In vitro inhibitory effects of palonosetron hydrochloride,bevacizumab and cyclophosphamide on purified paraoxonase-I (hPON1) from human serum

In this study, we investigated the effects of the drugs, palonosetron hydrochloride, bevacizumab and cyclophosphamide, on human serum paraoxonase-I (hPON1) enzyme activity in in vitro conditions. The enzyme was purified ∼231-fold with 34.2% yield by using ammonium sulphate precipitation, DEAE-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel-filtration chromatography from human serum. hPON1 exhibited a single protein band on the SDS polyacrylamide gel electrophoresis. The inhibition studies were performed on paraoxonase activity of palonosetron hydrochloride, bevacizumab and cyclophosphamide. K_i constants were found as 0.033 ± 0.001, 0.054 ± 0.003 mM and 3.419 ± 0.518 mM, respectively. Compared to the inhibition rates of the drugs, palonosetron hydrochloride has the maximum inhibition rate. However, inhibition mechanisms of the drugs were determined as noncompetitive by Lineweaver-Burk curves.     

The application of 2-NBDG as a fluorescent tracer for assessing hepatic glucose production in mice during hyperinsulinemic euglycemic clamp

Methods of performing insulin clamps vary between laboratories. Here we present a protocol of insulin clamping in conscious mice, with the significant advantage of avoiding multiple surgical catheterizations and non-physiologic metabolism during the induction of anesthesia. Using this technique we also established a new method for measuring hepatic glucose production (HGP) using a fluorescent d-glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose (2-NBDG). To prove the reliability and feasibility of this method, whole-body insulin sensitivity was compared between conscious normal ICR mice and diabetic KK^Ay mice using the insulin clamp. Basal and clamp HGP was compared between normal C57 mice and diabetic db/db mice by using the modified clamp with 2-NBDG as a tracer. The glucose infusion rate (GIR), an index of insulin sensitivity, was significantly lower in KK^Ay mice than normal ICR mice (6.2±1.3 mg/kg/min vs. 31.3±2.9 mg/kg/min, P<0.001). The db/db mice also showed higher basal hepatic glucose production (25.8±2.2 mg/kg/min vs. 16.7±2.5 mg/kg/min, P<0.05), higher clamp HGP after insulin suppression (7.3±1.0 mg/kg/min vs. 0 mg/kg/min, P<0.001), and lower GIR (71.6±2.8 mg/kg/min vs. 15.2±1.6 mg/kg/min, P<0.001) than that obtained with normal C57 mice. In conclusion, this is the first report of the application of 2-NBDG, rather than isotopic tracers, for the determination of HGP in vivo.     

Effect of calcium channel blockers on paraoxonase-1 (PON1) activity and oxidative stress

BackgroundIn this study, we investigated the in vitro effects of calcium channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1).MethodsPON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography.ResultsThe calcium channel blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors.ConclusionsOur results showed that calcium channel blockers exhibit inhibitory effects on PON1 at low concentrations. The IC₅₀ values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K_i constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.     

The opposite effects of nitric oxide donor,S‐nitrosoglutathione,on myocardial ischaemia/reperfusion injury in diabetic and non‐diabetic mice

