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AG8 Reduces Hypoxia-induced Triple Negative Breast Cancer Metastasis by Stemness Regulation AG8通过干性调控减少缺氧诱导的三阴性乳腺癌转移
Pub Date : 2023-09-20 DOI: 10.1016/j.ccmp.2023.100115
Lihua Mu , Yuan Hu , Hong Yan , Rui Jing , Ping Liu

Background

AG8, a triterpenoid saponin isolated from Ardisia gigantifolia Stapf., our previous studies found that AG8 inhibited the proliferation of triple negative breast cancers (TNBCs) by including ROS generation and triggering mitochondrial apoptotic pathways. Cancer stem cells (CSCs) capable of maintain relatively low levels of ROS, are vulnerable to the interference of redox state. Compounds capable of generating ROS can affect the finely balanced redox state of CSCs and have potency to selectively kill them.

Objective

We selected BT-549 which is most sensitive to AG8 to further study the effects of AG8 on hypoxia-induced proliferation, metastasis and CSCs.

Methods

The hypoxia condition was simulated by CoCl2 and cell viability assay of BT-549 cells was performed using MTT. Stemness phenotype were identified using breast CSCs marker (CD24/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Protein levels of HIF1-α, Oct-4, SOX-2, c-MYC were tested by western blotting.

Results

In this study, AG8 showed significant cytotoxic effects on BT-549 triple negative breast cancer cells, but the effects were impaired by HIF1 activation. AG8 inhibited the hypoxia-induced migration and invasion of BT-549 cells. Further studies revealed that hypoxia-induced increases of CD44+CD24/low and mammosphere population were significantly inhibited by AG8 dose-dependently. Moreover, AG8 decreased the Oct-4 and SOX-2 protein expression without affecting HIF1-α and c-MYC. AG8 significantly inhibited BT-549 xenograft tumors growth in BALB/c nude mice comparing with that of the control group.

Conclusion

In summary, AG8 inhibited hypoxia-induced cell migration and invasion through stemness regulations, indicating novel mechanisms for the antitumor effects of AG8 against triple negative breast cancer.

背景AG8是从大叶紫苏中分离得到的一种三萜皂苷。,我们之前的研究发现,AG8通过包括ROS的产生和触发线粒体凋亡途径来抑制三阴性乳腺癌(TNBCs)的增殖。癌症干细胞(CSCs)能够维持相对较低水平的ROS,容易受到氧化还原状态的干扰。能够产生ROS的化合物可以影响CSC的精细平衡氧化还原状态,并具有选择性杀死它们的效力。目的选择对AG8最敏感的BT-549细胞,进一步研究AG8对缺氧诱导的细胞增殖、转移和CSC的影响。使用乳腺CSCs标记物(CD24−/低/CD44+)和乳腺球形成测定法鉴定Stemness表型。通过伤口愈合测定和transwell迁移测定细胞运动性。免疫印迹法检测HIF1-α、Oct-4、SOX-2、c-MYC的蛋白水平。结果AG8对BT-549三阴性乳腺癌症细胞有明显的细胞毒作用,但HIF1激活后细胞毒作用减弱。AG8抑制缺氧诱导的BT-549细胞的迁移和侵袭。进一步的研究表明,AG8剂量依赖性地显著抑制缺氧诱导的CD44+CD24-低和乳腺细胞群的增加。此外,AG8降低了Oct-4和SOX-2蛋白的表达,而不影响HIF1-α和c-MYC。与对照组相比,AG8显著抑制了BALB/c裸鼠移植瘤BT-549的生长。结论AG8通过干度调节抑制低氧诱导的细胞迁移和侵袭,提示AG8抗三阴性乳腺癌的新机制。
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引用次数: 0
Phytochemical Loaded Nanovehicles of Biopolymer for Breast Cancer: A Systemic Review 植物化学负载的生物聚合物纳米载体用于乳腺癌:系统综述
Pub Date : 2023-09-09 DOI: 10.1016/j.ccmp.2023.100114
Vivek P. Chavda , Suneetha Vuppu , Rajashri Bezbaruah , Lakshmi Vineela Nalla , Siva Nageswara Rao Gajula , Pankti C. Balar , Toshika Mishra , Nikita Sharma , Sathvika Kamaraj , Thushar Suresh , Anand Sairam , Bedanta Bhattacharjee

Background

Breast cancer is one of the most common malignancies affecting women worldwide, emphasizing the need for effective therapeutic strategies. Phytochemicals derived from plants have gained significant attention due to their potential anticancer properties.

Objective

This review aims to comprehensively assess the existing literature on using phytochemical-loaded formulations as a therapeutic approach for breast cancer. By analyzing the available evidence, we aim to determine the potential benefits and limitations of these formulations in terms of their anticancer activity, bioavailability, and safety.

Methods

A systematic search of relevant databases was conducted to identify studies investigating phytochemical-loaded formulations in the context of breast cancer treatment. The inclusion criteria encompassed clinical trials, preclinical studies, and in-vitro experiments that reported using phytochemicals in various formulations for breast cancer treatment. Data extraction was performed to ensure the reliability and validity of the included studies.

Results

The review highlights the diverse range of phytochemicals used in different formulations for breast cancer treatment. Findings suggest that these formulations exhibit promising anticancer effects by targeting multiple signaling pathways in breast cancer progression, including cell proliferation, apoptosis, angiogenesis, and metastasis. Moreover, various delivery systems, such as nanoparticles, liposomes, and micelles, have enhanced phytochemicals' bioavailability and targeted delivery.

