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Phytocannabinoids: Pharmacological effects, biomedical applications, and worldwide prospection 植物大麻素:药理作用、生物医学应用和全球前景
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1016/j.jtcme.2023.08.006
Ana L.G. de Brito Siqueira , Pedro V.V. Cremasco , Juliana O. Bahú , Aline Pioli da Silva , Lucas R. Melo de Andrade , Paula G.A. González , Sara Crivellin , Viktor O. Cárdenas Concha , Karolline Krambeck , Leandro Lodi , Patrícia Severino , Eliana B. Souto

Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (−)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

神经系统疾病(如帕金森病、阿尔茨海默病、肌萎缩性侧索硬化症(ALS)、多发性硬化症、抑郁症和记忆力丧失)与氧化损伤之间存在关联的科学证据。这类疾病在世界范围内的发病率不断上升,引起研究人员的注意,寻找缓解症状和提高生活质量的药物,特别是在南美洲和非洲等发展中国家。在潜在的替代品中,大麻L.的提取物适用于因癌症和关节炎等疾病而患有神经系统疾病、痉挛、疼痛、恶心的人。本文综述了大麻的最新研究进展、大麻的亚型和成分、提取方法以及相关的药理作用。还讨论了大麻L.提取物的生物医学应用、上市产品和全球使用前景,并提供了南美洲(即巴西)和非洲(即南非)代表性国家发表的科学文献的文献计量图。由于缺乏关于大麻有效性和安全性的证据,再加上对成瘾和其他不良事件的担忧,许多国家在改变大麻相关法规之前都要谨慎行事。最近的研究结果预计将增加社会对大麻的接受程度,而新技术似乎将推动全球大麻市场,因为(−)-反式-德尔塔-9-四氢大麻酚(Δ9-THC)和大麻二酚(CBD)的使用除了可能创造一般新就业机会外,还在几项研究中得到了证明。
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引用次数: 0
Xiaozheng pill exerts an anti-mammary hyperplasia effect through Raf/ERK/ELK and HIF-1α/bFGF pathways 消正丸通过Raf/ERK/ELK和HIF-1α/bFGF通路发挥抗乳腺增生作用
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1016/j.jtcme.2023.05.002
Yu-fei Liu , Tian An , Hong Yu , Ying-yi Fan , Xiao-hua Pei

Background and aim

The purpose of this study is to explore whether the Xiaozheng pill (XZP) has the effect of anti-hyperplasia of mammary glands (HMG) and to identify the related signaling pathways.

Experimental procedure

We analyzed the effective chemical components of the XZP, as well as the key chemical components, key proteins, main biological processes, and pathways in the treatment of HMG; Secondly, the levels of Estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Progesterone (P), Raf/ERK/ELK and HIF-1α/bFGF pathways related proteins were detected; Finally, the effect of XZP on metabolites was analyzed by metabolomics.

Results and conclusion

In this study, we identified key targets and pathways for XZP therapy of HMG, including EGFR, VEGFA, ER, and Ras signaling pathways. Animal experiments show that XZP can reduce the levels of E2, LH, and FSH and increase the expression of P in HMG mice. XZP can restore the normal structure of breast tissue and reduce ERα, ERβ, and PR expression in breast tissue. In addition, metabolomics results show that XZP also regulates HMG metabolites, including HIF-1α and metabolic pathways. The Western blot results showed that XZP intervention can reduce the protein expression of p-Raf1, Raf1, p-ERK1/2, ERK1/2, ELK, HIF-1α, and bFGF in the breast tissue of HMG mice. XZP may eliminate abnormal breast hyperplasia through inhibition of apoptosis and angiogenesis, which may be linked with the regulation of the Raf/ERK/ELK and HIF-1α/bFGF signaling pathways in HMG mice. These results suggest that XZP treatment may be beneficial for the management of HMG.

