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Integrated skin metabolomics and network pharmacology to explore the mechanisms of Goupi Plaster for treating knee osteoarthritis 整合皮肤代谢组学和网络药理学,探索狗皮膏药治疗膝骨关节炎的机制
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-04-12 DOI: 10.1016/j.jtcme.2024.04.004

Background and aim

Goupi Plaster (GP) is topical traditional Chinese medicine preparation. It has been used to treat Knee Osteoarthritis (KOA) in clinical practice of traditional Chinese medicine (TCM). However, the mechanisms of GP relieve KOA are poorly understood.

Experimental procedure

Rabbit models of KOA were established and treated with GP. Knee cartilage pathology was analyzed using hematoxylin and eosin staining, while plasma levels of inflammatory factors (interleukin (IL)-4, IL-6, and IL-17) and skin neurotransmitters (calcitonin gene-related peptide (CGRP), substance P (SP), and5-hydroxytryptamine (5-HT)) were measured by enzyme linked immunosorbent assay. Metabolomics based on GC-TOF-MS analysis screened for skin biomarkers as well as relevant pathways. Network pharmacology screened for relevant skin targets as well as relevant pathways, and finally, MetScape software was utilized to integrate the results of metabolomics and network pharmacology to screen for key skin targets, key metabolites, and key pathways for GP treatment of KOA.

Results and conclusion

GP administration substantially repaired cartilage surface breaks in KOA and led to relatively intact cartilage structure and normal cell morphology. GP decreased plasma levels of IL-6 and IL-17 and skin levels of CGRP, SP and 5-HT while increased plasma IL-4. GP administration normalized the levels of 15 metabolites which were changed in KOA. Network pharmacology analysis identified 181 targets. Finally, 3 key targets, 5 key metabolites and 3 related pathways were identified, which suggested that GP improved skin barrier function and skin permeability by regulating skin lipid metabolism. GP treatment also regulated skin amino acid levels and subsequently affected neurotransmitters and signaling molecules. In addition, the purinergic signaling pathway was also involved in the treatment of GP against KOA.
In conclusion, GP treatment is associated with changes in skin lipid metabolism, neurotransmitters, and the purinergic signaling pathway.
背景和目的狗皮膏药(GP)是一种外用传统中药制剂。在中医临床实践中,它一直被用于治疗膝关节骨性关节炎(KOA)。实验过程建立 KOA 兔子模型,并使用 GP 治疗。用苏木精和伊红染色法分析膝关节软骨病理,用酶联免疫吸附法测定血浆中炎症因子(白细胞介素(IL)-4、IL-6 和 IL-17)和皮肤神经递质(降钙素基因相关肽(CGRP)、P 物质(SP)和 5-羟色胺(5-HT))的水平。基于 GC-TOF-MS 分析的代谢组学筛选了皮肤生物标记物和相关途径。最后,利用 MetScape 软件整合代谢组学和网络药理学的结果,筛选出 GP 治疗 KOA 的关键皮肤靶点、关键代谢物和关键通路。GP 降低了血浆中 IL-6 和 IL-17 的水平以及皮肤中 CGRP、SP 和 5-HT 的水平,同时提高了血浆中 IL-4 的水平。GP能使KOA中发生变化的15种代谢物水平恢复正常。网络药理学分析确定了 181 个靶点。最后,确定了 3 个关键靶点、5 个关键代谢物和 3 条相关通路,这表明 GP 可通过调节皮肤脂质代谢改善皮肤屏障功能和皮肤通透性。GP 治疗还能调节皮肤氨基酸水平,进而影响神经递质和信号分子。总之,GP 治疗与皮肤脂质代谢、神经递质和嘌呤能信号通路的变化有关。
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引用次数: 0
Effect of astragalus membranaceus on neurological function in acute aneurysmal subarachnoid hemorrhage patients with high inflammation: A preliminary randomized, double-blind, placebo-controlled clinical trial 黄芪对急性动脉瘤性蛛网膜下腔出血高炎症患者神经功能的影响:一项初步随机、双盲、安慰剂对照临床试验
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-04-11 DOI: 10.1016/j.jtcme.2024.04.002

Background and aim

Astragalus membranaceus (AM) is a traditional Chinese herb. Our previous study revealed that AM can enhance neurological function in patients with acute intracerebral hemorrhage. The aim of this study was to investigated the effects of AM on patients with acute aneurysmal subarachnoid hemorrhage (aSAH).

