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Wound healing potential of Acacia catechu in streptozotocin-induced diabetic mice using in vivo and in silico approach 儿茶对链脲佐菌素诱导的糖尿病小鼠伤口愈合潜力的体内和体外研究
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.05.001
Vinayak P. Nakhate , Natasha S. Akojwar , Saurabh K. Sinha , Amarsinh D. Lomte , Mahaveer Dhobi , Prakash R. Itankar , Satyendra K. Prasad

Background and aim

Acacia catechu Wild. (Fabaceae) barks are traditionally used in the treatment of diabetes and wounds. Therefore, the objective of the present study was to evaluate the wound healing potential of the alcoholic extract of A. catechu (EAC) in streptozotocin-induced diabetic mice.

Experimental procedures

EAC was first subjected to phytochemical estimations and standardization using (−) epicatechin as marker with the help of HPLC. Diabetes was induced in mice using streptozotocin and the wound healing potential of EAC was evaluated using excision and incision wound models on topical and oral treatment. Various biochemical parameters, in vivo antioxidants, cytokine profiling, VEGF, and histopathological examination were also performed. Further, molecular docking studies were performed using ligand (−) epicatechin on human inducible nitric oxide synthase.

Results and conclusion

Phytochemically, EAC showed the presence of tannins, flavonoids, phenolic compounds, and saponins, while the content of (−) epicatechin was reported to be 7.81% w/w. The maximum healing of wounds (91.84 ± 1.10%) was observed in mice treated with a combination of both topical (10% gel) and oral (extract at 200 mg/kg) followed by topically and orally treated groups respectively after 14 days of treatment. These groups also showed significant restoration of altered biochemical parameters, antioxidant enzymes and cytokines. The molecular docking studies confirmed the role of (−) epicatechin in stabilizing the human inducible nitric oxide synthase with inhibitor showing binding energy of −8.31 kcal/mol. The present study confirmed the role of (−) epicatechin as a major marker in diabetic wound healing potential of A. catechu.

背景和目的儿茶野生Acacia catechu Wild。(蚕豆科)树皮传统上用于治疗糖尿病和伤口。因此,本研究的目的是评估儿茶醇提取物(EAC)对链脲佐菌素诱导的糖尿病小鼠的伤口愈合潜力。实验程序首先用高效液相色谱法,以(−)表儿茶素为标记物,对EAC进行了植物化学评价和标准化。使用链脲佐菌素在小鼠中诱导糖尿病,并使用局部和口服治疗的切除和切口伤口模型评估EAC的伤口愈合潜力。还进行了各种生化参数、体内抗氧化剂、细胞因子谱、VEGF和组织病理学检查。此外,使用配体(−)表儿茶素对人类诱导型一氧化氮合酶进行了分子对接研究。结果和结论EAC的植物化学成分中含有鞣质、黄酮类、酚类化合物和皂苷,而表儿茶素的含量为7.81%w/w。在用局部(10%凝胶)和口服(200mg/kg提取物)联合治疗的小鼠中观察到伤口的最大愈合率(91.84±1.10%),然后在治疗14天后分别用局部和口服治疗组。这些组还显示出改变的生化参数、抗氧化酶和细胞因子的显著恢复。分子对接研究证实了(−)表儿茶素在稳定人类诱导型一氧化氮合酶中的作用,其抑制剂显示出−8.31 kcal/mol的结合能。本研究证实了表儿茶素作为儿茶属糖尿病伤口愈合潜力的主要标志物的作用。
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引用次数: 1
Exploring the effects and mechanisms of Guizhigancao Decoction on heart failure using an integrated approach based on experimental support and network pharmacology strategy 基于实验支持和网络药理学策略的综合研究桂枝甘草汤对心力衰竭的作用及机制
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.03.010
Jianhua Qu , Jiao Wang , Biao Zheng , Xiaoxiao Jiang , Jikui Liu , Jing Chen

Background and aim

HF (Heart Failure) is the leading cause of mortality and is a significant clinical problem affecting millions of patients worldwide. To date, the mechanisms of HF remain largely elusive. The effective treatments contributing to HF remain incompletely understood. Therefore, the development of an effective strategy for HF is urgently needed.

Experimental procedure

In the present study, we devoted to investigating the effective treatments and sought to systematically decipher the related molecular mechanisms of Guizhigancao Decoction (GZGCD, Cinnamomum cassia Presl and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle) for treating HF. We examined the therapeutic effect of GZGCD on HF in vivo. An integrative approach combining biomarker examination, echocardiography, myocardial fibrosis and cardiac apoptosis condition using Masson and TUNEL staining was performed to assess the efficacy of GZGCD against HF. Subsequently, comprehensive network pharmacology analyses were performed to explore the mechanisms involved in GZGCD therapeutic effects on HF.

