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Anti-inflammatory effects of orally and topically administered nanoformulations of Malva parviflora root extracts, and Prunus persica and Cupressus sempervirens exudates 口服和局部给药的小檗根提取物、桃李和柏树渗出物纳米制剂的抗炎作用
Pub Date : 2025-09-12 DOI: 10.1016/j.prmcm.2025.100685
Poloko Stephen Kheoane , Kingsley Chimaeze Mbara , Mosoatsi Lawrence Mputi , Ts’epo Arnold Lenkoe , Sebusiswe Magama , Mokonyana Mohale , Clemence Tarirai
<div><h3>Background</h3><div>Medicinal plants have been used traditionally as oral and topical herbs for treating inflammation and alleviating pain. Particularly in traditional Chinese medicine (TCM) practices, many plants from the genera <em>Malva, Prunus</em>, and <em>Cupressus</em> are used to treat various inflammation-related diseases. This study investigated <em>in vitro</em> and <em>in vivo</em> anti-inflammatory activity of the root extracts of <em>Malva parviflora</em>, the exudates of <em>Prunus persica, Cupressus sempervirens</em> and their chitosan nanoparticles and chitosan nanogels.</div></div><div><h3>Methods</h3><div><em>In vitro</em> anti-inflammatory activities of <em>M. parviflora</em> root extracts, <em>P. persica</em> and <em>C. sempervirens</em> exudates were investigated using the protein denaturation assay method. A 1% bovine albumin reaction mixture in phosphate buffer and 80% (v/v) methanol was incubated with plant extracts or exudates at 37 °C and 70 °C. Cross-linked chitosan nanoparticles loaded with plant extracts or exudates were prepared by the gelation method. The entrapment efficiency of the plants in the chitosan nanoformulation was estimated using the phenolic content of plant materials. The nanoparticles-based nanogel was formulated by suspending nanoparticles in a gel base. Inflammation was induced in Wistar rats (230 – 270 g) by subcutaneous injection of 0.1 mL of 1% (w/v) carrageenan in the plantar tissue of the right hind paw of the rats. The rats (<em>n</em> = 48) were randomly divided into two experimental groups (A and B) of 24 rats each for oral and topical administration of nanoformulations, respectively. Each group (<em>n</em> = 24) was subdivided into 6 test group (<em>n</em> = 4), where test groups 1, 2, and 3 were treated with 500 mg/kg/BW each of <em>M. parviflora, C. sempervirens</em>, and <em>P. persica</em> nanoparticle/nanogel, either orally or topically, respectively. Test groups 4, 5, and 6, respectively served as positive control, placebo nanoparticles (<em>i.e.</em>, chitosan nanoparticles), and negative control, treated orally or topically with indomethacin (50 mg/kg/BW), chitosan nanoparticle/nanogel alone (500 mg/kg/BW/100 mg/kg/BW), and saline (3 mL).</div></div><div><h3>Results</h3><div><em>P. persica</em> exudate had the highest TPC of 70.42 ± 0.53 µg of GAE/mg compared to <em>M. parviflora</em> root extract and <em>C. sempervirens</em> exudate with the 30.93 ± 1.65 µg of GAE/mg and 9.99 ± 0.65 µg of GAE/mg, respectively. <em>M. parviflora</em> root extracts had the highest <em>in vitro</em> protein denaturation (92.40%) compared to leaves and stem extracts. <em>P. persica</em> and <em>C. sempervirens</em> nanoparticles had the highest entrapment efficiencies (99.46% and 99.56%). <em>M. parviflora</em> root extract nanoparticles showed the greatest inhibition of oedema (90%) with oral administration, outperforming <em>P. persica</em> and <em>C. sempervirens</em> exudates nanoparticle
药用植物传统上被用作治疗炎症和减轻疼痛的口服和局部草药。特别是在传统中医(TCM)实践中,许多来自Malva, Prunus和柏树属的植物被用来治疗各种炎症相关疾病。研究了小檗根提取物、桃李、柏树渗出液及其壳聚糖纳米颗粒和壳聚糖纳米凝胶的体外和体内抗炎活性。方法采用蛋白变性法研究小檗根提取物、桃木根提取物和仙子根渗出液的体外抗炎活性。在磷酸盐缓冲液和80% (v/v)甲醇中,将1%牛白蛋白反应混合物与植物提取物或渗出液在37℃和70℃下孵育。采用凝胶法制备了负载植物提取物或渗出液的交联壳聚糖纳米颗粒。利用植物材料的酚类含量评价了壳聚糖纳米配方中植物的包封效率。将纳米颗粒悬浮在凝胶基中制备纳米颗粒基纳米凝胶。用1% (w/v)卡拉胶0.1 mL皮下注射于Wistar大鼠(230 ~ 270 g)右后爪足底组织诱导炎症反应。48只大鼠随机分为A、B两组,每组24只,分别口服和外用纳米制剂。每组(n = 24)再分为6个试验组(n = 4),其中试验组1、2、3分别口服或局部注射细枝假单胞菌、仙草假单胞菌和桃胶纳米颗粒/纳米凝胶各500 mg/kg/BW。试验4、5、6组分别作为阳性对照组、安慰剂纳米颗粒(即壳聚糖纳米颗粒)和阴性对照组,分别口服或外敷吲哚美辛(50 mg/kg/BW)、壳聚糖纳米颗粒/纳米凝胶(500 mg/kg/BW/100 mg/kg/BW)和生理盐水(3 mL)。桃仁挥发油的GAE含量最高,为70.42±0.53µg /mg,而小藤根挥发油的GAE含量为30.93±1.65µg /mg,仙子挥发油的GAE含量为9.99±0.65µg /mg。小檗根提取物的体外蛋白变性率最高,为92.40%,高于茎和叶提取物。桃红和仙桃纳米颗粒的捕集效率最高,分别为99.46%和99.56%。口服枇杷根提取物纳米颗粒对水肿的抑制作用最大(90%),优于木犀草和仙丹渗出纳米颗粒(均为87%)。在24 h后,小檗、桃树和金针梅纳米颗粒和安慰剂(壳聚糖)纳米颗粒的整体抗炎活性优于吲哚美辛。外用时,金针梅分泌物纳米凝胶对水肿的抑制作用最高,24 h后,安慰剂纳米凝胶的抑制作用优于其他植物纳米凝胶和吲哚美辛。结论药用植物纳米剂型的制备可有效治疗炎症。这一途径可以抵消药物对疾病迅速产生的耐药性以及与多种对抗药物的使用有关的一些副作用。建议使用甾体和非甾体抗炎对照进行进一步的体内研究。
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引用次数: 0
Targeting AMPK signaling: The therapeutic potential of berberine in diabetes and its complications 靶向AMPK信号:小檗碱在糖尿病及其并发症中的治疗潜力
Pub Date : 2025-09-12 DOI: 10.1016/j.prmcm.2025.100689
Kingsley Chimaeze Mbara , Poloko Stephen Kheoane , Clemence Tarirai
<div><h3>Introduction</h3><div>Berberine (黄连素, huáng lián sù) is a time-honored remedy in Traditional Chinese Medicine (TCM) that is found in various medicinal herbs and used to treat diabetes mellitus (DM), infections, diarrhea, and dysentery. Berberine, the major active component of <em>Coptidis rhizome</em> (黄连, huanglian), <em>Phellodendri cortex</em> (黄柏, huangbai), and <em>Mahoniae caulis</em> (亮叶十大功劳, Gong Lao Mu), exhibits several pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, cardioprotective, antineoplastic, antimicrobial, and antidiabetic effects. Antidiabetic effects of berberine are partly attributed to the activation of AMP-activated protein kinase (AMPK), which is a key mechanism and a potential treatment strategy for DM and its complications. This review discusses recent studies on the significant roles of berberine in activating AMPK for treating DM and its complications.</div></div><div><h3>Method</h3><div>We have comprehensively searched online databases like Scopus, PubMed, and Google Scholar for articles published in English between 2016 and 2025 using different permutations of these keywords: “Berberine”, “AMPK”, “Diabetes Mellitus”, “Diabetic nephropathy”, “Diabetic neuropathy”, “Diabetic retinopathy”, “Diabetic cardiomyopathy”, “Diabetic hepatic steatosis,” “Diabetic bone diseases”, “Diabetic atherosclerosis”, “Diabetic cognitive dysfunction”, “Diabetic lung injury” and “Other diabetic complications” to compile this narrative review. Out of 1750 initially retrieved articles, 183 were included based on their relevance to treating DM or its complications through the AMPK signaling pathway, pharmacokinetics, and translational potential. Non-English articles and studies not focused on AMPK activation by berberine and that did not address DM and its complications were excluded.</div></div><div><h3>Results</h3><div>The literature review found that berberine consistently activates AMPK across various preclinical studies of DM. The activation of AMPK is frequently mediated by pathways involving LKB1 and CAMKKβ. Berberine's activation of AMPK positively impacts glucose uptake, insulin sensitivity, lipid metabolism, oxidative stress, and inflammatory responses. Evidence from animal models demonstrated its efficacy in ameliorating complications such as diabetic nephropathy, neuropathy, retinopathy, cardiomyopathy, hepatic steatosis, bone diseases, atherosclerosis, cognitive dysfunction, and lung injury. Clinical trials reported significant reductions in fasting blood glucose (FBG), HbA1c, and lipid levels, with minimal side effects, at standard doses.</div></div><div><h3>Discussion</h3><div>AMPK activation by berberine plays a central role in cellular energy homeostasis, modulating key processes such as gluconeogenesis, lipogenesis, oxidative stress, and inflammation, which contribute to its therapeutic efficacy in metabolic dysfunction and DM-related complications. However, challenges remain re
小檗碱(黄连素,huáng lián sù)是一种历史悠久的中药(TCM)药物,存在于各种草药中,用于治疗糖尿病(DM),感染,腹泻和痢疾。小檗碱是黄连、黄柏和麻老木的主要活性成分,具有抗氧化、抗炎、抗细胞凋亡、保护心脏、抗肿瘤、抗菌和抗糖尿病等药理作用。小檗碱的降糖作用部分归因于amp活化蛋白激酶(AMPK)的激活,这是糖尿病及其并发症的关键机制和潜在治疗策略。本文综述了小檗碱在激活AMPK治疗糖尿病及其并发症中的重要作用。方法综合检索Scopus、PubMed、谷歌Scholar等在线数据库,检索2016 - 2025年期间发表的英文论文,对关键词进行不同排列:“小檗碱”、“AMPK”、“糖尿病”、“糖尿病肾病”、“糖尿病神经病变”、“糖尿病视网膜病变”、“糖尿病心肌病”、“糖尿病肝脂肪变性”、“糖尿病骨病”、“糖尿病动脉粥样硬化”、“糖尿病认知功能障碍”、“糖尿病肺损伤”和“其他糖尿病并发症”进行综述。在最初检索的1750篇文章中,183篇基于其通过AMPK信号通路、药代动力学和翻译潜力治疗糖尿病或其并发症的相关性被纳入。非英文文章和研究不关注小檗碱激活AMPK,不涉及糖尿病及其并发症被排除。结果文献综述发现,小檗碱在糖尿病的各种临床前研究中一致激活AMPK。AMPK的激活通常是由LKB1和CAMKKβ介导的。小檗碱激活AMPK对葡萄糖摄取、胰岛素敏感性、脂质代谢、氧化应激和炎症反应有积极影响。来自动物模型的证据表明,它可以改善糖尿病肾病、神经病变、视网膜病变、心肌病、肝脂肪变性、骨病、动脉粥样硬化、认知功能障碍和肺损伤等并发症。临床试验报告,在标准剂量下,空腹血糖(FBG)、糖化血红蛋白(HbA1c)和血脂水平显著降低,副作用最小。小檗碱激活ampk在细胞能量稳态中起核心作用,调节糖异生、脂肪生成、氧化应激和炎症等关键过程,这有助于其治疗代谢功能障碍和dm相关并发症。然而,挑战仍然存在,如其生物利用度差,潜在的药物相互作用,以及由于配方和给药策略的差异而导致的临床结果的可变性。生物增强剂和新型给药系统的结合可能有助于克服这些限制。需要进一步开展大规模、对照良好的临床试验和药代动力学优化研究,以充分确立小檗碱的治疗潜力,并为其应用制定临床指南。
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引用次数: 0
Gambogic acid: A review of its pharmacological mechanisms against cancer 藤黄酸:抗癌药理机制的研究进展
Pub Date : 2025-09-12 DOI: 10.1016/j.prmcm.2025.100692
Y. Yan , X. Liu , Y. Sun, H. Wang