Experimental procedure

Eighty-eight patients experiencing acute aSAH were randomly allocated to either the treatment group (TG) comprising 44 patients, who received 3 g of AM orally thrice daily for 14 days, or the control group (CG) with 44 patients, who received 3 g of a placebo.

Results

Eighty-three patients (41 in CG and 42 in TG) completed the trial. Stratified analyses revealed serum interleukin-6 (IL-6) median ≥7.28 pg/mL at baseline. The percentage of good GOS scores (GOS 4 or 5) at two weeks (W2) and four weeks (W4) was significantly higher in TG than in CG (W2: 35.3 % vs. 7.7 %, p = 0.042; W4: 62.5 % vs. 30.8 %, p = 0.044). Moreover, a higher percentage of Barthel index scores (>60) was observed in TG than in CG at W2 (35.3 % vs. 7.7 %, p = 0.042) after AM or placebo administration.

Conclusion

Administering AM for 14 days has shown potential in enhancing neurological function four weeks post-aSAH onset, especially in patients with a serum IL-6 level median ≥7.28 pg/mL. Therefore, further research is warranted to explore the anti-inflammatory role of AM. However, this study's limitations include a small sample size and the single-center design, signifying its status as a preliminary investigation.
背景和目的黄芪(AM)是一种传统中草药。我们之前的研究显示,黄芪能增强急性脑出血患者的神经功能。实验过程88名急性蛛网膜下腔出血患者被随机分配到治疗组(TG)和对照组(CG),治疗组有44名患者,每天口服3克AM,共14天;对照组有44名患者,每天口服3克安慰剂。分层分析显示,基线血清白细胞介素-6(IL-6)中位数≥7.28 pg/mL。在两周(W2)和四周(W4)的良好 GOS 评分(GOS 4 或 5 分)中,TG 显著高于 CG(W2:35.3% 对 7.7%,p = 0.042;W4:62.5% 对 30.8%,p = 0.044)。此外,在 W2(35.3 % vs. 7.7 %,p = 0.042)时,观察到 AM 或安慰剂给药后,TG 的 Barthel 指数评分(>60)百分比高于 CG(35.3 % vs. 7.7 %,p = 0.042)。因此,有必要进一步研究 AM 的抗炎作用。然而,这项研究的局限性包括样本量较小和单中心设计,这表明它只是一项初步研究。
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引用次数: 0
Exploring the ROS-mediated anti-cancer potential in human triple-negative breast cancer by garlic bulb extract: A source of therapeutically active compounds 探索大蒜球茎提取物介导的 ROS 在人类三阴性乳腺癌中的抗癌潜力:一种具有治疗活性的化合物来源
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-04-11 DOI: 10.1016/j.jtcme.2024.04.003

Background and aim

Allium sativum L. has been used medicinally and traditionally since antiquity. This study sought to examine the Allium sativum ethanolic extract (ASEE) in inducing apoptosis in human triple-negative breast cancer (TNBC) MDA-MB-231 cells and the molecular interactions of the identified components with cell death markers using in silico method.

Experimental procedure

Cytotoxicity of ASEE was tested on MCF-7, MDA-MB-231, and Normal Vero cells. The ROS production, apoptosis, MMP, and cell cycle study were conducted utilizing flow cytometer, and western blot was also performed for protein expression analysis. ASEE was phytochemically characterized by the HPLC while AutoDock Vina and iGEMDOCK tools investigated in-silico binding interactions.

