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Cardiotoxic effects of Bisphenol-A in male Wistar rats are attenuated by Garcinia kola and its biflavonoid, kolaviron, via antioxidant and antiinflammation-based mechanisms 双酚a对雄性Wistar大鼠的心脏毒性作用通过抗氧化和抗炎机制被藤黄菌及其双黄酮可拉维铁减弱
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.08.004
Amara C. Omodon, Osah M. Onwuka, Bernard O. Adele, Abayomi O. Ige

Introduction

The heart, due to its high energetic metabolic and reactive oxygen production rate, is a target for oxidative stress-related injuries. Therefore, environmental toxicants such as Bisphenol-A (BPA), that exert pathologies through oxidative and nitrite stress-related mechanism may target the heart for their deleterious effects. This study was therefore designed to investigate the effect of two naturally occurring antioxidants, Garcinia kola (GK) and kolaviron, on BPA-induced cardiac dysfunction and toxicity in male Wistar rats.

Methods

Fifty-six animals were divided into 7equal groups and treated orally for 28days as follows; groups I(control) and II(vehicle) received distilled water(1.5 mL/kg) and corn oil(1.5 mL/kg) respectively. Animals in groups III-V received BPA (50 mg/kg) only, BPA + GK (200 mg/kg), BPA + kolaviron (200 m/kg) respectively, while animals in groups VI-VII received GK and kolaviron only, respectively. Thereafter, blood pressure and electrocardiogram were evaluated in each group and under anesthesia, cardiac samples were excised and analyzed for oxidative stress status, inflammatory markers and histology, respectively.

Results

BPA-only exposed rats exhibited cardiac dysfunction manifested by elevated systolic blood pressure and cardiac inflammatory markers, reduced cardiac antioxidants and distorted structural aberrations. Treatment of BPA exposed animals with either GK or kolaviron mitigated the development of these dysfunctions in varying degrees, while treatment of either GK or kolaviron alone in the absence of BPA exposure showed significant antioxidant and anti-inflammatory potentials.

Conclusion

These results suggests that Garcinia kola and its biflavonoid, kolaviron, prevents the development of bisphenol-A induced cardiac dysfunction and toxicity by potentiating antioxidant defence and impeding inflammation mediated mechanism.
心脏,由于其高能量代谢和活性氧产生率,是氧化应激相关损伤的目标。因此,双酚a (BPA)等环境毒物,通过氧化和亚硝酸盐应激相关机制发挥病理作用,可能针对心脏产生有害影响。因此,本研究旨在探讨两种天然抗氧化剂,Garcinia kola (GK)和kolaviron对bpa诱导的雄性Wistar大鼠心功能障碍和毒性的影响。方法56只动物随机分为7组,口服治疗28d;I组(对照组)和II组(试验组)分别给予蒸馏水(1.5 mL/kg)和玉米油(1.5 mL/kg)。iii ~ v组分别给予双酚a (50 mg/kg)、双酚a + GK (200 mg/kg)、双酚a +可拉维铁(200 m/kg), vi ~ vii组分别给予双酚a和可拉维铁。在麻醉状态下,取心脏样本,分别分析氧化应激状态、炎症标志物和组织学。结果bpa暴露大鼠出现心脏功能障碍,表现为收缩压升高、心脏炎症指标升高、心脏抗氧化剂降低和结构畸变。用GK或可拉维铁治疗BPA暴露的动物在不同程度上减轻了这些功能障碍的发展,而在没有BPA暴露的情况下,单独使用GK或可拉维铁治疗显示出显著的抗氧化和抗炎潜力。结论栀子果及其双黄酮可拉维铁通过增强抗氧化防御和阻断炎症介导的机制,阻止双酚a诱导的心功能障碍和毒性的发生。
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引用次数: 0
Effectiveness of Zhengqing Fengtongning in combination with routine rheumatoid arthritis treatment: A real-world multicenter retrospective study 正清风痛宁联合常规类风湿关节炎治疗的临床多中心回顾性研究
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.08.005
Ze Yu , Zan Li , Ya Gao , Chunming Lyu , Fang Kou , Jialong Guo , Fei Gao , Hai Wei

Background

Zhengqing Fengtongning (ZF) is a modern traditional Chinese medicine preparation used to treat rheumatoid arthritis (RA). In this study, we aimed to prove the effectiveness of ZF in combination with routine RA treatment in the real world.

