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Effect of Ligustrazine on Lipopolysaccharide-induced Inflammatory Response of Vascular Endothelial Cells and its Possible Mechanism 川芎嗪对脂多糖诱导的血管内皮细胞炎症反应的影响及其可能机制
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231197077
Xia Meng Zhang, Zehong Ma, Chengjian Mao, Jihong Zhang, Zhongdanni Ma
Background Endothelial cell (EC) inflammation plays a crucial role in the development of several cardiovascular disorders (CD), including atherosclerosis and sepsis. Ligustrazine (Lig), a bioactive constituent derived from Traditional Chinese Medicine Ligusticum chuanxiong Hort, has exhibited in vivo anti-inflammatory properties. Despite the observed positive outcomes, the exact mechanisms underlying these beneficial effects remain unidentified. Aim The goal of this research is to investigate the influence and potential mechanism of Lig on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). Introduction These experiments investigate the effectiveness of Lig in preventing LPS-induced damage in HUVECs, with the goal of elucidating the underlying processes at work. Materials and Methods To evaluate HUVECs’ viability, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted. Enzyme-linked immunosorbent assay (ELISA) was employed to measure changes in ICAM-1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein (MCP-1) levels. Real-time polymerase chain reaction (RT-PCR) was used to determine the levels of ICAM-1, IL-6, TNF-α, MCP-1, and toll-like receptors (TLR4) mRNA. Additionally, we performed WB analysis to assess the levels of nuclear factor-κB (NF-κB) p65, TLR4, IκBα, and p-IκBα. Results The findings demonstrated significantly suppressed cell viability due to LPS treatment, while Lig treatment increased cell viability in a concentration-dependent manner. Lig also effectively reduced the mRNA levels of ICAM-1, TNF-α, IL-6, and MCP-1. Furthermore, Lig pretreatment led to downregulation of TLR4, p-IκBα, and NF-κB p65 in HUVECs. Discussion The findings indicate that Lig reduces LPS-induced inflammation in HUVECs, and that the TLR4/NF-κB pathway is critical in increasing cell survival and minimizing inflammatory damage. This provides possible anti-inflammatory techniques for treating CD. Conclusion In conclusion, our work demonstrates Lig’s anti-inflammatory actions on LPS-stimulated HUVECs. The data suggest that Lig lowers inflammation via regulating the TLR4/NF-B pathway, boosting cell survival, and decreasing inflammatory responses.
内皮细胞(EC)炎症在包括动脉粥样硬化和败血症在内的几种心血管疾病(CD)的发展中起着至关重要的作用。川芎嗪(Ligustrazine, ligg)是一种从中药川芎中提取的活性成分,具有体内抗炎作用。尽管观察到积极的结果,但这些有益效果的确切机制仍未确定。目的探讨Lig对脂多糖(LPS)诱导的人脐静脉内皮细胞(HUVECs)炎症反应的影响及其可能机制。这些实验研究了Lig在预防lps诱导的HUVECs损伤中的有效性,目的是阐明其工作的潜在过程。材料与方法采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基- 2h -溴化四氮唑(MTT)法测定HUVECs的活性。采用酶联免疫吸附法(ELISA)检测ICAM-1、白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)和单核细胞趋化蛋白(MCP-1)水平的变化。采用实时聚合酶链反应(RT-PCR)检测ICAM-1、IL-6、TNF-α、MCP-1和toll样受体(TLR4) mRNA水平。此外,我们进行WB分析以评估核因子-κB (NF-κB) p65、TLR4、i -κB α和p- i -κB α的水平。结果LPS处理能显著抑制细胞活力,而Lig处理能呈浓度依赖性地提高细胞活力。Lig还能有效降低ICAM-1、TNF-α、IL-6和MCP-1的mRNA水平。此外,轻度预处理导致HUVECs中TLR4、p -κB α和NF-κB p65的下调。研究结果表明,Lig可降低lps诱导的HUVECs炎症,TLR4/NF-κB通路在提高细胞存活率和减少炎症损伤中起关键作用。总之,我们的工作证明了Lig对lps刺激的huvec具有抗炎作用。数据表明,Lig通过调节TLR4/NF-B通路,促进细胞存活,减少炎症反应,从而降低炎症。
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引用次数: 0
In vitro Neuroprotective Activity of Vigna radiata L. and Vigna pilosa L. on Amyloid Beta-induced Cytotoxicity 放光藤和凤仙花对β -淀粉样蛋白诱导的细胞毒性的体外神经保护作用
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231200509
N. V. Prasanth, P. Pandian, T. Balasubramanian
Background Alzheimer’s disease (AD) is considered to be the most common form of dementia. The drugs that are available for the treatment of AD provide only partial improvement of the condition. In recent years, natural ingredients have received increased attention in generating novel medications for treating various neurological disorders, including AD. Vigna radiata and Vigna pilosa are plants that are routinely included in many Ayurvedic formulations used to manage memory impairment. Objectives The present study was conducted to evaluate the in vitro anticholinesterase and neuroprotective activities of the plants V. radiata and V. pilosa. Materials and Methods A modified 96-well microplate assay according to Ellman’s method was employed to measure acetyl choline esterase (AChE) inhibitory activity. In vitro neuroprotective effect was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay using the SHSY-5Y (neuroblastoma cells) cell line against β-amyloid induced neurotoxicity. The ethyl acetate extract of V. radiata and the ethanolic extract of V. pilosa, which showed maximum AChE inhibitory activity, were selected for the MTT assay. The cell viability was evaluated by direct observation of cells with the help of an inverted phase contrast microscope, followed by the MTT assay method. Results Maximum AChE inhibitory activity was exhibited by an ethyl acetate extract of V. radiata. It showed AChE activity with a half-maximal inhibitory concentration (IC 50 ) value of 286.40 µg/mL, while the ethanol extract of V. pilosa showed an IC 50 value of 160.19 µg/mL. Extracts of both plants, V. radiata and V. pilosa, significantly ( p ≤ 0.001) improved the percentage of cell viability in a dose-dependent manner. Conclusion The plants V. radiata and V. pilosa showed potent anti-Alzheimer activity when tested using in vitro AChE inhibitory activity and by MTT assay using an β-amyloid-induced in vivo cytotoxicity model. These findings demand the need for further studies using in vivo models.
