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The Effect of Xu's Influenza Decoction Combined with Oseltamivir on Influenza A: A Propensity Score Matching Study 徐流感汤联合奥司他韦治疗甲型流感疗效的倾向性评分匹配研究。
Pub Date : 2023-08-31 DOI: 10.1016/j.ccmp.2023.100113
Tianxi Chen , Shuyan Fu , Fengyuan Tian , Qiushuang Li , Hongyu Ling , Yijie Lou , Jun Tang , Hong Zheng

Background

The resurgence of seasonal influenza virus circulation has been seen in 2021–2022 after the temporary suppression in 2020–2021. Neuraminidase inhibitors (NAIs) are widely applied in the clinical treatment of influenza A despite several limitations.

Objective

To access the efficacy of Xu's influenza decoction (XID) in combination therapy with oseltamivir for the treatment of influenza A.

Methods

In this retrospective cohort study, the eligible participants were diagnosed with influenza A between June 1, 2018, and May 30, 2022, in the First Affiliated Hospital of Zhejiang Chinese Medical University. According to whether Xu's influenza decoction was applied, patients were divided into two groups: treated with or without XID. Propensity score matching (PSM) was used to further adjust the covariates between groups. The primary outcome was to compare time to defervescence via K-M curves, Breslow tests, and Cox regression analysis. In Cox proportional hazards model, a univariate analysis was performed to obtain preliminary results, while a further multivariate analysis was conducted to study the independent factors that influence defervescence. Subgroup analysis was conducted according to body temperature and time from onset to admission. The secondary outcome consisted of routine blood and C-reactive protein (CRP), length of stay, and medical costs.

Results

A total of 336 patients with influenza A were enrolled in this study (i.e., 163 patients in the XID+oseltamivir group; 173 patients in the oseltamivir group). After 1:1 matching via PSM, 230 patients meeting the criteria were included in the analysis, with 115 in each arm. The XID+oseltamivir group had shorter time to defervescence (36 h vs 44 h, P = 0.011), shorter length of stay (3 days vs 4 days, P = 0.018), and higher defervescence possibility (HR=1.384, 95%CI: 1.054–1.818). Subgroup analysis indicated that for patients during non-window period (≥ 48 h) with medium-grade fever (38.1℃–39℃), the XID+oseltamivir combination therapy reduced time to defervescence (P = 0.04995/0.004) with a higher defervescence possibility (HR=1.524/1.683). Meanwhile, there's no statistical significance but observable trends of the XID+oseltamivir group in the lower medical costs (3068.07 yuan vs 3120.68 yuan), the lower neutrophils% (48.53% vs 51.00%) and the higher lymphocyte% (39.83% vs 37.72%).

Conclusion

The combination of XID and oseltamivir can shorten the time to defervescence and length of stay in influenza A. Its antipyretic effect is mainly reflected in the medium-grade and non-window periods.

背景:在2020-2021年短暂抑制之后,2021-2022年季节性流感病毒传播再次抬头。神经氨酸酶抑制剂(NAIs)广泛应用于甲型流感的临床治疗,尽管存在一些局限性。目的探讨徐氏流感汤联合奥司他韦治疗甲型流感的疗效。方法本回顾性队列研究纳入2018年6月1日至2022年5月30日在浙江中医药大学第一附属医院确诊的甲型流感患者。根据是否应用徐氏流感汤,将患者分为两组:加用和不加用。采用倾向得分匹配(PSM)进一步调整组间协变量。主要结局是通过K-M曲线、Breslow检验和Cox回归分析比较时间与退热。在Cox比例风险模型中,单因素分析获得初步结果,并进一步进行多因素分析,研究影响退热的独立因素。根据患者体温及发病至入院时间进行亚组分析。次要结果包括常规血和c反应蛋白(CRP)、住院时间和医疗费用。结果共有336例甲型流感患者入组,其中XID+奥司他韦组163例;奥司他韦组173例患者)。经PSM 1:1匹配后,230例符合标准的患者纳入分析,每组115例。XID+奥司他韦组退热时间较短(36 h vs 44 h, P = 0.011),住院时间较短(3 d vs 4 d, P = 0.018),退热可能性较高(HR=1.384, 95%CI: 1.054 ~ 1.818)。亚组分析显示,对于中度发热(38.1℃~ 39℃)的非窗口期(≥48 h)患者,XID+奥司他韦联合治疗可缩短退热时间(P = 0.04995/0.004),退热可能性更高(HR=1.524/1.683)。同时,XID+奥司他韦组在较低的医疗费用(3068.07元对320.68元)、较低的中性粒细胞百分比(48.53%对51.00%)和较高的淋巴细胞百分比(39.83%对37.72%)方面无统计学意义,但有明显的趋势。结论XID联合奥司他韦可缩短甲流退热时间和住院时间,其退热作用主要体现在中度和非窗口期。
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引用次数: 0
GSZ Formula Enhances Sleep Quality: Exploring Its Active Ingredients and Mechanism Using a Network Medicine Approach GSZ配方提高睡眠质量:运用网络医学方法探讨其活性成分和作用机制
Pub Date : 2023-08-26 DOI: 10.1016/j.ccmp.2023.100107
Airong Ren , Mingxuan Ma , Yongyin Liang , Yarong Wang , Zhengkun Li , Yahui Liu , Qing Fan , Guozhen Cui

Background

Sleep is essential for maintaining human health, and insomnia is a widespread problem. Traditional Chinese medicine (TCM) has been used for centuries to treat sleep disorders, with fewer reported side effects compared to conventional treatments.

