopic xenografts by suppressing Skp2 expression. The sesquiterpene lactones that abundantly distributed in ECM, including 6-O-angeloylplenolin (6-OAP), arnicolide D (ArD) and arnicolide C (ArC), were also demonstrated to decrease Skp2 while increase p27 protein level, thereby significantly inducing cell cycle arrest and suppressing migration of NSCLC cells. Notably, CM-SFE, which mainly consisted of 6-OAP, ArD and ArC, exhibited much stronger anti-NSCLC activity than that of ECM in A549-luciferase cell orthotopic xenografts.

Conclusion

Our results demonstrate that the active components in C. minima possesses potential anti-NSCLC activities by suppressing Skp2/p27 signaling pathway, and these active sesquiterpene lactones can be further developed as potent Skp2 inhibitor to treat NSCLC.
民族药理学相关性:蜈蚣(L.)A. Braun & Asch (C. minima)在中医中用于治疗鼻过敏、头痛、咳嗽甚至鼻咽癌。然而,其潜在的抗癌机制及其有效成分尚未被系统地阐明。研究目的:本研究旨在探讨小草草乙醇提取物(ECM)及其有效成分对非小细胞肺癌(NSCLC)的治疗作用,并阐明其作用机制。材料与方法:采用超高效液相色谱-质谱联用技术(UPLC-MS)测定了小红花乙醇提取物(ECM)和超临界CO2流体提取物(CM-SFE)的主要化学成分。采用非小细胞肺癌细胞异种移植检测ECM和CM-SFE的抗肿瘤作用。通过流式细胞术、细胞集落形成、伤口愈合、transwell实验和Western blotting检测ECM、CM-SFE和这些提取物中丰富分布的倍半萜内酯的抗癌特性。结果:我们首先确定ECM含有高水平的倍半萜内酯。ECM能显著诱导细胞周期阻滞,抑制非小细胞肺癌细胞的迁移和侵袭。机制上,ECM促进蛋白酶体依赖性的Skp2蛋白降解并诱导其底物p27的积累;而Skp2过表达可以减弱ECM对NSCLC增殖和迁移的抑制作用。此外,200-600 mg/kg的ECM可以通过抑制Skp2的表达,显著抑制a549 -荧光素酶细胞原位异种移植物的肿瘤生长和转移。大量分布在ECM中的倍半萜内酯,包括6-O-angeloylplenolin (6-OAP)、arnicolide D (ArD)和arnicolide C (ArC),也被证明可以降低Skp2,提高p27蛋白水平,从而显著诱导细胞周期阻滞和抑制NSCLC细胞迁移。值得注意的是,CM-SFE主要由6-OAP、ArD和ArC组成,在a549荧光素酶细胞原位异种移植物中表现出比ECM更强的抗nsclc活性。结论:我们的研究结果表明,C. minima的活性成分通过抑制Skp2/p27信号通路具有潜在的抗NSCLC活性,这些活性倍半萜内酯可以进一步开发为有效的Skp2抑制剂治疗NSCLC。
{"title":"Centipeda minima extracts and the active sesquiterpene lactones have therapeutic efficacy in non-small cell lung cancer by suppressing Skp2/p27 signaling pathway","authors":"Han-Chen Wang ,&nbsp;Pei-En Wu ,&nbsp;Wen-Da He ,&nbsp;Chu-Ying Chen ,&nbsp;Rou-Qiao Zheng ,&nbsp;Yan-Chun Pang ,&nbsp;Li-Chuan Wu ,&nbsp;Yong-Xian Cheng ,&nbsp;Yong-Qiang Liu","doi":"10.1016/j.jep.2024.119277","DOIUrl":"10.1016/j.jep.2024.119277","url":null,"abstract":"<div><h3>Ethnophamacological relevance</h3><div><em>Centipeda minima</em> (L.) A. Braun &amp; Asch (<em>C. minima</em>) was applied to treat nasal allergy, headache, cough, and even nasopharyngeal carcinoma in traditional Chinese medicine. However, the underlying anticancer mechanisms of <em>C. minima</em> and its active components have not been systematically illustrated.</div></div><div><h3>Aim of the study</h3><div>The study aims to examine the therapeutic efficacy of the ethanol extract of <em>C. minima</em> (ECM) and its active components in non-small cell lung cancer (NSCLC) and illustrate the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>The main chemical components in the ethanol extract of <em>C. minima</em> (ECM) and the supercritical CO<sub>2</sub> fluid extract of <em>C. minima</em> (CM-SFE) were determined by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The antitumor effects of ECM and CM-SFE were examined by using NSCLC cell xenografts. The flow cytometry, cell colony formation, wound-healing, transwell assay, and Western blotting were conducted to investigate the anticancer properties of ECM, CM-SFE, and these sesquiterpene lactones that abundantly distributed in these extracts.</div></div><div><h3>Results</h3><div>We first determined that ECM contains high levels of sesquiterpene lactones. ECM can markedly induce cell cycle arrest and suppress migration and invasion of NSCLC cells. Mechanistically, ECM promoted proteasome-dependent degradation of Skp2 protein and induced the accumulation of its substrates p27; whereas Skp2 overexpression can attenuate the inhibitory effects of ECM on NSCLC proliferation and migration. Moreover, ECM at 200–600 mg/kg can significantly inhibit tumor growth and metastasis in A549-luciferase cell orthotopic xenografts by suppressing Skp2 expression. The sesquiterpene lactones that abundantly distributed in ECM, including 6-<em>O</em>-angeloylplenolin (6-OAP), arnicolide D (ArD) and arnicolide C (ArC), were also demonstrated to decrease Skp2 while increase p27 protein level, thereby significantly inducing cell cycle arrest and suppressing migration of NSCLC cells. Notably, CM-SFE, which mainly consisted of 6-OAP, ArD and ArC, exhibited much stronger anti-NSCLC activity than that of ECM in A549-luciferase cell orthotopic xenografts.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that the active components in <em>C. minima</em> possesses potential anti-NSCLC activities by suppressing Skp2/p27 signaling pathway, and these active sesquiterpene lactones can be further developed as potent Skp2 inhibitor to treat NSCLC.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119277"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895007","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
Network pharmacology, transcriptomics, and biological validation reveal a lipid secretion inhibitory and anti-inflammatory mechanism of tanreqing gel in the treatment of acne 网络药理学、转录组学和生物学验证揭示了痰热清凝胶治疗痤疮的脂质分泌抑制和抗炎机制。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119278
Xing Ren , Na Zhou , Dongying Li , Lu Li , Yunong Wang , Lishuang Li , Yuman Ma , Xinyu Gao , Yujia Zhao , Yanan Sun , Yi Wang