Results and conclusions

The results showed that GZGCD could reverse cardiac function in rats with HF by reducing NT-proBNP, increasing EF, decreasing LVESV, LVEDV, LVIDs, LVIDd, increasing running time, and ameliorate myocardial collagen fiber hyperplasia and cardiomyocyte apoptosis. We showed that GZGCD might contribute to HF treatment via oxidative related pathways through bioinformatics. Eventually, promising compound quercetin in GZGCD for HF therapeutics was proposed in database-based analysis. Collectively, our findings indicate that GZGCD has a treatment effect on HF. We proposed that GZGCD might contribute HF treatment via oxidative response-related pathways.

背景和目的心力衰竭是导致死亡的主要原因,也是影响全球数百万患者的一个重大临床问题。到目前为止,HF的机制在很大程度上仍然难以捉摸。导致HF的有效治疗方法仍不完全清楚。因此,迫切需要制定一项有效的HF战略。实验方法本研究旨在探讨桂枝甘草汤治疗HF的有效方法,系统地揭示桂枝甘草汤、桂皮、甘草治疗HF的相关分子机制。采用Masson和TUNEL染色结合生物标志物检查、超声心动图、心肌纤维化和心肌细胞凋亡状况的综合方法来评估GZGCD对HF的疗效,结果与结论GZGCD可通过降低NT-proBNP、增加EF、降低LVESV、LVEDV、LVIDs、LVIDd、增加运行时间、,改善心肌胶原纤维增生和心肌细胞凋亡。我们通过生物信息学表明,GZGCD可能通过氧化相关途径对HF治疗有贡献。最终,在基于数据库的分析中,提出了GZGCD中有前景的化合物槲皮素用于HF治疗。总之,我们的研究结果表明GZGCD对HF有治疗作用。我们提出GZGCD可能通过氧化反应相关途径对HF治疗有贡献。
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引用次数: 0
Comparison and effect of moxibustion and acupuncture on Nogo/NgR signaling pathway in rats with cerebral ischemia/reperfusion injury 艾灸与针刺对脑缺血再灌注损伤大鼠Nogo/NgR信号通路的影响及比较
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.03.006
You-jiang Min , Hai-hua Yao , Li Wang , Li-hong Cheng , En-si Hong

Background and aim

In China, acupuncture and moxibustion have been used effectively to treat various diseases for thousands of years. However, the evidence for a difference in the efficacies of moxibustion and acupuncture in cerebral infarction treatment is scarce. We aimed to compare the effects of acupuncture and moxibustion treatment on the Nogo/NgR signaling pathway in rats with cerebral ischemia/reperfusion (I/R) injury.

Experimental procedure

Eighty male SD rats were randomly divided into five groups, based on treatment received: sham surgery (sham group), middle cerebral artery occlusion (MCAO, MCAO group), MCAO and NEP(1–40) inhibitor injection (MCAO + block group), MCAO and moxibustion (MCAO + moxi group), and MCAO and minimal acupuncture (MCAO + MA group). Neurological status was evaluated before treatment, and cerebral infarction volume (IV) and neurological function; Nogo-A, NgR, p75NTR, and LINGO-1 expressions; and NgR and LINGO-1 co-expression were assessed after treatment.

Results and conclusion

After treatment, barring Nogo-A mRNA and protein expression in the MCAO + block group, the Longa score and IV significantly decreased; Nogo-A, NgR, p75NTR, and LINGO-1 mRNA and protein expressions as well as NgR and LINGO-1 co-expression significantly decreased in cerebral tissues; whereas the BWT score increased (P < 0.01) in the MCAO + moxi group, compared with the MCAO group. Except for NgR and LINGO-1 protein expressions, there were no significant differences in the abovementioned parameters between rats that underwent acupuncture and moxibustion. Acupuncture and moxibustion have similar effects on Nogo/NgR signaling pathway inhibition after cerebral infarction.