Objective

This study seeks to investigate the sleep-promoting effects of the GSZ formula, which comprises γ-aminobutyric acid (GABA), Schisandrae Chinensis Fructus (Wuweizi in Chinese), and Ziziphi Spinosae Semen (Suanzaoren in Chinese). In addition, we aim to explore the active ingredients and potential mechanisms underlying the sleep-enhancing effects of the formula.

Methods

The impact of GSZ on sleep was evaluated using two models, the complete sleep model and the subthreshold sleep model. Mice were randomly divided into five groups and orally administered GSZ solution (0.33 g/kg/day or 0.99 g/kg/day), positive drug diazepam (2.50 mg/kg) or a control solution for 30 days. Hypnosis model was established in mice using pentobarbital sodium. Sleep duration and incidence were measured by recording when the righting reflex of mice disappeared for more than 1 min. GABA and dopamine (DA) levels in mouse brain tissue were measured using ELISA kits. The ingredients of the GSZ formula were identified using mass spectrometry, and the targets of these ingredients and disease-related genes were retrieved from public databases. A network medicine approach was used to calculate the shortest path between ingredient targets and disease-related proteins. The expression levels of potential proteins, such as Akt, p-Akt, GSK-3β, and p-GSK-3β, were analyzed using Western blotting based on the predicted results.

Results

GSZ significantly prolonged sleep duration and enhanced the sleep rate in mice (P < 0.05). Furthermore, it elevated GABA levels and reduced DA levels in the mouse brain (P < 0.05). Network medicine analysis suggested that GABA, stearic acid, genistin, and coumestrol may be the most crucial active ingredients for sleep improvement. Western blotting analysis demonstrated that GSZ modulated the protein expression levels of p-Akt/Akt and p-GSK-3β/GSK-3β (P < 0.05).

Conclusion

Our study demonstrated that the GSZ formula could improve sleep, with key ingredients likely being GABA, stearic acid, genistin, and coumestrol. The mechanism might involve the regulation of the Akt/GSK-3β pathway, as revealed by the network medicine analysis and experimental validation. Our current new findings shed light on the potential mechanisms underlying the sleep-enhancing effects of the GSZ formula, which could provide experimental evidence to develop innovative treatments for insomnia.

睡眠对维持人体健康至关重要,而失眠是一个普遍存在的问题。几个世纪以来,中医一直被用于治疗睡眠障碍,与传统疗法相比,据报道其副作用更少。目的探讨由γ-氨基丁酸(GABA)、五味子、酸枣仁组成的GSZ方对睡眠的促进作用。此外,我们的目标是探索有效成分和潜在的机制下的睡眠增强效果的配方。方法采用完全睡眠模型和阈下睡眠模型评价GSZ对睡眠的影响。将小鼠随机分为5组,分别口服GSZ溶液(0.33 g/kg/d或0.99 g/kg/d)、阳性药物地西泮(2.50 mg/kg)或对照溶液30 d。采用戊巴比妥钠建立小鼠催眠模型。记录小鼠翻正反射消失1 min以上时的睡眠持续时间和睡眠发生率。ELISA试剂盒检测小鼠脑组织中GABA和多巴胺(DA)水平。采用质谱法鉴定GSZ配方的成分,并从公共数据库中检索这些成分的靶点和疾病相关基因。采用网络医学方法计算成分靶点与疾病相关蛋白之间的最短路径。根据预测结果,采用Western blotting分析Akt、p-Akt、GSK-3β、p-GSK-3β等潜在蛋白的表达水平。结果gsz显著延长小鼠睡眠时间,提高睡眠率(P <0.05)。此外,它提高了小鼠大脑中GABA水平,降低了DA水平(P <0.05)。网络医学分析表明,GABA、硬脂酸、genistin和coumestrol可能是改善睡眠最重要的活性成分。Western blotting分析表明,GSZ可调节P -Akt/Akt和P -GSK-3β/GSK-3β的蛋白表达水平(P <0.05)。结论GSZ配方具有改善睡眠的作用,其主要成分可能是GABA、硬脂酸、genistin和coumestrol。网络医学分析和实验验证表明,其机制可能与Akt/GSK-3β通路的调控有关。我们目前的新发现揭示了GSZ配方增强睡眠效果的潜在机制,这可能为开发创新的失眠治疗方法提供实验证据。
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引用次数: 0
LC-MS identification and preliminary pharmacological study of the aqueous and ethanol extracts from Combretum glutinosum Perr ex DC. (Combretaceae) 谷草水提物和乙醇提物的LC-MS鉴定及初步药理研究。(使君子科)
Pub Date : 2023-08-14 DOI: 10.1016/j.ccmp.2023.100106
Placide Mahougnan Toklo , Mathias Amour Ahomadegbe , Durand Dah-Nouvlessounon , Jean-Bosco Jouda , Billy Toussie Tchegnitegni , Steven Collins Njonte Wouamba , Djidénou Ahoton , Mahoudo Fidèle Assogba , Joseph Tchamgoue , Bruno Ndjakou Lenta , Simeon Fogue Kouam , Lamine Baba-Moussa , Eléonore Chikani Yayi Ladekan , Joachim Djimon Gbenou

Background

Combretum glutinosum is a plant whose leaves are consumed as a vegetable and used in traditional medicine for the treatment of microbial infections.