背景与目的探讨消正丸(XZP)是否具有抗乳腺增生(HMG)的作用,并确定相关信号通路。实验程序分析了XZP的有效化学成分,以及治疗HMG的关键化学成分、关键蛋白、主要生物过程和途径;其次,检测雌二醇(E2)、促卵泡激素(FSH)、促黄体生成素(LH)、孕酮(P)、Raf/ERK/ELK、HIF-1α/bFGF通路相关蛋白水平;最后通过代谢组学分析XZP对代谢产物的影响。结果与结论在本研究中,我们确定了XZP治疗HMG的关键靶点和通路,包括EGFR、VEGFA、ER和Ras信号通路。动物实验表明,XZP可降低HMG小鼠E2、LH、FSH水平,提高P的表达。XZP能恢复乳腺组织的正常结构,降低ERα、ERβ和PR的表达。此外,代谢组学结果显示XZP还调节HMG代谢产物,包括HIF-1α和代谢途径。Western blot结果显示,XZP干预可降低HMG小鼠乳腺组织中p-Raf1、Raf1、p-ERK1/2、ERK1/2、ELK、HIF-1α、bFGF蛋白的表达。XZP可能通过抑制细胞凋亡和血管生成来消除乳腺异常增生,这可能与调节HMG小鼠的Raf/ERK/ELK和HIF-1α/bFGF信号通路有关。这些结果提示XZP治疗可能有利于HMG的治疗。
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引用次数: 0
Betanin combined with virgin coconut oil inhibits neuroinflammation in aluminum chloride-induced toxicity in rats by regulating NLRP3 inflammasome 甜菜素联合初榨椰子油通过调节NLRP3炎性体抑制氯化铝诱导的大鼠神经炎症
3区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1016/j.jtcme.2023.11.001
Baban S. Thawkar, Ginpreet Kaur
Activating NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is crucial in the pathogenesis of Alzheimer's disease (AD). A multimodal treatment intervention is the most feasible way to alter the course of AD progression. Hence, the current study was conducted to study the combination of betanin (BET) and virgin coconut oil (VCO) on NLRP3 regulation in aluminum chloride-induced AD in Wistar rats. BET (100,200 mg/kg) and VCO (1, 5 g/kg) alone and in combination (BET 100 mg/kg + VCO 1 g/kg and BET 200 mg/kg + VCO 5 g/kg) were given orally for 42 days. On day 21 and 42nd, the behavioral test was performed to check the animal's cognition. Acetylcholinesterase (AChE) activity, oxidative stress markers, estimation of NLRP3 and IL-1β, and histological examinations were conducted in the hippocampus (H) and cortex (C). Treatment with BET and VCO alone or combined improved behavioral characteristics (MWM and PA p < 0.0001; EPM p = 0.5184), inhibited AChE activity (C, p = 0.0101; H, p < 0.0001), and lowered oxidative stress in the brain. Also, combination treatment restored the levels of NLRP3 (C, p = 0.0062; H, p < 0.0001) and IL1β (C, p = 0.0005; H, p = 0.0098). The combination treatment significantly reduced the degree of neuronal degeneration, amyloid deposition, and necrosis in the brain tissue. The current study revealed that the combination strategy effectively controlled neuroinflammation via modulation of the NLRP3 inflammasome pathway, paving the way for the new treatment.
激活NLRP3 (NOD-、LRR-和pyrin结构域蛋白3)在阿尔茨海默病(AD)的发病机制中至关重要。多模式干预治疗是改变阿尔茨海默病进展最可行的方法。因此,本研究拟研究甜菜素(betanin, BET)与初榨椰子油(virgin coconut oil, VCO)联合应用对氯化铝诱导的Wistar大鼠AD中NLRP3的调控作用。贝特(100、200 mg/kg)和VCO (1.5 g/kg)单独或联合(贝特100 mg/kg + VCO 1 g/kg和贝特200 mg/kg + VCO 5 g/kg)口服42 d。第21天和第42天分别进行行为学测试,检查动物的认知能力。在海马(H)和皮质(C)中进行乙酰胆碱酯酶(AChE)活性、氧化应激标志物、NLRP3和IL-1β的测定以及组织学检查。EPM p = 0.5184),抑制AChE活性(C, p = 0.0101;H, p < 0.0001),并降低大脑的氧化应激。此外,联合治疗可恢复NLRP3水平(C, p = 0.0062;H, p < 0.0001)和il - 1β (C, p = 0.0005;H, p = 0.0098)。联合治疗显著降低了脑组织中神经元变性、淀粉样蛋白沉积和坏死的程度。目前的研究表明,联合策略通过调节NLRP3炎性体途径有效控制神经炎症,为新的治疗方法铺平了道路。
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引用次数: 0
Antimalarial activity of Toona ciliata MJ Roem aqueous methanolic leaf extract and its antioxidant and phytochemical properties 香椿叶甲醇提取物的抗疟活性及其抗氧化和植物化学性质
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1016/j.jtcme.2023.05.004
Nalini Singh , Aditi Chatterjee , Wahengbam Kabita Chanu , Pradeep Mini Vaishalli , Chingakham Brajakishor Singh , Viswanathan Arun Nagaraj

Background and aim

Malaria is a global health issue causing substantial morbidity and mortality. Screening of various traditionally important medicinal plants is a key source for the discovery of new antimalarials. We evaluated the antimalarial and antioxidant activities, and performed detailed phytochemical analyses of Toona ciliata MJ Roem aqueous methanolic leaf extract (TcMLE).

