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A mechanistic review on Zanthoxylum species for anti-inflammatory and analgesic potentials 花椒属植物抗炎镇痛作用机制综述
Pub Date : 2024-12-01 DOI: 10.1016/j.prmcm.2024.100553
Acharya Balkrishna , Meenakshi Panwar , Sakshi Mishra , Vidushi Kala , Vedpriya Arya , Anurag Dabas

Introduction

In Traditional Chinese Medicine (TCM), Zanthoxylum species are valued for their analgesic and anti-inflammatory effects, relieving pain and controlling inflammation. The study aimed to provide insight into how Zanthoxylum species reduce inflammation and pain by targeting molecular pathways and regulating immune responses.

Methods

A structured literature search on PubMed, ScienceDirect, and Google Scholar using targeted keywords yielded a broad selection of sources, which were refined to include 104 articles and 50 books from 1978 to 2023 based on strict criteria. Data extraction focused on identifying bioactive compounds and synthesizing insights into the therapeutic mechanisms of Zanthoxylum species, particularly the key pathways involved.

Results

Only 13 of the 33 traditionally used species were shown to be effective in analgesic responses, and only two were employed in treating inflammation ailments. In comparison, 18 species were found to have both anti-inflammatory and analgesic properties. Furthermore, 16 species exhibited anti-inflammatory and analgesic potential in various in-vitro/in-vivo studies. Only ten species studied had anti-inflammatory responses, two had analgesic activity, and four had both anti-inflammatory and analgesic responses. Bioactive compounds like zanthoxylumamides, zanthoaustrones C, tetrahydrobungeanol, decarene, and zanthoxylumamide B exhibit anti-inflammatory effects through MyD88, IRF3, MAPK, and NF-κB pathways. Additionally, the alkaloid benzophenanthridine and essential oils from various plant parts provide analgesic effects by reducing writhing and flinching responses.

Discussion

Modern studies support the traditional use of Zanthoxylum species for inflammation and pain, highlighting anti-inflammatory and analgesic effects via key pathways and suggesting further clinical validation for safety and efficacy.
在中医中,花椒属植物因其镇痛、抗炎、镇痛、消炎等作用而受到重视。该研究旨在深入了解花椒属植物如何通过靶向分子途径和调节免疫反应来减轻炎症和疼痛。方法在PubMed、ScienceDirect和b谷歌Scholar上使用目标关键词进行结构化文献检索,得到广泛的来源选择,根据严格的标准,从1978年到2023年,将其细化为104篇文章和50本书。数据提取主要集中在鉴定花椒属植物的生物活性化合物和合成治疗机制,特别是所涉及的关键途径。结果在33种传统使用的药物中,只有13种具有镇痛效果,只有两种用于治疗炎症性疾病。相比之下,发现18种同时具有抗炎和镇痛特性。此外,在各种体外/体内研究中,16种植物表现出抗炎和镇痛的潜力。只有10种具有抗炎反应,2种具有镇痛活性,4种同时具有抗炎和镇痛反应。生物活性化合物如zanthoxylumamide、zanthoaustrones C、tetrahydrobungeanol、decarene和zanthoxylumamide B通过MyD88、IRF3、MAPK和NF-κB通路表现出抗炎作用。此外,生物碱苯并苯胺和各种植物部位的精油通过减少扭动和退缩反应提供镇痛作用。现代研究支持花椒属植物治疗炎症和疼痛的传统用途,强调了通过关键途径的抗炎和镇痛作用,并建议进一步的临床安全性和有效性验证。
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引用次数: 0
Exploring the pharmacological mechanism of Tongluo Qingnao formula in treating acute ischemic stroke: A combined approach of network pharmacology, molecular docking and experimental evidences 通络清脑方治疗急性缺血性脑卒中的药理机制探讨网络药理学、分子对接和实验证据相结合的方法
Pub Date : 2024-11-23 DOI: 10.1016/j.prmcm.2024.100550
Feng Li , Yilei Dong , Guangrui Wang , Zishan Huang , Wenting Song , Xiaoyu Zheng , Peng Zhang , Mingjiang Yao

Introduction

Tongluo Qingnao (TLQN) Formula is a patent Traditional Chinese Medicine injection designed for the treatment of Acute Ischemic Stroke (AIS) and associated complications. Previous researches had shown promising potential of TLQN in treating ischemic brain edema. This study aimed to reveal specific mechanisms of TLQN in treating AIS by bioinformatics analysis and following confirmatory experiments.

Methods

HPLC was used to analyze the active ingredients of TLQN. Network Pharmacology and Molecular Docking were introduced to screen treatment targets and pathways. And then middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in rats to verify the therapeutic effect of TLQN in neurological deficit score, cerebral infarction size, HE staining, TUNEL staining, and proteins expression related to inflammation, apoptosis and the PI3K-AKT signaling pathway.

Results

Seven main active ingredients were contained in TLQN. Network pharmacology identified IL-6 and IL-1β as the key targets, and PI3K-AKT as the critical pathway. Molecular Docking analysis indicated that the constituents of TLQN demonstrated a high affinity for crucial targets. TLQN could significantly reduce neurological deficits, pathological lesions and apoptosis caused by AIS. Western blotting results indicated that TLQN can activate the PI3K-AKT signaling pathway, inhibit the expression of pro-apoptotic proteins bax, Caspase-3 and inflammatory factors IL-6, IL-1β.