Objective

The present study was designed to identify the compounds in C. glutinosum leaves extracts, and evaluate its antimicrobial activity, antioxidant ability and its toxicity in Artemia salina larvae in vitro.

Methods

The aqueous and ethanol extracts obtained from the leaves of the plant as well as known compounds previously isolated and characterized from the leaves of C. glutinosum were tested on eleven different microbial strains. The antioxidant activity of the extracts was evaluated by the Ferric Reducing Antioxidant Power method and the larval toxicity on Artemia salina larvae was also detected. Phytochemical screening and HPLC-DAD-HRESI-MS analysis were performed on the extracts to characterize its chemical composition.

Results

When tested at a concentration of 20 mg‧mL−1, the extracts of C. glutinosum leaves strongly inhibited the growth of the bacterial strains with an inhibition diameter ranging from 7.25 mm to 44 mm, superior to those of the positive controls (tetracycline at 30 µg‧mL−1 and amikacin at 30 µg‧mL−1), inhibition diameters from 15 mm to 33 mm. The evaluated larval toxicity demonstrated that it had no harmful effects on Artemia salina larvae. The extracts present a good antioxidant activity at a concentration of 0.17 and 1.33 mmol ascorbic acid (per gram of extract) for the aqueous and ethanol extracts, respectively. However, none of the compounds tested at 500 µg‧mL−1 were able to show good activity on the 11 reference strains. Phytochemical analysis revealed the presence of alkaloids, polyphenols, steroids, triterpenoids, reducing compounds etc. in both extracts. The HPLC-DAD-HRESI-MS analyses revealed 18 compounds in the ethanol extract, from which 3 were identified, 15 compounds in the aqueous extract from which 5 could be identified.

Conclusion

The present work has shown that C. glutinosum extracts can be a good source of antimicrobial agents. They also possess the antioxidant property with absence of toxicity on A. salina larvae. A further bio-guided study could allow the identification and isolation of the active ingredients.

谷草combretum glutinosum是一种植物,其叶子作为蔬菜食用,在传统医学中用于治疗微生物感染。目的鉴定谷胱甘肽叶提取物的主要成分,并评价其体外抗菌活性、抗氧化能力和对盐蒿幼虫的毒性。方法采用水提物、醇提物和已知化合物对11种不同的微生物菌株进行检测。采用铁还原抗氧化力法评价提取物的抗氧化活性,并检测其对盐渍蒿幼虫的毒性。对提取物进行植物化学筛选和HPLC-DAD-HRESI-MS分析,表征其化学成分。结果当浓度为20 mg·mL−1时,谷草叶提取物对细菌生长的抑制直径为7.25 ~ 44 mm,优于阳性对照(四环素30µg·mL−1和阿米卡星30µg·mL−1),抑制直径为15 ~ 33 mm。幼虫毒性评价表明,其对盐渍蒿幼虫无有害作用。水提液和乙醇提液在抗坏血酸浓度分别为0.17和1.33 mmol / g时表现出良好的抗氧化活性。然而,在500µg·mL−1的条件下,化合物对11株参考菌株都没有表现出良好的活性。植物化学分析显示,两种提取物中均含有生物碱、多酚、类固醇、三萜、还原性化合物等。hplc - dad - hesi - ms分析发现,乙醇提取物中有18种化合物,其中3种被鉴定,水提取物中有15种化合物,其中5种被鉴定。结论谷胱甘肽提取物是一种良好的抗菌药物来源。它们还具有抗氧化性,对盐斑拟虫幼虫无毒性。进一步的生物引导研究可以使有效成分的鉴定和分离。
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引用次数: 0
Antihyperuricemic and Nephroprotective Effects of the Total Flavonoids from Carya cathayensis Leaves (CCTF) in Potassium Oxonate/hypoxanthine-induced Hyperuricemic Mice 山核桃叶总黄酮对草酸钾/次黄嘌呤诱导的高尿酸血症小鼠的抗高尿酸症和肾保护作用
Pub Date : 2023-07-28 DOI: 10.1016/j.ccmp.2023.100104
Jiahui Hao, Fangmei Zhou

Background

Abnormally high level of uric acid in the blood, defined as hyperuricemia (HUA), increases the chance of developing various disorders, such as gout, hypertension, and diabetes. There is a critical need to create safer and more potent therapeutic medications since the current clinical treatment for HUA has a number of negative effects.

Objective

To explore the antihyperuricemic benefits of the total flavonoids from Carya cathayensis leaves (CCTF) in HUA model mice and to elucidate the underlying mechanisms.

Methods

The mouse HUA model was induced with potassium oxonate and hypoxanthine and then the mice were given normal saline, allopurinol, or various dosages of CCTF for one week. The weight of the mice was recorded, followed by measurements of their blood uric acid (UA), creatinine (Cr), urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and xanthine oxidase (XOD) activity. Hematoxylin and eosin (H&E) staining and Manson staining were used to simultaneously detect pathological abnormalities in the liver and kidney tissues. Afterward, the mRNA expression of urate transporters in kidney was determined by qRT‒PCR experiments, including ATP-binding cassette transporter subfamily G member 2 (Abcg2), urate transporter 1 (Urat1), and glucose transporter 9 (Glut9). Finally, immunohistochemistry (IHC) staining was performed to confirm ABCG2 protein expression in the kidney.