Introduction

Gambogic acid (GA), a caged xanthone derived from the resin of Garcinia hanburyi (known as Téng Huáng in traditional Chinese medicine), has been historically utilized in TCM for its properties of “combating toxins, eroding sores, dispelling blood stasis, and resolving masses” in the treatment of abscesses, boils, and refractory skin diseases. In recent decades, GA has gained significant attention as a promising multi-target anticancer agent. This review aims to synthesize current preclinical evidence regarding GA’s antitumor mechanisms, its efficacy in combination therapies, and strategies to overcome its pharmacological limitations.

Methods

A systematic literature search was conducted across electronic databases including PubMed, Web of Science, and CNKI to identify relevant preclinical studies investigating the anticancer mechanisms and delivery strategies of GA. Articles were selected based on their relevance to GA’s molecular targets, efficacy in mono- and combination therapy, and novel formulation approaches.

Results

Preclinical studies demonstrate that GA exerts broad-spectrum antitumor effects through multiple mechanisms: induction of apoptosis via mitochondrial and death receptor pathways; cell cycle arrest at G0/G1 or G2/M phases; inhibition of angiogenesis via HIF-1α/VEGF/MMPs suppression; and reduction of metastasis through downregulation of MMPs. GA modulates key oncogenic pathways including NF-κB, PI3K/Akt/mTOR, and MAPKs. It overcomes drug resistance by targeting P-glycoprotein, Bcr-Abl, and SHH pathways. Notably, GA induces immunogenic pyroptosis via caspase-3/GSDME activation and reprograms tumor-associated macrophages by suppressing extracellular vesicle-mediated miR-21 transfer. Synergistic effects are observed when GA is combined with chemotherapy, targeted agents (e.g., bortezomib, gefitinib), radiotherapy, or photothermal therapy. However, GA’s clinical application is limited by poor solubility and bioavailability. Nanocarrier systems—such as polymeric nanoparticles, protein-based carriers, biomimetic designs, and stimuli-responsive formulations—have significantly improved GA’s stability, tumor targeting, and therapeutic index.