Conclusion

Phytochemical-loaded formulations hold immense potential as a therapeutic approach for breast cancer treatment. The reviewed evidence indicates their ability to inhibit tumor growth, enhance chemotherapy effectiveness, and reduce adverse effects. However, further research is warranted to optimize the formulation strategies, investigate the long-term safety profiles, and conduct large-scale clinical trials to establish their efficacy and applicability in clinical settings. These findings contribute to developing novel phytochemical-based therapies for breast cancer, offering new avenues for personalized and targeted treatment options.

乳腺癌是世界范围内影响女性的最常见的恶性肿瘤之一,强调需要有效的治疗策略。从植物中提取的植物化学物质因其潜在的抗癌特性而受到广泛关注。目的对植物化学制剂作为乳腺癌治疗手段的现有文献进行综述。通过分析现有证据,我们的目标是确定这些配方在抗癌活性、生物利用度和安全性方面的潜在益处和局限性。方法系统检索相关数据库,确定植物化学制剂在乳腺癌治疗中的应用研究。纳入标准包括临床试验、临床前研究和体外实验,这些实验报告了在各种配方中使用植物化学物质治疗乳腺癌。进行数据提取以确保纳入研究的信度和效度。结果该综述强调了用于乳腺癌治疗的不同配方中使用的植物化学物质的多样性。研究结果表明,这些制剂通过靶向乳腺癌进展中的多种信号通路,包括细胞增殖、细胞凋亡、血管生成和转移,显示出有希望的抗癌作用。此外,各种递送系统,如纳米颗粒、脂质体和胶束,提高了植物化学物质的生物利用度和靶向递送。结论植物化学负载制剂在乳腺癌治疗中具有巨大的潜力。综述的证据表明,它们能够抑制肿瘤生长,提高化疗效果,减少不良反应。然而,需要进一步的研究来优化配方策略,调查长期安全性,并进行大规模的临床试验,以确定其在临床环境中的有效性和适用性。这些发现有助于开发新的基于植物化学的乳腺癌治疗方法,为个性化和靶向治疗选择提供新的途径。
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引用次数: 1
The Antihypertensive Effect of Hydro-methanolic Extract of Tulbaghia acutiloba Harv. in L-NAME induced Hypertensive Rats 尖叶塔尔巴克氏菌Hydro-Methanolic提取物的降压作用。在L-NAME诱导的高血压大鼠中
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100101
Isaiah Arhin , Kogi Moodley , Himansu Baijnath , Usri H. Ibrahim , Irene Mackraj

Background

Traditional use of Tulbaghia acutiloba (TA) in South Africa includes treating various illnesses, such as infectious diseases and hypertension. However, the effect of this indigenous plant on renal and haematological parameters (as indicators of antihypertensive efficacy) has not been investigated yet.

Objective

This study aimed to evaluate the change of renal and haematological parameters after treatment with the hydro-methanolic extract of the leaf of Tulbaghia acutiloba Harv. in L-NAME- induced hypertensive rats.

Methods

Male albino Wistar rats received an oral dose of 50 mg·kg-1 body weight (bw) of Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) daily for 5 weeks. Five groups (7 animals in each group) were identified to receive different treatments as concurrent daily doses of (40, 60 and 80 mg·kg-1 bw), ramipril (10 mg·kg-1 bw) (positive control) and water (hypertension model). Mean arterial blood pressure was measured weekly using the tail-cuff method. A 24-hour urine sample was collected for each rat weekly. On day 36, the rats were euthanized, and blood samples were collected for the determination of renal function and haematological analysis. Kidney mRNA gene expression was performed for NF-kB, Ho1 and eNos.

Results

The treatment of the hypertensive rats with TA resulted in a significant reduction in the mean arterial blood pressure, with a pronounced effect observed in the 80 mg·kg-1 dose of TA compared to the positive control. The TA-treated group showed increased creatinine clearance (Ccr), urine volume and a reduction in serum creatinine, proteinuria and urine protein-creatinine ratio (UPr/UCr). TA treatment also decreased lipid peroxidation in renal tissues and erythrocytes while increasing SOD, CAT, GSH and NO levels. Moreover, red cell distribution width (RDW), white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet and mean platelet volume (MPV) were significantly reduced in the TA and ramipril treated groups with the maximum effect occurring at the dose of 80 mg·kg-1 of TA. No significant difference was observed in the haemoglobin levels in all experimental groups. TA administration resulted in a significant decrease in renal NF-kB gene expression while increasing Ho1 and eNos gene expression in renal tissues.

Conclusion

TA extract improved renal function and haematological profile (markers for the antihypertensive efficacy) in L-NAME-induced hypertensive rats.