Results

In contrast to the model group, the CCTF group lowered blood levels of UA, Cr, BUN, ALT, and AST in serum, downregulated XOD levels in serum and liver, and significantly improved liver and renal damage, exhibiting outstanding antihyperuricemic effects. The levels of Urat1 and Glut9 were further shown to be much lower in the kidney, whereas both Abcg2 expression and ABCG2 level were increased, according to the findings.

Conclusion

CCTF ameliorated hyperuricemia-related kidney damage and had antihyperuricemic effects, suggesting that CCTF might have the potential to protect against HUA by regulating the expression of relative urate transporters and XOD.

背景血液中异常高水平的尿酸,定义为高尿酸血症(HUA),增加了发生各种疾病的机会,如痛风、高血压和糖尿病。由于目前对HUA的临床治疗有许多负面影响,因此迫切需要创造更安全、更有效的治疗药物。目的探讨山核桃叶总黄酮(CCTF)对HUA模型小鼠的抗高尿酸作用,并阐明其作用机制。方法用氧酸钾和次黄嘌呤诱导小鼠HUA模型,然后给予生理盐水、别嘌呤醇或不同剂量的CCTF灌胃1周。记录小鼠体重,测定血尿酸(UA)、肌酐(Cr)、尿素氮(BUN)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和黄嘌呤氧化酶(XOD)活性。采用苏木精伊红(H&E)染色和Manson染色同时检测肝、肾组织病理异常。随后,通过qRT-PCR实验检测肾脏中尿酸转运蛋白mRNA的表达,包括atp结合盒转运蛋白亚家族G成员2 (Abcg2)、尿酸转运蛋白1 (Urat1)和葡萄糖转运蛋白9 (Glut9)。最后,免疫组织化学(IHC)染色证实ABCG2蛋白在肾脏中的表达。结果与模型组比较,CCTF组降低血清UA、Cr、BUN、ALT、AST水平,下调血清和肝脏XOD水平,显著改善肝肾损害,表现出明显的抗高尿酸血症作用。根据研究结果,Urat1和Glut9的水平进一步显示在肾脏中低得多,而Abcg2的表达和Abcg2水平都增加了。结论CCTF可改善高尿酸血症相关性肾损害并具有抗高尿酸血症作用,提示CCTF可能通过调节相对尿酸转运蛋白和XOD的表达来保护HUA。
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引用次数: 0
Electroacupuncture Alleviates HIF1-α-mediated Early Mitophagy in Spinal Cord Injury 电针可减轻HIF1-α-介导的脊髓损伤早期有丝分裂
Pub Date : 2023-07-05 DOI: 10.1016/j.ccmp.2023.100103
Rong Hu , Xingying Wu , Kelin He , Mengting Shi , Haipeng Xu , Yi Chen , Bowen Chen , Lei Wu , Ruijie Ma , Kang Liang

Background

The inhibitory microenvironment around spinal cord injury (SCI) severely restricted functional repair after injury. Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment. Hypoxia-inducible factor1α (HIF1-α) can mediate mitochondrial autophagy in neurodegenerative diseases, but the mechanisms are complex and diverse, which need to be further elucidated. Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury, promote long-term neurological function recovery in SCI patients, but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown.

Objective

Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture.

Methods

Following the successful construction of an SCI model of Sprague-Dawley rat utilizing a modified Allen method, electroacupuncture intervention was performed at T9 and T11 Jiaji acupoint (EX-B2), with further molecular biology and morphology examined by perfusion. To observe the effect of HIF1-α on local damage repair, the stereotypic injection of Hif1a knockdown virus was performed, and the changes of mitophagy in damaged local area was detected employing Western blotting, real-time fluorescence quantitative PCR, immunofluorescence, transmission electron microscopy and Nissl staining.

Results

HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury. Electroacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury, reduce cell apoptosis and injury area, promote neuronal survival.

Conclusion

Electroacupuncture may serve as a promising strategy for spinal cord injury treatment, by alleviating HIF1-α mediated early mitochondrial autophagy.

背景脊髓损伤周围的抑制微环境严重限制了损伤后的功能修复。线粒体自噬是维持细胞内稳态、保证神经细胞微环境和谐的重要措施之一。缺氧诱导因子1α (hypoxia inducible factor1α, HIF1-α)可介导神经退行性疾病的线粒体自噬,但其机制复杂多样,有待进一步阐明。电针在改善脊髓损伤后神经微环境,促进脊髓损伤患者长期神经功能恢复方面具有显著作用,但电针是否参与HIF1-α介导的有丝分裂尚不清楚。目的探讨HIF1-α对脊髓挫伤大鼠线粒体自噬的影响及电针作用的可能机制。方法采用改良Allen法成功构建Sprague-Dawley大鼠脊髓损伤模型后,采用电针干预T9、T11夹脊穴(EX-B2),灌注观察分子生物学和形态学变化。为观察HIF1-α对局部损伤修复的影响,采用Hif1a敲低病毒模型注射,采用Western blotting、实时荧光定量PCR、免疫荧光、透射电镜和尼氏染色检测损伤局部有丝分裂的变化。结果脊髓损伤后,shif1 -α及其线粒体自噬受体BNIP3和NIX表达上调。电针治疗或局部抑制HIF1-α表达可逆转脊髓损伤后早期自噬状态,减少细胞凋亡和损伤面积,促进神经元存活。结论电针可减轻HIF1-α介导的早期线粒体自噬,是一种治疗脊髓损伤的有效方法。
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引用次数: 0
Notoginsenoside R1 Protects against Diabetic Nephropathy through TXNIP-NLRP3 Signaling Pathway 三七皂苷R1通过TXNIP-NLRP3信号通路保护糖尿病肾病
Pub Date : 2023-06-11 DOI: 10.1016/j.ccmp.2023.100100
Chunting Zhang , Renyikun Yuan , Siyuan Li , Guodong Huang , Kaili Sun , Jiaping Pan , Qiuxia Liu , Xiang Gao , Zhijing Wang , Tongyu Li , Shilong Lu , Jianzhen Lv , Liting Huang , Hongwei Gao