Methods

This was a retrospective study including 3877 RA patients in multi-centers from August 2015 to April 2023. The experimental group received ZF and the control group received other RA regimens. Propensity score matching was used to eliminate bias. The effectiveness of ZF in combination with routine RA treatment was evaluated through DAS28, ESR, CRP and RF.

Results

The effectiveness of combining ZF with methotrexate (MTX), iguratimod (IGU), leflunomide (LEF), MTX + LEF, and MTX + nonsteroidal anti-inflammatory drugs in treating RA was significantly better than that of not combining ZF (p < 0.05). The effectiveness of combining ZF was significantly better than that of combining total glucosides of paeony, Kunxian capsule, or Biqi capsule (p < 0.05). No significant difference existed in effectiveness among MTX, IGU, and ZF combined with JAK inhibitor or TNF-ɑ inhibitor (p > 0.05).

Conclusions

This study provides evidence that the effectiveness of MTX, IGU, LEF, MTX + LEF, and MTX + NSAIDs combined with ZF in treating RA was better than those without ZF.
正清风痛宁(ZF)是一种治疗类风湿性关节炎(RA)的现代中药制剂。在这项研究中,我们的目的是在现实世界中证明ZF联合常规RA治疗的有效性。方法回顾性研究,纳入2015年8月至2023年4月多中心3877例RA患者。实验组给予ZF治疗,对照组给予其他RA治疗方案。倾向评分匹配用于消除偏差。通过DAS28、ESR、CRP、RF评价ZF联合常规RA治疗的有效性。结果ZF联合甲氨蝶呤(MTX)、iguratimod (IGU)、来氟米特(LEF)、MTX + LEF、MTX +非甾体抗炎药治疗RA的疗效显著优于不联合ZF组(p < 0.05)。联合用药效果显著优于丹参总苷、坤仙胶囊和痹气胶囊(p < 0.05)。MTX、IGU和ZF联合JAK抑制剂或TNF-抑制剂的疗效无显著差异(p > 0.05)。结论MTX、IGU、LEF、MTX + LEF、MTX +非甾体抗炎药联合ZF治疗RA的疗效优于非ZF组。
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引用次数: 0
Explore the action mechanism of Danggui Buxue decoction on chronic heart failure in rats by proteomics and untargeted metabolomics 通过蛋白质组学和非靶向代谢组学方法探讨当归补血汤对大鼠慢性心力衰竭的作用机制
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.08.007
Yongchang Zhou , Yichen Guan , Siman Tao , Zigang Pu , Kepei Yang , Juan Qi , Junxian Zhao , Yongjie Pang , Peng Wang , Qing Yang , Xinxu Tian , Xiuying Pu

Background and aim

Danggui Buxue Decoction (DBD) has been applied to alleviate chronic heart failure (CHF) in clinics, however, its mechanism is still unclear. This study investigates the potential action mechanism of DBD for rats with CHF combined with liver injury.

Experimental procedure

For this purpose, this study established a CHF rat model. The change of proteins in myocardial tissues was identified by proteomics and then further verified using western blotting. Additionally, metabolomics revealed the metabolic pathways associated with liver injury in CHF rats.