阿尔茨海默病(AD)被认为是最常见的痴呆症。可用于治疗阿尔茨海默病的药物只能部分改善病情。近年来,天然成分在治疗包括阿尔茨海默病在内的各种神经系统疾病的新药物中受到越来越多的关注。凤仙花和凤仙花是许多阿育吠陀配方中用于治疗记忆障碍的常规植物。目的研究辐射草和毛毛草的体外抗胆碱酯酶活性和神经保护活性。材料与方法采用改良的96孔微孔板法测定乙酰胆碱酯酶(AChE)抑制活性。利用SHSY-5Y(神经母细胞瘤细胞)细胞系,采用3-[4,5-二甲基噻唑-2-基]-2,5二苯基溴化四唑(MTT)法测定其对β-淀粉样蛋白诱导的神经毒性的体外神经保护作用。选取具有最大乙酰胆碱酯酶抑制活性的辐射紫茎叶乙酸乙酯提取物和毛叶紫茎叶乙醇提取物进行MTT试验。倒置相差显微镜下直接观察细胞,再用MTT法测定细胞活力。结果乙酸乙酯提取物对乙酰胆碱酯酶的抑制作用最大。其乙酰胆碱酯酶活性为286.40µg/mL,半最大抑制浓度(IC 50)为160.19µg/mL。辐射弧菌和毛毛弧菌提取物均能显著提高细胞存活率(p≤0.001),且呈剂量依赖性。结论采用体外乙酰胆碱酯酶(AChE)抑制活性和β-淀粉样蛋白诱导的体内细胞毒性模型MTT法检测辐射紫茎草和毛毛紫茎草具有较强的抗阿尔茨海默病活性。这些发现需要使用体内模型进行进一步研究。
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引用次数: 0
Quality Control and Multi-targeted Therapeutic Approach of Nyctanthes arbor-tristris for Management of Hepatic Disease and Associated Complications 三叶草治疗肝病及相关并发症的质量控制及多靶点治疗方法
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231189619
Sapna Salar, Pankaj Sharma, None Gaurav
Background Medicinal plants standardization is more concerning for its regulatory aspects based on safety, quality, and efficacy. Nyctanthes arbor-tristris is an Indian-origin medicinal plant that is used for numerous acute and chronic diseases. Due to the lack of an ethnopharmacological perspective based on biomolecular mechanisms, this study is associated to explore quality-based standardization and biomolecular mechanism of Nyctanthes arbor-tristris phytochemicals as a therapeutic application regimen in liver disease and associated complications. Materials and Methods 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and iron chelating effect of prepared extract of Nyctanthes arbor-tristris was examined for antioxidant effect. High-performance thin-layer chromatography (HPTLC) and liquid chromatography and mass spectroscopy (LC–MS) qualitative and quantitative analysis was conducted to unravel metabolites of Nyctanthes arbor-tristris. Network pharmacology as well as in-silico docking analysis were performed to examine molecular interaction of ligands and targeted genes that regulate liver malfunction. Results The results revealed that Nyctanthes arbor-tristris significantly ( P < 0.05) scavenge DPPH free radicals and iron chelating effect and thus exhibited an antioxidant effect. HPTLC and LC–MS analysis showed several major and minor metabolites Nyctanthes arbor-tristris the content of naringenin, ferulic acid, and caffeic acid was found to be 1.662 ± 0.027, 4.411 ± 0.201, and 4.846 ± 0.154, respectively. Network pharmacology and in-silico docking analysis revealed the multi-targeted therapeutic effect of metabolites identified in Nyctanthes arbor-tristris against liver disease and associated pathophysiology’s via regulation in the expression of several genes such as nitric oxide synthase (NOS), tumor necrosis factor alpha (TNF-α), interleukins (ILs), toll-like receptors (TLRs) and serum aminotransferase. Conclusion The study concludes that Nyctanthes arbor-tristris play a multi-mechanistic and therapeutic action against liver-associated distortion and functional inability against oxidative and inflammatory stress, hepatocytes fibrosis, and apoptosis.
背景药用植物标准化是基于安全性、质量和有效性的监管方面的问题。夜来香是一种源自印度的药用植物,用于治疗许多急性和慢性疾病。由于缺乏基于生物分子机制的民族药理学视角,本研究旨在探讨夜草-三叶草植物化学物质作为肝脏疾病及其相关并发症的治疗应用方案的质量标准化和生物分子机制。材料与方法研究了夜赤草提取物的抗氧化作用,考察了其DPPH和铁螯合作用。采用高效薄层色谱(HPTLC)和液相色谱质谱(LC-MS)进行定性和定量分析,揭开龙骨草代谢产物的面纱。通过网络药理学和计算机对接分析,研究了调节肝功能障碍的配体和靶基因之间的分子相互作用。结果结果表明,龙骨草的抗氧化作用显著(P <0.05)清除DPPH自由基和铁螯合作用,从而表现出抗氧化作用。HPTLC和LC-MS分析显示,苦参主要代谢物柚皮素、阿魏酸和咖啡酸的含量分别为1.662±0.027、4.411±0.201和4.846±0.154。网络药理学和计算机对接分析揭示了三叶仙草代谢物通过调控一氧化氮合酶(NOS)、肿瘤坏死因子α (TNF-α)、白细胞介素(il)、toll样受体(TLRs)和血清转氨酶等基因的表达,对肝脏疾病及相关病理生理具有多靶点的治疗作用。结论荆芥对肝脏相关畸形、抗氧化应激、抗炎症应激、抗肝细胞纤维化、抗细胞凋亡具有多机制的治疗作用。
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引用次数: 0
Prunetin Triggers ROS-mediated Apoptosis through the Suppression of MAPKs/STAT-3/NF-κB-p65 Signaling Pathway in Human Osteosarcoma Cells Prunetin通过抑制人骨肉瘤细胞MAPKs/STAT-3/NF-κB-p65信号通路触发ros介导的细胞凋亡
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231188784
Meng Gao, Ya Wang, Weibo Liu, Zelong Song, Xiangyu Wang, Xuesong Zhang
Osteosarcoma (OS) is a highly metastatic primary bone malignancy, and the treatment options remain inadequate. Hence, exploring innovative natural medications is required. Prunetin (PRU) is an isoflavone that has been a proven anticancer agent in numerous cancer cell lines. However, the activity of PRU against OS remains uncertain. Here, we studied the anticancer activity of PRU (20 and 25 µM) on human OS cells MG-63 and investigated its latent mechanism. The PRU activity of MG-63 cells cytotoxicity, intracellular ROS, metastasis, apoptosis, anti-apoptotic proteins, MAPK/STAT-3, and AKT signaling pathways was assessed by MTT assay, DCFH-DA, DAPI, PI, AO/EB, cell adhesion, and RT-PCR analysis. Findings unveiled that PRU could constrain MG-63 cell viability and adhesion through elevated intracellular ROS and elicited apoptosis. Likewise, PRU (20 and 25 µM) avert the MG-63 cell proliferation, which stimulates apoptosis by the enhancement of Bax and caspases, while it diminishes Bcl-2 in a dose-dependent way. Furthermore, PRU could reduce Pin-1, and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. Our data established that PRU alleviates MG-63 cell proliferation and metastasis via ROS-mediated apoptosis, which triggers MAPKs/STAT3 and AKT pathways, suggesting that PRU is a promising natural remedy for OS. In order to comprehend the therapeutic target for cancer, we assessed the effect of PRU on the expression of Pin1, which is thought to be over-expressed in many human malignancies. According to our findings, PRU specifically suppressed Pin1 expression to reduce the expression of Akt, STAT3, P38, JNK, P65, and IL-6. We evaluated the impact of PRU on the expression of Pin1, which is allegedly over-expressed in many human malignancies, to better understand the therapeutic target for cancer. Researchers state that PRU inhibited the expression of Akt, STAT3, P38, JNK, P65, and IL-6 in particular, by suppressing Pin1 expression. Together, these results suggest that PRU may be an effective treatment for bone cancer in people by preventing Pin1 expression.