Ethnopharmacological relevance

Acne vulgaris is a common skin disease affecting the pilosebaceous unit, in which abnormal sebum secretion and inflammation play crucial roles. The traditional Chinese medicine Tanreqing has been utilized in dermatology to effectively treat various diseases. However, its effects and underlying mechanisms in acne vulgaris remain unclear.

Aim of the study

This study aims to assess the potential benefits of Tanreqing gel (TRQ) in acne treatment and to explore the mechanisms by which TRQ inhibits sebum secretion and reduces inflammation.

Materials and methods

A mouse model of acne induced by Cutibacterium acnes (C. acnes) was established. The impact of TRQ on acne lesions was assessed using optical imaging and histopathology. Network pharmacology and transcriptomics were used to identify significant intervention pathways and targets. Both in vivo and in vitro experiments were conducted to detect the expression of genes and proteins associated with inflammation and sebum metabolism.

Results

TRQ significantly improved pathological changes in the lesion areas of mice, such as redness, vascular dilation, and increased blood flow. It also reduced inflammatory cell infiltration in the dermis and inhibited the accumulation of lipids in the sebaceous glands. Network pharmacology analysis indicated that TRQ might exert anti-inflammatory effects through the IL-17, TOLL-like receptor, and NF-κB signaling pathways. The transcriptomic analysis confirmed the importance of these pathways in the C. acnes-induced acne model. Furthermore, TRQ was found to reduce sebum secretion by inhibiting fatty acid biosynthesis through the suppression of proteins in the PI3K-Akt signaling pathway. Cell experiments confirmed that TRQ could suppress the release of inflammatory factors induced by C. acnes surface structure peptidoglycan (PGN) and metabolite porphyrins. Additionally, it was observed to reverse the elevated porphyrin secretion associated with abnormal sebum production, ultimately relieving acne inflammation.