Background

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus (DM). DN results from many factors, including changes in glomerular hemodynamics, oxidative stress and inflammation, and interstitial fibrosis and tubular atrophy. Panax notoginseng, a commonly used Chinese medicine, has been used in the treatment of kidney disease. Notoginsenoside R1 (NGR1), the main compound isolated from P. notoginseng, has been reported to have a renoprotective role in DN. However, the therapeutic effect and mechanism of NGR1 in DN remain unclear.

Objective

The present study aimed to investigate the therapeutic effect and mechanism of NGR1 in DN.

Methods

In this study, mouse podocytes (MPC-5 cells) and db/db mice were used to investigate the effect of NGR1 on DN in vitro and in vivo, respectively. Blood glucose, renal function, inflammatory factors, and PI3K/AKT-Nrf2-NLRP3 signaling pathway proteins were assessed.

Results

The study results indicated that NGR1 reversed cell viability induced by high glucose (HG, 30 mM). The related mechanism results showed that NGR1 decreased oxidative stress by inhibiting reactive oxygen species (ROS) level and upregulating the expression of Nrf2, NQO1, and HO-1 via TXNIP targeting. In addition, NLRP3 inflammasome and PI3K/AKT were engaged in NGR1-based protection against HG-stimulated podocytes. In db/db mice, NGR1 significantly decreased blood glucose, urine protein, urine output, blood urea nitrogen, and other parameters as well as reversed kidney injury by inhibiting oxidative stress and proinflammatory response.

Conclusion

Taken together, this study revealed that NGR1 exerted a significant therapeutic effect on DN both in vitro and in vivo via a mechanism related to the TXNIP-Nrf2 pathway and NLRP3 inflammasome, suggesting that NGR1 is a potential therapeutic option for DN.

背景:糖尿病肾病(DN)是糖尿病(DM)的微血管并发症。肾小球血流动力学改变、氧化应激和炎症、间质纤维化和肾小管萎缩是多种因素共同作用的结果。三七是一种常用的中药,已被用于治疗肾脏疾病。三七皂苷R1 (NGR1)是从三七中分离得到的主要化合物,据报道在DN中具有肾保护作用。然而,NGR1在DN中的治疗作用和机制尚不清楚。目的探讨NGR1对DN的治疗作用及机制。方法采用小鼠足细胞(MPC-5细胞)和db/db小鼠,分别在体外和体内研究NGR1对DN的影响。评估血糖、肾功能、炎症因子和PI3K/AKT-Nrf2-NLRP3信号通路蛋白。结果NGR1能逆转高糖(HG, 30 mM)诱导的细胞活力。相关机制结果表明,NGR1通过TXNIP靶向抑制活性氧(ROS)水平,上调Nrf2、NQO1和HO-1的表达,从而降低氧化应激。此外,NLRP3炎性体和PI3K/AKT参与了ngr1对hg刺激足细胞的保护作用。在db/db小鼠中,NGR1显著降低血糖、尿蛋白、尿量、血尿素氮等参数,并通过抑制氧化应激和促炎反应逆转肾损伤。综上所述,本研究表明,NGR1在体外和体内均通过与TXNIP-Nrf2通路和NLRP3炎性体相关的机制对DN具有显著的治疗作用,提示NGR1是一种潜在的DN治疗选择。
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引用次数: 0
Pathological Mechanism of “Phlegm, Blood stasis, Toxin” in a Rabbit Model of Carotid Atherosclerosis Based on Gut Microbiota-host Metabolism Interactions 基于肠道微生物群-宿主代谢相互作用的兔颈动脉粥样硬化“痰瘀毒”病理机制
Pub Date : 2023-06-01 DOI: 10.1016/j.ccmp.2022.100056
Feng Zhang , Yanyun Xu , Liye Shen , Junjie Huang , Songtao Xu , Minli Chen , Yongming Pan

Background

In Traditional Chinese Medicine (TCM) theory, "phlegm, blood stasis and toxin" are the pathogenesis of carotid atherosclerosis (CAS). The rabbit carotid atherosclerosis (CAS), which is induced by high-cholesterol diet combined with carotid artery balloon injury, is a classic model for studying CAS. Many studies indicate that gut microbiota and host metabolic disorders are involved in the pathogenesis of rabbit CAS. However, the TCM pathological features and syndromes of this classic rabbit CAS model have not been reported.

Objective

To explore the pathogenesis of the rabbit CAS model and its TCM syndrome types from the perspective of "phlegm, blood stasis, and toxin".