骨肉瘤(OS)是一种高度转移的原发性骨恶性肿瘤,治疗选择仍然不足。因此,探索创新的天然药物是必要的。Prunetin (PRU)是一种异黄酮,已被证明是许多癌细胞系的抗癌剂。然而,PRU对OS的活性仍然不确定。材料与方法本实验研究了PRU(20µM和25µM)对人OS细胞MG-63的抗肿瘤活性,并探讨其潜在机制。采用MTT法、DCFH-DA、DAPI、PI、AO/EB、细胞粘附和RT-PCR分析MG-63细胞的细胞毒性、细胞内ROS、转移、凋亡、抗凋亡蛋白、MAPK/STAT-3和AKT信号通路的PRU活性。结果表明,PRU可通过提高细胞内ROS水平抑制MG-63细胞活力和粘附,并诱导细胞凋亡。结果PRU(20µM和25µM)抑制MG-63细胞增殖,通过增强Bax和caspases促进细胞凋亡,并呈剂量依赖性地抑制Bcl-2。此外,PRU可以减少Pin-1和抗凋亡因子,并触发凋亡信号通路。我们的数据证实,PRU通过ros介导的凋亡途径,通过触发MAPKs/STAT3和AKT通路,缓解MG-63细胞的增殖和转移,这表明PRU是一种很有希望的治疗OS的天然药物。为了了解癌症的治疗靶点,我们评估了PRU对Pin1表达的影响,Pin1被认为在许多人类恶性肿瘤中过表达。根据我们的研究结果,PRU特异性抑制Pin1的表达,从而降低Akt、STAT3、P38、JNK、P65和IL-6的表达。我们评估了PRU对Pin1表达的影响,据称Pin1在许多人类恶性肿瘤中过表达,以更好地了解癌症的治疗靶点。研究人员指出,PRU通过抑制Pin1的表达,抑制了Akt、STAT3、P38、JNK、P65和IL-6的表达。结论PRU可能通过抑制Pin1的表达而有效治疗骨癌。
{"title":"Prunetin Triggers ROS-mediated Apoptosis through the Suppression of MAPKs/STAT-3/NF-κB-p65 Signaling Pathway in Human Osteosarcoma Cells","authors":"Meng Gao, Ya Wang, Weibo Liu, Zelong Song, Xiangyu Wang, Xuesong Zhang","doi":"10.1177/09731296231188784","DOIUrl":"https://doi.org/10.1177/09731296231188784","url":null,"abstract":"Osteosarcoma (OS) is a highly metastatic primary bone malignancy, and the treatment options remain inadequate. Hence, exploring innovative natural medications is required. Prunetin (PRU) is an isoflavone that has been a proven anticancer agent in numerous cancer cell lines. However, the activity of PRU against OS remains uncertain. Here, we studied the anticancer activity of PRU (20 and 25 µM) on human OS cells MG-63 and investigated its latent mechanism. The PRU activity of MG-63 cells cytotoxicity, intracellular ROS, metastasis, apoptosis, anti-apoptotic proteins, MAPK/STAT-3, and AKT signaling pathways was assessed by MTT assay, DCFH-DA, DAPI, PI, AO/EB, cell adhesion, and RT-PCR analysis. Findings unveiled that PRU could constrain MG-63 cell viability and adhesion through elevated intracellular ROS and elicited apoptosis. Likewise, PRU (20 and 25 µM) avert the MG-63 cell proliferation, which stimulates apoptosis by the enhancement of Bax and caspases, while it diminishes Bcl-2 in a dose-dependent way. Furthermore, PRU could reduce Pin-1, and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. Our data established that PRU alleviates MG-63 cell proliferation and metastasis via ROS-mediated apoptosis, which triggers MAPKs/STAT3 and AKT pathways, suggesting that PRU is a promising natural remedy for OS. In order to comprehend the therapeutic target for cancer, we assessed the effect of PRU on the expression of Pin1, which is thought to be over-expressed in many human malignancies. According to our findings, PRU specifically suppressed Pin1 expression to reduce the expression of Akt, STAT3, P38, JNK, P65, and IL-6. We evaluated the impact of PRU on the expression of Pin1, which is allegedly over-expressed in many human malignancies, to better understand the therapeutic target for cancer. Researchers state that PRU inhibited the expression of Akt, STAT3, P38, JNK, P65, and IL-6 in particular, by suppressing Pin1 expression. Together, these results suggest that PRU may be an effective treatment for bone cancer in people by preventing Pin1 expression.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135537205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Bee Pollen Stimulated BMP2 and RANK Signaling Pathway in Osteoprogenitors and Improved Bone Mineralization in Rat Model of Femur Fracture 蜂花粉刺激骨祖细胞BMP2和RANK信号通路,改善大鼠股骨骨折模型骨矿化
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231198286
Xiaowan Zeng, Yajing Lin, Chaonan Wang
Objectives Bee pollen (BP) contains isoflavonoids and minerals that can be effective in bone repair, stimulation of osteoprogenitors, differentiation of osteoblasts, and inhibition of osteoclasts. For this purpose, in the present study, BP was used to stimulate osteogenesis in an animal model of a femur fracture. Materials and Methods After induction of the femur fracture model, 80 Wistar rats in eight groups ( n = 10) were studied as follows. Normal control group (0.5 cc of distilled water, DW/gavage/90 days), BP group (200 mg/kg BP/daily/gavage/90 days), fracture (FX-0.5 cc of distilled water/gavage/90 days), FX group treated with 100 and 200 mg/kg BP (100 and 200 mg/kg BP/daily/gavage/90 days), FX group treated with osteocare (OC) syrup (1 mL/day/gavage/90 days) and combinatorial FX groups treated with BP and OC syrup (100 and 200 mg/kg BP plus 1 mL OC/daily/gavage/90 days). On the 30th, 60th, and 90th days, radiography of the lesion was done. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry during the mentioned days. At the end of the study, blood calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP), along with the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) enzymes, and nitric oxide levels, were measured. Calcitonin and parathyroid hormone levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. In order to evaluate the stimulation of osteoprogenitors, the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), and bone morphogenetic protein-2 (BMP-2) genes and proteins in bone tissue was measured. Results The evaluations of this study showed that BP could improve BMD parameters through stimulation of the OPG/RANK/BMP-2 pathway. BP also improved serum levels of biochemical factors (Ca, P, and ALP) and hormones related to osteogenesis. Conclusion BP can be used for bone fractures and disorders related to osteoporosis.