Discussion

GA represents a multi-mechanistic anticancer agent derived from TCM with high translational potential. Despite compelling preclinical results, further well-designed clinical trials are essential to validate its efficacy and safety in humans. The integration of GA with modern drug delivery technologies, especially nanotechnology, provides a promising approach to overcoming its physicochemical limitations. Future research should focus on context-dependent pathway modulation, immune microenvironment interactions, and clinical translation of advanced GA formulations.
黄曲霉酸(GA)是一种笼状的山酮,从黄曲霉的树脂中提取(在中医中称为黄曲霉Huáng),因其具有“抗毒素、腐蚀疮、化瘀、化块”的功效,在中医中一直被用于治疗脓肿、疖子和难治性皮肤病。近几十年来,GA作为一种有前景的多靶点抗癌药物受到了广泛的关注。本综述旨在综合目前关于GA抗肿瘤机制的临床前证据,其在联合治疗中的疗效,以及克服其药理学局限性的策略。方法系统检索PubMed、Web of Science、中国知网等电子数据库,收集GA抗癌机制和给药策略的相关临床前研究。文章的选择是基于它们与GA的分子靶点的相关性,单一和联合治疗的疗效,以及新的配方方法。结果临床前期研究表明,GA可通过多种机制发挥广谱抗肿瘤作用:通过线粒体和死亡受体途径诱导细胞凋亡;细胞周期阻滞于G0/G1或G2/M期;通过抑制HIF-1α/VEGF/MMPs抑制血管生成;并通过下调MMPs来减少转移。GA调节NF-κB、PI3K/Akt/mTOR和MAPKs等关键的致癌途径。它通过靶向p -糖蛋白、Bcr-Abl和SHH通路来克服耐药性。值得注意的是,GA通过caspase-3/GSDME激活诱导免疫原性焦亡,并通过抑制细胞外囊泡介导的miR-21转移对肿瘤相关巨噬细胞进行重编程。当GA与化疗、靶向药物(如硼替佐米、吉非替尼)、放疗或光热疗法联合使用时,可以观察到协同效应。然而,GA的临床应用受到溶解度和生物利用度差的限制。纳米载体系统,如聚合纳米颗粒、蛋白质载体、仿生设计和刺激反应配方,显著提高了GA的稳定性、肿瘤靶向性和治疗指数。ga是一种来自中药的多机制抗癌药物,具有很高的转化潜力。尽管有令人信服的临床前结果,但进一步精心设计的临床试验对于验证其在人体中的有效性和安全性至关重要。遗传基因与现代药物传递技术,特别是纳米技术的结合,为克服其物理化学局限性提供了一条有前途的途径。未来的研究应集中在上下文依赖性通路调节、免疫微环境相互作用和高级GA配方的临床翻译上。
{"title":"Gambogic acid: A review of its pharmacological mechanisms against cancer","authors":"Y. Yan ,&nbsp;X. Liu ,&nbsp;Y. Sun,&nbsp;H. Wang","doi":"10.1016/j.prmcm.2025.100692","DOIUrl":"10.1016/j.prmcm.2025.100692","url":null,"abstract":"<div><h3>Introduction</h3><div>Gambogic acid (GA), a caged xanthone derived from the resin of Garcinia hanburyi (known as <em>Téng Huáng</em> in traditional Chinese medicine), has been historically utilized in TCM for its properties of “combating toxins, eroding sores, dispelling blood stasis, and resolving masses” in the treatment of abscesses, boils, and refractory skin diseases. In recent decades, GA has gained significant attention as a promising multi-target anticancer agent. This review aims to synthesize current preclinical evidence regarding GA’s antitumor mechanisms, its efficacy in combination therapies, and strategies to overcome its pharmacological limitations.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted across electronic databases including PubMed, Web of Science, and CNKI to identify relevant preclinical studies investigating the anticancer mechanisms and delivery strategies of GA. Articles were selected based on their relevance to GA’s molecular targets, efficacy in mono- and combination therapy, and novel formulation approaches.</div></div><div><h3>Results</h3><div>Preclinical studies demonstrate that GA exerts broad-spectrum antitumor effects through multiple mechanisms: induction of apoptosis via mitochondrial and death receptor pathways; cell cycle arrest at G0/G1 or G2/M phases; inhibition of angiogenesis via HIF-1α/VEGF/MMPs suppression; and reduction of metastasis through downregulation of MMPs. GA modulates key oncogenic pathways including NF-κB, PI3K/Akt/mTOR, and MAPKs. It overcomes drug resistance by targeting P-glycoprotein, Bcr-Abl, and SHH pathways. Notably, GA induces immunogenic pyroptosis via caspase-3/GSDME activation and reprograms tumor-associated macrophages by suppressing extracellular vesicle-mediated miR-21 transfer. Synergistic effects are observed when GA is combined with chemotherapy, targeted agents (<em>e.g.</em>, bortezomib, gefitinib), radiotherapy, or photothermal therapy. However, GA’s clinical application is limited by poor solubility and bioavailability. Nanocarrier systems—such as polymeric nanoparticles, protein-based carriers, biomimetic designs, and stimuli-responsive formulations—have significantly improved GA’s stability, tumor targeting, and therapeutic index.</div></div><div><h3>Discussion</h3><div>GA represents a multi-mechanistic anticancer agent derived from TCM with high translational potential. Despite compelling preclinical results, further well-designed clinical trials are essential to validate its efficacy and safety in humans. The integration of GA with modern drug delivery technologies, especially nanotechnology, provides a promising approach to overcoming its physicochemical limitations. Future research should focus on context-dependent pathway modulation, immune microenvironment interactions, and clinical translation of advanced GA formulations.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100692"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Psoralen from Ficus carica: Fractionation, bioactivity, and toxicological-pharmacokinetic comparison with silymarin 无花果中的补骨脂素:分离、生物活性及与水飞蓟素的毒理药代动力学比较
Pub Date : 2025-09-11 DOI: 10.1016/j.prmcm.2025.100690
Kiren Mustafa , Noreen Akhtar , Hina Khalid , Madiha Younas , Muhammad Tariq Saeed , Yuanda Song , Zhihe Li , Hassan Mohamed

Background

Ficus carica (无花果 wúhuāguǒ) is valued in traditional Chinese medicine (TCM) and nutrition for its rich phytochemical content. Our prior research showed a crude fig extract (FLA) selectively fought liver cancer cells (HepG2) in vitro while sparing normal cells.

Purpose

We aimed to isolate an active compound from FLA and analyze the potent bioactivities, particularly anticancer potential, through in vitro and computational studies.

Method

An innovative strategy combined fractionation by vacuum liquid chromatography (VLC) on silica gel (using six non-polar to polar solvent gradients) with thin layer chromatography (TLC) and bioactivity screening on liver (HepG2) and gastric (SGC-7901) cancer cell lines, and antimicrobial assay. The active Fraction 2 (Fr-2) was repeatedly sub-fractionated using Sephadex LH-20 column chromatography and TLC to isolate psoralen. Its mechanism of action against key cancer markers was evaluated via RT-qPCR, molecular docking, and ADMET pharmacokinetic analysis, with silymarin as a comparator.