背景:在南非,土巴hia acutiloba (TA)的传统用途包括治疗各种疾病,如传染病和高血压。然而,这种本土植物对肾脏和血液学参数(作为降压疗效的指标)的影响尚未被调查。目的探讨白桦叶水甲醇提取物对大鼠肾脏和血液学指标的影响。L-NAME诱导的高血压大鼠。方法白化Wistar大鼠每日口服n ω-硝基- l -精氨酸甲酯盐酸盐(L-NAME) 50 mg·kg-1体重(bw),连续5周。选择5组(每组7只),分别采用日剂量(40、60、80 mg·kg-1 bw)、雷米普利(10 mg·kg-1 bw)(阳性对照)和水(高血压模型)进行治疗。采用尾袖法每周测量平均动脉血压。每只大鼠每周采集24小时尿液样本。第36天对大鼠实施安乐死,取血进行肾功能测定和血液学分析。进行肾mRNA基因NF-kB、Ho1和eNos的表达。结果用TA治疗高血压大鼠可显著降低其平均动脉血压,其中80 mg·kg-1剂量的TA较阳性对照组效果显著。ta治疗组肌酐清除率(Ccr)、尿量增加,血清肌酐、蛋白尿和尿蛋白-肌酐比值(UPr/UCr)降低。TA治疗还能降低肾组织和红细胞的脂质过氧化,同时提高SOD、CAT、GSH和NO水平。此外,TA和雷米普利治疗组红细胞分布宽度(RDW)、白细胞(WBC)、中性粒细胞与淋巴细胞比值(NLR)、淋巴细胞与单核细胞比值(LMR)、血小板和平均血小板体积(MPV)均显著降低,且TA剂量为80 mg·kg-1时影响最大。各组血红蛋白水平差异无统计学意义。TA可显著降低肾NF-kB基因表达,增加肾组织中Ho1和eNos基因表达。结论ta提取物能改善l - name诱导的高血压大鼠的肾功能和血液学指标(降压效果指标)。
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引用次数: 0
Anticonvulsant Effect of Xingnaojing Injection on Acute Seizure Models in Mice 醒脑静注射液对小鼠急性发作模型的抗惊厥作用
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100091
Minjuan Sun , Xiaoyun Qiu , Zhijian Yuan , Shuo Zhang , Qi Zhang , Xiaoli Da , Xuming Ji , Xuhong Jiang , Cenglin Xu , Zhong Chen

Background

Epilepsy is characterized by acute recurrent seizures. The control of seizures is largely hampered by the tolerance to current anti-seizure drugs. Complementary anti-convulsant pharmacotherapies are urgently needed.

Objective

Here, we aimed to investigate the anti-convulsant effects of Xingnaojing Injection (XNJ) which is an approved Traditional Chinese Medicine injection on different acute seizure models in mice.

Methods

The effects of XNJ were tested on the maximal electroshock (MES), pentylenetetrazol (PTZ) and kainic acid (KA) acute seizure models. Also, whether XNJ can directly inhibit hippocampal neuronal firings were examined by in vitro electrophysiology.

Results

XNJ could shorten the durations of generalized tonic-clonic seizures in the MES model. It also significantly prolonged the latencies to generalized myo-clonic seizures in the PTZ model. In the KA model, XNJ showed various efficacies including inhibiting the seizure stages, prolonging the latency to the occurrence of the first seizures or generalized seizures, shortening the seizure durations, decreasing the numbers of generalized seizures. In vitro electrophysiological recordings further verified XNJ directly inhibited both the spontaneous and evoked action potentials of hippocampal pyramidal neurons, but did not influence the excitatory or inhibitory synaptic transmissions.

Conclusion

These findings proposed XNJ as an alternative anti-convulsant pharmacotherapy for controlling acute epileptic seizures.

背景:癫痫的特点是急性反复发作。对癫痫发作的控制很大程度上受到当前抗癫痫药物耐受性的阻碍。迫切需要补充抗惊厥药物治疗。目的观察醒脑静注射液(XNJ)对不同急性发作模型小鼠的抗惊厥作用。方法采用大鼠最大电休克(MES)、戊四氮唑(PTZ)和kainic酸(KA)急性发作模型,观察XNJ的作用。体外电生理观察XNJ是否能直接抑制海马神经元放电。结果xnj可缩短MES模型全身性强直-阵挛性发作的持续时间。在PTZ模型中,它也显著延长了全身性肌阵挛发作的潜伏期。在KA模型中,XNJ表现出抑制发作阶段、延长首次发作或全面性发作的潜伏期、缩短发作持续时间、减少全面性发作次数等作用。体外电生理记录进一步证实XNJ直接抑制海马锥体神经元自发和诱发动作电位,但不影响兴奋性和抑制性突触传递。结论XNJ可作为控制急性癫痫发作的抗惊厥药物。
{"title":"Anticonvulsant Effect of Xingnaojing Injection on Acute Seizure Models in Mice","authors":"Minjuan Sun ,&nbsp;Xiaoyun Qiu ,&nbsp;Zhijian Yuan ,&nbsp;Shuo Zhang ,&nbsp;Qi Zhang ,&nbsp;Xiaoli Da ,&nbsp;Xuming Ji ,&nbsp;Xuhong Jiang ,&nbsp;Cenglin Xu ,&nbsp;Zhong Chen","doi":"10.1016/j.ccmp.2023.100091","DOIUrl":"10.1016/j.ccmp.2023.100091","url":null,"abstract":"<div><h3>Background</h3><p>Epilepsy is characterized by acute recurrent seizures. The control of seizures is largely hampered by the tolerance to current anti-seizure drugs. Complementary anti-convulsant pharmacotherapies are urgently needed.</p></div><div><h3>Objective</h3><p>Here, we aimed to investigate the anti-convulsant effects of <em>Xingnaojing</em> Injection (XNJ) which is an approved Traditional Chinese Medicine injection on different acute seizure models in mice.</p></div><div><h3>Methods</h3><p>The effects of XNJ were tested on the maximal electroshock (MES), pentylenetetrazol (PTZ) and kainic acid (KA) acute seizure models. Also, whether XNJ can directly inhibit hippocampal neuronal firings were examined by <em>in vitro</em> electrophysiology.</p></div><div><h3>Results</h3><p>XNJ could shorten the durations of generalized tonic-clonic seizures in the MES model. It also significantly prolonged the latencies to generalized myo-clonic seizures in the PTZ model. In the KA model, XNJ showed various efficacies including inhibiting the seizure stages, prolonging the latency to the occurrence of the first seizures or generalized seizures, shortening the seizure durations, decreasing the numbers of generalized seizures. <em>In vitro</em> electrophysiological recordings further verified XNJ directly inhibited both the spontaneous and evoked action potentials of hippocampal pyramidal neurons, but did not influence the excitatory or inhibitory synaptic transmissions.</p></div><div><h3>Conclusion</h3><p>These findings proposed XNJ as an alternative anti-convulsant pharmacotherapy for controlling acute epileptic seizures.</p></div>","PeriodicalId":72608,"journal":{"name":"Clinical complementary medicine and pharmacology","volume":"3 3","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46270078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emergency Protective Measures and Strategies of COVID-19: From Lifestyle to Traditional Chinese Medicine 新冠肺炎应急防护措施与策略:从生活方式到中医
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100089
Chunsong Hu