Conclusion

This study demonstrated that TRQ effectively alleviates C. acnes-induced acne symptoms by inhibiting sebum secretion and inflammatory responses through multiple pathways and targets. It provides new insights and directions for acne treatment.
民族药理学相关性:寻常痤疮是一种影响毛囊皮脂腺单位的常见皮肤病,其中皮脂分泌异常和炎症起关键作用。中药痰热清已被用于皮肤科有效治疗各种疾病。然而,其在寻常性痤疮中的作用和潜在机制尚不清楚。研究目的:本研究旨在评估痰热清凝胶(TRQ)治疗痤疮的潜在益处,并探讨TRQ抑制皮脂分泌和减轻炎症的机制。材料与方法:建立痤疮角质杆菌(C. acnes)致小鼠痤疮模型。通过光学成像和组织病理学评估TRQ对痤疮病变的影响。网络药理学和转录组学用于识别重要的干预途径和靶点。通过体内和体外实验检测与炎症和皮脂代谢相关的基因和蛋白质的表达。结果:TRQ显著改善小鼠病变区域的病理改变,如红肿、血管扩张、血流量增加。它还减少了真皮中炎症细胞的浸润,抑制了皮脂腺中脂质的积累。网络药理学分析表明,TRQ可能通过IL-17、toll样受体和NF-κB信号通路发挥抗炎作用。转录组学分析证实了这些途径在C.痤疮诱导的痤疮模型中的重要性。此外,研究发现TRQ通过抑制PI3K-Akt信号通路中的蛋白质抑制脂肪酸生物合成,从而减少皮脂分泌。细胞实验证实,TRQ可以抑制痤疮C.表面结构肽聚糖(PGN)和代谢产物卟啉诱导的炎症因子的释放。此外,观察到它可以逆转与异常皮脂产生相关的卟啉分泌升高,最终缓解痤疮炎症。结论:本研究表明,TRQ可通过多种途径和靶点抑制皮脂分泌和炎症反应,有效缓解C. acne诱导的痤疮症状。它为痤疮治疗提供了新的见解和方向。
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引用次数: 0
Pharmacodynamic material basis of licorice and mechanisms of modulating bile acid metabolism and gut microbiota in cisplatin-induced liver injury based on LC-MS and network pharmacology analysis 基于 LC-MS 和网络药理学分析的甘草的药效物质基础以及调节顺铂诱导肝损伤中胆汁酸代谢和肠道微生物群的机制
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119293
Jie Li , Xiaolong Lian , Baojian Li , Quhuan Ma , Lingling Yang , Guangmiao Gao , Tingmei Yin , Xiaoyan Fu , Yi Deng , Zhijun Yang , Xiujuan Yang

Ethnopharmacological relevance

Cisplatin (CP), a widely used antineoplastic agent, is a leading cause of drug-induced liver injury (DILI) due to its hepatotoxic effects. Licorice (GC), an established remedy in traditional Chinese medicine (TCM), has shown promise in addressing liver diseases and DILI. Nonetheless, the specific active components and underlying mechanisms of GC in mitigating CP-induced liver injury remain inadequately investigated.

Aim of the study

This study examined the active components and efficacy of GC in addressing CP-induced hepatotoxicity, focusing on its mechanisms related to bile acid metabolism and gut microbiota regulation.

Materials and methods

Utilizing a CP-induced rat liver injury model, this study evaluated changes in liver coefficient, liver function indices, and pathological morphology while assessing the efficacy of GC for both prevention and treatment of CP-induced liver injury. Subsequently, UPLC-Q-TOF-MS qualitatively analyzed GC's blood-entering components, elucidating its pharmacodynamic material basis. Network pharmacology analysis identified potential pathways and targets of GC's blood components in relation to CP-induced liver injury. Furthermore, metabolomics and 16S rRNA sequencing were employed to clarify the pharmacodynamic mechanisms of GC in modulating bile acid metabolism and gut microbiota, offering insights into its preventive and therapeutic roles.