Results

Fractionation of FLA yielded Fr- 2 (Hexane: Ethyl acetate, 50:50) with the IC50 (mg/mL) against HepG2 (0.31 ± 0.1) and SGC-7901 (0.124 ± 0.05) among the six tested fractions. It also exhibited antimicrobial activity, showing maximum inhibition zones (mm) against Aspergillus flavus FL (18± 0.4 mm), Penicillium chrysogenum FL (20 ± 0.7 mm), and Pseudomonas aeruginosa (17 ± 0.8 mm). Sub-fractionation of Fr- 2 led to the identification of psoralen, which decreased the genetic expression of tumor suppressor Tp53, anti-apoptotic (Bcl2) and Cell cycle kinases (CDK1 and CDK5). Molecular interaction via molecular docking against critical cancer regulators: Tp53, oncoproteins MDM2 and Bcl2, and CDK1/CDK5 also revealed the strong binding affinity of Psoralen. Psoralen demonstrates a novel mechanism of action by dual targeting of the MDM2-p53 axis: it binds p53′s N-TAD (Arg23, -8.8 kcal/mol) to reduce ubiquitination, while competitively inhibiting MDM2 (-5.8 kcal/mol) to stabilize Tp53 and induce apoptosis. Comparative ADMET analysis revealed psoralen's superior water solubility and oral bioavailability (96.67 % absorption) versus silymarin.

Conclusion

The active Fr-2, featuring psoralen, demonstrates broad antimicrobial and anticancer activity by potentially inhibiting the MDM2-p53 pathway to induce apoptosis, and it exhibits a superior ADMET profile compared to silymarin.
无花果(wúhuāguǒ)因其丰富的植物化学成分而具有重要的中药和营养价值。我们之前的研究表明,粗无花果提取物(FLA)在体外选择性地对抗肝癌细胞(HepG2),同时保留正常细胞。目的通过体外实验和计算研究,从黄芪多糖中分离出一种活性化合物,并分析其生物活性,特别是抗癌活性。方法采用真空液相色谱(VLC)和薄层色谱(TLC)相结合的方法,对肝癌细胞(HepG2)和胃癌细胞(SGC-7901)进行生物活性筛选和抑菌试验。采用Sephadex LH-20柱层析和薄层色谱对活性组分2 (Fr-2)进行反复亚分离,分离补骨脂素。以水飞蓟素为比较物,通过RT-qPCR、分子对接和ADMET药代动力学分析,评估其对关键肿瘤标志物的作用机制。结果FLA对HepG2(0.31±0.1)和SGC-7901(0.124±0.05)的IC50 (mg/mL),得到Fr- 2(己烷:乙酸乙酯,50:50)。对黄曲霉FL(18±0.4 mm)、青霉菌FL(20±0.7 mm)和铜绿假单胞菌FL(17±0.8 mm)的抑制范围最大(mm)。Fr- 2的亚分离鉴定出补骨脂素,从而降低肿瘤抑制因子Tp53、抗凋亡(Bcl2)和细胞周期激酶(CDK1和CDK5)的基因表达。通过分子对接与关键癌症调节因子:Tp53、癌蛋白MDM2和Bcl2、CDK1/CDK5的分子相互作用也揭示了补骨脂素的强结合亲和力。补骨脂素通过双重靶向MDM2-p53轴显示了一种新的作用机制:它结合p53的N-TAD (Arg23, -8.8 kcal/mol)来减少泛素化,同时竞争性地抑制MDM2 (-5.8 kcal/mol)来稳定Tp53并诱导细胞凋亡。ADMET对比分析显示,补骨脂素的水溶性和口服生物利用度优于水飞蓟素(96.67%的吸收率)。结论具有补骨脂素特征的活性Fr-2具有广泛的抗菌和抗癌活性,可能通过抑制MDM2-p53通路诱导细胞凋亡,与水飞蓟素相比,其ADMET谱更优越。
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引用次数: 0
Qingyi decoction modulates fibrotic pathways in severe acute pancreatitis: A histological and molecular study 清胰汤调节重症急性胰腺炎纤维化通路的组织学和分子研究
Pub Date : 2025-09-10 DOI: 10.1016/j.prmcm.2025.100684
Shayan Chen , Zhihuang Wu , Wendie Yu , Di Zou , Jiongtang Lu

Background

Qingyi Decoction (QYD), a traditional Chinese medicine (TCM) formulation derived from Dachaihu Decoction, is used to treat severe acute pancreatitis (SAP). While QYD's components, rhubarb and bupleurum, possess known anti-fibrotic properties, their mechanisms in SAP remain unclear. This study investigated QYD's anti-fibrotic effects and underlying mechanisms in a lipopolysaccharide (LPS)- and cerulein-induced mouse model of SAP.

Methods

SAP was induced in mice by intraperitoneal injection of cerulein and LPS. The QYD+SAP group received oral administration of QYD at twice the clinical dosage. Following modeling and QYD treatment, pancreatic tissues were harvested for examination of fibrotic parameters using histological methods. Additionally, the anti-fibrogenic effects of QYD on pancreatic tissue were investigated using Western blotting and laser scanning confocal microscopy.

Results

In SAP mice, histological examination of pancreatic tissues revealed significant tissue damage. However, QYD treatment ameliorated the histological severity of SAP. Furthermore, QYD decreased the expression of pancreatic fibrosis and PSC activation markers, including α-SMA, collagen, and fibronectin, while enhancing pancreatic acinar cell survival and restoring exocrine pancreatic function. Mechanistically, QYD treatment inhibited the activation of JNK, ERK, and p38 MAPK pathways, as well as prevented IκBα degradation in pancreatic tissues.