Results

The HPLC method identified two active organosulfur chemicals, allicin and alliin, in ASEE. MTT test revealed significant (p < 0.05) inhibition of breast cancer cells proliferation. The inhibitory effect of ASEE was more pronounced in MDA-MB-231 cells than in MCF-7 cells, however, no substantial cytotoxicity was seen in normal Vero cells. TNBC cells treated with high concentrations of ASEE were found in the late apoptotic stage and exhibited an increase in ROS level and a reduction in MMP. ASEE exposure increased the percentage of cells in the G2/M phase. ASEE upregulated the p53 and Bax proteins while downregulated the Bcl-2, p-Akt, and p-p38 proteins. Allicin and alliin compounds had strong binding affinity with targeted proteins of breast cancer, and both compounds also showed good pharmacokinetics and druglikeness properties.

Conclusion

ASEE could be useful in the treatment of human triple-negative breast cancer without any safety risks.
背景和目的薤白自古以来就有药用和传统用途。本研究试图利用硅学方法研究薤白乙醇提取物(ASEE)在诱导人类三阴性乳腺癌(TNBC)MDA-MB-231 细胞凋亡方面的作用,以及所发现的成分与细胞死亡标志物之间的分子相互作用。利用流式细胞仪对 ROS 生成、细胞凋亡、MMP 和细胞周期进行了研究,并对蛋白质表达进行了 Western 印迹分析。HPLC 方法鉴定了 ASEE 中的两种活性有机硫化学物质:大蒜素和大蒜素。MTT测试显示,ASEE对乳腺癌细胞的增殖有明显的抑制作用(p < 0.05)。ASEE 对 MDA-MB-231 细胞的抑制作用比对 MCF-7 细胞的抑制作用更明显,但对正常 Vero 细胞没有明显的细胞毒性。经高浓度 ASEE 处理的 TNBC 细胞处于凋亡晚期,ROS 水平升高,MMP 降低。ASEE 暴露增加了处于 G2/M 期的细胞百分比。ASEE 上调了 p53 和 Bax 蛋白,同时下调了 Bcl-2、p-Akt 和 p-p38 蛋白。大蒜素和大蒜素化合物与乳腺癌的靶向蛋白有很强的结合亲和力,这两种化合物还表现出良好的药代动力学和药物亲和性。
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引用次数: 0
Zhilong Huoxue Tongyu capsule protects against atherosclerosis by suppressing EndMT via modulating Hippo/YAP signaling pathway 芝龙藿香通脉胶囊通过调节 Hippo/YAP 信号通路抑制 End MT 防止动脉粥样硬化
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-29 DOI: 10.1016/j.jtcme.2024.03.015

Background and aim

Zhilong Huoxue Tongyu Capsule (ZL capsule) has been demonstrated to be an effective and widely-used traditional Chinese medicine (TCM) formula for the treatment of various diseases, especially for atherosclerosis (AS) related cardiovascular and cerebrovascular diseases. Reversal of endothelial-mesenchymal transition (EndMT) plays a crucial role in the cure of AS. But the curative impact of ZL capsule on EndMT remains obscure during the development of AS. The purpose of this study is to explore the effect of ZL capsule on AS and to study the regulation mechanism on EndMT in AS by ZL capsule in vivo and in vitro.

Experimental procedure

An in vivo model of AS was induced in ApoE−/− mice by administrating them with an 8-week period of high-fat diet (HFD). After oral gavage of different doses of ZL capsule and Atorvastatin calcium tablets (ATO) for 4 weeks, the lipid levels, plaque area, lipid deposition, and EndMT were evaluated using standard assays. In order to simulate EndMT in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to oxidized low-density lipoprotein (ox-LDL). Western blotting (WB) and immunofluorescence techniques were used to evaluate the intervention effect of ZL capsule on EndMT and Hippo/YAP pathways.