Results

The pharmacodynamic results revealed that GC significantly reduced liver function biomarkers and improved pathological changes in liver tissue. UPLC-Q-TOF-MS analysis identified 16 blood-entering components as potential pharmacodynamic agents of GC for preventing and treating CP-induced liver injury. Network pharmacology analysis suggested a link between GC's efficacy and the bile acid metabolic pathway. Furthermore, metabolomics analysis, immunoblotting, and 16S rRNA sequencing demonstrated that GC regulated bile acid metabolites in both liver and feces, enhanced FXR and BSEP expressions in the liver, and decreased CYP27A1 expression. Additionally, GC mitigated CP-induced intestinal dysbiosis by altering the abundance of gut microbiota.

Conclusions

UPLC-Q-TOF-MS performed a qualitative analysis of 16 blood-entering components linked to GC, providing a basis for further exploration of the pharmacodynamic material underpinning GC. The protective role of GC in CP-induced liver injury appears connected to enhanced bile acid metabolism and restoration of gut microbiota balance.
民族药理学相关性:顺铂(CP)是一种广泛使用的抗肿瘤药物,由于其肝毒性作用而成为药物性肝损伤(DILI)的主要原因。甘草(GC)是一种成熟的中药,在治疗肝脏疾病和DILI方面显示出希望。尽管如此,GC减轻cp诱导的肝损伤的具体活性成分和潜在机制仍未得到充分研究。研究目的:本研究考察了GC的有效成分及其对cp肝毒性的治疗作用,重点探讨了其与胆汁酸代谢和肠道菌群调节相关的机制。材料和方法:本研究利用cp诱导的大鼠肝损伤模型,在评估GC预防和治疗cp诱导的肝损伤的作用的同时,评估肝系数、肝功能指标和病理形态学的变化。随后,UPLC-Q-TOF-MS对GC的入血成分进行定性分析,阐明其药效学物质基础。网络药理学分析确定了GC血液成分与cp诱导肝损伤相关的潜在途径和靶点。此外,通过代谢组学和16S rRNA测序,阐明了GC调节胆汁酸代谢和肠道微生物群的药效学机制,为其预防和治疗作用提供了新的思路。结果:药效学结果显示,GC可显著降低肝功能生物标志物,改善肝组织病理改变。UPLC-Q-TOF-MS分析鉴定出16种进入血液成分为GC预防和治疗cp诱导的肝损伤的潜在药效学因子。网络药理学分析表明,GC的功效与胆汁酸代谢途径有关。此外,代谢组学分析、免疫印迹和16S rRNA测序表明,GC调节肝脏和粪便中的胆汁酸代谢物,增强肝脏中FXR和BSEP的表达,降低CYP27A1的表达。此外,GC通过改变肠道菌群的丰度来减轻cp诱导的肠道生态失调。结论:UPLC-Q-TOF-MS对16种与气相色谱相关的入血成分进行了定性分析,为进一步探索气相色谱的药效学基础物质提供了基础。GC在cp诱导的肝损伤中的保护作用似乎与增强胆汁酸代谢和恢复肠道菌群平衡有关。
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引用次数: 0
Astragali Radix-Angelicae Sinensis Radix inhibits the activation of vascular adventitial fibroblasts and vascular intimal proliferation by regulating the TGF-β1/Smad2/3 pathway 黄芪-当归通过调节TGF-β1/Smad2/3通路抑制血管外膜成纤维细胞的活化和血管内膜增殖。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119302
Wanyu Li , Shunzhou Xu , Lingbo Chen , Wei Tan , Nujiao Deng , Yanling Li , Wei Zhang , Changqing Deng
<div><h3>Ethnopharmacological relevance</h3><div>Astragali Radix-Angelicae Sinensis Radix is an important traditional Chinese medicine used for the treatment of cardiovascular diseases. Our previous studies have shown that Astragali Radix-Angelicae Sinensis Radix can inhibit vascular intimal hyperplasia and improve the blood vessel wall's ECM deposition, among which six main active components can be absorbed into the blood, suggesting that these components may be the main pharmacodynamic substances of Astragali Radix-Angelicae Sinensis Radix against vascular intimal hyperplasia.</div></div><div><h3>Aim of the study</h3><div>A mouse model of atherosclerosis was used to study the relationship between the anti-intimal hyperplasia effect of Astragali Radix-Angelicae Sinensis Radix and the inhibition of VAF activation and ECM synthesis. Furthermore, an <em>in vitro</em> rat VAF activation model was used. The effects of the main active ingredients of Astragali Radix-Angelicae Sinensis Radix on the proliferation, migration and ECM synthesis of VAF were observed. The mechanism of its action was investigated by focusing on TGF-β1/Smads signaling pathway.