Discussion

TLQN has a therapeutic effect on AIS, and these results highlight the therapeutic effects of TLQN on AIS by activating PI3K-AKT signaling pathway to inhibit inflammation and apoptosis.
导言 通络活血方(TLQN)是一种中药专利注射剂,专门用于治疗急性缺血性中风(AIS)及其相关并发症。先前的研究表明,通络清脑汤在治疗缺血性脑水肿方面具有良好的潜力。本研究旨在通过生物信息学分析和确证实验,揭示TLQN治疗AIS的具体机制。方法采用高效液相色谱法分析TLQN的有效成分,引入网络药理学和分子对接法筛选治疗靶点和通路。结果TLQN中含有7种主要活性成分。网络药理学确定 IL-6 和 IL-1β 为主要靶点,PI3K-AKT 为关键通路。分子对接分析表明,TLQN 的成分与关键靶点具有很高的亲和力。TLQN 能明显减轻 AIS 引起的神经功能缺损、病理损伤和细胞凋亡。Western blotting结果表明,TLQN能激活PI3K-AKT信号通路,抑制促凋亡蛋白bax、Caspase-3和炎症因子IL-6、IL-1β的表达。
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引用次数: 0
Effect of Eriobotrya japonica L. (Chinese medicinal plant) on the regulation of lipid metabolism in atherosclerosis-induced mice and in HepG-2 cells Eriobotrya japonica L.(中药植物)对动脉粥样硬化诱导小鼠和 HepG-2 细胞脂质代谢调节的影响
Pub Date : 2024-11-22 DOI: 10.1016/j.prmcm.2024.100552
Imane Mokhtari , Dragan Milenkovic , Souliman Amrani , Hicham Harnafi

Background

Hyperlipidemia and related metabolic disorders are the main cause of nonalcoholic fatty liver diseases, atherosclerosis and cardiovascular complications. Loquat (Eriobotrya japonica) leaf infusion is an innovative formula derived from Traditional Chinese medicine, known for its therapeutic properties against a number of ailments including inflammation, diabetes and hyperlipidemia.

Aim of the study

This study was designed to identify the active compounds of an aqueous extract of E. japonica leaves (ELE) and to investigate its effect on hyperlipidemia and related metabolic complications in high-fat high-sucrose diet-fed mice as well as to elucidate the possible underlying mechanisms.

Materials and Methods

Mice were fed a high-fat high-sucrose diet for 3 months and treated with the ELE at doses of 50 mg/kg and 100 mg/kg. Lipids in plasma, liver, adipose tissue, bile and feces were quantified using enzymatic kits. Liver steatosis and oxidative status were highlighted by measuring AST, ALT, ALP, MDA, SOD and catalase activities as well as monitoring of lipid droplets in histological sections. The identification and quantification of possible active compounds were carried out using the HPLC-DAD method. The underlying mechanisms were predicted by in silico study and confirmed by quantifying the expression of the principal involved proteins including PCSK-9, CYP7A1 and p-AMPK in HepG2 cells.

Results

The ELE restored lipid metabolism and improved liver histological structures. It also reduced oxidative stress by lowering MDA levels and activating SOD and catalase enzymes. The ELE prevented hepatic steatosis and corrected transaminases profile. HPLC analysis reveals seven phenolic compounds, with ferulic acid being the major one. The extract and its identified phenolic compounds upregulated the expression of CYP7A1 and p-AMPK while downregulated the expression of PCSK-9 in HepG2 cells. The ELE appears to be nontoxic in mice (LD50>5000 mg/kg) and in HepG2 cells at pharmacologically active doses.

Conclusion

the ELE could be considered as a source of active biomolecules to produce phytotherapeutics drugs or dietary supplements to treat hyperlipidemia and related cardio-metabolic diseases.
背景高脂血症及相关代谢紊乱是导致非酒精性脂肪肝、动脉粥样硬化和心血管并发症的主要原因。枇杷叶注射液是一种创新的中药配方,以其对炎症、糖尿病和高脂血症等多种疾病的治疗特性而闻名。材料和方法小鼠以高脂肪、高蔗糖饮食喂养 3 个月,并分别以 50 毫克/千克和 100 毫克/千克的剂量接受 ELE 治疗。使用酶试剂盒对血浆、肝脏、脂肪组织、胆汁和粪便中的脂质进行定量。通过测量 AST、ALT、ALP、MDA、SOD 和过氧化氢酶的活性以及监测组织切片中的脂滴,突出了肝脏脂肪变性和氧化状态。采用 HPLC-DAD 方法对可能的活性化合物进行了鉴定和定量。结果 ELE 恢复了脂质代谢,改善了肝脏组织学结构。它还通过降低 MDA 水平、激活 SOD 和过氧化氢酶来减少氧化应激。乙烯利防止了肝脏脂肪变性,并纠正了转氨酶谱。高效液相色谱分析显示了七种酚类化合物,其中阿魏酸是主要的酚类化合物。该提取物及其确定的酚类化合物能上调 CYP7A1 和 p-AMPK 的表达,同时下调 HepG2 细胞中 PCSK-9 的表达。ELE似乎对小鼠无毒(LD50>5000 mg/kg),在药理活性剂量下对HepG2细胞也无毒。
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引用次数: 0
Unraveling biomolecules, antidiabetic and antioxidants properties of DelitesTM via pharmacoinformatics and in vitro investigation 通过药物信息学和体外研究揭示得利特TM的生物分子、抗糖尿病和抗氧化特性
Pub Date : 2024-11-20 DOI: 10.1016/j.prmcm.2024.100551
Juan Leonardo , Purnawan Pontana Putra , Trina Ekawati Tallei , Fatimawali Fatimawali , Nurpudji Astuti Taslim , Raymond Rubianto Tjandrawinata , Vincent Lau , Saad Mustafa , Miguel A Prieto , Fahrul Nurkolis

Introduction

Type 2 diabetes (T2D) remains a global health burden characterized by insulin resistance and chronic hyperglycemia, often exacerbated by oxidative stress, leading to severe complications. Despite the efficacy of pharmacological treatments such as metformin, their side effects and costs highlight the need for alternative therapies. Delites™ (Chong Cao Ling Zhi Xiang Tang), a multi-herbal formulation, presents a promising solution with its bioactive compounds including Apocynin, Curcumin, and Quercetin, which are hypothesized to target T2D pathways.