Results and conclusion

ZL capsule demonstrated therapeutic effects on dyslipidemia and EndMT among atherosclerotic mice. To be specific, ZL capusle diminished the total cholesterol (TC), total triglyceride (TG) and low-density lipoprotein (LDL-C) levels, whereas increased that of high-density lipoproteins (HDL-C). Meanwhile, ZL capusle upregulated the expression of endothelial markers (CD31 and VE-cadherin) and reduced that of mesenchymal markers (ɑ-SMA and FSP1), indicating that ZL capusle could inhibit EndMT during the development of AS. Furthermore, molecular docking results indicated that active ingredients including formononetin, calycosin, astragaloside III, astragaloside A in ZL capsule have strong affinity with YAP proteins, and ZL capsule can significantly repress the initiation of Hippo/YAP pathway during AS. In conclusion, ZL capsule effectively attenuated AS progression by exerting inhibitory effects on EndMT through modulation of the Hippo/YAP signaling pathway.
背景和目的芝龙藿香通脉胶囊(ZL胶囊)已被证实是治疗多种疾病,尤其是动脉粥样硬化(AS)相关心脑血管疾病的有效而广泛使用的传统中药配方。内皮-间质转化(EndMT)的逆转在AS的治疗中起着至关重要的作用。但在强直性脊柱炎的发展过程中,ZL 胶囊对 EndMT 的治疗作用仍不明显。本研究的目的是探讨 ZL 胶囊对强直性脊柱炎的影响,并研究 ZL 胶囊在体内和体外对强直性脊柱炎 EndMT 的调节机制。口服不同剂量的ZL胶囊和阿托伐他汀钙片(ATO)4周后,使用标准检测方法评估血脂水平、斑块面积、脂质沉积和内膜增生。为了在体外模拟内切迹,将人脐静脉内皮细胞(HUVECs)置于氧化低密度脂蛋白(ox-LDL)中。结果和结论ZL胶囊对动脉粥样硬化小鼠的血脂异常和内膜增生具有治疗作用。具体而言,ZL 胶囊降低了总胆固醇(TC)、总甘油三酯(TG)和低密度脂蛋白(LDL-C)的水平,而提高了高密度脂蛋白(HDL-C)的水平。同时,ZL 茵陈毛果芸香碱可上调内皮标志物(CD31 和 VE-cadherin)的表达,降低间质标志物(ɑ-SMA 和 FSP1)的表达,表明 ZL 茵陈毛果芸香碱可抑制强直性脊柱炎发病过程中的内膜增生。此外,分子对接结果表明,ZL胶囊中的甲酮素、钙苷、黄芪皂苷Ⅲ、黄芪皂苷A等有效成分与YAP蛋白有很强的亲和力,ZL胶囊能显著抑制强直性脊柱炎发生过程中Hippo/YAP通路的启动。综上所述,ZL胶囊通过调控Hippo/YAP信号通路抑制内生肌生长,从而有效地延缓了AS的进展。
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引用次数: 0
Electroacupuncture of ST36 and PC6 for postoperative gastrointestinal recovery: A systematic review and meta-analysis 电针 ST36 和 PC6 促进术后胃肠道恢复:系统回顾和荟萃分析
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-22 DOI: 10.1016/j.jtcme.2024.03.014

Objective

This study was designed to determine the efficacy and safety of electroacupuncture (EA) at acupoints ST36 and/or PC6 for postoperative gastrointestinal (GI) recovery.

Method

Studies were retrieved from the PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang, and Airiti library databases from inception to January 23, 2024. Randomized controlled trials (RCTs) that evaluated the effect of EA at ST36 and/or PC6 on postoperative GI recovery were reviewed. Studies that involved acupoints other than the two or treatment modalities other than EA were excluded.

Results

Meta-analysis of 17 RCTs revealed that the time to first flatus (Mean difference (MD) = −5.06 h; 95% Confidence interval (CI), −7.12 to −3.01) and time to first defecation (MD = −12.29 h; 95% CI, −20.64 to −5.21) were significantly shorter in the EA group compared with the control group. The incidence of post-operative nausea and vomiting (PONV) was also significantly lower in the EA group than in the control group (Risk ratio (RR) = 0.62; 95% CI, 0.49–0.78).