目的蜂花粉(BP)含有异黄酮和矿物质,可有效修复骨,刺激骨祖细胞,成骨细胞分化和抑制破骨细胞。为此,在本研究中,BP被用于刺激股骨骨折动物模型的成骨。材料与方法股骨骨折模型建立后,取8组80只Wistar大鼠(n = 10)进行实验。正常对照组(0.5毫升的蒸馏水,DW /填喂法/ 90天),BP集团(200毫克/公斤BP /每天/填喂法/ 90天),骨折(FX - 0.5毫升的蒸馏水/填喂法/ 90天),外汇组治疗100和200毫克/公斤BP (BP 100和200毫克/公斤/日/填喂法/ 90天),外汇组处理osteocare (OC)糖浆(1毫升/天/填喂法/ 90天)和组合FX团体治疗与英国石油(BP)和OC糖浆(100和200毫克/公斤BP + 1毫升OC /每天/填喂法/ 90天)。在第30天、第60天和第90天对病变进行x线摄影。采用双能x线骨密度仪测定骨矿物质密度(BMD)。研究结束时,测定血钙(Ca)、磷(P)、碱性磷酸酶(ALP)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及一氧化氮水平。采用酶联免疫吸附测定(ELISA)试剂盒检测降钙素和甲状旁腺激素水平。为了评价骨祖细胞的刺激作用,我们检测了骨组织中骨保护素(OPG)、核因子κ b受体激活因子(RANK)、核因子κ b配体受体激活因子(RANKL)和骨形态发生蛋白2 (BMP-2)基因和蛋白的表达。结果本研究结果表明,BP可通过刺激OPG/RANK/BMP-2通路改善BMD参数。BP还能改善血清生化因子(钙、磷、碱性磷酸酶)和与成骨相关的激素水平。结论BP可用于骨折及骨质疏松相关疾病的治疗。
{"title":"Bee Pollen Stimulated BMP2 and RANK Signaling Pathway in Osteoprogenitors and Improved Bone Mineralization in Rat Model of Femur Fracture","authors":"Xiaowan Zeng, Yajing Lin, Chaonan Wang","doi":"10.1177/09731296231198286","DOIUrl":"https://doi.org/10.1177/09731296231198286","url":null,"abstract":"Objectives Bee pollen (BP) contains isoflavonoids and minerals that can be effective in bone repair, stimulation of osteoprogenitors, differentiation of osteoblasts, and inhibition of osteoclasts. For this purpose, in the present study, BP was used to stimulate osteogenesis in an animal model of a femur fracture. Materials and Methods After induction of the femur fracture model, 80 Wistar rats in eight groups ( n = 10) were studied as follows. Normal control group (0.5 cc of distilled water, DW/gavage/90 days), BP group (200 mg/kg BP/daily/gavage/90 days), fracture (FX-0.5 cc of distilled water/gavage/90 days), FX group treated with 100 and 200 mg/kg BP (100 and 200 mg/kg BP/daily/gavage/90 days), FX group treated with osteocare (OC) syrup (1 mL/day/gavage/90 days) and combinatorial FX groups treated with BP and OC syrup (100 and 200 mg/kg BP plus 1 mL OC/daily/gavage/90 days). On the 30th, 60th, and 90th days, radiography of the lesion was done. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry during the mentioned days. At the end of the study, blood calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP), along with the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) enzymes, and nitric oxide levels, were measured. Calcitonin and parathyroid hormone levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. In order to evaluate the stimulation of osteoprogenitors, the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), and bone morphogenetic protein-2 (BMP-2) genes and proteins in bone tissue was measured. Results The evaluations of this study showed that BP could improve BMD parameters through stimulation of the OPG/RANK/BMP-2 pathway. BP also improved serum levels of biochemical factors (Ca, P, and ALP) and hormones related to osteogenesis. Conclusion BP can be used for bone fractures and disorders related to osteoporosis.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135539018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Voacangine Mitigates Human Nasopharyngeal Carcinoma Cells HK-1 Proliferation and Triggers Apoptosis Through the Suppression of NF-κB Facilitated PI3K/AKT/mTOR Pathway Voacangine通过抑制NF-κB促进的PI3K/AKT/mTOR通路抑制人鼻咽癌细胞HK-1增殖并引发细胞凋亡
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231197274
Aihui Hou, Huimin Zhen, Xiaofeng Qiao, Herong Dang, Yuanfeng Shen
The nasopharyngeal epithelium, which is frequently found in Southeast Asia and Southern China, gives rise to nasopharyngeal carcinoma (NPC). Despite improvements in diagnostic tools and remedial modalities, the prognosis of NPC remains meager. Thus, innovative and effective anti-cancer agents are desirable. Voacangine (VCG) is a recognized alkaloid sequestered from the plant Voacanga foetida. Hence, the current research assessed the anti-proliferative and apoptotic action of VCG on HK-1 human NPC cells and its underlying molecular actions. The results exposed that VCG (20 and 25 µ/ml) avert the HK-1 cells proliferation, which stimulates apoptosis by the amelioration of Bcl-2-associated X protein (Bax) and caspases, while it lessens cyclin-D1, B-cell lymphoma 2 (Bcl-2), c-Myc, survivin in a dose-dependent way. Furthermore, VCG alleviates inflammation, cell proliferation, and augmented cell death through the attenuation of Nuclear factor kappa B (NF-κB) facilitated Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signaling. This creates a Bax/Bcl-2 proportion imbalance, which triggers caspases cascade, Cyt-c, and induces apoptosis. Our findings deliver novel perceptions into exploring VCG as a beneficial bioactive alkaloid for the handling of NPC.