Experimental procedures

In vitro antiplasmodial studies in Plasmodium falciparum (Pf) 3D7 and PfCam3.IR539T strains were performed by [3H]-hypoxanthine uptake assays. In vitro cytotoxicity in HeLa and HEK293T cell lines was evaluated using MTT assays. Hemolysis assay was performed using RBCs. Phytochemical analysis by GC-MS and in vitro antioxidant studies by DPPH and ABTS assays were performed. In vivo antimalarial studies in Pb-infected mice were carried out using Rane's test and Peters' 4-day test.

Results and conclusions

TcMLE showed significant in vitro antioxidant activity and had phytochemicals reported for antimalarial activity. In vitro studies showed prominent antiplasmodial activity against Pf3D7 strain (IC50 ∼22 μg/ml) and PfCam3. IR539Tstrain (IC50 value ∼43 μg/ml). In vitro cytotoxicity studies, in vitro hemolytic assays, and in vivo acute toxicity studies further suggested that TcMLE is nontoxic. In vivo antimalarial studies using Rane's test showed a significant decrease in parasitemia by ∼70% at 1200 mg/kg doses and delayed the mortality of mice by ∼10–14 days. Peters' 4-day test also showed a similar pattern. The present study demonstrated the antimalarial potential of TcMLE. These findings deliver a platform for further studies to identify the active components of TcMLE and discover new antimalarials.

背景和目的疟疾是造成大量发病率和死亡率的全球性健康问题。筛选各种传统上重要的药用植物是发现新的抗疟药物的关键来源。研究了香椿叶甲醇水提物(TcMLE)的抗疟活性和抗氧化活性,并进行了详细的植物化学分析。实验方法:恶性疟原虫(Pf) 3D7和PfCam3的体外抗疟原虫研究。采用[3H]-次黄嘌呤摄取法测定IR539T菌株。采用MTT法评价HeLa和HEK293T细胞株的体外细胞毒性。采用红细胞进行溶血试验。采用气相色谱-质谱法进行植物化学分析,DPPH和ABTS法进行体外抗氧化研究。采用Rane试验和Peters 4天试验对pb感染小鼠进行体内抗疟研究。结果与结论stcmle具有显著的体外抗氧化活性,并有植物化学物质具有抗疟活性。体外研究显示对Pf3D7菌株(IC50 ~ 22 μg/ml)和PfCam3具有显著的抗疟原虫活性。ir539strain (IC50值~ 43 μg/ml)。体外细胞毒性研究、体外溶血试验和体内急性毒性研究进一步表明,TcMLE是无毒的。使用Rane试验的体内抗疟疾研究表明,在1200mg /kg剂量下,寄生虫血症显著降低~ 70%,并将小鼠的死亡延迟~ 10-14天。彼得斯为期4天的测试也显示出类似的模式。本研究证实了TcMLE的抗疟潜力。这些发现为进一步研究确定TcMLE的有效成分和发现新的抗疟药物提供了一个平台。
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引用次数: 2
FM2 - Aims and scope FM2 -目标和范围
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1016/S2225-4110(23)00106-2
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引用次数: 0
Study on the mechanism of action of effective monomeric, berberine of Xianglian Pill in inhibiting human colon cancer cells based on fatty acid synthase target 基于脂肪酸合酶靶点的香连丸有效单体小檗碱抑制人结肠癌细胞的作用机制研究
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1016/j.jtcme.2023.05.008
Shi-ying Li , Yun Li , Zhong-hua Wu , Zhang-jie Zhou , Cun-ya Li , Ting-ting Wu , Shu-juan Fu , Zhi-ying Wang , Zhi-xian Zhong , Yi Zhong

Background and aim

Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway.

Experimental procedure

The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN.

Results and conclusion

The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.