Conclusion

EA application to ST36 or PC6 alone as an adjunctive therapy is effective and safe in promoting postoperative GI recovery and reducing PONV. The benefits are less obvious when ST36 and PC6 are combined. Acupoint selection and EA parameters are important factors that influence therapeutic effects. The establishment of a standardized EA protocol is imperative to minimize bias in research and to maximize applicability in clinical practice.
方法从 PubMed、EMBASE、中国国家知识基础设施(CNKI)、万方和 Airiti 图书馆数据库中检索从开始到 2024 年 1 月 23 日的研究。回顾了评估 ST36 和/或 PC6 穴位 EA 对术后消化道恢复影响的随机对照试验(RCT)。结果对 17 项随机对照试验进行的元分析表明,与对照组相比,EA 组首次排便时间(平均差 (MD) = -5.06 h;95% 置信区间 (CI),-7.12 至 -3.01)和首次排便时间(平均差 (MD) = -12.29 h;95% 置信区间 (CI),-20.64 至 -5.21)明显缩短。EA组术后恶心和呕吐(PONV)的发生率也明显低于对照组(风险比(RR)= 0.62;95% CI,0.49-0.78)。当 ST36 和 PC6 结合使用时,疗效就不那么明显了。穴位选择和 EA 参数是影响治疗效果的重要因素。必须建立标准化的 EA 方案,以最大限度地减少研究中的偏差,并最大限度地提高临床实践中的适用性。
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引用次数: 0
The influence of the gut-brain axis on anxiety and depression: A review of the literature on the use of probiotics 肠脑轴对焦虑症和抑郁症的影响:关于使用益生菌的文献综述
IF 4.5 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-21 DOI: 10.1016/j.jtcme.2024.03.011
Sara Ferrari , Simone Mulè , Francesca Parini , Rebecca Galla , Sara Ruga , Giorgia Rosso , Arianna Brovero , Claudio Molinari , Francesca Uberti

This review aims to argue how using probiotics can improve anxiety and depressive behaviour without adverse effects, also exploring the impact of postbiotics on it. Specifically, probiotics have drawn more attention as effective alternative treatments, considering the rising cost of antidepressant and anti-anxiety drugs and the high risk of side effects. Depression and anxiety disorders are among the most common mental illnesses in the world's population, characterised by low mood, poor general interest, and cognitive or motor dysfunction. Thus, this study analysed published literature on anxiety, depression, and probiotic supplementation from PubMed and Scopus, focusing on the last twenty years. This study focused on the effect of probiotics on mental health as they have drawn more attention because of their extensive clinical applications and positive impact on various diseases. Numerous studies have demonstrated how the gut microbiota might be critical for mood regulation and how probiotics can affect host health by regulating the gut-brain axis. By comparing the different works analysed, it was possible to identify a strategy by which they are selected and employed and, at the same time, to assess how the effect of probiotics can be optimised using postbiotics, an innovation to improve mental well-being in humans.