This article reviews various aspects of COVID-19, including its current status, its side-effects, emergency protective measures and strategies from lifestyle to traditional Chinese medicine (TCM) for fighting against the SARS-CoV-2, and its major variants (Delta and Omicron), with the ongoing global COVID-19 pandemic, which include “Carassius auratus lifestyle” for high effective isolation, social and high-tech medical strategies, traditional Chinese herbs “Bark-Flower-Fruit-Grass-Leaf-Nucleolus(seed)-Root (BFFGLNR)”, and the combination of Chinese and western medicine. As a choice, little is known whether the Chinese acupuncture is an effective method for confirming and suspecting COVID-19 patients, which include imported and asymptomatic cases. Definitely, acupuncture has been proven effective treatment for the recovery of COVID-19 cases. However, further animal experiments and clinical trials are required to confirm its effects and disclose underlying mechanisms. In conclusion, these emergency protective measures and strategies for COVID-19 will help to effectively combat the SARS-CoV-2 and its variants during the pandemic and post-COVID-19 era.

本文综述了新冠肺炎的各个方面,包括其现状、副作用、从生活方式到中医药的紧急保护措施和策略,以对抗SARS-CoV-2及其主要变异株(德尔塔和奥密克戎),以及正在进行的全球新冠肺炎大流行,社会高科技医疗策略,中草药“树皮花果草叶核(种子)-根(BFFGLNR)”,中西医结合。作为一种选择,目前尚不清楚中国针灸是否是确认和怀疑新冠肺炎患者(包括输入性和无症状病例)的有效方法。毫无疑问,针灸已被证明是新冠肺炎病例康复的有效治疗方法。然而,还需要进一步的动物实验和临床试验来证实其作用并揭示其潜在机制。总之,这些针对新冠肺炎的紧急防护措施和策略将有助于在大流行和新冠肺炎后时代有效对抗SARS-CoV-2及其变种。
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引用次数: 1
Clinical Use of COX-2 Inhibitors Containing Quinoline Heterocycle as a Selective Therapeutic Agents for Complementary Medicine 含喹啉杂环的COX-2抑制剂作为辅助药物选择性治疗剂的临床应用
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100102
Megha P. Ambatkar, Nilesh R. Rarokar, Pramod B. Khedekar

Inflammation represents an initial response of immune system and is involved in a number of biochemical incidents. Such incidents may multiply and further develop the provocative response. Over the past 15 years, various classes of secondary metabolites that were isolated from plant and marine sources have been described as natural cyclooxygenase (COX) inhibitors. The majority of natural COX inhibitors could be used as a selective therapeutic agent for complementary medicine and clinical applications. Currently, the inflammation is commonly treated by non-steroidal anti-inflammatory drugs (NSAIDs), several medications of which, however, have been linked to renal and gastrointestinal side effects. A variety of inhibitors of COX-2 that are selective (celecoxib, rofecoxib, valdecoxib and others) have been designed as NSAIDs mostly with enhanced stomach safety profiles. This helps to improve the compliance and functions in the geriatric patients as they have so many complications and problems associated with the diseases. The use of complementary medicine in combination with clinical therapy might give better results than medicine alone. Some disease condition like cancer which shows the COX-2 expressions could also have treatment related problems in such cases the selective inhibitors used as a complementary medicine. On the other hand, elevated cardiovascular risks have brought increasing worries about the safety of using specific inhibitors of COX-2. This current review focuses on how quinoline heterocycle was used for creation of inhibitors of COX-2 since 2009 along with its clinical significance in complementary medicine. These agents included the variety of substituents on the ring or ring attached to other heterocycles. As a result, the quinoline heterocycle will be used for creating and finding anti-inflammatory COX-2 medicines.