背景与目的在中国,针灸治疗各种疾病已有数千年的历史。然而,艾灸和针灸治疗脑梗死的疗效差异的证据很少。我们旨在比较针灸治疗对脑缺血/再灌注(I/R)损伤大鼠Nogo/NgR信号通路的影响。实验方法将80只雄性SD大鼠随机分为5组:假手术组(假手术组)、大脑中动脉闭塞组(MCAO、MCAO组)、MCAO和NEP(1-40)抑制剂注射组(MCAO+阻断组)、MCAO+艾灸组(MCAO+莫西组)、以及MCAO和微创针刺组(MCA0+MA组)。治疗前评估神经系统状况、脑梗死体积(IV)和神经功能;Nogo-A、NgR、p75NTR和LINGO-1表达;并在治疗后评估NgR和LINGO-1的共表达。结果与结论治疗后,MCAO+阻断组除Nogo-A mRNA和蛋白表达外,Longa评分和IV均显著下降;脑组织中Nogo-A、NgR、p75NTR和LINGO-1的mRNA和蛋白表达以及NgR和LINGO-1的共表达显著降低;而MCAO+莫西组的BWT评分与MCAO组相比增加(P<0.01)。除NgR和LINGO-1蛋白表达外,针灸组大鼠上述参数无显著差异。针灸对脑梗死后Nogo/NgR信号通路的抑制作用相似。
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引用次数: 0
FM2- Aims & Scope FM2-目标和范围
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/S2225-4110(23)00092-5
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引用次数: 0
Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-β1/Smad3 pathways 大承气汤通过抑制TGF-β1/Smad3通路改善脓毒症肝损伤
3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.09.001
Guangtao Pan, Yanran Wu, Yuhan Liu, Fangyuan Zhou, Sen Li, Yang Shenglan
Sepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1β/Smad3 pathways. A septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism. DCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-β1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway. DCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.
脓毒症引起的急性肝损伤(ALI)是脓毒症患者死亡的主要原因。探索脓毒症诱发ALI的发病机制和制定有效的治疗策略对改善患者预后至关重要。大成气汤(DCQD)是一种经典的中草药,已被证明具有有效的抗炎特性。然而,DCQD对脓毒症诱导的ALI的保护作用和潜在机制尚不清楚。本研究旨在探讨DCQD对脓毒症诱导的ALI的保护作用,并阐明TGF-1β/Smad3通路的参与。采用盲肠结扎穿刺法(CLP)建立脓毒症小鼠模型,在体内评价DCQD对脓毒症ALI的保护作用。采用lps刺激LO2细胞建立体外细胞炎症模型,进一步探讨其机制。DCQD(2.5、5.0和10.0 g/kg体重)每天两次,连续2天,对败血症诱导的ALI有剂量依赖性的保护作用。DCQD治疗显著抑制肝组织不适当的炎症反应和氧化应激。此外,DCQD通过抑制肝细胞凋亡和改善败血症引起的肝损伤来维持肝脏稳态。体内和体外研究表明,TGF-β1/Smad3信号通路在脓毒症诱导的ALI中发挥重要作用,DCQD治疗可显著抑制该通路的激活。DCQD可以有效抑制过度的炎症反应和氧化应激,导致脓毒症诱导的ALI中肝细胞凋亡的显著减少。
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引用次数: 0
Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway 泽气汤通过调节PI3K/Akt/p53信号通路抑制非小细胞肺癌的生长和转移
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.03.008
Jingtao Zhang , Zifan Zhuang , Minghao Guo , Kai Wu , Qingfeng Yang , Xin Min , Wenqiang Cui , Fei Xu

Background

The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation.

Methods

Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments.

Results

In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2.

Conclusions

ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.

泽芪汤是我国治疗癌症常用的中药复方。本研究旨在基于网络药理学和实验验证,评估ZQD治疗非小细胞肺癌癌症(NSCLC)的有效成分和分子机制。方法采用网络药理学、生物信息学和分子对接分析等方法,探讨ZQD治疗NSCLC的作用机制,并通过动物实验进一步证实。结果共鉴定出ZQD的117种生物活性成分和499种靶蛋白。网络药理学揭示了7种核心活性成分和74种核心靶蛋白。京都基因和基因组百科全书富集分析表明,PI3K/Akt和p53信号通路可能在NSCLC治疗中至关重要。分子对接分析显示,七种关键的生物活性成分与PI3K、Akt和p53复合。动物实验结果证实,ZQD治疗促进了细胞凋亡和细胞周期停滞,从而抑制了NSCLC的生长和转移。此外,ZQD治疗导致p53和Bax显著增加,同时导致p-PI3K(Tyr317)、p-Akt(Ser473)、VEGFA、CD31、MMP2、MMP9、Bcl2和CDK2显著减少。结论ZQD通过PI3K/Akt/p53信号通路抑制C57BL/6J小鼠NSCLC皮下肿瘤的生长和转移。
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引用次数: 1
Barleria prionitis L. extracts ameliorate doxorubicin-induced acute kidney injury via modulation of oxidative stress, inflammation, and apoptosis 朊芽孢杆菌提取物通过调节氧化应激、炎症和细胞凋亡改善阿霉素诱导的急性肾损伤
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.05.007
Sachinthi S. Amarasiri , Anoja P. Attanayake , Liyanage D.A.M. Arawwawala , Lakmini K.B. Mudduwa , Kamani A.P.W. Jayatilaka