Methods

Twelve male New Zealand white rabbits were randomly divided into NC group and CAS group according to their body weight, followed by feeding of basic feed and a 1% high cholesterol diet, respectively. After two weeks, the rabbits in the CAS group underwent common carotid artery (CCA) balloon injury, while the rabbits in the NC group underwent only CCA separation without balloon injury. The two groups received differential feed postoperatively for six more weeks, after which, changes in lipids, hemorheology, inflammation, oxidative stress, and CAS phenotypes were analyzed. In addition, the colon contents and serum were collected for 16S rRNA sequencing and 1H-NMR metabonomic analysis.

Results

The CAS rabbits were observed to form noticeable abnormalities in lipid metabolism and blood rheology, a sharp increase in oxidative stress levels, excessive release of inflammatory factors and apparent CAS plaque formation. Furthermore, 10 specific gut microbiota (such as Akkermansia muciniphila, Barnesiellaceae and Faecalibacterium) and 14 characteristic metabolites (such as trimethylamine oxide, acetic acid and L-carnitine) were identified in the CAS rabbits, which were significantly related to the CAS phenotypes. The pathway function analysis showed that the gut microbiota and its metabolites mainly affected cholesterol metabolism, energy metabolism, inflammation and oxidative stress.

Conclusion

The rabbit CAS model conforms to the “phlegm, blood stasis and toxin damage” theory. The gut microbiota and host metabolic disorders of the CAS rabbits interact and promote internal and external toxins, aggravating the progression of CAS. Our study provided experimental evidence for the application of this model in the TCM-based research of CAS.

在中医理论中,“痰瘀毒”是颈动脉粥样硬化(CAS)的病机。高胆固醇饮食联合颈动脉球囊损伤诱发的家兔颈动脉粥样硬化(CAS)是研究颈动脉粥样硬化的经典模型。许多研究表明,肠道菌群和宿主代谢紊乱参与了兔CAS的发病机制。然而,这一经典兔CAS模型的中医病理特征和证候尚未见报道。目的从“痰、瘀、毒”的角度探讨兔CAS模型的病机及中医证型。方法将12只雄性新西兰大白兔按体重随机分为NC组和CAS组,分别饲喂基础饲料和1%高胆固醇饲粮。2周后,CAS组兔颈总动脉(CCA)球囊损伤,NC组兔颈总动脉仅分离,球囊未损伤。两组术后分别饲喂差异饲料6周以上,分析血脂、血液流变学、炎症、氧化应激和CAS表型的变化。收集结肠内容物和血清进行16S rRNA测序和1H-NMR代谢组学分析。结果观察到CAS家兔脂质代谢和血液流变学明显异常,氧化应激水平急剧升高,炎症因子过度释放,明显形成CAS斑块。此外,在CAS家兔中鉴定出10个特异性肠道菌群(如Akkermansia muciniphila、Barnesiellaceae和Faecalibacterium)和14个特征代谢物(如三甲胺氧化物、乙酸和左肉碱),它们与CAS表型显著相关。途径功能分析表明,肠道菌群及其代谢产物主要影响胆固醇代谢、能量代谢、炎症和氧化应激。结论家兔CAS模型符合“痰瘀毒损”理论。CAS家兔的肠道菌群与宿主代谢紊乱相互作用,促进内源性和外源性毒素,加重了CAS的进展。本研究为该模型在基于tcm的CAS研究中的应用提供了实验依据。
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引用次数: 0
Gypenoside, the Main Active Compound of Gynostemma pentaphyllum, Mitigates the Diabetic Nephropathy through Down-regulating mTOR 绞股蓝的主要活性化合物绞股蓝总皂苷通过下调mTOR减轻糖尿病肾病
Pub Date : 2023-06-01 DOI: 10.1016/j.ccmp.2022.100060
Chao Chen , Danqing Fu , Yuqian Wu , Chen Huang , Ping Huang

Background

Diabetic nephropathy (DN), as a complication of diabetes, is featured with hypertension, hyperglycemia, proteinuria and edema. Gypenoside (GP), the main active compound of Gynostemma pentaphyllum, is proved to be effective for DN. In our previous research, we found that GP could protect the glomerulus and reduce proteinuria by up-regulating the expression of nestin and down-regulating TGFB1. However, the panoramic mechanism of GP against DN is still unclear.

Objective

This research is designed to reveal the mechanism of GP on DN through network pharmacology and in vivo and in vitro experimental verification.

Methods

In this study, active compounds and targets of Gynostemma pentaphyllum were collected from TCMSP. DisGeNET was used for obtaining the targets of DN. The protein-protein interaction network was acquired from the STRING database and analyzed by the MCODE plugin. GO and KEGG enrichment analysis were constructed to explore further information. In vivo and in vitro experiments were also carried out to evaluate the reliability of this study. Western blotting and RT-PCR were used to detect mTOR, 4E-BP1, p70s6k protein expression and Mtor mRNA expression in DN rats, respectively. AKT1, TP53, ESR1 and PTEN protein expression in MPC-5 cells were detected by Western blotting.

Results

Twenty-four compounds and 217 targets were selected from Gynostemma pentaphyllum, of which 36 targets overlapped with DN were taken for the potential targets. The results showed that Quercetin, Rhamnazin, Isofucosterol and 3′-methyleriodictyol corresponded to more targets, AKT1, TP53, MYC, ESR1, PTEN were more active. 36 potential targets were mainly involved in autoimmunity, inflammatory response, metabolism and autophagy. In vivo and in vitro experiments showed that GP might protect the podocytes of DN rats by decreasing the protein expression of mTOR, 4EBP1, p70s6k, as well as the mRNA expression of Mtor, and it had the function in regulating the potential targets through decreasing the protein expression of AKT1, TP53 and ESR1 and increasing the expression of PTEN.