</div></div><div><h3>Materials and methods</h3><div>Male ApoE<sup>−/−</sup> mice were used to establish an AS model. Observe the morphological changes of blood vessels, the expression of Vimentin, α-SMA, ECM-related factors and TGF-β1/Smads signaling pathway-related proteins. Ang Ⅱ was used to induce the VAF activation model. The cell activity, cell proliferation, cell migration, cell phenotypic markers, ECM-related factors, cell cycle regulation-related proteins and TGF-β1/Smads signaling pathway-related proteins were determined. On this basis, TGF-β1/Smads signaling pathway agonists and inhibitors were used to study the effects of the compatibility of six active components on TGF-β1/Smads signaling pathway.</div></div><div><h3>Results</h3><div>Astragali Radix-Angelicae Sinensis Radix can reduce aortic intimal hyperplasia, inhibit the expression of aortic α-SMA, Vimentin, ECM components, TGF-β1, p-Samd2 and p-Samd3. Cell experiments showed that the six active ingredients could inhibit the proliferation and migration of VAF to varying degrees, inhibit the expression of α-SMA, cell cycle promoters, ECM components, up-regulate the expression of Vimentin, P21, MMP2 and MMP9. The above effects were enhanced after the combination of the six components. The 6 components and their combinations could inhibit the expression of TGF-β1/Smads signaling pathway-related proteins and up-regulate the expression of Samd7 to varying degrees. The above effects were enhanced after the combination of the 6 components. TGF-β1/Smads signaling pathway inhibitor LY2157299 showed similar effects with the six components. The inhibitory effects of the six active ingredients on TGF-β1/Smads signaling pathway-related proteins and the promotion of Smad7 expression were attenuated when agonists were added into the six active ingredient c
民族药理学相关性:黄芪-当归是治疗心血管疾病的重要中药。我们前期研究表明,黄芪可抑制血管内膜增生,改善血管壁ECM沉积,其中6种主要活性成分可被血液吸收,提示这些成分可能是黄芪抗血管内膜增生的主要药效物质。研究目的:采用小鼠动脉粥样硬化模型,研究黄芪-当归抗内膜增生作用与抑制VAF激活和ECM合成的关系。此外,采用体外大鼠VAF激活模型。观察了黄芪-当归主要活性成分对VAF增殖、迁移及ECM合成的影响。重点从TGF-β1/Smads信号通路探讨其作用机制。材料与方法:采用ApoE-/-雄性小鼠建立AS模型。观察血管形态学变化,观察Vimentin、α-SMA、ecm相关因子及TGF-β1/Smads信号通路相关蛋白的表达。AngⅡ诱导VAF激活模型。检测细胞活性、细胞增殖、细胞迁移、细胞表型标志物、ecm相关因子、细胞周期调节相关蛋白、TGF-β1/Smads信号通路相关蛋白。在此基础上,利用TGF-β1/Smads信号通路激动剂和抑制剂,研究六种活性成分的相容性对TGF-β1/Smads信号通路的影响。结果:黄芪、当归均能减轻主动脉内膜增生,抑制主动脉α-SMA、Vimentin、ECM成分、TGF-β1、p-Samd2、p-Samd3的表达。细胞实验表明,6种活性成分均能不同程度抑制VAF的增殖和迁移,抑制α-SMA、细胞周期启动子、ECM成分的表达,上调Vimentin、P21、MMP2和MMP9的表达。六组分合用后,上述效果增强。6种成分及其组合均能不同程度抑制TGF-β1/Smads信号通路相关蛋白的表达,上调Samd7的表达。6种成分联用后,上述效果均有增强。TGF-β1/Smads信号通路抑制剂LY2157299与这六种成分的作用相似。在6种活性成分组合中加入激动剂后,6种活性成分对TGF-β1/Smads信号通路相关蛋白的抑制作用和对Smad7表达的促进作用减弱。然而,在6种有效成分组合中加入tgf - β1/Smads信号通路抑制剂EGF对上述效果没有影响。结论:黄芪、当归对动脉粥样硬化的内膜增生、VAF激活及ECM合成有抑制作用。这6种活性成分可能是黄芪-当归抑制VAF激活的主要药理物质,6种成分联用可增强其作用,其作用机制可能是通过抑制TGF-β1/Smad2/3信号通路的激活来介导的。
{"title":"Astragali Radix-Angelicae Sinensis Radix inhibits the activation of vascular adventitial fibroblasts and vascular intimal proliferation by regulating the TGF-β1/Smad2/3 pathway","authors":"Wanyu Li ,&nbsp;Shunzhou Xu ,&nbsp;Lingbo Chen ,&nbsp;Wei Tan ,&nbsp;Nujiao Deng ,&nbsp;Yanling Li ,&nbsp;Wei Zhang ,&nbsp;Changqing Deng","doi":"10.1016/j.jep.2024.119302","DOIUrl":"10.1016/j.jep.2024.119302","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Ethnopharmacological relevance&lt;/h3&gt;&lt;div&gt;Astragali Radix-Angelicae Sinensis Radix is