本综述旨在论证使用益生菌如何在无不良影响的情况下改善焦虑和抑郁行为,同时探讨后益生菌对焦虑和抑郁行为的影响。具体而言,考虑到抗抑郁和抗焦虑药物的成本不断上升,且副作用风险较高,益生菌作为有效的替代疗法已引起越来越多的关注。抑郁症和焦虑症是世界人口中最常见的精神疾病之一,其特点是情绪低落、兴趣不高、认知或运动功能障碍。因此,本研究分析了 PubMed 和 Scopus 上已发表的有关焦虑、抑郁和补充益生菌的文献,重点关注过去二十年的情况。本研究重点关注益生菌对心理健康的影响,因为益生菌在临床上的广泛应用以及对各种疾病的积极影响已引起了更多关注。大量研究表明,肠道微生物群对情绪调节至关重要,益生菌可通过调节肠道-大脑轴影响宿主健康。通过比较所分析的不同著作,我们有可能确定选择和使用益生菌的策略,同时评估如何利用后益生菌来优化益生菌的效果,这是改善人类精神健康的一项创新。
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引用次数: 0
A proteasome-dependent inhibition of SIRT-1 by the resveratrol analogue 4,4′-dihydroxy-trans-stilbene 白藜芦醇类似物 4,4′-二羟基-反式-二苯乙烯对蛋白酶体 SIRT-1 的依赖性抑制作用
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-08 DOI: 10.1016/j.jtcme.2024.03.001
Vittoria Livraghi , Laura Mazza , Federica Chiappori , Miriana Cardano , Ornella Cazzalini , Roberto Puglisi , Rossana Capoferri , Anna Pozzi , Lucia Anna Stivala , Laura Zannini , Monica Savio

Background and aim

Resveratrol (RSV), is a stilbene-based compound exerting wide biological properties. Its analogue 4,4′-dihydroxy-trans-stilbene (DHS) has shown improved bioavailability and antiproliferative activity in vitro and in vivo. One of the hypotheses on how resveratrol works is based on SIRT1 activation. Since their strict structural similarities, we have explored a potential interaction between DHS and SIRT1, in comparison with the parental molecule.

Experimental procedure

Timing of incubation and concentrations of DHS have been determined using MTT assay in normal human lung fibroblasts. Untreated, DHS- or RSV-treated cells were harvested and analysed by Western Blotting or RT-PCR, in order to evaluate SIRT1 levels/activity and expression, and by Cellular Thermal shift assay (CETSA) to check potential DHS or RSV-SIRT1 interaction. Transfection experiments have been performed with two SIRT1 mutants, based on the potential binding pockets identified by Molecular Docking analysis.

Results and conclusion

We unexpectedly found that DHS, but not RSV, exerted a time-dependent inhibitory effect on both SIRT1 protein levels and activity, the latter measured as p53 acetylation. At the mRNA level no significant changes were observed, whereas a proteasome-dependent mechanism was highlighted for the reduction of SIRT1 levels by DHS in experiments performed with the proteasome inhibitor MG132. Bioinformatics analysis suggested a higher affinity of RSV in binding all SIRT1 complexes compared to DHS, except comparable results for complex SIRT1-p53. Nevertheless, both CETSA and SIRT1 mutants transfected in cells did not confirm this interaction. In conclusion, DHS reduces SIRT1 protein level, thereby inhibiting its activity through a proteasome-mediated mechanism.

背景和目的白藜芦醇(RSV)是一种以芪类化合物为基础的化合物,具有广泛的生物学特性。其类似物 4,4′-二羟基-反式-白藜芦醇(DHS)在体外和体内显示出更高的生物利用度和抗增殖活性。关于白藜芦醇如何发挥作用的假说之一是基于 SIRT1 的激活。实验过程在正常人肺成纤维细胞中使用 MTT 试验确定了 DHS 的孵育时间和浓度。收获未经处理、经 DHS 或 RSV 处理的细胞,并通过 Western 印迹法或 RT-PCR 进行分析,以评估 SIRT1 的水平/活性和表达情况,并通过细胞热转移试验(CETSA)检查 DHS 或 RSV 与 SIRT1 的潜在相互作用。根据分子对接分析确定的潜在结合口袋,用两个 SIRT1 突变体进行了转染实验。结果和结论我们意外地发现,DHS 而不是 RSV 对 SIRT1 蛋白水平和活性(后者以 p53 乙酰化衡量)都有时间依赖性抑制作用。在 mRNA 水平上没有观察到明显的变化,而在使用蛋白酶体抑制剂 MG132 进行的实验中,DHS 对 SIRT1 水平的降低凸显了蛋白酶体依赖性机制。生物信息学分析表明,与 DHS 相比,RSV 与所有 SIRT1 复合物的结合亲和力都更高,但与 SIRT1-p53 复合物的结合结果不相上下。然而,转染细胞的 CETSA 和 SIRT1 突变体并未证实这种相互作用。总之,DHS 可降低 SIRT1 蛋白水平,从而通过蛋白酶体介导的机制抑制其活性。
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引用次数: 0
Jintiange capsule ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats by regulating the activity and differentiation of BMSCs 金天戈胶囊通过调节BMSCs的活性和分化改善糖皮质激素诱发的大鼠股骨头坏死
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-07 DOI: 10.1016/j.jtcme.2024.03.013