Background and aim

Doxorubicin (DOX) is a chemotherapeutic drug with potential nephrotoxic effects on patients who are on cancer chemotherapy. An interest has been observed in using natural products to ameliorate the potential side effects of DOX. The present study is to investigate the cellular mechanisms underlying the protective effects of Barleria prionitis L. (BP) (Acanthaceae) extracts, DOX-induced acute kidney injury (AKI).

Experimental procedure

Hexane (25 mg/kg/day), ethyl acetate (80 mg/kg/day), n-butanol (70 mg/kg/day), and water (120 mg/kg/day) extracts of BP, were administered to DOX-induced (5 mg/kg (2500 μL/kg), ip) Wistar rats for four consecutive weeks. At the end of the study, investigations were carried out for the assessment of biomarkers of nephrotoxicity, oxidative stress, inflammation, and apoptosis.

Results

Treatments with BP extracts significantly reversed DOX-induced elevations in serum and urine biochemical markers of nephrotoxicity (serum creatinine; 21–33%, blood urea nitrogen; 26–58%, β2-microglobulin; 19–22% and urine total protein; 47–67%). There was a reduction in the levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde in kidney homogenates of rats treated with the n-butanol extract (by 43, 62, and 24%) and water extract (by 57%, 85%, and 26%) (p < 0.05). Immunohistochemical expression of the pro-apoptotic B-cell associated X protein was reduced while the anti-apoptotic B-cell lymphoma gene product 2 protein was increased in kidney tissues after the treatments with BP extracts.

Conclusions

The selected BP extracts significantly ameliorated DOX-induced AKI. The findings would open new vistas for the development of a drug using the BP extracts to minimize DOX-induced AKI in cancer patients.

背景与目的阿霉素(DOX)是一种对癌症化疗患者具有潜在肾毒性的化疗药物。已经观察到人们对使用天然产品来改善DOX的潜在副作用感兴趣。本研究旨在探讨Barleria prionitis L.(BP)(无患子科)提取物、DOX诱导的急性肾损伤(AKI)保护作用的细胞机制,ip)Wistar大鼠连续4周。在研究结束时,对肾毒性、氧化应激、炎症和细胞凋亡的生物标志物进行了评估。结果BP提取物治疗可显著逆转DOX诱导的肾毒性血清和尿液生化标志物(血清肌酐;21-33%,血尿素氮;26-58%,β2-微球蛋白;19-22%,尿总蛋白;47-67%)的升高。肿瘤坏死因子-α、白细胞介素-1β、,以及用正丁醇提取物(增加43%、62%和24%)和水提取物(增加57%、85%和26%)处理的大鼠肾匀浆中的丙二醛(p<0.05)。在用BP提取物处理后,肾组织中促凋亡B细胞相关X蛋白的免疫组化表达减少,而抗凋亡B细胞淋巴瘤基因产物2蛋白增加。结论所选BP提取物能显著改善DOX诱导的AKI。这一发现将为开发一种使用BP提取物最大限度减少癌症患者DOX诱导的AKI的药物开辟新的前景。
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引用次数: 1
Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice 枳实树皮对酸性乙醇致小鼠胃溃疡的保护作用
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.05.006
Shih-Cheng Huang , Wen-Jun Wu , Yi-Ju Lee , Ming-Shiun Tsai , Xiang-Zhe Yan , Hsiao-Chun Lin , Pin-Yen Lai , Kun-Teng Wang , Jiunn-Wang Liao , Jen-Chieh Tsai , Sue-Hong Wang

Background and aim

In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice.

Experimental procedure

The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied.