Methods

This study employed pharmacoinformatics, in vitro assays, and molecular dynamics simulations to evaluate the antidiabetic and antioxidative properties of Delites™. Metabolomic profiling using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry identified active compounds, while in silico docking analyzed interactions with T2D-related proteins (e.g., KCNJ11, TCF7L2). Enzyme inhibition assays measured alpha-glucosidase and alpha-amylase activity, and antioxidant potential was assessed using ABTS inhibition.

Results

Delites™ demonstrated significant enzyme inhibition (EC50 < metformin), strong binding affinity to T2D proteins (e.g., Sachaliside 2: -9.4 kcal/mol with TCF7L2), and antioxidant activity comparable to Trolox (EC50: 54.44 mg/mL). Molecular dynamics confirmed stable interactions of its compounds with target proteins, while network pharmacology highlighted multi-target potential against diabetes-related pathways.

Discussion

The findings underline Delites™ as a multi-target therapeutic candidate for T2D management. Its ability to inhibit carbohydrate-hydrolyzing enzymes, interact strongly with key proteins, and mitigate oxidative stress positions it as a holistic alternative. However, further clinical trials are essential to validate these promising in vitro and in silico results, particularly its long-term efficacy and safety.
导言2型糖尿病(T2D)仍然是一个全球性的健康负担,其特点是胰岛素抵抗和慢性高血糖,往往因氧化应激而加剧,导致严重的并发症。尽管二甲双胍等药物治疗具有一定的疗效,但其副作用和成本凸显了对替代疗法的需求。Delites™(冲草灵芝香汤)是一种多草药制剂,其生物活性化合物包括阿朴昔宁、姜黄素和槲皮素,据推测可靶向治疗 T2D 的途径,是一种很有前景的解决方案。利用超高效液相色谱法和高分辨质谱法进行的代谢组学分析确定了活性化合物,而硅学对接分析了与 T2D 相关蛋白(如 KCNJ11、TCF7L2)的相互作用。酶抑制试验测定了α-葡萄糖苷酶和α-淀粉酶的活性,并使用 ABTS 抑制剂评估了抗氧化潜力。结果Delites™ 显示出显著的酶抑制作用(EC50 <;二甲双胍)、与 T2D 蛋白质的强结合亲和力(例如,Sachaliside 2:与 TCF7L2 的结合亲和力为 -9.4 kcal/mol)以及与 Trolox 相当的抗氧化活性(EC50:54.44 mg/mL)。分子动力学证实了其化合物与靶蛋白的稳定相互作用,而网络药理学则强调了针对糖尿病相关通路的多靶点潜力。它能够抑制碳水化合物水解酶,与关键蛋白产生强烈的相互作用,并能减轻氧化应激,是一种全面的替代疗法。然而,要验证这些有前景的体外和硅学结果,特别是其长期疗效和安全性,还需要进一步的临床试验。
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引用次数: 0
Protective effects of Bidens pilosa alleviates against alcohol—induced hepatic steatosis in rats: In vivo studies and in silico analysis Bidens pilosa 的保护作用可减轻酒精引起的大鼠肝脂肪变性:体内研究和硅学分析
Pub Date : 2024-11-16 DOI: 10.1016/j.prmcm.2024.100546
Melva Silitonga , Hudson Sidabutar , Hendro Pranoto , Adriana Yulinda Dumaria LumbanGaol , Feimmy Ruth Pratiwi Sipahutar

Background

Steatosis has become the critical indicator of the higher alcohol exposure to liver injury. Traditional Chinese medicine, notably Bidens pilosa, is used as anti-inflammatory, antihyperglycemic, and hepatoprotective. This current study aimed to investigate the protective effect of Bidens pilosa leaves ethanolic extract (EEB) against alcohol induced hepatic steatosis.

Methods

Using the rat model of alcoholic hepatic steatosis (AHS), this study investigated EEB efficacy through the experimental analysis and in silico method. The animals received EEB at doses of 300 and 600 mg/kg for 42 days in the acute alcoholic experiment. Biochemical analysis and histopathological alteration are examined in alcohol-induced liver rats. Additionally, the pharmacological analysis, molecular docking and dynamic study were evaluated.

Results

The results indicated that the EEB has ameliorative effects against hepatic steatosis. It significantly improved hepatic histopathological change, the level of blood glucose, triglyceride, LDL and cholesterol in rats exposed to alcohol. Furthermore, the virtual screening study demonstrated the predominant compounds of EEB might regulate the top core targets linked to AHS, particularly AKT/PIK3CA, MAPK, and MTOR, respectively.

Conclusion

Thus, the preventive effect of EEB could be an underlying mechanism for the development of herbal medicine to treat AHS in clinical therapy.
背景脂肪变性已成为较高酒精暴露对肝损伤的重要指标。传统中药,尤其是白花蛇舌草,具有抗炎、降血糖和保肝的作用。本研究旨在探讨白花蛇舌草乙醇提取物(EEB)对酒精诱导的肝脂肪变性的保护作用。方法本研究采用酒精性肝脂肪变性(AHS)大鼠模型,通过实验分析和硅学方法研究 EEB 的功效。在急性酒精中毒实验中,大鼠分别以 300 和 600 mg/kg 的剂量接受 EEB 治疗 42 天。对酒精诱导的肝脏大鼠进行生化分析和组织病理学改变研究。结果表明,EEB 对肝脏脂肪变性有改善作用。结果表明,EEB 对肝脂肪变性有改善作用,能明显改善酒精暴露大鼠的肝组织病理学变化、血糖、甘油三酯、低密度脂蛋白和胆固醇水平。此外,虚拟筛选研究表明,EEB 的主要化合物可能分别调节与 AHS 相关的顶级核心靶标,特别是 AKT/PIK3CA、MAPK 和 MTOR。
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引用次数: 0
Acorus gramineus extract decreases cancer stem cell properties and stimulates ROS signaling pathway in HepG2 hepatocellular carcinoma cells 石菖蒲提取物在 HepG2 肝癌细胞中降低癌症干细胞特性并刺激 ROS 信号通路
Pub Date : 2024-11-16 DOI: 10.1016/j.prmcm.2024.100548
Van Hung Hoang , Thi Thanh Huong Le , Phu Hung Nguyen , Viet Hoang , Van Khang Pham , Thi Kieu Oanh Nguyen , Dinh Quang Hung Can