Conclusion

This study demonstrates the presence of mild pancreatic fibrosis in SAP and reveals QYD's anti-fibrotic effects through the inhibition of JNK, ERK, and p38 MAPK signaling pathways and the prevention of IκBα degradation.
清胰汤(QYD)是一种由大柴胡汤衍生而来的中药制剂,用于治疗严重急性胰腺炎(SAP)。虽然QYD的成分,大黄和柴胡,具有已知的抗纤维化特性,但它们在SAP中的机制尚不清楚。本研究在脂多糖(LPS)和蓝蛋白诱导的小鼠sap模型中探讨了清芪多糖的抗纤维化作用及其机制。方法通过腹腔注射蓝蛋白和LPS诱导小鼠sap。芪黄酮+SAP组口服芪黄酮,剂量为临床剂量的2倍。在建模和QYD治疗后,采集胰腺组织,用组织学方法检查纤维化参数。此外,采用Western blotting和激光扫描共聚焦显微镜观察芪黄酮对胰腺组织的抗纤维化作用。结果SAP小鼠胰腺组织组织学检查显示明显的组织损伤。然而,QYD治疗改善了SAP的组织学严重程度。此外,QYD降低了胰腺纤维化和PSC激活标志物(包括α-SMA、胶原和纤维连接蛋白)的表达,同时提高了胰腺腺泡细胞的存活率,恢复了外分泌胰腺功能。在机制上,QYD治疗抑制JNK、ERK和p38 MAPK通路的激活,并阻止胰腺组织中i - κ b α的降解。结论本研究证实SAP患者存在轻度胰腺纤维化,并揭示清芪多糖通过抑制JNK、ERK、p38 MAPK信号通路及抑制i- κ b α降解而具有抗纤维化作用。
{"title":"Qingyi decoction modulates fibrotic pathways in severe acute pancreatitis: A histological and molecular study","authors":"Shayan Chen ,&nbsp;Zhihuang Wu ,&nbsp;Wendie Yu ,&nbsp;Di Zou ,&nbsp;Jiongtang Lu","doi":"10.1016/j.prmcm.2025.100684","DOIUrl":"10.1016/j.prmcm.2025.100684","url":null,"abstract":"<div><h3>Background</h3><div>Qingyi Decoction (QYD), a traditional Chinese medicine (TCM) formulation derived from Dachaihu Decoction, is used to treat severe acute pancreatitis (SAP). While QYD's components, <em>rhubarb</em> and <em>bupleurum</em>, possess known anti-fibrotic properties, their mechanisms in SAP remain unclear. This study investigated QYD's anti-fibrotic effects and underlying mechanisms in a lipopolysaccharide (LPS)- and cerulein-induced mouse model of SAP.</div></div><div><h3>Methods</h3><div>SAP was induced in mice by intraperitoneal injection of cerulein and LPS. The QYD+SAP group received oral administration of QYD at twice the clinical dosage. Following modeling and QYD treatment, pancreatic tissues were harvested for examination of fibrotic parameters using histological methods. Additionally, the anti-fibrogenic effects of QYD on pancreatic tissue were investigated using Western blotting and laser scanning confocal microscopy.</div></div><div><h3>Results</h3><div>In SAP mice, histological examination of pancreatic tissues revealed significant tissue damage. However, QYD treatment ameliorated the histological severity of SAP. Furthermore, QYD decreased the expression of pancreatic fibrosis and PSC activation markers, including α-SMA, collagen, and fibronectin, while enhancing pancreatic acinar cell survival and restoring exocrine pancreatic function. Mechanistically, QYD treatment inhibited the activation of JNK, ERK, and p38 MAPK pathways, as well as prevented IκBα degradation in pancreatic tissues.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the presence of mild pancreatic fibrosis in SAP and reveals QYD's anti-fibrotic effects through the inhibition of JNK, ERK, and p38 MAPK signaling pathways and the prevention of IκBα degradation.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100684"},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessing the efficacy and safety of traditional Chinese medicine for cancer-related fatigue in lung cancer patients: A comprehensive meta-analysis of randomized controlled trials 评估中药治疗肺癌患者癌症相关性疲劳的疗效和安全性:一项随机对照试验的综合meta分析
Pub Date : 2025-09-08 DOI: 10.1016/j.prmcm.2025.100683
Jingya Yang , Yuxiao Li , Yurou Li , Menghuan Song , Hao Hu , Carolina Oi Lam Ung

Background

Cancer-related fatigue (CRF) is a persistent condition that significantly impacts the health of lung oncology patients. While the conventional and non-pharmacological therapy for CRF remain uncertain, traditional Chinese medicine (TCM) has become a trending option. This study aimed to assess the efficacy and safety of TCM for CRF in lung cancer from randomized controlled trials (RCTs).

Methods

According to PRISMA guidelines, seven databases were searched up to 30 June 2024. Only TCM interventions were eligible in this review. Meta-analysis and network meta-analysis (NMA) were designed to pool outcomes results and compared various TCM interventions. The CONSORT-CHM and Risk of Bias tool were used to evaluate the quality and potential biases.

Results

This review included 41 RCTs. Compared with the routine treatment (RT), TCM + RT had significant improved efficacy rate (Risk Ratio (RR) = 1.333, 95 % Confidence Intervals (CI): 1.227 to 1.448, P < 0.01), Karnofsky Performance Status scores (KPS) (Mean Difference (MD) = 7.182, 95 % CI: 4.160 to 10.203, P < 0.01) and Quality of Life Questionnaires-C30 scores (QLQ-30) (MD = 9.186, 95 % CI: 6.707 to 11.665, P < 0.01). Also, TCM + RT showed significance in reducing Piper Fatigue Scale scores (PFS) (MD = -1.145, 95 % CI: -1.452 to -0.838, P < 0.01), Cancer-Fatigue Scale scores (MD = -6.411; 95 %CI: -8.837 to -3.985; P < 0.01) and Brief Fatigue Inventory scores (MD = -1.687; 95 %CI: -2.350 to -1.023; P < 0.01). From NMA results, Jianpi Yiqi Huatan Formula + RT was the best for improving efficacy rate, Kangai Injection + RT excelled in reducing PFS scores and enhancing QLQ-C30 scores, and Aidi Injection + RT was the most effective in elevating KPS scores. No serious adverse events were reported. However, poor RCTs quality and uncertain bias risk were common in this study.