Results and conclusion

Animal studies demonstrated that DBD could relieve CHF as it significantly reduced serum levels of brain natriuretic peptide (BNP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in CHF rats, and promoted the activity of catalase (CAT), glutathione peroxidase (GSH-Px), cytochrome oxidase (COX), and succinate dehydrogenase (SDH) in myocardial tissues. Myocardial proteomics analysis revealed that DBD improved myocardial mitochondria and peroxisomes function by regulating the expression of proteins associated with energy metabolism and oxidative damage. Western blotting confirmed that DBD upregulated the expression of proteins in the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog-1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α)/peroxisome proliferator-activated receptor beta (PPAR β) signaling pathway, which also proved the efficacy of DBD in alleviating CHF in rats. Hepatic metabolomics analysis showed that DBD could restore the damaged liver function of CHF rats via metabolic pathways, including the metabolism of lipid, vitamin, and amino acids. In conclusion, this study unveiled a novel action mechanism of DBD in the treating ISO-induced CHF and liver injury based on proteomics and metabolomics. These results lay a scientific basis for the widespread application of DBD in the cardiovascular field.
背景和目的当归补血汤(DBD)已被应用于临床治疗慢性心力衰竭(CHF),但其作用机制尚不清楚。本研究探讨DBD对CHF合并肝损伤大鼠的潜在作用机制。为此,本研究建立CHF大鼠模型。用蛋白质组学方法鉴定心肌组织蛋白的变化,再用western blotting进一步验证。此外,代谢组学揭示了与CHF大鼠肝损伤相关的代谢途径。结果和结论DBD可显著降低CHF大鼠血清脑钠肽(BNP)、谷草转氨酶(AST)、丙氨酸转氨酶(ALT)水平,提高心肌组织过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、细胞色素氧化酶(COX)、琥珀酸脱氢酶(SDH)活性,具有缓解CHF的作用。心肌蛋白质组学分析显示,DBD通过调节与能量代谢和氧化损伤相关的蛋白质表达,改善心肌线粒体和过氧化物酶体功能。Western blotting证实,DBD可上调腺苷5′-单磷酸腺苷(AMP)活化蛋白激酶(AMPK)/沉默交配型信息调控2同源物-1 (SIRT1)/过氧化物酶体增殖物激活受体γ辅助激活因子1 α (PGC-1 α)/过氧化物酶体增殖物激活受体β (PPAR β)信号通路中蛋白的表达,也证实了DBD对大鼠CHF的缓解作用。肝脏代谢组学分析显示,DBD可通过脂质代谢、维生素代谢、氨基酸代谢等代谢途径恢复CHF大鼠受损的肝功能。综上所述,本研究基于蛋白质组学和代谢组学揭示了DBD治疗iso诱导的CHF和肝损伤的新作用机制。这些结果为DBD在心血管领域的广泛应用奠定了科学基础。
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引用次数: 0
Optimization of the formulation of Tubiechong gel plaster and its effect on fracture healing by promoting angiogenesis in a rat model 管必冲凝胶膏配方的优化及其促进大鼠骨折模型血管生成的作用
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.08.009
Yu-Ying Deng , Bing-Hao Shao , Yi-Bo Wang, Jing Wang, Ze-Feng Zhang, Xue-Qing Xie, Xue Wei, Xing Chen, Chun-Mei Wang

Background and aim

Transdermal drug delivery has been used in traditional Chinese medicine for thousands of years and is worth further developing. The purpose of this study was to investigate the preparation method of Tubiechong gel plaster (TGP) and evaluate its activity to promote fracture healing.

Experimental procedure

Using rat skin as a barrier, and the human umbilical vein endothelial cells (HUVECs) proliferation promotion rate of the receiving solution as the evaluation index, the in vitro permeability of the plaster was studied by Franz diffusion cell method. A modified Einhorn method was used to model rat tibia fractures. The bone healing process was monitored by radiography. Bone development and angiogenesis were assessed by Safranin O Fast Green staining and CD31 immunohistochemistry, respectively. Serum bone metabolites and VEGF levels were determined by ELISA method.

Results and conclusion

The optimal dose of azone for TGP is 2 %. The transdermal penetration equation for this plaster is consistent with the Ritger-Peppas equation. The prepared plaster was stable for at least 3 months. X-ray images showed that the fracture healing was promoted by TGP in a dose-related form at all periods. Serum BALP, OC, CTX-I, and VEGF levels also indicated better fracture healing after treatment. TGP significantly stimulated angiogenesis and bone growth at the fracture site on days 7,14 and 21, and the effect of promoting bone growth was shown on the third day. These data prove that the prepared Tubiechong gel plasters can promote fracture healing by promoting angiogenesis.
背景与目的经皮给药在中药中已有几千年的历史,值得进一步发展。本研究的目的是研究管必冲凝胶石膏(TGP)的制备方法,并评价其促进骨折愈合的活性。实验方法:以大鼠皮肤为屏障,以接受液对人脐静脉内皮细胞(HUVECs)增殖促进率为评价指标,采用Franz扩散细胞法研究石膏的体外通透性。采用改良的Einhorn方法建立大鼠胫骨骨折模型。通过x线摄影监测骨愈合过程。采用Safranin O Fast Green染色和CD31免疫组化检测大鼠骨发育和血管生成情况。ELISA法测定血清骨代谢物及VEGF水平。结果与结论氮酮治疗TGP的最佳剂量为2%。这种膏药的透皮渗透方程与里格-佩帕斯方程一致。制备的石膏至少稳定3个月。x线图像显示,TGP在各时期均以剂量相关的形式促进骨折愈合。血清BALP、OC、CTX-I和VEGF水平也表明治疗后骨折愈合较好。TGP在第7、14、21天显著刺激骨折部位血管生成和骨生长,并在第3天显示出促进骨生长的作用。这些数据证明制备的管必冲凝胶膏剂可以通过促进血管生成来促进骨折愈合。
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引用次数: 0
Chinese herbal medicine alleviates renal impairment induced by immunosuppressants in patients post living donor liver transplantation 中药对活体肝移植后免疫抑制剂所致肾损害的缓解作用
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.09.004
Hsiang-Chun Lai , Kuan-Wen Lin , Cheng-Li Lin , Shi-Chen Ou , Hung-Jen Lin , Ju-Chien Cheng , Chao-Chun Huang , Sheng-Teng Huang , Long-Bin Jeng