Background

Acorus gramineus is called “Shi Chang Pu'” in Chinese and has been used in traditional Chinese medicine (TCM) for over 2,000 years. The records in the 'Shennong Bencao Jing' show that many species in the genus Acorus are used to treat various diseases in humans such as epilepsy, cardiovascular issues, abdominal pain, memory loss, etc. Several species of the genus Acorus have been demonstrated to exhibit antiproliferative effects against various cancer cell lines. This study aims to evaluate the inhitory effects of Acorus gramineus extract (AGE) on HepG2 liver cancer cells.

Methods

The inhibitory effect of AGE on HepG2 cell proliferation was assessed using the MTT assay. Migration was analyzed using the wound healing technique. The 3D culture technique was employed to evaluate tumorsphere formation and the invasive potential of cancer cells. Real-time PCR was used for mRNA expression analysis. Changes in the expression levels of CD44 protein and ROS were analyzed using fluorescence staining techniques. Chemical compounds of AGE were identified using UPLC-QToF-MS.

Results

The results indicate that AGE exhibits potent inhibitory activity against cell proliferation, with an IC50 value of 34.1 mg/mL. AGE significantly inhibited both the formation and growth of tumorspheres in 3D cultures, reducing both their number and size. Additionally, AGE was found to suppress the invassion of cancer cells. AGE regulated the downregulation of stem cell-related markers including NANOG, SOX2, OCT4, and ALDH. AGE was also shown to increase the production of reactive oxygen species (ROS) within cells by activating genes involved in ROS signaling pathways, which may lead to a decrease in cell proliferation, migration, and invasion, as well as a reduction in cancer stem cell properties. Finally, 58 compounds present in AGE were identified by UPLC-QtoF-MS analysis, and Mulberrofuran K, Akebonoic acid, and Shancilin were evaluated for their affinity with protein markers related to liver cancer stem cells.