an important traditional Chinese medicine used for the treatment of cardiovascular diseases. Our previous studies have shown that Astragali Radix-Angelicae Sinensis Radix can inhibit vascular intimal hyperplasia and improve the blood vessel wall's ECM deposition, among which six main active components can be absorbed into the blood, suggesting that these components may be the main pharmacodynamic substances of Astragali Radix-Angelicae Sinensis Radix against vascular intimal hyperplasia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of the study&lt;/h3&gt;&lt;div&gt;A mouse model of atherosclerosis was used to study the relationship between the anti-intimal hyperplasia effect of Astragali Radix-Angelicae Sinensis Radix and the inhibition of VAF activation and ECM synthesis. Furthermore, an &lt;em&gt;in vitro&lt;/em&gt; rat VAF activation model was used. The effects of the main active ingredients of Astragali Radix-Angelicae Sinensis Radix on the proliferation, migration and ECM synthesis of VAF were observed. The mechanism of its action was investigated by focusing on TGF-β1/Smads signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Male ApoE&lt;sup&gt;−/−&lt;/sup&gt; mice were used to establish an AS model. Observe the morphological changes of blood vessels, the expression of Vimentin, α-SMA, ECM-related factors and TGF-β1/Smads signaling pathway-related proteins. Ang Ⅱ was used to induce the VAF activation model. The cell activity, cell proliferation, cell migration, cell phenotypic markers, ECM-related factors, cell cycle regulation-related proteins and TGF-β1/Smads signaling pathway-related proteins were determined. On this basis, TGF-β1/Smads signaling pathway agonists and inhibitors were used to study the effects of the compatibility of six active components on TGF-β1/Smads signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Astragali Radix-Angelicae Sinensis Radix can reduce aortic intimal hyperplasia, inhibit the expression of aortic α-SMA, Vimentin, ECM components, TGF-β1, p-Samd2 and p-Samd3. Cell experiments showed that the six active ingredients could inhibit the proliferation and migration of VAF to varying degrees, inhibit the expression of α-SMA, cell cycle promoters, ECM components, up-regulate the expression of Vimentin, P21, MMP2 and MMP9. The above effects were enhanced after the combination of the six components. The 6 components and their combinations could inhibit the expression of TGF-β1/Smads signaling pathway-related proteins and up-regulate the expression of Samd7 to varying degrees. The above effects were enhanced after the combination of the 6 components. TGF-β1/Smads signaling pathway inhibitor LY2157299 showed similar effects with the six components. The inhibitory effects of the six active ingredients on TGF-β1/Smads signaling pathway-related proteins and the promotion of Smad7 expression were attenuated when agonists were added into the six active ingredient c","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119302"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915110","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
Treatment of Qin Gui Wan (QGW) in PCOS abnormal oocytes development via AMPK/PGC-1ɑ pathway
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2025.119434
Xiaojuan Li , Yiwei Cui , Chuxin Zhang , Weiyu Zang, Yuli Cheng, Chenyu Yang, Shujing Zhang, Xue Yu, Lin Gao