在东南亚和中国南部,鼻咽癌是由鼻咽上皮引起的。尽管诊断工具和治疗方式有所改进,但鼻咽癌的预后仍然很差。因此,需要创新和有效的抗癌药物。Voacangine (VCG)是从植物Voacanga foetida中分离出来的一种公认的生物碱。因此,本研究评估了VCG对HK-1人鼻咽癌细胞的抗增殖和凋亡作用及其潜在的分子作用。结果表明,VCG(20和25µ/ml)抑制HK-1细胞增殖,通过改善Bcl-2相关X蛋白(Bax)和caspases刺激细胞凋亡,同时以剂量依赖性方式降低cyclin-D1、b细胞淋巴瘤2 (Bcl-2)、c-Myc、survivin。此外,VCG通过抑制核因子κB (NF-κB),促进磷酸肌肽3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)信号通路,减轻炎症、细胞增殖和细胞死亡。这造成Bax/Bcl-2比例失衡,触发caspases级联,Cyt-c,诱导细胞凋亡。我们的研究结果为探索VCG作为处理NPC的有益生物活性生物碱提供了新的看法。
{"title":"Voacangine Mitigates Human Nasopharyngeal Carcinoma Cells HK-1 Proliferation and Triggers Apoptosis Through the Suppression of NF-κB Facilitated PI3K/AKT/mTOR Pathway","authors":"Aihui Hou, Huimin Zhen, Xiaofeng Qiao, Herong Dang, Yuanfeng Shen","doi":"10.1177/09731296231197274","DOIUrl":"https://doi.org/10.1177/09731296231197274","url":null,"abstract":"The nasopharyngeal epithelium, which is frequently found in Southeast Asia and Southern China, gives rise to nasopharyngeal carcinoma (NPC). Despite improvements in diagnostic tools and remedial modalities, the prognosis of NPC remains meager. Thus, innovative and effective anti-cancer agents are desirable. Voacangine (VCG) is a recognized alkaloid sequestered from the plant Voacanga foetida. Hence, the current research assessed the anti-proliferative and apoptotic action of VCG on HK-1 human NPC cells and its underlying molecular actions. The results exposed that VCG (20 and 25 µ/ml) avert the HK-1 cells proliferation, which stimulates apoptosis by the amelioration of Bcl-2-associated X protein (Bax) and caspases, while it lessens cyclin-D1, B-cell lymphoma 2 (Bcl-2), c-Myc, survivin in a dose-dependent way. Furthermore, VCG alleviates inflammation, cell proliferation, and augmented cell death through the attenuation of Nuclear factor kappa B (NF-κB) facilitated Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signaling. This creates a Bax/Bcl-2 proportion imbalance, which triggers caspases cascade, Cyt-c, and induces apoptosis. Our findings deliver novel perceptions into exploring VCG as a beneficial bioactive alkaloid for the handling of NPC.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135537196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Scutellarin Protects Myocardial Ischemia-Reperfusion Injury ERK1/2-CREB Regulated Mitophagy 黄芩苷保护心肌缺血再灌注损伤ERK1/2-CREB调控的线粒体自噬
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231199860
Wei-Wei Wang, Xiao-Lei Liu, Yu Ding, Ya-Di Chen, Dan Ma, Rui Bu, Tian-Hao Bao
Objectives Scutellarin, which is obtained from Erigeron breviscapus Hand-Mazz (EBHM), is a flavonoid that has demonstrated the ability to safeguard neural stem cells from hypoxia-induced damage and prevent cell apoptosis. The aim of this study was to investigate the beneficial impacts of Scutellarin on mitophagy in both in vivo and in vitro models of myocardial ischemia-reperfusion (I/R) injury. Materials and Methods Prior to inducing models of myocardial I/R injury, mice were administered either Scutellarin (50 mg/kg/day) or a vehicle for seven consecutive days. The mice underwent I/R injury (30 min of left anterior descending (LAD) coronary artery ligation followed by 120 min of reperfusion). Myocardial injury markers were assessed by the enzyme-linked immunosorbent assay (ELISA). The size of the myocardial infarction was measured via 2,3,5-triphenyl tetrazolium chloride triazole staining, and the protein expression of LC3 and caspase-3 was determined through Western blot analysis. In vitro experiments were conducted utilizing cultured H9C2 cells subjected to an oxygen-glucose deprivation/reoxygenation model to investigate the underlying mechanism(s) of Scutellarin’s positive effects (50 µM). Results It shows that Scutellarin treatment reduced the size of the myocardial infarctions and decreased the levels of myocardial injury markers. Western blot analysis showed that protein expression of caspase-3 was decreasing and the ratio of LC3Ⅱ to LC3Ⅰ was increasing in the Scutellarin group. In vitro, Scutellarin decreased oxidative stress markers, stabilized mitochondrial membrane potential (∇Ψm), decreased mitochondrial permeability transition pore (mPTP) opening rate, promoted mitochondrial fusion, inhibited mitochondrial fission, and increased adenosine triphosphate (ATP) production and cell viability. Scutellarin increased the commitment of mitophagy by regulating Pink and Parkin, while apoptosis decreased. cAMP-response element-binding protein (CREB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation were also modulated by Scutellarin. Conclusion The myocardial protective effect of Scutellarin may be associated with the phosphorylation of CREB and ERK1/2.
目的从灯盏花(Erigeron breviscapus Hand-Mazz, EBHM)中提取的黄酮类化合物黄芩苷(Scutellarin)具有保护神经干细胞免受缺氧损伤和防止细胞凋亡的作用。本研究旨在探讨黄芩苷对体内和体外心肌缺血再灌注(I/R)损伤模型中线粒体自噬的有益影响。材料与方法在建立心肌I/R损伤模型前,小鼠连续7天给予黄芩苷(50 mg/kg/d)或载药。小鼠进行I/R损伤(左前降支冠脉结扎30 min,再灌注120 min)。采用酶联免疫吸附试验(ELISA)评估心肌损伤标志物。采用2,3,5-三苯基氯化四唑三唑染色法测定心肌梗死面积,Western blot法检测LC3、caspase-3蛋白表达。体外实验采用体外培养的H9C2细胞进行氧-葡萄糖剥夺/再氧化模型,探讨黄芩苷(50µM)的积极作用机制。结果黄芩苷能明显减少心肌梗死面积,降低心肌损伤标志物水平。Western blot分析显示,黄芩苷组caspase-3蛋白表达降低,LC3Ⅱ/ LC3Ⅰ比值升高。在体外,黄芩苷降低氧化应激标志物,稳定线粒体膜电位(∇Ψm),降低线粒体通透性过渡孔(mPTP)打开率,促进线粒体融合,抑制线粒体裂变,增加三磷酸腺苷(ATP)的产生和细胞活力。黄芩苷通过调节Pink和Parkin来增加线粒体自噬的承诺,同时减少细胞凋亡。黄芩苷还能调节camp反应元件结合蛋白(CREB)和细胞外信号调节激酶1和2 (ERK1/2)磷酸化。结论黄芩苷的心肌保护作用可能与CREB和ERK1/2的磷酸化有关。