Conclusion

This study is the first report on the inhibitory activity of AGE against cancer stem cell characteristics in HepG2 cells, highlighting the potential of this plant species as an anti-liver cancer agent.
背景石菖蒲在中国被称为 "石长普",用于传统中药已有两千多年的历史。根据《神农本草经》的记载,石菖蒲属的许多物种都可用于治疗人类的各种疾病,如癫痫、心血管问题、腹痛、记忆力减退等。石菖蒲属的多个品种已被证实对多种癌细胞株具有抗增殖作用。本研究旨在评估石菖蒲提取物(AGE)对 HepG2 肝癌细胞的抑制作用。迁移采用伤口愈合技术进行分析。采用三维培养技术评估肿瘤球的形成和癌细胞的侵袭潜力。实时 PCR 用于 mRNA 表达分析。采用荧光染色技术分析 CD44 蛋白和 ROS 表达水平的变化。结果表明,AGE 对细胞增殖有很强的抑制作用,其 IC50 值为 34.1 mg/mL。AGE 能明显抑制三维培养物中肿瘤球的形成和生长,减少肿瘤球的数量和大小。此外,AGE 还能抑制癌细胞的侵袭。AGE 可抑制干细胞相关标记物的下调,包括 NANOG、SOX2、OCT4 和 ALDH。研究还表明,AGE通过激活参与ROS信号通路的基因,增加了细胞内活性氧(ROS)的产生,这可能会导致细胞增殖、迁移和侵袭的减少,以及癌症干细胞特性的降低。最后,通过UPLC-QtoF-MS分析鉴定了AGE中的58种化合物,并评估了Mulberrofuran K、Akebonoic acid和Shancilin与肝癌干细胞相关蛋白质标记物的亲和性。
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引用次数: 0
Gu Sui Bu (Drynaria fortunei J. Smith) prevents osteoporosis in ovariectomized rats by inhibiting pyroptosis through NLRP3/GSDMD/CASPASE-1 古遂布(Drynaria fortunei J. Smith)通过 NLRP3/GSDMD/CASPASE-1 抑制热蛋白沉积,从而预防卵巢切除大鼠的骨质疏松症
Pub Date : 2024-11-12 DOI: 10.1016/j.prmcm.2024.100544
Hui su , Jun Dong , Luyao Liu , Zechen Yan , Rujie Zhuang , Guangxin Huang , Haipeng Xue , Zhanwang Xu , Yu Pan
<div><div>Traditional Chinese medicine Gu Sui Bu (<em>Drynaria fortunei J. Smith</em>), has the effect of tonifying the kidneys and strengthening bone. There are many modern studies on the anti-osteoporosis pharmacological mechanism of Gu Sui Bu (<em>Drynaria fortunei J. Smith</em>) but no reports on the pharmacological mechanism of Gu Sui Bu (<em>Drynaria fortunei J. Smith</em>) improving cell pyroptosis and anti-osteoporosis have been found.</div></div><div><h3>Aim</h3><div>This study aims to verify the changes in cellular standard indicators in postmenopausal osteoporosis, thereby revealing the participating mechanism of pyroptosis and the intervention effect of Gu Sui Bu (<em>Drynaria fortunei J. Smith)</em> .</div></div><div><h3>Methods</h3><div>Gu Sui Bu (<em>Drynaria fortunei J. Smith</em>) subjected to UHPLC-Q-Orbitrap-MS/MS analysis, and the OVX rat model was constructed in vivo as the research object. It was divided into sham operation group (SHAM), ovariectomized osteoporosis model group (OVX) and Gu Sui Bu (<em>Drynaria fortunei J. Smith</em>) group (TFRD-L, TFRD-H). After 3 months of modeling, the medication group was treated with Gu Sui Bu (<em>Drynaria fortunei J. Smith</em>) and the samples were collected after 12 weeks of intervention. ELISA was used to detect the levels of Caspase-1, NLRP3, GSDMD, IL-1β, and IL-18 in rat serum; the right femur was taken for Micro-CT large bone microstructure scanning and femoral BMD detection; the femur was subjected to rat histopathology HE, TRAP staining; immunohistochemistry and immunofluorescence staining of rat histopathology were performed. WB and PCR were used to observe the expression of Osteoblasts and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD and RUNX2, IL-1β, and IL-18.</div></div><div><h3>Results</h3><div>UHPLC-Q-Orbitrap-MS/MS analysis the main compounds in Gu Sui Bu (<em>Drynaria fortunei J. Smith)</em> samples were identified. These 9 chemical components are Palmitic acid, Fisetin, Caffeic acid, Naringin, Rutin, Uridine, Cafestol, Astilbin . Rat Micro-CT, The results of HE staining and TRAP showed that compared with the rats in the OVX group, the number of bone trabeculae in the rats in the <em>Gu Sui Bu (Drynaria fortunei J. Smith)</em> medication group (TFRD-L, TFRD-H) increased, became wider and thicker, and the bone density increased. Continuity increases and bone lacunae decrease. Rat serum ELISA, femoral tissue immunohistochemistry, immunofluorescence staining and WB, PCR showed that compared with the OVX group, Caspase-1, NLRP3, The expression levels of GSDMD and inflammation were reduced (p<0.05), and the expression of osteogenic marker RUNX2 was reduced and increased (p<0.05).</div></div><div><h3>Conclusion</h3><div>The traditional Chinese medicine Gu Sui Bu (<em>Drynaria fortunei J. Smith)</em> can improve the bone density of ovariectomized osteoporosis model rats and significantly enhance the bone microstructure. At the same time, it reduced the expres
中药古遂布(Drynaria fortunei J. Smith)具有补肾壮骨的功效。现代有许多关于归脾汤抗骨质疏松药理机制的研究,但尚未发现归脾汤改善细胞热解和抗骨质疏松药理机制的报道。本研究旨在验证绝经后骨质疏松症细胞标准指标的变化,从而揭示古遂布参与骨质疏松的机制及其干预作用。 方法将古遂布(Drynaria fortunei J. Smith)进行超高效液相色谱-Q-Orbitrap-MS/MS分析,在体内构建OVX大鼠模型作为研究对象。该模型分为假手术组(SHAM)、卵巢切除骨质疏松症模型组(OVX)和古遂布(Drynaria fortunei J. Smith)组(TFRD-L、TFRD-H)。建模 3 个月后,药物组接受顾遂布(Drynaria fortunei J. Smith)治疗,干预 12 周后收集样本。采用ELISA法检测大鼠血清中Caspase-1、NLRP3、GSDMD、IL-1β和IL-18的水平;取右股骨进行Micro-CT大骨显微结构扫描和股骨BMD检测;对大鼠股骨进行组织病理学HE、TRAP染色;对大鼠组织病理学进行免疫组化和免疫荧光染色。结果UHPLC-Q-Orbitrap-MS/MS分析确定了古遂布(Drynaria fortunei J. Smith)样品中的主要化合物。这 9 种化学成分分别是棕榈酸、鱼腥苷、咖啡酸、柚皮苷、芦丁、尿苷、咖啡酚、黄芪苷。大鼠显微 CT:HE 染色和 TRAP 结果显示,与卵巢功能缺失组大鼠相比,服用古遂布(Drynaria fortunei J. Smith)药物组(TFRD-L、TFRD-H)大鼠的骨小梁数量增加,骨小梁变宽、变粗,骨密度增加。连续性增加,骨裂减少。大鼠血清ELISA、股骨组织免疫组化、免疫荧光染色和WB、PCR结果显示,与OVX组相比,Caspase-1、NLRP3、GSDMD和炎症的表达水平降低(p<0.05),成骨标志物 RUNX2 的表达减少和增加(p<0.05)。 结论中药古遂布(Drynaria fortunei J. Smith)能提高卵巢切除骨质疏松症模型大鼠的骨密度,显著增强骨的微结构。同时,它还能降低体内Caspase-1、NLRP3和GSDMD的表达,证实古遂布可通过NLRP3/GSDMD/Caspase-1途径发挥抗骨质疏松症的作用。
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引用次数: 0
In silico and in vivo evaluations of fisetin and fisetin-loaded nanosuspension on monoamine oxidase inhibition in Aβ(25–35) induced dementia in mice model 鱼腥草素和鱼腥草素纳米悬浮液对 Aβ(25-35)诱导的小鼠痴呆模型中单胺氧化酶抑制作用的硅学和体内评估
Pub Date : 2024-11-12 DOI: 10.1016/j.prmcm.2024.100547
Siti Zaidathul Iman Zolkiffly , Mizaton Hazizul Hasan , Siti Azma Jusoh , Ashok Kumar Janakiraman , Sathesh Kumar Sukumaran , Noreen Husain , Yuslina Zakaria , Hanish Singh Jayasingh Chellammal

Background

Amyloid beta (Aβ) plaques on the extracellular matrix and intracellular neurofibrillary tangles comprise the key indicative pathology of Alzheimer's disease (AD). Fisetin, an antioxidant bioactive compound having pharmacotherapeutic effects is applied by traditional Chinese medicine (TCM) such as Toxicodendron vernicifum (Chinese lacquer tree), Cotinus coggygria Scop, Gan Shuang granulates and formula of Acacia catechu-Scutellariae Radix. Nevertheless, fisetin has constraints such as low oral bioavailability, insignificant aqueous solubility and high hepatic metabolisms.