Objectives

To investigate the therapeutic effects of Qin Gui Wan (QGW) and its disassembled functional drug groups, Wenyang Zhuhuo (WYZH) and Xinwen Zhuyang (XWZY), on letrozole-induced PCOS rats.

Methods

PCOS rat model was established by administering letrozole for 21 days. The rats were divided into control, PCOS, Diane-35, QGW, WYZH and XWZY groups. The changes of body weight, ovarian coefficient, estrous cycle and sex hormone levels were observed. The ovarian histological characteristics and ovulation were observed by HE staining. P450arom, SF-1, and AMPK/PGC-1ɑ pathway mRNA and protein expression were analyzed using qRT-PCR, WB, and IHC. The AMPK inhibitor Compound C (CC) was used to explore the treatment mechanism of QGW in granulosa cells. And UHPLC-MS/MS was used to performed chemical composition analysis.

Results

QGW, WYZH, and XWZY can correct the disordered estrous cycle of PCOS rats and improve the serum hormone status of rats to varying degrees. HE results indicated that QGW, WYZH, and XWZY improved ovarian polycystic changes and normalized ovulation. qRT-PCR, WB, and IHC results demonstrated that QGW, WYZH, and XWZY increased PGC-1α, SF-1, and P450arom mRNA and protein expression in the ovaries of PCOS rats. The level of AMPK mRNA in the ovaries of QGW and its disassembled prescriptions increased, while only WYZH and XWZY rats showed increased ovarian AMPK levels. CC attenuated the activation of AMPK, PGC-1α, SF-1, and P450arom mRNA by QGW.

Conclusions

This study demonstrates that QGW alleviates abnormal oocyte development in PCOS rats, possibly by enhancing P450arom expression via the AMPK/PGC-1α pathway, thus restoring normal androgen-estrogen balance and follicular development.
{"title":"Treatment of Qin Gui Wan (QGW) in PCOS abnormal oocytes development via AMPK/PGC-1ɑ pathway","authors":"Xiaojuan Li ,&nbsp;Yiwei Cui ,&nbsp;Chuxin Zhang ,&nbsp;Weiyu Zang,&nbsp;Yuli Cheng,&nbsp;Chenyu Yang,&nbsp;Shujing Zhang,&nbsp;Xue Yu,&nbsp;Lin Gao","doi":"10.1016/j.jep.2025.119434","DOIUrl":"10.1016/j.jep.2025.119434","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the therapeutic effects of <em>Qin Gui Wan</em> (QGW) and its disassembled functional drug groups, <em>Wenyang Zhuhuo</em> (WYZH) and <em>Xinwen Zhuyang</em> (XWZY), on letrozole-induced PCOS rats.</div></div><div><h3>Methods</h3><div>PCOS rat model was established by administering letrozole for 21 days. The rats were divided into control, PCOS, Diane-35, QGW, WYZH and XWZY groups. The changes of body weight, ovarian coefficient, estrous cycle and sex hormone levels were observed. The ovarian histological characteristics and ovulation were observed by HE staining. P450arom, SF-1, and AMPK/PGC-1ɑ pathway mRNA and protein expression were analyzed using qRT-PCR, WB, and IHC. The AMPK inhibitor Compound C (CC) was used to explore the treatment mechanism of QGW in granulosa cells. And UHPLC-MS/MS was used to performed chemical composition analysis.</div></div><div><h3>Results</h3><div>QGW, WYZH, and XWZY can correct the disordered estrous cycle of PCOS rats and improve the serum hormone status of rats to varying degrees. HE results indicated that QGW, WYZH, and XWZY improved ovarian polycystic changes and normalized ovulation. qRT-PCR, WB, and IHC results demonstrated that QGW, WYZH, and XWZY increased PGC-1α, SF-1, and P450arom mRNA and protein expression in the ovaries of PCOS rats. The level of AMPK mRNA in the ovaries of QGW and its disassembled prescriptions increased, while only WYZH and XWZY rats showed increased ovarian AMPK levels. CC attenuated the activation of AMPK, PGC-1α, SF-1, and P450arom mRNA by QGW.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that QGW alleviates abnormal oocyte development in PCOS rats, possibly by enhancing P450arom expression via the AMPK/PGC-1α pathway, thus restoring normal androgen-estrogen balance and follicular development.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"342 ","pages":"Article 119434"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080240","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
Unveiling potent bioactive compounds and anti-angiogenic pathways in Gekko swinhonis Guenther for gastric cancer therapy 揭示虎葛治疗胃癌的有效生物活性化合物和抗血管生成途径。
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-01-31 DOI: 10.1016/j.jep.2024.119156
Yu Zheng , Chang Lu , Yong Jiang , Nina Wei , Chenqi Chang , Weidong Li , Linwei Chen , Rui Chen , Zhipeng Chen