Conclusion

This research demonstrates that various compounds of Gynostemma pentaphyllum may intervenes in DN through targets of multiple signaling pathways, which involves a large number of biological processes. It can provide novel insights for further research of the mechanism of GP in the treatment of DN.

背景:糖尿病肾病(DN)是糖尿病的一种并发症,以高血压、高血糖、蛋白尿和水肿为特征。绞股蓝(Gynostemma pentaphyllum)的主要活性成分绞股蓝苷(Gypenoside, GP)对DN有一定的治疗作用。我们在前期研究中发现,GP通过上调nestin的表达,下调TGFB1的表达,起到保护肾小球、减少蛋白尿的作用。然而,GP对抗DN的全景机制尚不清楚。目的通过网络药理学和体内外实验验证,揭示GP对DN的作用机制。方法本研究从绞股蓝药材中提取绞股蓝的活性成分和靶点。使用DisGeNET获取DN的靶标。从STRING数据库中获取蛋白质-蛋白质相互作用网络,并使用MCODE插件进行分析。构建GO和KEGG富集分析以进一步探索信息。我们还进行了体内和体外实验来评估本研究的可靠性。采用Western blotting和RT-PCR分别检测DN大鼠mTOR、4E-BP1、p70s6k蛋白表达和mTOR mRNA表达。Western blotting检测MPC-5细胞中AKT1、TP53、ESR1和PTEN蛋白的表达。结果从绞绞线中筛选出24个化合物和217个靶点,其中36个与DN重叠的靶点为潜在靶点。结果显示槲皮素、鼠李糖苷、异花甾醇和3′-甲基戊二醇对应的靶点较多,AKT1、TP53、MYC、ESR1、PTEN活性较强。36个潜在靶点主要涉及自身免疫、炎症反应、代谢和自噬。体内和体外实验表明,GP可能通过降低mTOR、4EBP1、p70s6k的蛋白表达以及mTOR的mRNA表达来保护DN大鼠足细胞,并通过降低AKT1、TP53、ESR1的蛋白表达和增加PTEN的表达来调节潜在靶点。结论绞股蓝中多种化合物可能通过多种信号通路的靶点干预DN,涉及大量的生物学过程。为进一步研究GP治疗DN的机制提供了新的思路。
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引用次数: 1
The Anti-parasitic Effect of Extract of Ceiba pentandra (L.) Gaertn Is Related to Its Anti-inflammatory, Analgesic and Anthelmintic Activities on Haemonchus contortus 五角草提取物的抗寄生作用葛藤对屈血螨的抗炎、镇痛和驱虫作用有关
Pub Date : 2023-06-01 DOI: 10.1016/j.ccmp.2023.100088
Bogning Zangueu Calvin , Alowanou Goue Géorcelin , Belle Ebanda Kedi Phillipe , Olounlade Abiodoun Pascal , Magne Fongang Annie Laure , Kojom Wanche Jacquy Joyce , Nguemfo Edwige Laure , Azebaze Anatole Guy Blaise , Dongmo Alain Bertrand , Hounzangbe-Adote Mawulé Sylvie

Background

Ceiba pentandra is a medicinal plant used as alternative therapy to control parasitic nematodes in livestock.

Objective

This study aims to investigate anti-parasitic effect of aqueous stem back extract of Ceiba pentandra (L.) Gaertn through the evaluation of its anthelmintic, anti-inflammatory and analgesic activities.

Methods

In vitro, the efficacy of aqueous extract (75 to 2400 µg·mL−1) diluted in phosphate buffered saline (PBS) was tested against three stages of the life cycle of Haemonchus contortus through larval migration inhibition assay (LMIA), egg hatch assay (EHA), and adult worms motility inhibition assay (AMIA). In vivo, anti-inflammatory and antinociceptive properties of the aqueous extract (150 and 300 mg·kg−1) was evaluated on rodent using phlogistic and algic chemicals.

Results

Significant inhibition activity (P < 0.05) was obtained on EHA with the greatest inhibition of 46.63% obtained at 2400 µg·mL−1. The plant treatment dramatically (P < 0.05) inhibited L3 larval migration as compared to PBS. The highest inhibition rate was 53.33 % at 1200 µg·mL−1. Adding of polyvinylpolyrrolidone (PVPP) to the extract significantly (P < 0.01) reduced at 38.6% the activity of the plant extract on larval migration compared to extract without PVPP. The Ceiba pentandra extract reduced (P < 0.05) worm motility after 24 h post exposure as compared to control. In vitro, aqueous extract significantly (P < 0.05) inhibited the paw inflammation induced by carragenine, with a significant (P < 0.05) reduction of the number of abdominal contortions induced by acetic acid to 41.11% at 300 mg·kg−1 and the paw licking time induced by formaline in both phases to 57.22% and 63.59% at 300 mg·kg−1 likened to control.

Conclusions

In vitro results suggest that, this plant possess anti-parasitic properties. Antinociceptive and anti-inflammatory effects of C. pentandra can contribute to its anti- parasitic property.