Objective

This investigation aimed to envisage the effects of fisetin and its optimised nanoformulation on Aβ(25–35) desirous neurotoxicity in mice through deciphering inhibitory actions against monoamine oxidase A and B (MAO-A and B) enzymes following molecular docking.

Methods

Molecular docking with MAO-A and B enzymes were accomplished by AMDock's integrated AutoDock Tools (ADT) scripts. For in vivo studies, fisetin nanosuspension was prepared by nanoprecipitation method and evaluated for standard characterization. 10 and 20 mg/kg of fisetin and 10 mg/kg of fisetin nanosuspension were given once daily to mice for 21 days. On the 15th day, the mice were challenged with Aβ(25–35) by intracerebroventricular injection (ICV) and behavioural tests (open field and elevated plus maze) were performed on the 20th day. Biochemical and histology were examined in brain tissues.

Results

Fisetin docked to the catalytic positions of MAO-A and B, unveiling good binding scores and molecular interactions with amino acid residues for inhibition activities. Fisetin nanosuspension has average particle size (225.4 ± 2.95 nm) with low polydispersity index (0.19) and standard zeta potential (-19.13 ± 1.17 mV). Findings showed that fisetin increased locomotor activity and reduced anxiety-like behaviour. Fisetin and its nanosuspension significantly reduced the concentration of MAO-A (P < 0.01) and MAO-B enzymes suggesting a potential neuroprotection effect in Aβ peptide-induced amnesia in mice.

Conclusion

Fisetin with optimized bioavailability, effectively exhibits neuroprotection through molecular interactions of MAO enzymes. Further investigations affidavits the neuroprotection through bidirectional pathways related to biogenic amines and their deamination on Aβ stress conditions.
背景细胞外基质上的淀粉样β(Aβ)斑块和细胞内的神经纤维缠结是阿尔茨海默病(AD)的主要病理指标。鱼腥草素是一种具有药物治疗作用的抗氧化生物活性化合物,传统中药(如漆树、茯苓、甘爽颗粒和合欢芩连方)均有应用。然而,鱼腥草素存在口服生物利用度低、水溶性差和肝脏代谢率高等限制。本研究的目的是通过分子对接法解读鱼腥草素对单胺氧化酶 A 和 B(MAO-A 和 B)酶的抑制作用,从而了解鱼腥草素及其优化纳米制剂对小鼠 Aβ(25-35)嗜欲神经毒性的影响。在体内研究中,采用纳米沉淀法制备了鱼腥草素纳米悬浮液,并进行了标准特性评估。每天给小鼠注射一次 10 毫克/千克和 20 毫克/千克的鱼腥草素和 10 毫克/千克的鱼腥草素纳米悬浮液,连续 21 天。第15天,小鼠脑室内注射(ICV)Aβ(25-35),第20天进行行为测试(开阔地和高架加迷宫)。结果 鱼腥草素与 MAO-A 和 B 的催化位置对接,显示出良好的结合得分以及与氨基酸残基的分子相互作用,从而产生抑制活性。鱼腥草素纳米悬浮液具有平均粒径(225.4 ± 2.95 nm)、低多分散指数(0.19)和标准zeta电位(-19.13 ± 1.17 mV)。研究结果表明,鱼腥草素能提高运动活性,减少焦虑行为。鱼腥草素及其纳米悬浮液可明显降低 MAO-A 酶(P < 0.01)和 MAO-B 酶的浓度,这表明其对 Aβ 肽诱导的小鼠健忘症具有潜在的神经保护作用。进一步的研究证实,在 Aβ 应激条件下,通过与生物胺及其脱氨相关的双向途径,可发挥神经保护作用。
{"title":"In silico and in vivo evaluations of fisetin and fisetin-loaded nanosuspension on monoamine oxidase inhibition in Aβ(25–35) induced dementia in mice model","authors":"Siti Zaidathul Iman Zolkiffly ,&nbsp;Mizaton Hazizul Hasan ,&nbsp;Siti Azma Jusoh ,&nbsp;Ashok Kumar Janakiraman ,&nbsp;Sathesh Kumar Sukumaran ,&nbsp;Noreen Husain ,&nbsp;Yuslina Zakaria ,&nbsp;Hanish Singh Jayasingh Chellammal","doi":"10.1016/j.prmcm.2024.100547","DOIUrl":"10.1016/j.prmcm.2024.100547","url":null,"abstract":"<div><h3>Background</h3><div>Amyloid beta (Aβ) plaques on the extracellular matrix and intracellular neurofibrillary tangles comprise the key indicative pathology of Alzheimer's disease (AD). Fisetin, an antioxidant bioactive compound having pharmacotherapeutic effects is applied by traditional Chinese medicine (TCM) such as <em>Toxicodendron vernicifum</em> (Chinese lacquer tree), <em>Cotinus coggygria Scop</em>, Gan Shuang granulates and formula of <em>Acacia catechu</em>-<em>Scutellariae Radix</em>. Nevertheless, fisetin has constraints such as low oral bioavailability, insignificant aqueous solubility and high hepatic metabolisms.</div></div><div><h3>Objective</h3><div>This investigation aimed to envisage the effects of fisetin and its optimised nanoformulation on Aβ<sub>(25–35)</sub> desirous neurotoxicity in mice through deciphering inhibitory actions against monoamine oxidase A and B (MAO-A and B) enzymes following molecular docking.</div></div><div><h3>Methods</h3><div>Molecular docking with MAO-A and B enzymes were accomplished by AMDock's integrated AutoDock Tools (ADT) scripts. For <em>in vivo</em> studies, fisetin nanosuspension was prepared by nanoprecipitation method and evaluated for standard characterization. 10 and 20 mg/kg of fisetin and 10 mg/kg of fisetin nanosuspension were given once daily to mice for 21 days. On the 15th day, the mice were challenged with Aβ<sub>(25–35)</sub> by intracerebroventricular injection (ICV) and behavioural tests (open field and elevated plus maze) were performed on the 20th day. Biochemical and histology were examined in brain tissues.</div></div><div><h3>Results</h3><div>Fisetin docked to the catalytic positions of MAO-A and B, unveiling good binding scores and molecular interactions with amino acid residues for inhibition activities. Fisetin nanosuspension has average particle size (225.4 ± 2.95 nm) with low polydispersity index (0.19) and standard zeta potential (-19.13 ± 1.17 mV). Findings showed that fisetin increased locomotor activity and reduced anxiety-like behaviour. Fisetin and its nanosuspension significantly reduced the concentration of MAO-A (<em>P &lt;</em> 0.01) and MAO-B enzymes suggesting a potential neuroprotection effect in Aβ peptide-induced amnesia in mice.</div></div><div><h3>Conclusion</h3><div>Fisetin with optimized bioavailability, effectively exhibits neuroprotection through molecular interactions of MAO enzymes. Further investigations affidavits the neuroprotection through bidirectional pathways related to biogenic amines and their deamination on Aβ stress conditions.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"13 ","pages":"Article 100547"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Progress on Tripterygium wilfordii Hook f. as a treatment option for neurodegenerative diseases 作为神经退行性疾病治疗方案的三尖杉研究进展
Pub Date : 2024-11-12 DOI: 10.1016/j.prmcm.2024.100545
Zhong-mou Zhang , Tian-tian Zuo , Ming-hui Chen , Cai-xia Zang , Yong-jian Wang , Ya-dan Wang , Shuang-cheng Ma