{"title":"Scutellarin Protects Myocardial Ischemia-Reperfusion Injury ERK1/2-CREB Regulated Mitophagy","authors":"Wei-Wei Wang, Xiao-Lei Liu, Yu Ding, Ya-Di Chen, Dan Ma, Rui Bu, Tian-Hao Bao","doi":"10.1177/09731296231199860","DOIUrl":"https://doi.org/10.1177/09731296231199860","url":null,"abstract":"Objectives Scutellarin, which is obtained from Erigeron breviscapus Hand-Mazz (EBHM), is a flavonoid that has demonstrated the ability to safeguard neural stem cells from hypoxia-induced damage and prevent cell apoptosis. The aim of this study was to investigate the beneficial impacts of Scutellarin on mitophagy in both in vivo and in vitro models of myocardial ischemia-reperfusion (I/R) injury. Materials and Methods Prior to inducing models of myocardial I/R injury, mice were administered either Scutellarin (50 mg/kg/day) or a vehicle for seven consecutive days. The mice underwent I/R injury (30 min of left anterior descending (LAD) coronary artery ligation followed by 120 min of reperfusion). Myocardial injury markers were assessed by the enzyme-linked immunosorbent assay (ELISA). The size of the myocardial infarction was measured via 2,3,5-triphenyl tetrazolium chloride triazole staining, and the protein expression of LC3 and caspase-3 was determined through Western blot analysis. In vitro experiments were conducted utilizing cultured H9C2 cells subjected to an oxygen-glucose deprivation/reoxygenation model to investigate the underlying mechanism(s) of Scutellarin’s positive effects (50 µM). Results It shows that Scutellarin treatment reduced the size of the myocardial infarctions and decreased the levels of myocardial injury markers. Western blot analysis showed that protein expression of caspase-3 was decreasing and the ratio of LC3Ⅱ to LC3Ⅰ was increasing in the Scutellarin group. In vitro, Scutellarin decreased oxidative stress markers, stabilized mitochondrial membrane potential (∇Ψm), decreased mitochondrial permeability transition pore (mPTP) opening rate, promoted mitochondrial fusion, inhibited mitochondrial fission, and increased adenosine triphosphate (ATP) production and cell viability. Scutellarin increased the commitment of mitophagy by regulating Pink and Parkin, while apoptosis decreased. cAMP-response element-binding protein (CREB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation were also modulated by Scutellarin. Conclusion The myocardial protective effect of Scutellarin may be associated with the phosphorylation of CREB and ERK1/2.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135579190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Evaluation of Preclinical in vitro Cytotoxicity, Genotoxicity, and Cardiac-Toxicity Screenings of Hydrogenated Cannabidiol 评价氢化大麻二酚的临床前体外细胞毒性、遗传毒性和心脏毒性筛选
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231195941
Tesfay T. Tesfatsion, Giovanni A. Ramirez, Maite L. Docampo-Palacios, Arianna C. Collins, Kyle P. Ray, Westley Cruces
Introduction Cannabidiol (CBD) is one of many naturally biosynthesized compounds produced by Cannabis sativa. There is limited information available in the literature on hydrogenated CBD (tetrahydro cannabidiol or H4CBD) ( Adams et al., 1940b ). As hydrogenated derivatives of tetrahydrocannabinol (THC) and CBD become increasingly popular in consumer markets, toxicological assessments are vital in identifying toxic characteristics, if any, caused by hydrogenated cannabinoids. Objectives Assessment of the preclinical toxicology of hydrogenated CBD is provided through the in vitro safety study of racemic H4CBD in hepatocytes, normal human lung fibroblasts (NHLF), and primary human neural progenitor (NPC) cell lines. The importance of these cell lines is related to major organs and is the primary focus in determining any major toxic characteristics when consuming products. The inclusion of the human ether-a-go-go related gene (hERG) patch clamp test, observes any inhibition of sodium and potassium ion channels related to the arrhythmia of the heart. Also, the AMES test was conducted to determine any carcinogenic characteristics that H4CBD might impose. Materials and Methods Plated NHLF, hepatocytes, and NPC were used in a preclinical 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay for cytotoxicity observations with the visible color change of cellular use of formazan, while a plated AMES test was conducted to monitor any visible mutations within Escherichia coli for carcinogenic activity. Plated cloned HEK293 cells were given set voltages to determine ion channel activity to determine if H4CBD causes inhibition within these pathways, which would mimic any arrhythmia potential in cardiomyocytes. Results Screening of the MTT assay had a median calculated 3.25 micromolar concentration where cell viability remained high in NHLF and NPC, with higher concentrations leading to decreased cell viability. A 3.25 micromolar concentration is also the median for hepatocytes, with a discrepancy in some of the data that could be accounted for by miscounting colonies. The hERG patch clamp test provided a zero net inhibition with values adding up to zero, determining that the compound did not inhibit normal processes within the ion channels of the plated HEK293 cells. The analysis of the different cell types revealed varying responses to H4CBD. NHLF exhibited a concentration-dependent reduction in cell viability, with sustained concentrations over 24 h at 6.25 µM resulting in a significant loss of viability. Conversely, hepatocytes showed a trend of decreased viability at longer exposure times and higher concentrations, but severe cytotoxicity was not observed. This suggests that hepatocytes are less susceptible to the cytotoxic effects of H4CBD compared to NHLF. In the hERG assay, H4CBD did not inhibit the action potentials within cardiomyocytes, indicating no inhibition of ion channels involved in cardiac function. This finding is importan
大麻二酚(CBD)是由大麻产生的多种天然生物合成化合物之一。关于氢化CBD(四氢大麻二酚或H4CBD)的文献资料有限(Adams et al., 1940b)。随着四氢大麻酚(THC)和CBD的氢化衍生物在消费市场上越来越受欢迎,毒理学评估对于确定氢化大麻素引起的毒性特征至关重要。目的通过体外对肝细胞、正常人肺成纤维细胞(NHLF)和人原代神经祖细胞(NPC)进行安全性研究,评估氢化CBD的临床前毒理学。这些细胞系的重要性与主要器官有关,是确定食用产品时任何主要毒性特征的主要焦点。包括人类乙醚-a- a-go-go相关基因(hERG)膜片钳试验,观察到与心律失常有关的钠和钾离子通道的任何抑制。此外,AMES测试是为了确定H4CBD可能带来的任何致癌特征。材料与方法采用3-[4,5-二甲基噻唑-2-酰基]-2,5二苯基溴化四唑(MTT)临床前细胞毒性试验,观察使用福马嗪后细胞的可见颜色变化,同时采用电镀AMES试验监测大肠杆菌内任何可见突变的致癌活性。将克隆的HEK293细胞镀上固定电压以测定离子通道活性,以确定H4CBD是否在这些通路中引起抑制,这将模拟心肌细胞中的任何心律失常电位。结果MTT试验筛选的中位数计算浓度为3.25微摩尔,NHLF和NPC的细胞活力保持较高,浓度越高,细胞活力越低。3.25微摩尔浓度也是肝细胞的中位数,其中一些数据的差异可能是由于菌落计数错误造成的。hERG膜片钳试验提供了零净抑制值,其值相加为零,确定该化合物不抑制镀HEK293细胞离子通道内的正常过程。对不同细胞类型的分析揭示了对H4CBD的不同反应。NHLF表现出浓度依赖性的细胞活力降低,在6.25µM下持续浓度超过24小时,导致细胞活力明显丧失。相反,在较长的暴露时间和较高的浓度下,肝细胞表现出活力下降的趋势,但未观察到严重的细胞毒性。这表明,与NHLF相比,肝细胞对H4CBD的细胞毒性作用不太敏感。在hERG实验中,H4CBD没有抑制心肌细胞内的动作电位,表明没有抑制参与心功能的离子通道。这一发现对于评估H4CBD对心血管的潜在影响非常重要。AMES试验结果为阴性,表明H4CBD在被试菌株中不表现出诱变活性。结论本实验支持了H4CBD不具有致癌潜力的结论。人鼻咽癌和NHLF的中位浓度均为3.25µM,细胞活力显著降低。这些信息对于确定H4CBD的研究或消费者使用限制是有价值的。值得注意的是,这项研究代表了临床前评估,需要进一步的研究。实验设计遵循通常用于新药临床前评估的方案。这些发现提供了对H4CBD细胞毒性作用的深入了解,并有助于建立研究和安全参数,因为这些化合物继续受到关注。