香连丸作为中药经典方剂保护消化功能的研究背景及目的然而,很少有研究调查其抗结直肠癌的作用。本研究验证了XLW的有效单体小檗碱通过调节乙酰辅酶a羧化酶(ACC)/脂肪酸合成酶(FASN)脂质代谢相关信号通路发挥抗肿瘤作用。通过文献挖掘、生物信息学和结构生物学等方法确定XLW与FASN之间的联系。体内实验验证了小檗碱通过调控ACC/FASN通路抗肿瘤作用的合理性,体外实验验证了小檗碱与FASN之间的调控关系。结果与结论XLW中最常见的中药成分为黄连。小檗碱是XLW的活性成分,具有FASN结合位点。FASN在肿瘤组织中的表达高于正常组织。FASN与结肠腺癌的发生及患者生存时间有关。实验表明,XLW、小檗碱和奥利司他(FASN抑制剂)可与棕榈酸(PA)协同抑制小鼠肿瘤。小檗碱可以下调肿瘤组织中FASN和ACC的表达,抑制外源性PA摄入的中间产物乙酰辅酶a的增加。小檗碱通过降脂抑制结肠癌细胞增殖的机制与其下调FASN蛋白表达有关。ACC/FASN信号通路是XLW有效单体小檗碱在结肠癌中发挥抗肿瘤作用的关键通路。
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引用次数: 0
Antispasmodic, cardioprotective and blood-pressure lowering properties of Gomphrena perennis L. and its mechanisms of action Gomphrena perennis L.的解痉、心脏保护和降血压特性及其作用机制
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-10-31 DOI: 10.1016/j.jtcme.2023.10.005
Adriana Milena Bonilla Bonilla , Tatiana C. Gavilánez Buñay , Matías Bayley , Germán A. Colareda , Soledad I. Matera , María Luján Flores , Osvaldo León Córdoba , Julián J. Prieto , María Esperanza Ruiz , Alicia E. Consolini , María Inés Ragone

Background

Gomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet.

Aim

To evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved.

Experimental procedure

The chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats.

Results

Fifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery.

Conclusions

This study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

背景Gomphrena perennis L.是南美洲的一种原生植物,其药理特性尚未得到研究。目的评估Gomphrena perennis L.叶酊(GphT)对心血管和肠道的药理作用及其机制。通过在离体大鼠小肠中发现的激动剂卡巴胆碱或钙获得的收缩浓度-反应曲线(CRCs)以及松弛剂 CRCs 对其体内效应进行了评估。对暴露于缺血/再灌注(I/R)的离体大鼠心脏的心脏效应进行了评估。通过高效液相色谱-紫外检测,在 GphT 中发现了 15 种黄酮类化合物,其中包括地奥司明。GphT 对大鼠小肠上的卡巴胆碱和钙 CRC 均有非竞争性抑制作用。前者不受吲哚美辛的影响。此外,与地奥司明不同,GphT 能以剂量依赖的方式放松高钾溶液产生的收缩。普萘洛尔和l-NAME都不能改变它。GphT没有利尿活性,但能诱导对l-NAME不敏感的低血压。虽然GphT灌注离体心脏会加重I/R造成的损伤,但口服GphT对心脏有保护作用,并能被l-NAME逆转。结论 本研究支持将 Gomphrena perennis L. 酊剂用作解痉和降压药。此外,它还被证明可预防缺血后心功能不全。然而,这些作用并不是由地奥司明引起的。
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引用次数: 0
Qingguang'an-induced autophagy in TFs inhibits scar formation: A follow-up in vivo mechanistic investigation 青光庵诱导的 TFs 自噬可抑制瘢痕形成:体内机制的后续研究
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-10-18 DOI: 10.1016/j.jtcme.2023.10.002
Rong Hu , Xian-jing Wang , Shu Chen , Yun Huang , Juan Yu

Purpose

To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS).

Methods

Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1–28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks.

Results

In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P < 0.05). Its blebs kept better filtering function and less complications in follow-up, which be detected to have less fibroblasts and collagen deposition histologically. Compared with the PBS group, ATG5, Beclin1 and LC3-II mRNA levels were significantly increased while P62 was downregulated in the Qingguang'an group (P < 0.05). Correspondingly, ATG5 and Beclin1 protein amounts in the Qingguang'an group were increased while P62 was downregulated. The LC3-II/Ⅰ ratio tended to rise to the process of autophagy. Abundant autophagosomes were captured under TEM in this condition.

Conclusions

Qingguang'an granules can inhibit scar formation in rabbits after GFS and restrain IOP increase by inducing autophagy in TFs.