Introduction

Neurodegenerative diseases are becoming increasingly widespread as the global population ages. Although neurodegenerative diseases have received continued attention from researchers, there are currently no drugs that can reverse the progression of these diseases. Tripterygium wilfordii Hook f., a traditional form of Chinese medicine, has been widely used to treat many diseases due to its numerous bioactivities and shows considerable potential for the improvement of neurodegenerative diseases.

Methods

Articles for this review were searched on Pubmed, Scifinder, CNKI and Web of Science. Keyword included “Tripterygium wilfordii and neurodegenerative disease,” “triptolide and neurodegenerative disease,” “celastrol and neurodegenerative disease,” and “tripchlorolide and neurodegenerative disease.” 178 articles were initially retrieved and 119 articles were cited finally.

Results

In this study, we summarize the progress of T. wilfordii, especially its bioactive components such as triptolide, celastrol and tripchlorolide for the treatment of neurodegenerative diseases and review the therapeutic mechanisms involved. This article provides reference guidelines for the use of T. wilfordii to treat neurodegenerative diseases.

Discussion

The bioactive components like triptolide, celastrol, tripchlorolide and others extracted from T. wilfordii has enormous potential in the treatment of neurodegenerative diseases. However, the vague pathogenic mechanisms underlying neurodegenerative diseases, as well as toxicity and side effects of T. wilfordii on clinical use still exist. Further research is needed to investigate these issues.
引言 随着全球人口老龄化的加剧,神经退行性疾病正变得越来越普遍。尽管神经退行性疾病一直受到研究人员的关注,但目前还没有药物能够逆转这些疾病的发展。Tripterygium wilfordii Hook f.是一种传统的中药,因其多种生物活性而被广泛用于治疗多种疾病,在改善神经退行性疾病方面显示出相当大的潜力。关键词包括 "Tripterygium wilfordii 和神经退行性疾病"、"triptolide 和神经退行性疾病"、"celastrol 和神经退行性疾病 "以及 "tripchlorolide 和神经退行性疾病"。结果在本研究中,我们总结了威灵仙的研究进展,尤其是其生物活性成分如三苯内酯、青霉烯醇和三氯内酯治疗神经退行性疾病的研究进展,并回顾了其中的治疗机制。本文为使用威灵仙治疗神经退行性疾病提供了参考指南。讨论从威灵仙中提取的生物活性成分,如三苯甲基内酯、芹菜醇、三氯内酯等,在治疗神经退行性疾病方面具有巨大的潜力。然而,神经退行性疾病的致病机制尚不明确,临床应用中的毒性和副作用也依然存在。这些问题都需要进一步研究。
{"title":"Progress on Tripterygium wilfordii Hook f. as a treatment option for neurodegenerative diseases","authors":"Zhong-mou Zhang ,&nbsp;Tian-tian Zuo ,&nbsp;Ming-hui Chen ,&nbsp;Cai-xia Zang ,&nbsp;Yong-jian Wang ,&nbsp;Ya-dan Wang ,&nbsp;Shuang-cheng Ma","doi":"10.1016/j.prmcm.2024.100545","DOIUrl":"10.1016/j.prmcm.2024.100545","url":null,"abstract":"<div><h3>Introduction</h3><div>Neurodegenerative diseases are becoming increasingly widespread as the global population ages. Although neurodegenerative diseases have received continued attention from researchers, there are currently no drugs that can reverse the progression of these diseases. <em>Tripterygium wilfordii</em> Hook f., a traditional form of Chinese medicine, has been widely used to treat many diseases due to its numerous bioactivities and shows considerable potential for the improvement of neurodegenerative diseases.</div></div><div><h3>Methods</h3><div>Articles for this review were searched on Pubmed, Scifinder, CNKI and Web of Science. Keyword included “<em>Tripterygium wilfordii</em> and neurodegenerative disease,” “triptolide and neurodegenerative disease,” “celastrol and neurodegenerative disease,” and “tripchlorolide and neurodegenerative disease.” 178 articles were initially retrieved and 119 articles were cited finally.</div></div><div><h3>Results</h3><div>In this study, we summarize the progress of <em>T. wilfordii</em>, especially its bioactive components such as triptolide, celastrol and tripchlorolide for the treatment of neurodegenerative diseases and review the therapeutic mechanisms involved. This article provides reference guidelines for the use of <em>T. wilfordii</em> to treat neurodegenerative diseases.</div></div><div><h3>Discussion</h3><div>The bioactive components like triptolide, celastrol, tripchlorolide and others extracted from <em>T. wilfordii</em> has enormous potential in the treatment of neurodegenerative diseases. However, the vague pathogenic mechanisms underlying neurodegenerative diseases, as well as toxicity and side effects of <em>T. wilfordii</em> on clinical use still exist. Further research is needed to investigate these issues.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"13 ","pages":"Article 100545"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Traditional Chinese medicine in Alzheimer's disease: From the perspective of GSK-3β and Tau hyperphosphorylation 中药在阿尔茨海默病中的应用:从GSK-3β和Tau过度磷酸化的角度看阿尔茨海默病
Pub Date : 2024-11-06 DOI: 10.1016/j.prmcm.2024.100543
Mei Wang , Wendi Huang , Juan Huang , Jingshan Shi , Nanqu Huang , Yong Luo