Results and conclusion

Pretreatment with MZ (100 and 200 mg/kg) significantly decreased 10 μL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1β levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200 mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

背景与目的在传统医学中,zuihoensis Hayata bark(MZ)与其他药物联合用于治疗胃癌症、胃溃疡、肝脏和心血管疾病。本研究旨在评估MZ粉末对酸性乙醇(AE)诱导的GU的胃保护作用及其可能机制及其对小鼠的毒性。实验方法在AE诱发GU前连续14天口服MZ,分析MZ粉的胃保护作用。计算溃疡指数和保护率,进行苏木精-伊红染色和周期性酸性希夫染色,并测量胃粘液重量。研究了抗氧化、抗炎和抗细胞凋亡的机制,以及可能的信号通路。结果和结论MZ(100和200mg/kg)预处理可显著降低10μL/g AE引起的粘膜出血、水肿、炎症和UI,保护率分别为88.9%和93.4%。MZ预处理通过降低丙二醛水平和恢复超氧化物歧化酶活性来降低AE诱导的氧化应激。MZ预处理通过降低血清和胃肿瘤坏死因子-α、白细胞介素(IL)-6和IL-1β水平显示出抗炎作用。此外,MZ预处理通过降低Bcl-2相关的X蛋白/B-细胞淋巴瘤2的比率而表现出抗凋亡作用。MZ的胃保护机制涉及活化B细胞的核因子κ轻链增强子(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路的失活。除此之外,200mg/kg MZ不会引起肝或肾毒性。总之,MZ通过分泌粘液、抗氧化、抗炎和抗凋亡机制以及抑制NF-κB和MAPK信号通路来保护AE诱导的GU。
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引用次数: 0
FM1 - Title Page FM1 -标题页
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/S2225-4110(23)00091-3
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引用次数: 0
Xin-Li formula attenuates heart failure induced by a combination of hyperlipidemia and myocardial infarction in rats via Treg immunomodulation and NLRP3 inflammasome inhibition 心利方通过Treg免疫调节和NLRP3炎性体抑制作用减轻高脂血症合并心肌梗死大鼠心力衰竭
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.03.009
Taohua Lan , Qiaohuang Zeng , Ying Zhu , Guangjuan Zheng , Keji Chen , Wei Jiang , Weihui Lu

Background and aim

Heart failure (HF) is a complex clinical syndrome that represents the end result of several pathophysiologic processes. Despite a dramatic evolution in diagnosis and management of HF, most patients eventually become resistant to therapy. Xin-Li Formula (XLF) is a Chinese medicine formula which shows great potential in the treatment of HF according to our previous studies. The present study was designed to investigate the effects of XLF on HF induced by a combination of hyperlipidemia and myocardial infarction (MI) in rats and reveal the underlying mechanism.

Experimental procedure

A rat model of HF induced by hyperlipidemia and MI was established with intragastric administration of XLF and Perindopril. In vitro, CD4+ T cells from mouse spleen and LPS/ATP-stimulated THP-1 macrophages were employed.

Results and conclusion

XLF was shown to have markedly protective effects on MI-induced HF with hyperlipidemia in rats, including improvement of left ventricular function, reduction of left ventricular fibrosis and infarct size. Moreover, XLF administration significantly increased the number of Foxp3+ Tregs, and inhibited mTOR phosphorylation and NLRP3 signaling pathway. In vitro, we found that XLF had induced Treg activation via the inhibition of mTOR phosphorylation in CD4+ T cells. Additionally, XLF inhibited NLRP3 inflammasome activation in LPS/ATP-stimulated THP-1 macrophages. Taken together, this study raises the exciting possibility that Xin-Li Formula may benefit HF patients due to its immunomodulatory and anti-inflammatory effects via Treg activation and NLRP3 inflammasome inhibition.

背景和目的心力衰竭(HF)是一种复杂的临床综合征,代表了几个病理生理过程的最终结果。尽管HF的诊断和治疗发生了戏剧性的变化,但大多数患者最终对治疗产生了耐药性。根据我们以往的研究,辛离方是一种在治疗HF方面显示出巨大潜力的中药配方。本研究旨在研究XLF对高脂血症和心肌梗死(MI)联合诱导的大鼠HF的影响,并揭示其潜在机制。实验方法灌胃XLF和培哚普利,建立高脂血症和心肌梗死大鼠HF模型。在体外,使用来自小鼠脾脏的CD4+T细胞和LPS/ATP刺激的THP-1巨噬细胞。结果和结论XLF对MI诱导的高脂血症大鼠HF具有明显的保护作用,包括改善左心室功能、减少左心室纤维化和梗死面积。此外,XLF给药显著增加Foxp3+Treg的数量,并抑制mTOR磷酸化和NLRP3信号通路。在体外,我们发现XLF通过抑制CD4+T细胞中mTOR磷酸化来诱导Treg活化。此外,XLF抑制LPS/ATP刺激的THP-1巨噬细胞中NLRP3炎症小体的激活。总之,这项研究提出了一种令人兴奋的可能性,即新力方可能通过Treg激活和NLRP3炎症小体抑制发挥免疫调节和抗炎作用,从而使HF患者受益。
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引用次数: 0
期刊
Journal of Traditional and Complementary Medicine
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