目的 研究青光眼滤过手术(GFS)对兔子瘢痕形成的抑制机制。方法 对100只确诊为青光眼的兔子进行联合小梁切除术,将其分为五组,包括不手术组、单纯手术组、丝裂霉素C组(MMC;阳性对照组)、青光眼滤过手术组(实验组)和PBS组(阴性对照组)。术后第 1-28 天对动物进行随访。在透射电子显微镜(TEM)下观察超微结构。结果 在青光眼组,术后第 28 天的眼压(IOP)明显低于未手术组、单纯手术组和 PBS 组(P < 0.05)。其出血点在随访中保持了较好的滤过功能,并发症较少,在组织学上可检测到较少的成纤维细胞和胶原沉积。与 PBS 组相比,青光眼组的 ATG5、Beclin1 和 LC3-II mRNA 水平明显升高,而 P62 水平下调(P < 0.05)。相应地,青光庵组 ATG5 和 Beclin1 蛋白含量增加,而 P62 蛋白含量下降。LC3-Ⅱ/Ⅰ比值呈上升趋势,这与自噬过程有关。结论 青光庵颗粒通过诱导TFs自噬,可抑制家兔GFS后瘢痕形成,抑制眼压升高。
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引用次数: 0
Corrigendum to ’ Wound healing efficacy of Jamun honey in diabetic mice model through reepithelialization, collagen deposition and angiogenesis’ [Journal of Traditional and Complementary Medicine Volume 10, Issue 6, November 2020, Pages 529-543] “Jamun蜂蜜在糖尿病小鼠模型中通过再上皮化、胶原沉积和血管生成的伤口愈合功效”的勘误表[Journal of Traditional and Complementary Medicine, vol . 10, Issue 6,十一月2020,Pages 529-543]
3区 医学 Q1 Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.jtcme.2023.10.001
Amrita Chaudhary, Swarnendu Bag, Provas Banerjee, Jyotirmoy Chatterjee
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引用次数: 0
Computational studies on searching potential phytochemicals against DNA polymerase activity of the monkeypox virus 寻找抗猴痘病毒DNA聚合酶活性的潜在植物化学物质的计算研究
IF 4.5 3区 医学 Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.jtcme.2023.04.002
Seshu Vardhan, Suban K. Sahoo

Objectives

The outbreak of monkeypox virus (MPXV) is an emerging epidemic of medical concern with 65353 confirmed cases of infection and a fatality of 115 worldwide. Since May 2022, MPXV has been rapidly disseminating across the globe through various modes of transmission, including direct contact, respiratory droplets, and consensual sex. Because of the limited medical countermeasures available to treat MPXV, the present study aimed to identify potential phytochemicals (limonoids, triterpenoids, and polyphenols) as antagonists to target the DNA polymerase protein of MPXV with the ultimate goal to inhibit the viral DNA replication mechanism and immune-mediated responses.

Methods

The protein-DNA and protein-ligand molecular docking were performed with the help of computational programs AutoDock Vina, iGEMDOCK and HDOCK server. The BIOVIA Discovery studio and ChimeraX were used to evaluate the protein-ligand interactions. The GROMACS 2021 was used for the molecular dynamics simulations. The ADME and toxicity properties were computed by using online servers SwissADME and pKCSM.

Results

Molecular docking of 609 phytochemicals and molecular dynamics simulations of lead phytochemicals glycyrrhizinic acid and apigenin-7-O-glucuronide generated useful data that supported the ability of phytochemicals to obstruct the DNA polymerase activity of the monkeypox virus.

Conclusions

The computational results supported that appropriate phytochemicals can be used to formulate an adjuvant therapy for the monkeypox virus.

目的猴痘病毒(MPXV)的爆发是一种新出现的医学关注流行病,全球确诊感染病例65353例,死亡115例。自2022年5月以来,MPXV通过各种传播方式在全球迅速传播,包括直接接触、呼吸道飞沫和双方自愿的性行为。由于可用于治疗MPXV的药物对策有限,本研究旨在确定潜在的植物化学物质(柠檬苦素、三萜和多酚)作为靶向MPXV的DNA聚合酶蛋白的拮抗剂,最终目的是抑制病毒DNA复制机制和免疫介导的反应。方法利用AutoDock Vina、iGEMDOCK和HDOCK server程序进行蛋白质DNA和蛋白质配体分子对接。BIOVIA探索工作室和ChimeraX用于评估蛋白质与配体的相互作用。GROMACS 2021用于分子动力学模拟。使用在线服务器SwissADME和pKCSM计算ADME和毒性特性。结果609种植物化学物质的分子对接和主要植物化学物质甘草酸和芹菜素-7-O-葡糖苷酸的分子动力学模拟产生了有用的数据,支持了植物化学物质阻断猴痘病毒DNA聚合酶活性的能力。结论计算结果支持适当的植物化学物质可以用于猴痘病毒的辅助治疗。
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引用次数: 1
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Journal of Traditional and Complementary Medicine
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