Background and aim

A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent.

Experimental procedure

In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA.

Results

Our final results demonstrated that with the involvement of Wnt/β-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis.

Conclusion

According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

背景和目的 糖皮质激素(GC)过剩是导致非创伤性股骨头坏死(ONFH)的主要原因,而金天歌作为传统中药之一,在缓解骨质流失方面也同时发挥着重要作用。因此,人们认为金天格能在一定程度上逆转 GC 诱导的 ONFH(GC-ONFH)。实验过程在体内,使用显微计算机断层扫描(micro-CT)、TdT介导的dUTP缺口末端标记(TUNEL)和组织学染色法研究了JTG对股骨头软骨下骨小梁的影响;在体外,研究了纯化的骨间充质干细胞(BMSCs)的增殖、活力、凋亡和衰老,以证明JTG对这些细胞的直接影响。同时,在使用一系列干预措施后,JTG 对骨间充质干细胞分化的作用可通过测量蛋白质和 mRNA 水平的成骨和成脂标志物来评估。结果我们的最终结果表明,在Wnt/β-catenin通路的参与下,JTG能显著促进BMSCs的成骨、抑制脂肪生成、延缓衰老、减少破骨细胞数量、减弱细胞凋亡、促进成骨细胞增殖,这些作用都能缓解软骨下骨坏死的进展。结论根据体外和体内的实验结果,JTG可通过防止软骨下骨的破坏来缓解早期GC-ONFH,这有助于调节BMSCs的分化和破骨细胞的数量。
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引用次数: 0
Phase 1 clinical trial evaluating safety, bioavailability, and gut microbiome with a combination of curcumin and ursolic acid in lipid enhanced capsules 评估姜黄素和熊果酸脂质强化胶囊组合的安全性、生物利用率和肠道微生物组的 1 期临床试验
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-07 DOI: 10.1016/j.jtcme.2024.03.002

As screening strategies employ better biomarkers and genetics to identify individuals at an increased risk of prostate cancer, there are currently no chemotherapeutic prevention strategies. With any chemoprevention strategy, the population will be younger and healthier; therefore, they will be less tolerant of side effects. This study translated findings from screening a natural product library and pre-clinical evaluation of curcumin (CURC) in combination with ursolic acid (UA) in prostate cancer models. After manufacturing capsules for each compound, 18 subjects were enrolled. The study used a 3 × 3 phase 1 clinical trial to evaluate CURC (1200 mg/day) and UA (300 mg/day) alone and in combination over a 2-week period with endpoints of safety, bioavailability, and microbiome alterations. After enrolling six subjects in each arm, we found no grade 3 or 4 events and only minor changes in the safety laboratory values. In the pooled analysis of groups, we noted a statistically significant difference between median serum levels of UA when administered alone vs administered in the combination (2.7 ng/mL vs 43.8 ng/mL, p = 0.03). Individuals receiving the combination also had a favorable impact on gut microbiome status and a reduction in “microbiome score” predictive of prostate cancer risk.