Background and aim

Patients post liver transplantation (LT) with long-term immunosuppression agents will suffer from renal function impairment. Chinese herbal medicine (CHM) has been reported to relieve chronic kidney disease progression. Nevertheless, there are a lack of high-quality reports related to CHM reducing renal dysfunction in post-LT patients. We aim to investigate whether CHM alleviates renal impairment induced by immunosuppressants in patients having undergone LT.

Materials and methods

We conducted a hospital-based retrospective cohort study including patients with LT from January 1, 2003 to March 31, 2020. We matched the CHM users to non-users at a 1:1 ratio according to baseline variables, comorbidities and drug use status by propensity score (PS) matching.

Results

The study enrolled a total of 1052 LT patients. After PS matching, 554 patients were included with a 1:1 ratio. CHM and non-CHM users exhibited a significant difference of improved urine protein to creatinine ratio (UPCR) over several 3-month follow-up periods. CHM users exhibited an alleviated decrease in GFR compared to non-CHM users after 12 months of follow-up (CHM: 58.1 to 56.3 ml/min/1.73 m2; non-CHM: 59.8 to 54.7 ml/min/1.73 m2). Among HCC patients, CHM users had alleviated GFR, UPCR and blood urea nitrogen impairments compared to non-CHM users. The most commonly prescribed herbs and formulas are noted.