炎症反应是免疫系统的一种初始反应,与许多生物化学事件有关。这类事件可能会增多,并进一步发展挑衅性反应。在过去的15年中,从植物和海洋中分离出的各种次生代谢物被描述为天然环氧合酶(COX)抑制剂。大多数天然COX抑制剂可作为一种选择性治疗剂用于补充医学和临床应用。目前,这种炎症通常由非甾体抗炎药(NSAIDs)治疗,然而,其中一些药物与肾脏和胃肠道副作用有关。多种选择性COX-2抑制剂(塞来昔布、罗非昔布、伐地昔布等)已被设计为非甾体抗炎药,大多数具有增强的胃安全性。这有助于改善老年患者的依从性和功能,因为他们有很多与疾病相关的并发症和问题。与临床治疗相结合使用补充药物可能比单独使用药物产生更好的效果。一些疾病,如癌症,显示COX-2表达也可能有治疗相关的问题,在这种情况下,选择性抑制剂用作补充药物。另一方面,心血管风险的升高使得人们越来越担心使用特异性COX-2抑制剂的安全性。本文综述了喹啉杂环自2009年以来在COX-2抑制剂制造中的应用及其在补充医学中的临床意义。这些试剂包括环上的各种取代基或环上附加的其他杂环。因此,喹啉杂环将用于制造和发现抗炎COX-2药物。
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引用次数: 1
Carya cathayensis Leaf Extract Exerts Estrogenic Effects on Hepatic Lipogenesis and Adipocytes Differentiation in Ovariectomized Rats Fed Normal or High-fat Diets 山核桃叶提取物对去卵巢大鼠肝脏脂肪生成和脂肪细胞分化的雌激素影响
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2022.100061
Xiwen Jia , Simeng Guo , Youling Huang , Dongheng Zheng , Yuqi Ding , Xilin Qiao , Zhishan Ding , Yanfen Huang

Background

Our previous in vitro study has shown that total flavonoids from the leaves of Carya cathayensis exert estrogenic activities by promoting the expressions of ERα and ERβ. C. cathayensis leaf extract (CCE) was rich in flavonoids. Oral administration of CCE reduced the serum lipids and hepatic lipids, alleviated liver steatosis in ovariectomized rats.

Objective

To investigate whether CCE has estrogenic effects on reproductive tissue and influences lipid metabolism in ovariectomized rats, and whether CCE has a direct effect on regulation of lipid synthesis and/or oxidation and adipocyte differentiation of ovariectomized (OVX) rats.

Methods

Female Sprague–Dawley rats were ovariectomized and treated with CCE or estradiol in combination with a normal diet (ND), a high-fat diet (HFD) for 8 weeks. Histological analysis of uterus were performed and the lipid metabolism-related enzyme activity were examined. Expression of liver lipogenesis-related genes, adipocyte differentiation- and fat accumulation-related genes and protein were measured.

Rusults

Ovariectomy accelerated the uterine atrophy, development of dyslipidemia and hepatic steatosis, which were effectively mitigated by CCE supplementation. CCE significantly elevated ovariectomy-induced reduction in the cross-section area of the uterus and uterine glands. Compared with the OVX group, CCE increased the activities of lipoprtein lipase (LPL) and hepatic lipase (HL), decreased the hepatic mRNA expressions of Fas, Srebf1, Sla2a2, and increased Ppar α expressions at the mRNA levels under both ND and HFD conditions. CCE also decreased the Pck1 and G6pc mRNA expressions under HFD conditions, and show no significant effects on Hmgcr. The expressions of SREBF1, CEBPA and VEGF at the protein level were effectively regulated by CCE supplementation.

Conclusion

CCE effectively alleviated ovariectomy-induced dyslipidemia and visceral fat accumulation by modulating hepatic lipogenesis and adipocyte differentiation. Furthermore, CCE exhibited estrogenic activity for the prevention of postmenopausal fatty liver.

前期体外实验表明山核桃叶总黄酮通过促进ERα和ERβ的表达而发挥雌激素活性。山核桃叶提取物(CCE)含有丰富的黄酮类化合物。口服CCE可降低去卵巢大鼠的血脂和肝脏脂质,减轻肝脏脂肪变性。目的探讨CCE是否对去卵巢大鼠生殖组织有雌激素作用,是否影响去卵巢大鼠的脂质代谢,以及CCE是否对去卵巢大鼠脂质合成和/或氧化及脂肪细胞分化有直接影响。方法雌性Sprague-Dawley大鼠切除卵巢,用CCE或雌二醇联合正常饮食(ND)、高脂饮食(HFD)治疗8周。对子宫进行组织学分析,检测脂质代谢相关酶活性。测定肝脏脂肪生成相关基因、脂肪细胞分化和脂肪积累相关基因和蛋白质的表达。结果子宫切除术加速了子宫萎缩、血脂异常和肝脂肪变性的发生,而补充CCE可有效缓解这些症状。CCE显著提高卵巢切除术引起的子宫和子宫腺横截面积的减少。与OVX组相比,CCE提高了ND和HFD组肝脏脂蛋白脂肪酶(LPL)和肝脏脂肪酶(HL)活性,降低了肝脏Fas、Srebf1、Sla2a2 mRNA的表达,提高了Ppar α mRNA的表达水平。CCE还降低了HFD条件下Pck1和G6pc mRNA的表达,对Hmgcr无显著影响。添加CCE可有效调节SREBF1、CEBPA和VEGF在蛋白水平上的表达。结论cce通过调节肝脏脂肪生成和脂肪细胞分化,有效缓解卵巢切除所致的血脂异常和内脏脂肪堆积。此外,CCE在预防绝经后脂肪肝方面表现出雌激素活性。
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引用次数: 1
Advanced Oxidation Protein Products Regulate the Pharmacokinetics of Aloe-emodin, Emodin, Rhein, and Chrysophanol in Chronic Kidney Disease Rats 高级氧化蛋白产品调节芦荟-大黄素、大黄素、大黄酚在慢性肾病大鼠体内的药代动力学
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100087
Tianrong Xun , Xiaokang Wang , Jingqian Zhao , Zhufen Lin , Haixing Feng , Liqian Mo , Xixiao Yang

Background

As accelerators and products of the progression of chronic kidney disease (CKD), advanced oxidation protein products (AOPPs) affect the function of the liver. Huang Gan granules (HGGs) are commonly used to prevent the progression of CKD, but the pharmacokinetics of aloe-emodin, emodin, rhein, and chrysophanol in HGGs in CKD remain unknown.