{"title":"Evaluation of Preclinical <i>in vitro</i> Cytotoxicity, Genotoxicity, and Cardiac-Toxicity Screenings of Hydrogenated Cannabidiol","authors":"Tesfay T. Tesfatsion, Giovanni A. Ramirez, Maite L. Docampo-Palacios, Arianna C. Collins, Kyle P. Ray, Westley Cruces","doi":"10.1177/09731296231195941","DOIUrl":"https://doi.org/10.1177/09731296231195941","url":null,"abstract":"Introduction Cannabidiol (CBD) is one of many naturally biosynthesized compounds produced by Cannabis sativa. There is limited information available in the literature on hydrogenated CBD (tetrahydro cannabidiol or H4CBD) ( Adams et al., 1940b ). As hydrogenated derivatives of tetrahydrocannabinol (THC) and CBD become increasingly popular in consumer markets, toxicological assessments are vital in identifying toxic characteristics, if any, caused by hydrogenated cannabinoids. Objectives Assessment of the preclinical toxicology of hydrogenated CBD is provided through the in vitro safety study of racemic H4CBD in hepatocytes, normal human lung fibroblasts (NHLF), and primary human neural progenitor (NPC) cell lines. The importance of these cell lines is related to major organs and is the primary focus in determining any major toxic characteristics when consuming products. The inclusion of the human ether-a-go-go related gene (hERG) patch clamp test, observes any inhibition of sodium and potassium ion channels related to the arrhythmia of the heart. Also, the AMES test was conducted to determine any carcinogenic characteristics that H4CBD might impose. Materials and Methods Plated NHLF, hepatocytes, and NPC were used in a preclinical 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay for cytotoxicity observations with the visible color change of cellular use of formazan, while a plated AMES test was conducted to monitor any visible mutations within Escherichia coli for carcinogenic activity. Plated cloned HEK293 cells were given set voltages to determine ion channel activity to determine if H4CBD causes inhibition within these pathways, which would mimic any arrhythmia potential in cardiomyocytes. Results Screening of the MTT assay had a median calculated 3.25 micromolar concentration where cell viability remained high in NHLF and NPC, with higher concentrations leading to decreased cell viability. A 3.25 micromolar concentration is also the median for hepatocytes, with a discrepancy in some of the data that could be accounted for by miscounting colonies. The hERG patch clamp test provided a zero net inhibition with values adding up to zero, determining that the compound did not inhibit normal processes within the ion channels of the plated HEK293 cells. The analysis of the different cell types revealed varying responses to H4CBD. NHLF exhibited a concentration-dependent reduction in cell viability, with sustained concentrations over 24 h at 6.25 µM resulting in a significant loss of viability. Conversely, hepatocytes showed a trend of decreased viability at longer exposure times and higher concentrations, but severe cytotoxicity was not observed. This suggests that hepatocytes are less susceptible to the cytotoxic effects of H4CBD compared to NHLF. In the hERG assay, H4CBD did not inhibit the action potentials within cardiomyocytes, indicating no inhibition of ion channels involved in cardiac function. This finding is importan","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"83 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135537057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Anti-obesity Effects of Triphala at Biochemical and Molecular Level in High-Fat Diet-induced Obese Rats Triphala在高脂饮食诱导的肥胖大鼠的生化和分子水平的抗肥胖作用
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-27 DOI: 10.1177/09731296231198316
Supriya Sudhakar Bhalerao, Asavari Anirudha Joshi, Suresh Khadke, and Arulmozhi Sathiyanarayan
Background The prevalence of obesity is rising worldwide. Due to the side effects associated with modern drugs, there is a need for an alternative treatment for obesity management. Triphala (TP), a polyherbal formulation from Ayurveda, is used by Ayurvedic physicians for weight loss. Purpose This study was designed to evaluate the effects of TP on obesity at the biochemical, histological, and molecular levels. Materials and Methods Male Wistar rats (125–150 g, 6–7 weeks old) were fed with a high-fat diet (HFD) for total of 48 days. From day 24 to day 48, along with HFD, rats were given an aqueous extract of TP (50, 100, and 200 mg/kg/day) or atorvastatin (1.2 mg/kg/day). Biochemical parameters were estimated in serum. Histopathology was done for the liver and adipose tissue. Levels of the genes involved in lipid metabolism were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Monoamine levels were estimated from the brain tissue. Results At the end of the study (day 48), compared to only HFD receiving group (DC), all TP-treated groups showed a significant decrease in body weight, serum glucose, total cholesterol, triglycerides, leptin, interleukin-6, C-reactive protein, malondialdehyde, and noradrenaline levels. High-density lipoprotein, adiponectin, superoxide dismutase, serotonin, and dopamine levels were found to be increased compared to DC rats. Expression of various genes involved in lipid metabolism was found to be down regulated only in TP 100 group compared with DC. Additionally, all TP groups showed a reduction in adipocyte size and restored monoamine levels. Conclusion The aqueous extract of TP had shown an anti-obesity effect as demonstrated by lowering inflammation and oxidative stress, adipocyte size, and modulation of expression of genes involved in lipid metabolism.