Ethnopharmacological relevance

Gekko swinhonis Guenther, commonly referred to as Gecko in the following text, belongs to the genus Gekko within the family Gekko. Its dried whole body is a widely utilized traditional Chinese medicine, demonstrating significant efficacy in the treatment of gastrointestinal malignancies, particularly gastric cancer (GC). Nevertheless, the composition of the gecko is complex, necessitating further research into its active ingredients for the treatment of GC.

Aim of the study

Isolation and characterization of the most active components in Gecko based on their anti-GC mechanisms of vascular endothelial cell inhibition and anti-neovascularization.

Materials and methods

We utilized the enzymatic hydrolysate of Geckos to investigate its effectiveness and underlying mechanisms. Initially, we assessed its efficacy in ectopic and in-situ GC tumor-bearing mouse models. Subsequently, we evaluated the effectiveness of peptides, aliphatics, and small molecules derived from Gecko using CCK-8 and 3D tumor spheroid assays. The activities of peptides S1-S4 were further examined through these experiments. Finally, we screened, synthesized, and investigated five potential peptides for their pharmacodynamics in the CCK-8 assay and in the in-situ GC model mice.

Results

The Gecko can inhibit the formation of blood vessels in the tumor microenvironment, providing a localized treatment for GC. The peptide components significantly inhibit vascular endothelial cells and impede the formation of new blood vessels, with the S2 peptide sections (0.3 KD - 3 KD) demonstrating the most potent inhibitory activity against angiogenesis. One of the active peptides effectively suppresses the growth of in-situ GC in nude mice through angiogenesis inhibition and also modulates immunity, all while exhibiting excellent biosafety.

Conclusions

We have achieved a significant breakthrough in the local treatment of GC using Gecko. Through pharmacodynamic experiments and a systematic process of isolation and identification, we identified the most effective anti-GC ingredients of Gecko, based on their mechanisms of inhibiting vascular endothelial cells and promoting anti-angiogenesis. Furthermore, we synthesized a lead peptide that demonstrates promising therapeutic efficacy and safety.
民族药理学相关性:壁虎(Gekko swinhonis Guenther),在下文中通常被称为壁虎,属于壁虎科中的壁虎属。其干全身是一种被广泛应用的中药,在治疗胃肠道恶性肿瘤,特别是胃癌(GC)方面具有显著的疗效。然而,壁虎的成分是复杂的,需要进一步研究其有效成分,以治疗气相色谱。目的:基于壁虎抗gc抑制血管内皮细胞和抗新生血管的机制,对壁虎中最有效的活性成分进行分离和鉴定。材料和方法:利用壁虎的酶解物研究其有效性和作用机制。首先,我们评估了其在异位和原位胃癌小鼠模型中的疗效。随后,我们使用CCK-8和3D肿瘤球体测定法评估了从壁虎中提取的肽、脂肪和小分子的有效性。通过这些实验进一步检测了肽S1-S4的活性。最后,我们在CCK-8实验和原位GC模型小鼠中筛选、合成并研究了5种潜在肽的药效学。结果:壁虎能抑制肿瘤微环境中血管的形成,为胃癌提供了一种局部治疗方法。肽组分显著抑制血管内皮细胞并阻碍新血管的形成,其中S2肽段(0.3 KD - 3kd)对血管生成的抑制活性最强。其中一种活性肽通过抑制血管生成有效抑制裸小鼠原位GC的生长,并调节免疫,同时具有良好的生物安全性。结论:我们在壁虎局部治疗胃癌方面取得了重大突破。通过药理学实验和系统的分离鉴定过程,我们根据其抑制血管内皮细胞和促进抗血管生成的机制,确定了壁虎中最有效的抗gc成分。此外,我们还合成了一种具有良好疗效和安全性的先导肽。
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引用次数: 0
期刊
Journal of ethnopharmacology
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