Conclusion

Our study showed that TCM was effective and safe for CRF in lung cancer. However, given the poor quality and uncertain risk of bias, the results should be interpreted cautiously. More standardized RCTs are needed in the future.
癌症相关性疲劳(cancer -related fatigue, CRF)是一种显著影响肺癌患者健康的持续性疾病。虽然慢性肾功能衰竭的常规和非药物治疗仍不确定,但中药已成为一种趋势选择。本研究旨在通过随机对照试验(RCTs)评估中药治疗肺癌慢性肾功能衰竭的疗效和安全性。方法根据PRISMA指南检索截至2024年6月30日的7个数据库。本综述仅纳入中医干预措施。meta分析和网络meta分析(NMA)旨在汇总结果并比较各种中医干预措施。使用conber - chm和风险偏倚工具来评估质量和潜在偏倚。结果本综述纳入41项随机对照试验。与常规治疗(RT)相比,中药+ RT的有效率(风险比(RR) = 1.333, 95%可信区间(CI): 1.227 ~ 1.448, P < 0.01)、Karnofsky Performance Status评分(KPS) (Mean Difference (MD) = 7.182, 95% CI: 4.160 ~ 10.203, P < 0.01)和生活质量问卷- c30评分(QLQ-30) (MD = 9.186, 95% CI: 6.707 ~ 11.665, P < 0.01)均有显著提高。中药+放疗对降低Piper Fatigue Scale评分(PFS) (MD = -1.145, 95% CI: -1.452 ~ -0.838, P < 0.01)、Cancer-Fatigue Scale评分(MD = -6.411, 95% CI: -8.837 ~ -3.985, P < 0.01)和Brief Fatigue Inventory评分(MD = -1.687, 95% CI: -2.350 ~ -1.023, P < 0.01)均有显著意义。从NMA结果来看,健脾益气化痰方+ RT对提高有效率效果最好,康爱注射液+ RT对降低PFS评分、提高QLQ-C30评分效果最好,爱地注射液+ RT对提高KPS评分效果最好。无严重不良事件报告。然而,本研究普遍存在随机对照试验质量差和不确定的偏倚风险。结论中药治疗肺癌慢性肾功能衰竭是一种安全有效的方法。然而,鉴于质量差和不确定的偏倚风险,结果应谨慎解释。未来需要更多标准化的随机对照试验。
{"title":"Assessing the efficacy and safety of traditional Chinese medicine for cancer-related fatigue in lung cancer patients: A comprehensive meta-analysis of randomized controlled trials","authors":"Jingya Yang ,&nbsp;Yuxiao Li ,&nbsp;Yurou Li ,&nbsp;Menghuan Song ,&nbsp;Hao Hu ,&nbsp;Carolina Oi Lam Ung","doi":"10.1016/j.prmcm.2025.100683","DOIUrl":"10.1016/j.prmcm.2025.100683","url":null,"abstract":"<div><h3>Background</h3><div>Cancer-related fatigue (CRF) is a persistent condition that significantly impacts the health of lung oncology patients. While the conventional and non-pharmacological therapy for CRF remain uncertain, traditional Chinese medicine (TCM) has become a trending option. This study aimed to assess the efficacy and safety of TCM for CRF in lung cancer from randomized controlled trials (RCTs).</div></div><div><h3>Methods</h3><div>According to PRISMA guidelines, seven databases were searched up to 30 June 2024. Only TCM interventions were eligible in this review. Meta-analysis and network meta-analysis (NMA) were designed to pool outcomes results and compared various TCM interventions. The CONSORT-CHM and Risk of Bias tool were used to evaluate the quality and potential biases.</div></div><div><h3>Results</h3><div>This review included 41 RCTs. Compared with the routine treatment (RT), TCM + RT had significant improved efficacy rate (Risk Ratio (RR) = 1.333, 95 % Confidence Intervals (CI): 1.227 to 1.448, <em>P</em> &lt; 0.01), Karnofsky Performance Status scores (KPS) (Mean Difference (MD) = 7.182, 95 % CI: 4.160 to 10.203, <em>P</em> &lt; 0.01) and Quality of Life Questionnaires-C30 scores (QLQ-30) (MD = 9.186, 95 % CI: 6.707 to 11.665, <em>P</em> &lt; 0.01). Also, TCM + RT showed significance in reducing Piper Fatigue Scale scores (PFS) (MD = -1.145, 95 % CI: -1.452 to -0.838, <em>P</em> &lt; 0.01), Cancer-Fatigue Scale scores (MD = -6.411; 95 %CI: -8.837 to -3.985; <em>P</em> &lt; 0.01) and Brief Fatigue Inventory scores (MD = -1.687; 95 %CI: -2.350 to -1.023; <em>P</em> &lt; 0.01). From NMA results, Jianpi Yiqi Huatan Formula + RT was the best for improving efficacy rate, Kangai Injection + RT excelled in reducing PFS scores and enhancing QLQ-C30 scores, and Aidi Injection + RT was the most effective in elevating KPS scores. No serious adverse events were reported. However, poor RCTs quality and uncertain bias risk were common in this study.</div></div><div><h3>Conclusion</h3><div>Our study showed that TCM was effective and safe for CRF in lung cancer. However, given the poor quality and uncertain risk of bias, the results should be interpreted cautiously. More standardized RCTs are needed in the future.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"17 ","pages":"Article 100683"},"PeriodicalIF":0.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Re: Progress in the application of AI in the standardization of traditional Chinese medicine: Discussion and prospects 人工智能在中医标准化中的应用进展:讨论与展望
Pub Date : 2025-09-06 DOI: 10.1016/j.prmcm.2025.100681
James O. Fajemiroye
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引用次数: 0
Trypanocidal potentials of Jatropha curcas L. 1753 leaf extracts and fractions in vivo 麻疯树(Jatropha curcas L. 1753)叶提取物及组分体内杀锥虫活性研究
Pub Date : 2025-09-01 DOI: 10.1016/j.prmcm.2025.100670
Haolat Yusuf , Abdulhakeem Binhambali , Mutiu Olawale Rahmon , Ridwan Bolaji Yusuf , Suleiman Garba Salihu , Barnabas Jarumi Musa
<div><h3>Introduction</h3><div>Trypanosomiasis is a debilitating parasitic disease affecting both humans and animals, leading to substantial economic losses in the livestock sector due to reduced productivity and increased mortality. As resistance to conventional drugs escalates, interest in plant-based alternatives has grown. <em>Jatropha curcas</em> (JC), widely used in traditional medicine systems including Traditional Chinese Medicine (TCM), has demonstrated promising anti-trypanosomal activity. It is known as mǎfēng shù (麻风树) or “Leprosy Tree’’ in TCM and its varies potential has been widely described in various studies. However, this study specifically evaluated the therapeutic potential of various JC aqueous extracts on weight, body temperature, and parasitaemia levels in <em>Trypanosoma congolense</em>-infected mice.</div></div><div><h3>Methods</h3><div>Ninety mice were randomly assigned to 8 (groups 4–8 have 3 subgroups) experimental groups. Mice in all groups, except the control, were inoculated with <em>Trypanosoma congolense</em> (TC) and treated with Diminazene aceturate (DA) and varying doses of aqueous, methanol, and solvent fractions of JC extracts. Parasitaemia was monitored daily, and blood samples were collected for hematological analysis. Tissue (spleen and liver) were accessed for changes in microscopic examination.</div></div><div><h3>Result</h3><div>The results indicated no statistically significant weight changes between treatment groups (<em>p</em> > 0.05), although slight fluctuations in weight were observed across groups. Similarly, the treatment had minimal effects on body temperature, with no significant differences observed across groups (<em>p</em> > 0.05). On parasitaemia, aqueous extracts at higher doses (of 80 and 40 mg/kg) significantly reduced parasitaemia (<em>p</em> < 0.05) compared to controls, particularly between 2–6 days. Methanol and ethyl acetate extracts also showed significant parasitaemia reduction (<em>p</em> < 0.05), with the 15 mg/kg methanol dose demonstrating the highest efficacy. However, butanol and hexane extracts did not significantly reduce parasitaemia (<em>p</em> > 0.05) and many of the tissues showed different changes on histological analysis.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that JC extracts, particularly aqueous, methanol, and ethyl acetate, exhibit significant anti-trypanosomal activity, by reducing parasitaemia levels in infected mice, likely due to the presence of bioactive phytochemicals such as alkaloids, flavonoids, and saponins. Although the extracts did not completely eliminate the parasites like common drug, however they contributed to improvements in weight, packed cell volume (PCV), red blood cell counts and histological changes, proving their potential therapeutic effects when used appropriately. Also, toxicity concerns, evidenced by the observed histology changes in higher-dose groups, warrant further investigation. The study s
锥虫病是一种影响人类和动物的使人衰弱的寄生虫病,由于生产力下降和死亡率增加,导致畜牧业遭受重大经济损失。随着对传统药物的耐药性不断升级,人们对植物替代品的兴趣也在增长。麻疯树(Jatropha curcas, JC)广泛应用于包括中药在内的传统医学体系中,具有良好的抗锥虫活性。它在中医中被称为mǎfēng shù或“麻风树”,其各种潜力在各种研究中被广泛描述。然而,本研究专门评估了各种JC水提取物对刚果锥虫感染小鼠体重、体温和寄生虫血症水平的治疗潜力。方法90只小鼠随机分为8个实验组(4 ~ 8组共3个亚组)。除对照组外,所有组小鼠均接种刚果锥虫(TC),并用乙酸迪咪那烯(DA)和不同剂量的JC提取物的水、甲醇和溶剂部分处理。每天监测寄生虫血症,并采集血样进行血液学分析。取组织(脾和肝)进行镜下检查。结果各组患者体重差异无统计学意义(p > 0.05),但组间体重有轻微波动。同样,治疗对体温的影响很小,各组间无显著差异(p > 0.05)。在寄生虫血症方面,与对照相比,较高剂量(80和40 mg/kg)的水提取物显著降低了寄生虫血症(p < 0.05),特别是在2-6天之间。甲醇和乙酸乙酯提取物也有显著的降低寄生虫率的作用(p < 0.05),其中甲醇剂量为15 mg/kg时效果最好。然而,丁醇和己烷提取物并没有显著降低寄生虫血症(p > 0.05),许多组织在组织学分析上表现出不同的变化。本研究表明,JC提取物,特别是水、甲醇和乙酸乙酯提取物,通过降低感染小鼠的寄生虫血症水平,表现出显著的抗锥虫活性,可能是由于生物碱、类黄酮和皂苷等生物活性植物化学物质的存在。虽然提取物不能像普通药物那样完全消除寄生虫,但它们有助于改善体重、堆积细胞体积(PCV)、红细胞计数和组织学变化,证明如果使用得当,它们具有潜在的治疗效果。此外,高剂量组观察到的组织学变化证明了毒性问题,值得进一步研究。该研究支持对JC作为潜在的抗锥虫药物的优化配方和给药方案的需求。
{"title":"Trypanocidal potentials of Jatropha curcas L. 1753 leaf extracts and fractions in vivo","authors":"Haolat Yusuf ,&nbsp;Abdulhakeem Binhambali ,&nbsp;Mutiu Olawale Rahmon ,&nbsp;Ridwan Bolaji Yusuf ,&nbsp;Suleiman Garba Salihu ,&nbsp;Barnabas Jarumi Musa","doi":"10.1016/j.prmcm.2025.100670","DOIUrl":"10.1016/j.prmcm.2025.100670","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Trypanosomiasis is a debilitating parasitic disease affecting both humans and animals, leading to substantial economic losses in the livestock sector due to reduced productivity and increased mortality. As resistance to conventional drugs escalates, interest in plant-based alternatives has grown. &lt;em&gt;Jatropha curcas&lt;/em&gt; (JC), widely used in traditional medicine systems including Traditional Chinese Medicine (TCM), has demonstrated promising anti-trypanosomal activity. It is known as mǎfēng shù (麻风树) or “Leprosy Tree’’ in TCM and its varies potential has been widely described in various studies. However, this study specifically evaluated the therapeutic potential of various JC aqueous extracts on weight, body temperature, and parasitaemia levels in &lt;em&gt;Trypanosoma congolense&lt;/em&gt;-infected mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Ninety mice were randomly assigned to 8 (groups 4–8 have 3 subgroups) experimental groups. Mice in all groups, except the control, were inoculated with &lt;em&gt;Trypanosoma congolense&lt;/em&gt; (TC) and treated with Diminazene aceturate (DA) and varying doses of aqueous, methanol, and solvent fractions of JC extracts. Parasitaemia was monitored daily, and blood samples were collected for hematological analysis. Tissue (spleen and liver) were accessed for changes in microscopic examination.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Result&lt;/h3&gt;&lt;div&gt;The results indicated no statistically significant weight changes between treatment groups (&lt;em&gt;p&lt;/em&gt; &gt; 0.05), although slight fluctuations in weight were observed across groups. Similarly, the treatment had minimal effects on body temperature, with no significant differences observed across groups (&lt;em&gt;p&lt;/em&gt; &gt; 0.05). On parasitaemia, aqueous extracts at higher doses (of 80 and 40 mg/kg) significantly reduced parasitaemia (&lt;em&gt;p&lt;/em&gt; &lt; 0.05) compared to controls, particularly between 2–6 days. Methanol and ethyl acetate extracts also showed significant parasitaemia reduction (&lt;em&gt;p&lt;/em&gt; &lt; 0.05), with the 15 mg/kg methanol dose demonstrating the highest efficacy. However, butanol and hexane extracts did not significantly reduce parasitaemia (&lt;em&gt;p&lt;/em&gt; &gt; 0.05) and many of the tissues showed different changes on histological analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This study demonstrates that JC extracts, particularly aqueous, methanol, and ethyl acetate, exhibit significant anti-trypanosomal activity, by reducing parasitaemia levels in infected mice, likely due to the presence of bioactive phytochemicals such as alkaloids, flavonoids, and saponins. Although the extracts did not completely eliminate the parasites like common drug, however they contributed to improvements in weight, packed cell volume (PCV), red blood cell counts and histological changes, proving their potential therapeutic effects when used appropriately. Also, toxicity concerns, evidenced by the observed histology changes in higher-dose groups, warrant further investigation. The study s","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100670"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plumbagin attenuates neuropathic pain via inhibition of spinal astrogliosis and modulation of hippocampal CA1 opioidergic receptors 白丹素通过抑制脊髓星形胶质增生和调节海马CA1阿片能受体来减轻神经性疼痛
Pub Date : 2025-09-01 DOI: 10.1016/j.prmcm.2025.100679
Prashant N. Amale , Rajesh R. Ugale , Ashish P. Bharne , Sapan K. Shah , Shilpa A. Deshpande , Kartik T. Nakhate