世界范围内肥胖的患病率正在上升。由于与现代药物相关的副作用,有必要对肥胖管理的替代治疗。Triphala (TP)是一种来自阿育吠陀的多草药配方,被阿育吠陀医生用于减肥。目的从生化、组织学和分子水平探讨TP对肥胖的影响。材料与方法雄性Wistar大鼠(125 ~ 150 g, 6 ~ 7周龄)饲喂高脂饲料(HFD),共48 d。从第24天到第48天,与HFD一起给予大鼠TP(50、100和200 mg/kg/天)或阿托伐他汀(1.2 mg/kg/天)的水提取物。测定血清生化指标。对肝脏和脂肪组织进行组织病理学检查。通过实时定量聚合酶链反应(qRT-PCR)检测脂质代谢相关基因的水平。从脑组织中估计单胺水平。结果在研究结束时(第48天),与仅HFD接受组(DC)相比,所有tp治疗组的体重、血清葡萄糖、总胆固醇、甘油三酯、瘦素、白细胞介素-6、c反应蛋白、丙二醛和去甲肾上腺素水平均显著降低。高密度脂蛋白、脂联素、超氧化物歧化酶、血清素和多巴胺水平与DC大鼠相比有所增加。与DC相比,只有TP 100组脂质代谢相关基因表达下调。此外,所有TP组均显示脂肪细胞大小减小,单胺水平恢复。结论TP水提物具有降低炎症和氧化应激、减少脂肪细胞大小、调节脂质代谢相关基因表达等抗肥胖作用。
{"title":"Anti-obesity Effects of <i>Triphala</i> at Biochemical and Molecular Level in High-Fat Diet-induced Obese Rats","authors":"Supriya Sudhakar Bhalerao, Asavari Anirudha Joshi, Suresh Khadke, and Arulmozhi Sathiyanarayan","doi":"10.1177/09731296231198316","DOIUrl":"https://doi.org/10.1177/09731296231198316","url":null,"abstract":"Background The prevalence of obesity is rising worldwide. Due to the side effects associated with modern drugs, there is a need for an alternative treatment for obesity management. Triphala (TP), a polyherbal formulation from Ayurveda, is used by Ayurvedic physicians for weight loss. Purpose This study was designed to evaluate the effects of TP on obesity at the biochemical, histological, and molecular levels. Materials and Methods Male Wistar rats (125–150 g, 6–7 weeks old) were fed with a high-fat diet (HFD) for total of 48 days. From day 24 to day 48, along with HFD, rats were given an aqueous extract of TP (50, 100, and 200 mg/kg/day) or atorvastatin (1.2 mg/kg/day). Biochemical parameters were estimated in serum. Histopathology was done for the liver and adipose tissue. Levels of the genes involved in lipid metabolism were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Monoamine levels were estimated from the brain tissue. Results At the end of the study (day 48), compared to only HFD receiving group (DC), all TP-treated groups showed a significant decrease in body weight, serum glucose, total cholesterol, triglycerides, leptin, interleukin-6, C-reactive protein, malondialdehyde, and noradrenaline levels. High-density lipoprotein, adiponectin, superoxide dismutase, serotonin, and dopamine levels were found to be increased compared to DC rats. Expression of various genes involved in lipid metabolism was found to be down regulated only in TP 100 group compared with DC. Additionally, all TP groups showed a reduction in adipocyte size and restored monoamine levels. Conclusion The aqueous extract of TP had shown an anti-obesity effect as demonstrated by lowering inflammation and oxidative stress, adipocyte size, and modulation of expression of genes involved in lipid metabolism.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"102 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135537950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Network Pharmacology-based Analysis of the Effects of Huangqi Guizhi Wuwu Decoction on Ischemic Stroke* 基于网络药理学的黄芪桂枝五物汤对缺血性脑卒中疗效分析*
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-09-26 DOI: 10.1177/09731296231189106
Xiaoyang Gong, Jiaqi Zhou, Haonan Xia, Chong You, Yong Liu
Background The purpose of this study was to investigate the molecular mechanisms and material basis of Huangqi Guizhi Wuwu Decoction (HGWD) in treating clinical Ischemic stroke (IS) using network pharmacology and molecular docking techniques. Materials and Methods The study retrieved and screened the practical components of HGWD from the TCMSP, BATMAN-TCM, and ETCM databases. Target prediction was performed using the SwissTargetPrediction database, and disease targets for IS were obtained from the Gene Cards, DisGeNET, and OMIM databases. The regulatory targets for HGWD in treating IS were obtained by VENN analysis, and the protein-protein interaction network of disease targets was constructed using the STRING database. GO analysis and KEGG enrichment analysis were performed using the DAVID database. Results A total of 227 active ingredients and 354 drug targets were obtained for HGWD, and after combining them with 4,402 disease targets, 253 potential targets for HGWD to treat IS were identified. GO and KEGG enrichment analyses yielded 251 gene functions and 422 pathways. The study found that the active components in HGWD may treat IS through the IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, and other targets. Conclusion The study identified potential molecular mechanisms and the material basis of HGWD in treating clinical IS. The results suggest that HGWD could be a promising therapeutic approach for treating IS, and further experimental validation is needed.
背景利用网络药理学和分子对接技术,探讨黄芪桂枝五物汤治疗临床缺血性脑卒中的分子机制和物质基础。材料与方法从tcm数据库、BATMAN-TCM数据库和ETCM数据库中检索并筛选复方黄芪多糖的有效成分。使用SwissTargetPrediction数据库进行靶标预测,从Gene Cards、DisGeNET和OMIM数据库获得IS的疾病靶标。通过VENN分析获得HGWD治疗IS的调控靶点,并利用STRING数据库构建疾病靶点的蛋白-蛋白相互作用网络。使用DAVID数据库进行GO分析和KEGG富集分析。结果共获得227种有效成分和354个药物靶点,与4402个疾病靶点联合后,鉴定出253个HGWD治疗IS的潜在靶点。GO和KEGG富集分析得到251个基因功能和422条通路。研究发现,HGWD中的有效成分可能通过IL-17信号通路、TNF信号通路、PI3K-Akt信号通路等靶点治疗IS。结论本研究确定了HGWD治疗临床IS的潜在分子机制和物质基础。结果表明,HGWD可能是治疗IS的一种有前景的治疗方法,需要进一步的实验验证。
{"title":"Network Pharmacology-based Analysis of the Effects of <i>Huangqi Guizhi Wuwu</i> Decoction on Ischemic Stroke<sup>*</sup>","authors":"Xiaoyang Gong, Jiaqi Zhou, Haonan Xia, Chong You, Yong Liu","doi":"10.1177/09731296231189106","DOIUrl":"https://doi.org/10.1177/09731296231189106","url":null,"abstract":"Background The purpose of this study was to investigate the molecular mechanisms and material basis of Huangqi Guizhi Wuwu Decoction (HGWD) in treating clinical Ischemic stroke (IS) using network pharmacology and molecular docking techniques. Materials and Methods The study retrieved and screened the practical components of HGWD from the TCMSP, BATMAN-TCM, and ETCM databases. Target prediction was performed using the SwissTargetPrediction database, and disease targets for IS were obtained from the Gene Cards, DisGeNET, and OMIM databases. The regulatory targets for HGWD in treating IS were obtained by VENN analysis, and the protein-protein interaction network of disease targets was constructed using the STRING database. GO analysis and KEGG enrichment analysis were performed using the DAVID database. Results A total of 227 active ingredients and 354 drug targets were obtained for HGWD, and after combining them with 4,402 disease targets, 253 potential targets for HGWD to treat IS were identified. GO and KEGG enrichment analyses yielded 251 gene functions and 422 pathways. The study found that the active components in HGWD may treat IS through the IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, and other targets. Conclusion The study identified potential molecular mechanisms and the material basis of HGWD in treating clinical IS. The results suggest that HGWD could be a promising therapeutic approach for treating IS, and further experimental validation is needed.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134958217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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