Conclusion

We herein report that CHM could protect renal function after 12 months of follow-up compared to non-CHM users, without liver function impairment. However, the long-term effects and exact renal protection mechanisms require further investigations to confirm.
背景与目的肝移植术后长期使用免疫抑制剂的患者会出现肾功能损害。据报道,中草药(CHM)可以缓解慢性肾脏疾病的进展。然而,目前还缺乏高质量的关于CHM降低肾移植后患者肾功能的报道。我们的目的是研究中草药是否能减轻肝移植患者免疫抑制剂引起的肾损害。材料和方法我们进行了一项基于医院的回顾性队列研究,纳入了2003年1月1日至2020年3月31日的肝移植患者。根据基线变量、合并症和药物使用状况,通过倾向评分(PS)匹配,我们将CHM使用者与非使用者按1:1的比例进行匹配。结果本研究共纳入1052例LT患者。PS匹配后,按1:1比例纳入554例患者。在几个3个月的随访期间,CHM和非CHM使用者表现出尿蛋白与肌酐比率(UPCR)改善的显著差异。随访12个月后,与非CHM使用者相比,CHM使用者的GFR下降有所缓解(CHM: 58.1至56.3 ml/min/1.73 m2;非CHM: 59.8至54.7 ml/min/1.73 m2)。在HCC患者中,与未使用中草药的患者相比,中草药使用者的GFR、UPCR和血尿素氮损伤有所减轻。最常用的草药和配方被注意到。结论与未使用中草药的患者相比,经过12个月的随访,中草药可以保护肾功能,无肝功能损害。然而,长期的影响和确切的肾脏保护机制需要进一步的研究来证实。
{"title":"Chinese herbal medicine alleviates renal impairment induced by immunosuppressants in patients post living donor liver transplantation","authors":"Hsiang-Chun Lai ,&nbsp;Kuan-Wen Lin ,&nbsp;Cheng-Li Lin ,&nbsp;Shi-Chen Ou ,&nbsp;Hung-Jen Lin ,&nbsp;Ju-Chien Cheng ,&nbsp;Chao-Chun Huang ,&nbsp;Sheng-Teng Huang ,&nbsp;Long-Bin Jeng","doi":"10.1016/j.jtcme.2024.09.004","DOIUrl":"10.1016/j.jtcme.2024.09.004","url":null,"abstract":"<div><h3>Background and aim</h3><div>Patients post liver transplantation (LT) with long-term immunosuppression agents will suffer from renal function impairment. Chinese herbal medicine (CHM) has been reported to relieve chronic kidney disease progression. Nevertheless, there are a lack of high-quality reports related to CHM reducing renal dysfunction in post-LT patients. We aim to investigate whether CHM alleviates renal impairment induced by immunosuppressants in patients having undergone LT.</div></div><div><h3>Materials and methods</h3><div>We conducted a hospital-based retrospective cohort study including patients with LT from January 1, 2003 to March 31, 2020. We matched the CHM users to non-users at a 1:1 ratio according to baseline variables, comorbidities and drug use status by propensity score (PS) matching.</div></div><div><h3>Results</h3><div>The study enrolled a total of 1052 LT patients. After PS matching, 554 patients were included with a 1:1 ratio. CHM and non-CHM users exhibited a significant difference of improved urine protein to creatinine ratio (UPCR) over several 3-month follow-up periods. CHM users exhibited an alleviated decrease in GFR compared to non-CHM users after 12 months of follow-up (CHM: 58.1 to 56.3 ml/min/1.73 m<sup>2</sup>; non-CHM: 59.8 to 54.7 ml/min/1.73 m<sup>2</sup>). Among HCC patients, CHM users had alleviated GFR, UPCR and blood urea nitrogen impairments compared to non-CHM users. The most commonly prescribed herbs and formulas are noted.</div></div><div><h3>Conclusion</h3><div>We herein report that CHM could protect renal function after 12 months of follow-up compared to non-CHM users, without liver function impairment. However, the long-term effects and exact renal protection mechanisms require further investigations to confirm.</div></div>","PeriodicalId":17449,"journal":{"name":"Journal of Traditional and Complementary Medicine","volume":"15 6","pages":"Pages 659-667"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Keratinocyte Piezo1 and CD39 initiated the acupuncture analgesic signals via Co-regulating extracellular ATP mobilization at acupoints 角化细胞Piezo1和CD39通过协同调节穴位细胞外ATP动员启动针刺镇痛信号
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.09.006
Yu-Jia Li , Si-Qi Tang , Jie Lin , Wei-Min Zuo , Ya-Wen Zheng , Meng Huang , Guang-Hong Ding , Li-Na Wang , Xue-Yong Shen
Acupoints are the initiation sites for acupuncture analgesic signals, where adenosine signaling plays a crucial role. A comprehensive understanding of this matter will guide clinicians to optimize acupuncture manipulations to improve acupuncture effectiveness. Recently, keratinocyte Piezo1 channels and cascade ATP release are independently unveiled to be essential for the skin tactile sensation. Thus, we aimed to investigate whether keratinocyte Piezo1-mediated ATP release, in orchestration with CD39, contributed to this initiation mechanism via producing adenosine. 20-min needling was administered at the unilateral ST36 acupoint on the acute ankle arthritis rats. The pain thresholds in the affected hindpaws were determined. Interstitial ATP and adenosine were extracted with microdialysis and assessed by luciferase-luciferin and HPLC, respectively. To simulate needling stimulation, keratinocyte HaCaT cells were subjected to hypotonic shock. ATP release and live calcium imaging were conducted. Immunofluorescence labeling showed the presence of Piezo1 and CD39 on keratinocytes. Acupuncture led to a prompt analgesic effect, as well as a temporary accumulation of ATP and adenosine. Activating adenosine A1 receptors, promoting ATP release by activating Piezo1, or facilitating ATP hydrolysis by potentiating CD39 achieved anti-nociceptive effects. Conversely, altering these modulations in the opposite direction reversed the subsequent effects of acupuncture. Needling-induced accumulation of interstitial ATP parallelly changed with these modulations. Hypotonic shock led to ATP release and [Ca2+]i rise in HaCaT, which were impeded by introducing siRNA-Piezo1, or replicated by agonism at Piezo1. These findings suggest that keratinocyte Piezo1 and CD39 co-mediated ATP mobilization at acupoints contributes to the initiation signals of acupuncture analgesia via triggering adenosine signaling.

Section

Physical/Mental practices (acupuncture)

Taxonomy (classification by evise)