Introduction

Plumbagin (PL), a natural phytochemical obtained from Plumbago zeylanica roots, known as Bai Hua Dan in traditional Chinese medicine, has become a thriving area of research. Emerging evidence suggests that PL exhibits analgesic effects in various rodent pain models. Therefore, exploring the mechanisms underlying PL's central antinociceptive effect is interesting. Despite extensive research into alternative therapies, chronic neuropathic pain (NP) remains a persistent clinical challenge. We investigated the role of spinal astrogliosis and hippocampal opioid receptors in the antinociceptive action of PL in rats with chronic constriction injury (CCI) of sciatic nerve-induced NP.

Methods

A CCI of the sciatic nerve was performed to induce NP in rats. PL (1–8 µg/rat, intracerebroventricular-4 V) and opioid antagonist naloxone (1–8 µg/rat, intra-hippocampal cornu ammonis-1 (CA1) were administered per se or in combination, followed by a thermal-mechanical-cold sensitivity test. Using a molecular docking study, the affinity of PL at opioidergic receptors was investigated. Immunohistochemistry of glial-fibrillary acidic protein (GFAP) was used to evaluate the effect of PL on astrogliosis in the spinal dorsal horn (SDH).

Results

Treatment with PL showed a dose-dependent antinociceptive effect. Interestingly, pretreatment with naloxone attenuated the antinociceptive effect of PL. Furthermore, PL reduced the NP-triggered integrated density of GFAP+ve astrocytes in the SDH. The in-silico binding revealed a potent binding of PL to kappa, delta-, and mu-opioid receptors in the order of binding, comparable to morphine.