Objective

To investigate the influence and its molecular mechanism of AOPPs on the in vivo pharmacokinetics of aloe-emodin, emodin, rhein, and chrysophanol in HGGs.

Methods

We constructed 5/6 nephrectomised (5/6 nx), adenine-induced (adenine) and AOPP-treated rat models. After oral administration of HGG, the concentrations of aloe-emodin, emodin, rhein, and chrysophanol in the plasma samples were detected by high-performance liquid chromatography (HPLC), and their pharmacokinetics were analysed with the PKSolver software. The plasma concentrations of IL-6 and TNF-α are detected by enzyme linked immunosorbent assay (ELISA). The RT-PCR was performed in the HepG2 cells to explore the effect of TNF-α and IL-6 on the mRNA expression of CYP1A2 and CYP3A4.

Result

The results showed that the method was suitable for the quantification of four anthraquinones in plasma and excreta samples with satisfactory linear (R2 > 0.9931), precision (< 9.4%) and accuracy (± 10%). In 5/6 nx, adenine and AOPPs-treated rats, the concentrations of TNF-α and IL-6 were increased. In 5/6 nx and adenine rats, the pharmacokinetic parameters (t1/2, MRT0-∞ and AUC0-∞) of aloe-emodin, emodin, rhein, and chrysophanol were, respectively, significantly increased and correlated with the concentration of AOPPs. In AOPPs-treated rats, the concentration of AOPPs was significantly increased and the pharmacokinetic parameters of four anthraquinones were also increased.

Conclusion

In summary, inflammatory cytokine production may be one of the important causes in AOPPs' regulating the pharmacokinetic of aloe-emodin, emodin, rhein, and chrysophanol in the CKD rats. Studies of aloe-emodin, emodin, rhein, and chrysophanol in CKD facilitate the appropriate prescription of HGGs in the clinical.

作为慢性肾脏疾病(CKD)进展的加速器和产物,晚期氧化蛋白产物(AOPPs)影响肝脏功能。黄肝颗粒(HGGs)通常用于预防CKD的进展,但黄肝颗粒中芦荟大黄素、大黄素、大黄素和大黄酚在CKD中的药代动力学尚不清楚。目的探讨黄芪黄芪多糖(AOPPs)对芦荟大黄素、大黄素、大黄素、大黄酚体内药动学的影响及其分子机制。方法构建5/6大鼠肾切除(5/6 nx)、腺嘌呤诱导(adenine)和aopp处理模型。口服HGG后,采用高效液相色谱法(HPLC)检测血浆样品中芦荟大黄素、大黄素、大黄素和大黄酚的浓度,并用PKSolver软件分析其药代动力学。采用酶联免疫吸附试验(ELISA)检测血浆中IL-6和TNF-α的浓度。在HepG2细胞中进行RT-PCR,探讨TNF-α和IL-6对CYP1A2和CYP3A4 mRNA表达的影响。结果该方法适用于血浆和排泄物样品中4种蒽醌类药物的定量,线性(R2 >0.9931),精度(<9.4%),准确度(± 10%)。在5/6 nx、腺嘌呤和aopps处理的大鼠中,TNF-α和IL-6浓度升高。在5/6 nx和腺嘌呤大鼠中,芦荟大黄素、大黄素、大黄酚的药代动力学参数(t1/2、MRT0-∞和AUC0-∞)均显著升高,并与AOPPs浓度相关。AOPPs处理后大鼠体内AOPPs浓度显著升高,4种蒽醌类药物的药动学参数升高。结论综上所述,炎症细胞因子的产生可能是AOPPs调节芦荟大黄素、大黄素、大黄酚在CKD大鼠体内的药代动力学的重要原因之一。研究芦荟-大黄素、大黄素、大黄酚在CKD中的作用,有助于临床合理处方hgg。
{"title":"Advanced Oxidation Protein Products Regulate the Pharmacokinetics of Aloe-emodin, Emodin, Rhein, and Chrysophanol in Chronic Kidney Disease Rats","authors":"Tianrong Xun ,&nbsp;Xiaokang Wang ,&nbsp;Jingqian Zhao ,&nbsp;Zhufen Lin ,&nbsp;Haixing Feng ,&nbsp;Liqian Mo ,&nbsp;Xixiao Yang","doi":"10.1016/j.ccmp.2023.100087","DOIUrl":"10.1016/j.ccmp.2023.100087","url":null,"abstract":"<div><h3>Background</h3><p>As accelerators and products of the progression of chronic kidney disease (CKD), advanced oxidation protein products (AOPPs) affect the function of the liver. <em>Huang Gan granules</em> (HGGs) are commonly used to prevent the progression of CKD, but the pharmacokinetics of aloe-emodin, emodin, rhein, and chrysophanol in HGGs in CKD remain unknown.</p></div><div><h3>Objective</h3><p>To investigate the influence and its molecular mechanism of AOPPs on the <em>in vivo</em> pharmacokinetics of aloe-emodin, emodin, rhein, and chrysophanol in HGGs.</p></div><div><h3>Methods</h3><p>We constructed 5/6 nephrectomised (5/6 nx), adenine-induced (adenine) and AOPP-treated rat models. After oral administration of HGG, the concentrations of aloe-emodin, emodin, rhein, and chrysophanol in the plasma samples were detected by high-performance liquid chromatography (HPLC), and their pharmacokinetics were analysed with the PKSolver software. The plasma concentrations of IL-6 and TNF-α are detected by enzyme linked immunosorbent assay (ELISA). The RT-PCR was performed in the HepG2 cells to explore the effect of TNF-α and IL-6 on the mRNA expression of CYP1A2 and CYP3A4.</p></div><div><h3>Result</h3><p>The results showed that the method was suitable for the quantification of four anthraquinones in plasma and excreta samples with satisfactory linear (<em>R</em><sup>2</sup> &gt; 0.9931), precision (&lt; 9.4%) and accuracy (± 10%). In 5/6 nx, adenine and AOPPs-treated rats, the concentrations of TNF-α and IL-6 were increased. In 5/6 nx and adenine rats, the pharmacokinetic parameters (t<sub>1/2</sub>, MRT<sub>0-∞</sub> and AUC<sub>0-∞</sub>) of aloe-emodin, emodin, rhein, and chrysophanol were, respectively, significantly increased and correlated with the concentration of AOPPs. In AOPPs-treated rats, the concentration of AOPPs was significantly increased and the pharmacokinetic parameters of four anthraquinones were also increased.</p></div><div><h3>Conclusion</h3><p>In summary, inflammatory cytokine production may be one of the important causes in AOPPs' regulating the pharmacokinetic of aloe-emodin, emodin, rhein, and chrysophanol in the CKD rats. Studies of aloe-emodin, emodin, rhein, and chrysophanol in CKD facilitate the appropriate prescription of HGGs in the clinical.</p></div>","PeriodicalId":72608,"journal":{"name":"Clinical complementary medicine and pharmacology","volume":"3 3","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47433388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protection of Viola odorata L. against Neurodegenerative Diseases: Potential of the Extract and Major Phytoconstituents 堇菜对神经退行性疾病的保护作用:提取物和主要植物成分的潜力
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100105
Sunny Dhiman , Shivali Singla , Inder Kumar , Priyankul Palia , Pankaj Kumar , Sachin Goyal