pain and analgesia.
穴位是针刺镇痛信号的起始点,腺苷信号在其中起着至关重要的作用。全面了解这一问题将指导临床医生优化针灸手法,提高针灸疗效。近年来,角质细胞Piezo1通道和级联ATP释放被独立地揭示为皮肤触觉的必要条件。因此,我们的目的是研究角化细胞piezo1介导的ATP释放是否与CD39协同作用,通过产生腺苷促进了这种启动机制。急性踝关节关节炎大鼠单侧ST36穴针刺20 min。确定受影响后爪的疼痛阈值。微透析法提取间质ATP和腺苷,荧光素-荧光素法和高效液相色谱法测定。为了模拟针刺刺激,角化细胞HaCaT受到低渗休克。ATP释放和活钙成像。免疫荧光标记显示在角质形成细胞上存在Piezo1和CD39。针刺可引起迅速的镇痛作用,并使ATP和腺苷暂时积累。激活腺苷A1受体,通过激活Piezo1促进ATP释放,或通过增强CD39促进ATP水解实现抗伤害作用。相反,在相反的方向改变这些调节会逆转针灸的后续效果。针刺诱导的间质ATP积累与这些调节平行变化。低渗休克导致HaCaT中ATP释放和[Ca2+]i升高,这些过程被siRNA-Piezo1的引入所阻碍,或通过Piezo1的激动作用被复制。这些发现表明,角化细胞Piezo1和CD39共同介导ATP在穴位的动员,通过触发腺苷信号,有助于针灸镇痛的启动信号。物理/心理实践(针灸)分类(根据视觉分类)疼痛和镇痛。
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引用次数: 0
Qingre huazhuo tang regulates IgA nephropathy through immune checkpoints and ferroptosis 清热化浊汤通过免疫检查点和铁下垂调节IgA肾病
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.11.005
Yan Xu , Shanshan Han , Ting Guo , Yudi Li , Donglin Li , Ying Ding

Background

Qingre huazhuo tang (QRHZT) is a traditional Chinese medicine decoction that has been used clinically by traditional Chinese medicine masters for more than 50 years with good results. However, its mechanism is unknown, and further elucidation is necessary.

Aim of the study

To verify the mechanism by which QRHZT regulates IgA nephropathy through immune checkpoints and ferroptosis by combining network pharmacology, single-cell sequencing and experimental studies.

Materials and methods

The single-cell sequencing data obtained from podocytes of immunoglobulin A (IgA) nephropathy (IgAN) patients were screened, and the QRHZT target information was obtained from the ETCM database. Moreover, the KEGG, GSEA, immune checkpoint and ferroptosis data were analyzed and plotted using R language. Finally, the relevant immune checkpoint and ferroptosis targets were validated experimentally.

Results

QRHZT can regulate IgAN through the immune checkpoints FIT, FTH1, AKR1C3, and IL6 and the ferroptosis-related genes PVR and IFNG.