研究背景五指草是一种药用植物,可作为控制家畜寄生线虫的替代疗法。目的本研究旨在通过评价绞股蓝茎背水提取物的驱虫、抗炎和镇痛活性,探讨其抗寄生虫作用。方法在体外,通过幼虫迁移抑制试验(LMIA)、卵孵化试验(EHA)和成虫运动抑制试验(AMIA),测试在磷酸盐缓冲盐水(PBS)中稀释的水提取物(75至2400µg·mL−1)对扭曲血蜱生命周期三个阶段的效力。在体内,使用消炎和止痛化学物质评估了水提取物(150和300 mg·kg−1)对啮齿动物的抗炎和镇痛性能。结果对EHA的抑制作用显著(P<0.05),2400µg·mL−1时抑制率最高,达46.63%。与PBS相比,植物处理显著地(P<0.05)抑制了L3幼虫的迁移。在1200µg·mL−1时,抑制率最高,为53.33%。与没有PVPP的提取物相比,向提取物中加入聚乙烯吡咯烷酮(PVPP)显著(P<0.01)降低了植物提取物对幼虫迁移的38.6%的活性。与对照相比,Ceiba pentandra提取物在暴露后24小时后降低了(P<;0.05)蠕虫运动性。在体外,水提取物显著(P<;0.05)抑制了角叉菜胶诱导的爪炎症,与对照组相比,在300mg·kg−1时,乙酸诱导的腹部扭曲次数显著(P>;0.05)减少到41.11%,在两个阶段,甲林诱导的舔爪时间分别减少到57.22%和63.59%。结论该植物具有一定的抗寄生特性。五ndra的抗伤害和抗炎作用有助于其抗寄生虫的特性。
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引用次数: 0
Evaluation of the Antidiabetic Activity and Toxicological Properties of Hippocratea Velutina (Afzel.) 海马抗糖尿病活性和毒理学特性的评价
Pub Date : 2023-06-01 DOI: 10.1016/j.ccmp.2023.100080
Farouk A. Oladoja , Emmanuel S. Irokosu , Marcus D. Ayoola , Oyinloye O. Elijah , Murtala A. Akanji , Ogunleye T. Beatrice , Odewo A. Samuel

Background

Hippocratea velutina (HV) is a novel plant folklorically used for lowering blood glucose, hence a potential source of new antidiabetic medication.

Objective

The study evaluated the anti-diabetic potentials of the methanol extract of Hippocratea velutina leaf and its toxicity profile in mice and rats.

Methods

Acute and subacute toxicity tests of the plant extract were carried out by using a modified OECD guideline. Its antidiabetic activity in streptozotocin-induced diabetic rats at 50, 150, and 300 mg/kg for 28 days was assayed, while glibenclamide (5 mg/kg) and distilled water were the positive and negative controls, respectively. Histopathological examination of vital organs was also carried out.

Results

Preliminary phytochemical screening of the leaf extract showed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, deoxy-sugars, and anthraquinones in HV. The extract had LD50 greater than 2000 mg/kg in mice. It had no toxic effects on the haematological and biochemical components from blood samples collected but caused significant blood glucose level reduction in normal rats at 150 and 300 mg/kg. In streptozotocin-induced diabetic rats, the extract elicited a non–dose-dependent antidiabetic effect on day seven at all the tested doses, significantly higher than glibenclamide (10 mg/kg). However, on days 14, 21, and 28, the extract activity at all the tested doses and glibenclamide were comparable. The extract did not affect the liver, brain, kidney, and pancreas histology at 200 mg/kg but caused slight and severe effects on these organs at 400 and 800 mg/kg, respectively.

Conclusion

The study concluded that Hippocratea velutina possessed antihyperglycaemic activity and was non-toxic at low doses but could have deleterious effects to the liver and kidney at high concentrations.

背景:海马尾草(hippocratea velutina, HV)是一种民间用于降血糖的新型植物,因此是一种潜在的新型降糖药物。目的研究海马尾叶甲醇提取物的抗糖尿病作用及其对小鼠和大鼠的毒性。方法采用经修订的OECD指南对该植物提取物进行急性和亚急性毒性试验。以格列本脲(5 mg/kg)和蒸馏水分别为阳性对照和阴性对照,观察其在链脲霉素诱导的糖尿病大鼠体内50、150和300 mg/kg剂量28 d的抗糖尿病活性。并对重要脏器进行组织病理学检查。结果经初步植物化学筛选,黄酮类、皂苷类、生物碱类、萜类、脱氧糖类和蒽醌类化合物均存在。该提取物对小鼠的LD50大于2000 mg/kg。它对采集的血液样本的血液学和生化成分没有毒性作用,但在150和300 mg/kg的正常大鼠中引起血糖水平显著降低。在链脲佐菌素诱导的糖尿病大鼠中,在所有测试剂量下,提取物在第7天产生非剂量依赖性的降糖作用,显著高于格列本脲(10 mg/kg)。然而,在第14、21和28天,所有测试剂量的提取物活性与格列本脲相当。当浓度为200 mg/kg时,对肝、脑、肾和胰腺组织无明显影响,而当浓度为400和800 mg/kg时,对肝、脑、肾和胰腺组织分别有轻微和严重影响。结论海马尾草具有抗高血糖活性,在低剂量下无毒,但在高浓度时可能对肝脏和肾脏产生有害作用。
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Clinical complementary medicine and pharmacology
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