Background

Neurodegenerative diseases cause cognitive impairment owing to neuronal death and deterioration. Only a few brain-protecting chemical investigations yielded neuroprotective medications. Viola odoata L. is a traditional medicinal herb that has lately been shown to have strong pharmacological effectiveness against major neurological illnesses with fewer adverse effects.

Objective

The objective of the current review is to provide a thorough overview of the key biologically active components and extract of Viola odorata L. in their capacity to safeguard nerve cells.

Methods

Science Direct, PubMed, Springer Nature, and Google Scholar were scoured for relevant articles using the terms ``Viola odorata L.'', and in the heading and abstract or main text, ``neuroprotective activity'', ``neurodegenerative disease'', ``pharmacological potential'', and ``therapeutic activity'' along with ``extract'' or ``phytoconstituents''. Neuroprotective activity of Viola odorata L. extract or phytoconstituents were used to classify and investigate the articles that passed the screening process.

Results

A total of one hundred twenty one papers were reviewed based on the collected data. The following topics have been elaborated upon in the text: pathological factors of neurodegenerative diseases; role of medicinal plants in neurodegenerative diseases; Viola odorata L. taxonomy, pharmacological activities, toxicity and adverse effect; neuroprotective activity of extract and various active components of Viola odorata L. The primary phytocomponents of Viola odorata L. were discovered to be anthocyanins, flavonoids, melatonin, salicylic acid, cumarins and various alkaloids, which are primarily responsible for its neuroprotective action. These natural plant compounds can boost antioxidant levels, reduce harmful oxidants, alleviate nerve pain, decrease the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, lower the total amount of nitrite produced, and trigger various neuroprotective mechanisms in the nervous system. It has been also concluded in several investigations that Viola odorata L. extract and some of its major molecular components can protect against toxic affronts, either directly through neuroprotective mechanisms or indirectly through antioxidant properties.

Conclusion

Despite the need for further research, the presence of bioactive components in Viola odarata L. that hold the potential to become effective neuroprotective therapeutic agents shows its potential use in treating neurodegenerative diseases characterized by neuro-inflammation and neurotransmitter deficiency.