Conclusion

QRHZT has the potential to regulate IgAN, and omics strategies combined with network pharmacology is a feasible method for exploring the mechanisms of traditional Chinese medicines.
清热化浊汤是一种中药汤剂,已被中医大师在临床上使用了50多年,效果良好。然而,其机制尚不清楚,需要进一步阐明。研究目的结合网络药理学、单细胞测序和实验研究,验证QRHZT通过免疫检查点和铁下垂调控IgA肾病的机制。材料与方法筛选免疫球蛋白A (IgA)肾病(IgAN)患者足细胞单细胞测序数据,从ETCM数据库获取QRHZT靶点信息。使用R语言对KEGG、GSEA、免疫检查点和铁下垂数据进行分析和绘制。最后,实验验证了相关免疫检查点和铁下垂靶点。结果qrhzt可通过免疫检查点FIT、FTH1、AKR1C3、IL6和铁衰相关基因PVR、IFNG调控IgAN。结论qrhzt具有调节IgAN的潜力,组学策略与网络药理学相结合是探索中药作用机制的可行方法。
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引用次数: 0
Repurposing Suan-Zao-Ren-Tang as anticancer agents in apoptotic sensitization against non-small cell lung cancer cell lines through amplification of spindle assembly checkpoint activation 通过扩增纺锤体组装检查点激活,再利用酸藻仁汤作为抗癌药物对非小细胞肺癌细胞系的凋亡致敏
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.08.008
Yu-Chi Hsiao , Yi-Hua Sheng , Tse-Yu Chen , Wohn-Jenn Leu , Jui-Ling Hsu , Lih-Ching Hsu , Lie-Chwen Lin , Jih-Hwa Guh
Treatment of non-small cell lung cancer (NSCLC) is a high unmet medical need. We repurposed Suan-Zao-Ren-Tang (SZRT), a widely used traditional Chinese medicine in alleviating insomnia, to sensitize vinorelbine-induced anti-NSCLC effect and have unveiled the underlying mechanism. B7E2, the partial purified extract from SZRT, was used through bioactivity-guided fractionation based on anti-proliferative activity in NSCLC cell lines A549 and NCI-H460. Three batches of B7E2 and their individual components were prepared for the examination of components and bioactivity and mechanistic study. B7E2 alone had no cytotoxic effect but its combination with vinorelbine displayed a synergistic activity in killing NSCLC cells. Apoptotic sensitization was verified by a remarkable increase of caspase activation and phosphorylation of Bcl-2 and Bcl-xL. Combination treatment prolonged mitotic arrest and induced a substantial activation of spindle assembly checkpoint (SAC) characterized by BUBR1 phosphorylation at Ser670 and Thr680, and cyclin B1 upregulation. Combination treatment enhanced the interaction between mitotic checkpoint complex (MCC) components, including BUBR1, MAD2, BUB3 and CDC20. Further analysis revealed that SZRT components, including senkyunolide-A, trans-neocnidilide, 3-butylidenephthalide, betulinic acid and linoleic acid, were responsible for B7E2 activities. Three B7E2 batches showed a good chemical similarity and similar activities between batches. The data suggest that B7E2 is a potential chemosensitizer in potentiating vinorelbine-induced anti-NSCLC activity through amplification and prolongation of SAC activation.
治疗非小细胞肺癌(NSCLC)是一个高度未满足的医疗需求。我们将广泛应用于缓解失眠的中药酸辣仁汤(SZRT)用于长春瑞滨诱导的抗nsclc效应的增敏,并揭示了其潜在机制。基于对NSCLC细胞系A549和NCI-H460的抗增殖活性,采用生物活性引导分离的方法对SZRT部分纯化提取物B7E2进行了应用。制备了3批B7E2及其各组分,进行了组分检测、生物活性和机理研究。B7E2单用无细胞毒作用,但与长春瑞滨联用对非小细胞肺癌细胞有协同杀伤作用。凋亡致敏作用通过caspase激活和Bcl-2和Bcl-xL磷酸化的显著增加得到证实。联合治疗延长了有丝分裂停滞,并诱导纺锤体组装检查点(SAC)的大量激活,其特征是BUBR1在Ser670和Thr680位点磷酸化,以及细胞周期蛋白B1上调。联合治疗增强了有丝分裂检查点复合体(MCC)组分之间的相互作用,包括BUBR1、MAD2、BUB3和CDC20。进一步分析发现,SZRT的主要成分为仙球烯内酯a、反式新烯内酯、3-丁基苯酞、白桦酸和亚油酸。三个批次的B7E2具有良好的化学相似性和相似的活性。这些数据表明,B7E2是一种潜在的化学增敏剂,通过放大和延长SAC的激活,增强长春瑞滨诱导的抗nsclc活性。
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引用次数: 0
Hovenia dulcis Thunb. monofloral honey attenuates LPS-induced inflammation and endotoxemia through the activation of the Nrf2/HO-1 axis 霍维尼亚·杜尔西斯·图恩。单花蜂蜜通过激活Nrf2/HO-1轴来减轻lps诱导的炎症和内毒素血症
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.09.003
Wisurumuni Arachchilage Hasitha Maduranga Karunarathne , Sungjoon Na , Mi-Hwa Lee , Chang-Hee Kang , Yung Hyun Choi , Gi-Young Kim