Introduction

Alzheimer's disease (AD) accounts for the majority of dementia cases, characterized by a gradual decline in memory and cognitive functions. Traditional Chinese medicine (TCM) has a long history of treating AD and has proposed a series of causes, pathogenesis and treatment methods, and has extremely rich experience in the treatment of AD. TCM believes that deficiency of the spleen, which is the main organ for the body to absorb nutrients, is one of the important causes of AD. Which coincides with the theory that AD is type 3 diabetes in recent years. Therefore, effectively regulating the common targets of AD and diabetes is a potential strategy for treating spleen deficiency type AD.

Method

By conducting an in-depth search in PubMed and China National Knowledge Infrastructure (CNKI), using the keywords " Traditional Chinese Medicine", "Alzheimer's Disease", "GSK-3β", "Tau Protein" and "Tau Hyperphosphorylation". Ultimately, 92 papers were included for review.

Result

Glycogen synthase kinase 3 beta (GSK-3β) plays a significant role in the pathogenesis of AD, and numerous in vitro and in vivo experiments have demonstrated that Chinese medicine monomers and compounds can inhibit its activity, reducing the hyperphosphorylation of Tau.

Discussion

TCM can affect the activity of GSK-3β through various pathways, thereby reducing the hyperphosphorylation of Tau protein and improving the cognitive function of AD. These studies highlight the potential of TCM in treating AD, but further basic and clinical research is still required to validate their safety and efficacy. It is expected that our review will yield novel insights and a scientific foundation for investigating the underlying mechanisms of AD and developing novel anti-AD therapeutics.
导言阿尔茨海默病(AD)占痴呆症病例的绝大多数,以记忆力和认知功能逐渐减退为特征。中医治疗阿尔茨海默病历史悠久,提出了一系列病因、病机和治疗方法,在治疗阿尔茨海默病方面有着极为丰富的经验。中医认为,脾主运化,脾虚是AD的重要病因之一。这与近年来AD是3型糖尿病的理论不谋而合。方法以 "中医药"、"阿尔茨海默病"、"GSK-3β"、"Tau蛋白"、"Tau过度磷酸化 "为关键词,在PubMed和中国知网(CNKI)进行深入检索。结果糖原合酶激酶3β(GSK-3β)在AD的发病机制中起着重要作用,大量体外和体内实验证明,中药单体和复方可以抑制其活性,降低Tau的过度磷酸化。这些研究凸显了中药治疗AD的潜力,但仍需进一步的基础和临床研究来验证其安全性和有效性。希望我们的综述能为研究AD的内在机制和开发新型抗AD疗法提供新的见解和科学依据。
{"title":"Traditional Chinese medicine in Alzheimer's disease: From the perspective of GSK-3β and Tau hyperphosphorylation","authors":"Mei Wang ,&nbsp;Wendi Huang ,&nbsp;Juan Huang ,&nbsp;Jingshan Shi ,&nbsp;Nanqu Huang ,&nbsp;Yong Luo","doi":"10.1016/j.prmcm.2024.100543","DOIUrl":"10.1016/j.prmcm.2024.100543","url":null,"abstract":"<div><h3>Introduction</h3><div>Alzheimer's disease (AD) accounts for the majority of dementia cases, characterized by a gradual decline in memory and cognitive functions. Traditional Chinese medicine (TCM) has a long history of treating AD and has proposed a series of causes, pathogenesis and treatment methods, and has extremely rich experience in the treatment of AD. TCM believes that deficiency of the spleen, which is the main organ for the body to absorb nutrients, is one of the important causes of AD. Which coincides with the theory that AD is type 3 diabetes in recent years. Therefore, effectively regulating the common targets of AD and diabetes is a potential strategy for treating spleen deficiency type AD.</div></div><div><h3>Method</h3><div>By conducting an in-depth search in PubMed and China National Knowledge Infrastructure (CNKI), using the keywords \" Traditional Chinese Medicine\", \"Alzheimer's Disease\", \"GSK-3β\", \"Tau Protein\" and \"Tau Hyperphosphorylation\". Ultimately, 92 papers were included for review.</div></div><div><h3>Result</h3><div>Glycogen synthase kinase 3 beta (GSK-3β) plays a significant role in the pathogenesis of AD, and numerous <em>in vitro</em> and <em>in vivo</em> experiments have demonstrated that Chinese medicine monomers and compounds can inhibit its activity, reducing the hyperphosphorylation of Tau.</div></div><div><h3>Discussion</h3><div>TCM can affect the activity of GSK-3β through various pathways, thereby reducing the hyperphosphorylation of Tau protein and improving the cognitive function of AD. These studies highlight the potential of TCM in treating AD, but further basic and clinical research is still required to validate their safety and efficacy. It is expected that our review will yield novel insights and a scientific foundation for investigating the underlying mechanisms of AD and developing novel anti-AD therapeutics.</div></div>","PeriodicalId":101013,"journal":{"name":"Pharmacological Research - Modern Chinese Medicine","volume":"13 ","pages":"Article 100543"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Pharmacological Research - Modern Chinese Medicine
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