背景:神经退行性疾病由于神经元的死亡和退化而引起认知障碍。只有少数脑保护化学研究产生了神经保护药物。紫堇是一种传统的草药,最近被证明对主要神经系统疾病有很强的药理作用,副作用少。目的综述了堇菜的主要生物活性成分及其提取物对神经细胞的保护作用。方法使用“Viola odorata L”检索词对science Direct、PubMed、Springer Nature和Google Scholar进行检索。,并在标题和摘要或正文中注明“神经保护活性”、“神经退行性疾病”、“药理潜力”和“治疗活性”以及“提取物”或“植物成分”。利用堇菜提取物或植物成分的神经保护活性对通过筛选的文章进行分类和研究。结果根据收集到的资料,共审查论文121篇。本文阐述了以下主题:神经退行性疾病的病理因素;药用植物在神经退行性疾病中的作用堇菜的分类、药理活性、毒副作用研究发现,气味堇菜的主要植物成分为花青素、黄酮类化合物、褪黑素、水杨酸、香豆素和各种生物碱,这些成分是其神经保护作用的主要成分。这些天然植物化合物可以提高抗氧化水平,减少有害氧化剂,减轻神经疼痛,减少促炎细胞因子如IL-6, IL-1β和TNF-α的产生,降低亚硝酸盐的总量,并在神经系统中触发各种神经保护机制。在一些研究中也得出结论,堇菜提取物及其一些主要分子成分可以通过直接的神经保护机制或间接的抗氧化特性来防止毒性侵犯。结论尽管还需要进一步的研究,但堇菜中存在的生物活性成分可能成为有效的神经保护药物,在治疗以神经炎症和神经递质缺乏为特征的神经退行性疾病方面具有潜在的应用前景。
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引用次数: 1
Sub-chronic (Ninety Days) Toxicity Study of Hydroethanolic Leaf Extract of Datura stramonium L. in Rodents 曼陀罗水乙醇叶提取物对啮齿动物亚慢性(90天)毒性研究
Pub Date : 2023-09-01 DOI: 10.1016/j.ccmp.2023.100090
Abdullahi A. Murtala , Oyinloye E. Oladapo , Aderonke A. Aderionla , Wasiu E. Olooto , Oluwatosin O. Soyinka , Royhan O. Folarin , Farouk A. Oladoja , Oluwatoyin O. Shonde , Luqmon E. Osipitan , Emmanuel B. Adegbe , Julius A. Abolarinwa

Background

Phyto-medicine represents a vast pool of novel drug development, but understanding their safety requires elaborate, multifaceted approaches, including toxicity studies.

Objective

This study investigated the effects of 90 days of oral administration of Datura stramonium (DSE) leaf extract in Rats.

Methods

In the oral acute toxicity study, mice were treated with a single oral gavage of DSE at 500, 1000, and 2000 mg·kg-1/d, po and observed for signs of acute toxicity for 14 days. In the sub-chronic study, rats were randomized into four Groups (A–D). Group A received distilled water (10 mL·kg-1, po) while groups B–D received DSE (10, 50 and 250 mg·kg-1/d, po, respectively) orally for 90 days uninterrupted. Animals were weighed weekly, with food and water measured daily and relevant parameters assayed at the end of the 90days administration.

Results

In acute toxicity studies, oral administration of up to 2 g·kg-1/d, po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days. In the 90days studies, DSE (250 mg·kg-1/d, po) decreased the body weight, brain weight, and food intake in female rats. DSE (10–250 mg·kg-1/d, po) increased the red blood cell (RBC), packed cell volume (PCV) and hemoglobin (Hb) in both sexes. DSE (10–250 mg·kg-1/d, po) increased the triglycerides (TG), cholesterol and low-density lipoprotein (LDL); and decreased HDL in both sexes. DSE (10–250 mg·kg-1/d, po) increased the white blood cells (WBC) and platelets in female rats. DSE (10–250 mg·kg-1/d, po) decreased the alkaline phosphatase (ALP) and alanine transaminase (ALT) in both studies. Serum urea level was decreased in both sexes. DSE (250 mg·kg-1/d, po) decreased male rats' serum sodium ion levels. Liver, brain, testes and kidney showed severe lesions at 250 mg·kg-1/d, po of the extract.

Conclusion

D. stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration. However, prolonged use, especially at high doses, could cause Liver, brain and kidney toxicities; and abnormal lipid metabolism.

植物药代表了一个巨大的新药物开发池,但了解它们的安全性需要复杂的、多方面的方法,包括毒性研究。目的观察曼陀罗叶提取物给药90 d后对大鼠的影响。方法在急性毒性研究中,小鼠分别以500、1000、2000 mg·kg-1/d单次灌胃DSE,观察14 d急性毒性症状。在亚慢性研究中,大鼠随机分为四组(A-D)。A组灌胃蒸馏水(10 mL·kg-1, po), B-D组灌胃DSE(分别为10、50、250 mg·kg-1/d, po),连续90 d。每周称重,每天测量食物和水,在给药90d结束时测定相关参数。结果在急性毒性研究中,口服2 g·kg-1/d的DSE在24 h ~ 14 d内未引起任何毒性或死亡。在90天的研究中,DSE (250 mg·kg-1/d, po)降低了雌性大鼠的体重、脑重和摄食量。DSE (10 ~ 250 mg·kg-1/d, po)使两性红细胞(RBC)、堆积细胞体积(PCV)和血红蛋白(Hb)增加。DSE (10 ~ 250 mg·kg-1/d, po)使甘油三酯(TG)、胆固醇和低密度脂蛋白(LDL)升高;以及两性中高密度脂蛋白的减少DSE (10 ~ 250 mg·kg-1/d, po)使雌性大鼠白细胞和血小板增加。DSE (10 ~ 250 mg·kg-1/d, po)降低了碱性磷酸酶(ALP)和丙氨酸转氨酶(ALT)。两性血清尿素水平均下降。DSE (250 mg·kg-1/d, po)降低雄性大鼠血清钠离子水平。给药剂量为250 mg·kg-1/d时,肝、脑、睾丸和肾脏出现严重病变。急性接触史曲铵是安全的,亚慢性口服相对安全。然而,长期使用,特别是高剂量使用,可能导致肝、脑和肾毒性;脂质代谢异常。
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引用次数: 0
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Clinical complementary medicine and pharmacology
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