Monofloral honey derived from Hovenia dulcis Thunb. (HMH) is known for its antimicrobial and antioxidant properties. However, its potential to alleviate the inflammatory response has not yet been explored. The aim of this study was to investigate the anti-inflammatory and anti-endotoxemic effects of HMH. The findings showed that HMH did not exhibit toxicity to RAW 264.7 macrophages at low concentrations and suppressed the production of proinflammatory mediators, such as nitric oxide and prostaglandin E2, as well as cytokines, including tumor necrosis factor-α and interleukin-12 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, by inhibiting NF-κB activation. Additionally, HMH prevented mortality and abnormalities in LPS-microinjected zebrafish larvae along with the inhibition of proinflammatory genes. In addition, HMH was found to reduce mitochondrial membrane potential depolarization and mitochondrial reactive oxygen species production in both LPS-stimulated RAW 264.7 macrophages and zebrafish larvae. Furthermore, HMH induced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and promotes the nuclear translocation of Nrf2. The anti-inflammatory effects of HMH are mediated via the Nrf2-HO-1 axis, and an HO-1 inhibitor reverses HMH-induced responses. This study is the first to demonstrate the anti-inflammatory and anti-endotoxemic effects of HMH, highlighting its potential as a therapeutic.
单花蜂蜜,产自蜂蜜。(HMH)以其抗菌和抗氧化特性而闻名。然而,其减轻炎症反应的潜力尚未被探索。本研究的目的是研究HMH的抗炎和抗内毒素作用。研究结果表明,HMH在低浓度下对RAW 264.7巨噬细胞无毒性,并通过抑制NF-κB活化,抑制脂多糖刺激的RAW 264.7巨噬细胞中促炎介质如一氧化氮和前列腺素E2的产生,以及细胞因子如肿瘤坏死因子-α和白细胞介素-12的产生。此外,HMH通过抑制促炎基因,防止lps微注射斑马鱼幼鱼的死亡和异常。此外,研究发现,在lps刺激的RAW 264.7巨噬细胞和斑马鱼幼虫中,HMH均能减少线粒体膜电位去极化和线粒体活性氧的产生。HMH诱导核因子红细胞2相关因子2 (Nrf2)和血红素加氧酶-1 (HO-1)的表达,促进Nrf2的核易位。HMH的抗炎作用是通过Nrf2-HO-1轴介导的,HO-1抑制剂可逆转HMH诱导的反应。这项研究首次证明了HMH的抗炎和抗内毒素作用,突出了其作为治疗药物的潜力。
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引用次数: 0
Acupoint stimulation by microneedle alleviates motor dysfunction through modulating striatal dopamine and choline levels and reducing neuroinflammation in the Parkinson's disease mouse model 微针穴位刺激通过调节纹状体多巴胺和胆碱水平,减轻帕金森病小鼠模型的神经炎症,减轻运动功能障碍
IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Pub Date : 2025-10-01 DOI: 10.1016/j.jtcme.2024.09.002
Jin Hee Kim , In Gyoung Ju , Yujin Choi , Jin Se Kim , Hanbyeol Lee , Ju-Young Oh , Keun Ho Lee , Sookie La , Do Hyeon Jeong , Changsu Na , Hi-Joon Park , Myung Sook Oh
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the basal ganglia. Despite the development of numerous drugs to treat PD, the limitations of these drugs have led to the exploration of various therapies. Previous clinical trials and in vivo studies have demonstrated that stimulation of acupuncture points (acupoints) effectively improve PD phenotype. Recently, microneedles (MNs) have emerged as promising therapeutic tools and may offer a novel approach for easy acupoint stimulation. This study explored the effects of MN patches attached to acupoints on PD phenotypes. The MN patches were attached to the Fengchi (GB20) and Yanglingquan (GB34) acupoints in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced mice for 12 consecutive days. Following this treatment, tissue analysis was performed using immunohistochemistry and Western blot. Mice with MN patches showed significantly improved motor function in the pole and rotarod tests. In the SN of a mouse with MN patches attached, the expression of Heme Oxygenase 1 (HO-1)/Nuclear factor erythroid-2-related factor 2 (Nrf2) was increased, and dopaminergic neurons damaged by MPTP were protected. In the brain tissues of mice with MN patches, the balance of dopaminergic and cholinergic neurons was regulated, and the hyperactivation of microglia and astrocytes was inhibited. Furthermore, the levels of cytokines in the plasma of mice with MN patches were significantly decreased. Collectively, the stimulation of GB20 and GB34 acupoints by MN patches may be a novel therapy for delaying PD.
帕金森病(PD)是一种以基底神经节多巴胺能神经元丧失为特征的神经退行性疾病。尽管开发了许多治疗PD的药物,但这些药物的局限性导致了各种治疗方法的探索。以往的临床试验和体内研究表明,刺激穴位(腧穴)可有效改善PD表型。最近,微针(MNs)作为一种有前景的治疗工具出现,并可能提供一种简便的穴位刺激新方法。本研究探讨穴位贴敷MN贴片对PD表型的影响。将MN贴片贴于1-甲基-4-苯基-1,2,3,6-盐酸四氢吡啶(MPTP)诱导小鼠风池穴(GB20)和阳陵泉穴(GB34)连续12天。治疗后,使用免疫组织化学和Western blot进行组织分析。在杆状和旋转体实验中,MN贴片小鼠的运动功能明显改善。在MN贴片小鼠SN中,血红素加氧酶1 (HO-1)/核因子红细胞2相关因子2 (Nrf2)表达增加,MPTP损伤的多巴胺能神经元受到保护。在MN贴片小鼠脑组织中,多巴胺能和胆碱能神经元的平衡得到调节,小胶质细胞和星形胶质细胞的过度活化受到抑制。此外,MN贴片小鼠血浆中细胞因子水平显著降低。综上,MN贴片刺激GB20和GB34穴位可能是延缓PD的一种新疗法。
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引用次数: 0
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Journal of Traditional and Complementary Medicine
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