由于筛查策略采用了更好的生物标志物和遗传学方法来确定前列腺癌的高危人群,目前还没有化疗预防策略。任何化学预防策略的适用人群都将更年轻、更健康;因此,他们对副作用的耐受性将更低。本研究将筛选天然产品库和姜黄素(CURC)与熊果酸(UA)联合用于前列腺癌模型的临床前评估结果进行了转化。在为每种化合物生产胶囊后,共招募了 18 名受试者。该研究采用 3 × 3 的 1 期临床试验,对 CURC(1200 毫克/天)和 UA(300 毫克/天)在 2 周时间内单独或联合使用进行评估,终点是安全性、生物利用度和微生物组改变。在每组招募 6 名受试者后,我们未发现 3 级或 4 级事件,安全性实验室值也仅有轻微变化。在各组的汇总分析中,我们注意到单独用药与联合用药的 UA 血清中位数水平之间存在显著的统计学差异(2.7 纳克/毫升 vs 43.8 纳克/毫升,p = 0.03)。接受联合用药的个体还对肠道微生物组状态产生了有利影响,并降低了预测前列腺癌风险的 "微生物组评分"。
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引用次数: 0
Chemical profiling and mechanisms of Agarikon pill in a rat model of cigarette smoke-induced chronic obstructive pulmonary disease 阿加瑞康丸在香烟烟雾诱发慢性阻塞性肺病大鼠模型中的化学分析和作用机制
IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2024-03-06 DOI: 10.1016/j.jtcme.2024.03.006

Background and aim

Agarikon pill (AGKP), a traditional Chinese herbal formula, and has been used for chronic obstructive pulmonary disease (COPD) treatment clinically. However, the active components and exact pharmacological mechanisms are still unclear. We aimed to investigate the therapeutic effects and mechanisms of AGKP on COPD and identify the chemical constituents and active compounds.

Experimental procedure

The chemical components of AGKP were identified by ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Network pharmacology analysis was performed to uncover the potential mechanism of AGKP. The efficiencies and mechanisms of AGKP were further confirmed in COPD animal models.

Results and conclusion

Ninety compounds from AGKP, such as flavonoids, triterpenoids, saponins, anthracenes, derivatives, phenyl propionic acid, and other organic acids, were identified in our study. AGKP improved lung function and pathological changes in COPD model rats. Additionally, inflammatory cell infiltration and proinflammatory cytokine levels were markedly reduced in COPD rats administered AGKP. Network pharmacology analysis showed that the inflammatory response is the crucial mechanism by which AGKP exerts therapeutic effects on COPD rats. WB and PCR data indicated that AGKP attenuated the inflammatory response in COPD model rats. AGKP reduces the pulmonary inflammatory response through the PI3K/AKT and MAPK TLR/NF-κB signaling pathways and exerts therapeutic effects via inhibition of inflammation and mucus hypersecretion on COPD model rats.

背景和目的阿胶浆(AGKP)是一种传统的中药配方,临床上一直用于慢性阻塞性肺病(COPD)的治疗。然而,其活性成分和确切的药理机制仍不清楚。实验过程采用超高效液相色谱-四极杆/比特阱高分辨质谱(UHPLC-Q-Orbitrap-HRMS)鉴定 AGKP 的化学成分。为揭示 AGKP 的潜在机制,研究人员进行了网络药理学分析。结果与结论我们的研究从 AGKP 中鉴定出 90 种化合物,如黄酮类、三萜类、皂苷类、蒽类、衍生物、苯丙酸和其他有机酸。AGKP 可改善慢性阻塞性肺疾病模型大鼠的肺功能和病理变化。此外,给慢性阻塞性肺病大鼠服用 AGKP 后,炎症细胞浸润和促炎细胞因子水平明显降低。网络药理学分析表明,炎症反应是 AGKP 对慢性阻塞性肺病大鼠产生治疗效果的关键机制。WB 和 PCR 数据表明,AGKP 可减轻 COPD 模型大鼠的炎症反应。AGKP通过PI3K/AKT和MAPK TLR/NF-κB信号通路降低肺部炎症反应,并通过抑制炎症和粘液高分泌对慢性阻塞性肺病模型大鼠产生治疗效果。
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引用次数: 0
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Journal of Traditional and Complementary Medicine
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