Conclusion

Our findings suggest that PL possibly ameliorates NP by suppressing astroglial activation in the SDH and inhibiting nociceptive processing in the hippocampal CA1 region via opioid receptors.
白桦金(plbagin, PL)是一种从白桦根中提取的天然植物化学物质,在中医中被称为白桦丹,目前已成为一个蓬勃发展的研究领域。新出现的证据表明,PL在各种啮齿动物疼痛模型中表现出镇痛作用。因此,探索PL中枢抗感觉作用的机制是有趣的。尽管对替代疗法进行了广泛的研究,慢性神经性疼痛(NP)仍然是一个持续的临床挑战。我们研究了脊髓星形胶质细胞增生和海马阿片受体在坐骨神经慢性缩窄性NP大鼠PL抗感觉作用中的作用。方法采用坐骨神经CCI诱导大鼠NP。单独或联合给药PL(1-8µg/大鼠,脑室内-4 V)和阿片拮抗剂纳洛酮(1-8µg/大鼠,海马内谷氨醇-1 (CA1)),然后进行热-机械-冷敏感性试验。通过分子对接研究,研究了PL对阿片能受体的亲和力。采用神经胶质纤维酸性蛋白(GFAP)免疫组化方法评价PL对脊髓背角(SDH)星形胶质细胞形成的影响。结果普乐治疗具有剂量依赖性的抗感知效应。有趣的是,纳洛酮预处理减弱了PL的抗伤害感受作用。此外,PL降低了np触发的SDH中GFAP+ve星形胶质细胞的综合密度。硅结合显示了PL与kappa, delta-和mu-阿片受体的有效结合顺序,与吗啡相当。结论PL可能通过阿片受体抑制SDH星形胶质细胞激活和海马CA1区伤害性加工,从而改善NP。
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引用次数: 0
Modulating obesity-related metabolic dysfunction: Additive effects of Rubi fructus extract and statin in mice 调节肥胖相关代谢功能障碍:Rubi fructus提取物和他汀类药物在小鼠中的叠加效应
Pub Date : 2025-09-01 DOI: 10.1016/j.prmcm.2025.100677
Md Murad , Md. Monirul Islam , Nusrat Jahan Suchana , Md. Mamun Or Rashid , Firoz Ahmed , Fahad Hussain

Introduction

Obesity, marked by excessive adipose tissue accumulation and associated metabolic dysfunctions, remains a major global health concern. Rubi fructus (Chinese name: Fu-pen-zi), the fruit of plants belonging to the Rubus genus, has been traditionally used in Chinese medicine. This study investigates the anti-obesity effects of Rubi fructus (RF) extract and Atorvastatin (AS), both individually and in combination, using a high-fat diet (HFD)-induced obese mouse model. Materials & methods: Twenty-five male Swiss albino mice were randomly assigned to five groups (normal diet, HFD, HFD+RF, HFD+RF+AS, HFD+AS) and treated over a six-week period. The RF and AS were administered at 400 and 3 mg/kg body weight. Post-treatment evaluations included measurements of body weight, abdominal fat mass, serum lipid profiles, hepatic enzyme levels, several organ weights, and expression of adipogenic and inflammatory genes.

Results

Both RF and AS monotherapies significantly (p < 0.05) reduced body weight gain, abdominal adiposity, organ weight, serum triglycerides, total cholesterol, and LDL-C levels, while increasing HDL-C levels. Notably, combined administration of RF and AS produced more substantial improvements across all measured parameters. Liver function was also markedly improved, as evidenced by significant reductions in alkaline phosphatase and aspartate aminotransferase levels. Gene expression analysis demonstrated downregulation of TNF-α, MCP-1, and PPAR-γ, along with upregulation of GLUT-4 in adipose tissue, indicating attenuated inflammation and enhanced insulin sensitivity.

Conclusion

This study provides the first evidence for the additive anti-obesity effects of RF and AS, suggesting a promising new combination therapy for the management of obesity and its metabolic sequelae.
以脂肪组织过度积累和相关代谢功能障碍为特征的肥胖,仍然是一个主要的全球健康问题。Rubi fructus(中文名:Rubi - penzi)是一种属于Rubus属植物的果实,传统上被用于中药。本研究采用高脂饮食(HFD)诱导的肥胖小鼠模型,研究了Rubi fructus (RF)提取物和阿托伐他汀(Atorvastatin, AS)单独和联合使用的抗肥胖作用。材料与方法:25只雄性瑞士白化小鼠随机分为5组(正常饮食、HFD、HFD+RF、HFD+RF+AS、HFD+AS),为期6周。给药剂量分别为400和3 mg/kg体重。治疗后的评估包括测量体重、腹部脂肪量、血脂谱、肝酶水平、几个器官重量以及脂肪生成和炎症基因的表达。结果RF和AS单药治疗均显著(p < 0.05)降低了体重增加、腹部脂肪、器官重量、血清甘油三酯、总胆固醇和LDL-C水平,同时升高了HDL-C水平。值得注意的是,RF和AS联合使用在所有测量参数中产生了更实质性的改善。肝功能也明显改善,如碱性磷酸酶和天冬氨酸转氨酶水平显著降低。基因表达分析显示,TNF-α、MCP-1和PPAR-γ下调,脂肪组织中GLUT-4上调,表明炎症减轻,胰岛素敏感性增强。结论本研究首次证实了RF和AS的联合抗肥胖作用,为肥胖及其代谢后遗症的治疗提供了一种新的联合治疗方法。
{"title":"Modulating obesity-related metabolic dysfunction: Additive effects of Rubi fructus extract and statin in mice","authors":"Md Murad ,&nbsp;Md. Monirul Islam ,&nbsp;Nusrat Jahan Suchana ,&nbsp;Md. Mamun Or Rashid ,&nbsp;Firoz Ahmed ,&nbsp;Fahad Hussain","doi":"10.1016/j.prmcm.2025.100677","DOIUrl":"10.1016/j.prmcm.2025.100677","url":null,"abstract":"<div><h3>Introduction</h3><div>Obesity, marked by excessive adipose tissue accumulation and associated metabolic dysfunctions, remains a major global health concern. <em>Rubi fructus</em> (Chinese name: Fu-pen-zi), the fruit of plants belonging to the Rubus genus, has been traditionally used in Chinese medicine. This study investigates the anti-obesity effects of <em>Rubi fructus</em> (RF) extract and Atorvastatin (AS), both individually and in combination, using a high-fat diet (HFD)-induced obese mouse model. Materials &amp; methods: Twenty-five male Swiss albino mice were randomly assigned to five groups (normal diet, HFD, HFD+RF, HFD+RF+AS, HFD+AS) and treated over a six-week period. The RF and AS were administered at 400 and 3 mg/kg body weight. Post-treatment evaluations included measurements of body weight, abdominal fat mass, serum lipid profiles, hepatic enzyme levels, several organ weights, and expression of adipogenic and inflammatory genes.</div></div><div><h3>Results</h3><div>Both RF and AS monotherapies significantly (<em>p</em> &lt; 0.05) reduced body weight gain, abdominal adiposity, organ weight, serum triglycerides, total cholesterol, and LDL-C levels, while increasing HDL-C levels. Notably, combined administration of RF and AS produced more substantial improvements across all measured parameters. Liver function was also markedly improved, as evidenced by significant reductions in alkaline phosphatase and aspartate aminotransferase levels. Gene expression analysis demonstrated downregulation of TNF-α, MCP-1, and PPAR-γ, along with upregulation of GLUT-4 in adipose tissue, indicating attenuated inflammation and enhanced insulin sensitivity.</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence for the additive anti-obesity effects of RF and AS, suggesting a promising new combination therapy for the management of obesity and its metabolic sequelae.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"16 ","pages":"Article 100677"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Pharmacological Research - Modern Chinese Medicine
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