Nitric oxide is a potent anti‐apoptotic and cardioprotective molecule in healthy animals. However, recent study demonstrates that overexpression of eNOS exacerbates the liver injury in diabetic animals. whether diabetes may also alter NO's biologic activity in ischaemic/reperfused heart remains unknown. The present experiment was designed to determine whether the nitric oxide donor, S‐nitrosoglutathione, may exert different effects on diabetic and non‐diabetic myocardial ischaemia/reperfusion (MI/R) injury. Diabetic state was induced in mice by multiple intraperitoneal injections of low‐dose streptozotocin (STZ). The control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours reperfusion. At 10 minutes before reperfusion, diabetic and non‐diabetic mice were received an intraperitoneal injection of S‐nitrosoglutathione (GSNO, a nitric oxide donor, 1 μmol/kg). GSNO attenuated MI/R injury in non‐diabetic mice, as measured by improved cardiac function, reduced infarct size and decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but, rather, aggravated the MI/R injury in diabetic mice. Mechanically, the diabetic heart exhibited an increased nitrative/oxidative stress level, as measured by peroxynitrite formation, compared with non‐diabetic mice. Co‐administration of GSNO with EUK134 (a peroxynitrite scavenger) or MnTE‐2‐PyP5 (a superoxide dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before reperfusion significantly decreased the MI/R‐induced peroxynitrite formation and the MI/R injury. Collectively, the present study for the first time demonstrated that diabetes may cause superoxide overproduction, increase NO inactivation and peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule to a cardiotoxic molecule.     

Preparation and preclinical evaluation of 131I‐trastuzumab for breast cancer

Trastuzumab that targets the human epidermal growth factor receptor type 2 (HER2) is known to benefit patients with HER2+ metastatic breast cancer. The objective was to explore the potential of ¹³¹I‐trastuzumab for treatment of breast cancers. Radioiodination of trastuzumab was carried out by chloramine‐T method, purified by using PD‐10 column, and characterized by size exclusion high‐performance liquid chromatography on a gel column. In vitro studies were carried out in HER2+ cells to determine the specificity of the radioimmunoconjugate. Uptake and retention of ¹³¹I‐trastuzumab were determined by biodistribution studies in tumor‐bearing non‐obese diabetic/severe combined immunodeficiency and normal severe combined immunodeficiency mice. The radiochemical purity (RCP) of ¹³¹I‐trastuzumab was 98 ± 0.4% with retention time of 17 minutes by high‐performance liquid chromatography. In vitro stability studies exhibited RCP of more than 90% in serum at 37°C after 120 hours of radioiodination. In vitro cell binding with ¹³¹I‐trastuzumab in HER2+ cells showed binding of 28% to 35% which was inhibited significantly, with unlabeled trastuzumab confirming its specificity. K_d value of ¹³¹I‐trastuzumab was 0.5 nM, while its immunoreactivity was more than 80%. Uptake of more than 12% and retention were observed in the tumors up to 120 hours p.i. ¹³¹I‐trastuzumab prepared in‐house‐exhibited RCP of more than 98%, excellent immunoreactivity, affinity to HER2+ cell lines and good tumor uptake thereby indicating its potential for further evaluation in HER2+ breast cancers.     

Exendin-4对非糖尿病小鼠的血糖和糖耐量的影响

目的:观察exendin4对非糖尿病小鼠的血糖和糖耐量的影响。方法:非糖尿病小鼠分为exendin4(Exe4)各剂量组和生理盐水(NS)组。腹腔内注射Exe40.1μg·g-1,观察注射1h后、连续注射10d期间和停药后2wk内血糖,并于停药后20d行腹腔葡萄糖耐量试验(IPGTT)。另外,非糖尿病小鼠每日注射不同剂量Exe40.1,0.2,0.4μg·g-1×3d,观察每日血糖。结果:非糖尿病小鼠注射Exe40.1μg·g-11h后血糖为(6.2±s1.3)mmol·L-1,低于NS组(10.6±1.1)mmol·L-1,P<0.01。连续注射Exe4期间的平均血糖以及停药后2wk内的平均血糖与NS组比较,均无明显差异,P>0.05;且IPGTT中2组各点血糖差异无显著意义,不同剂量Exe4注射组小鼠的3d平均血糖与NS组比较也无明显差别。结论:Exe4对非糖尿病小鼠的血糖具有即刻降低作用,但是每日1次腹腔内注射对非糖尿病小鼠的血糖和糖耐量无明显影响。     

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin–nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.     

Tetrodotoxin and paralytic shellfish poisons in gastropod species from Vietnam analyzed by high-performance liquid chromatography and liquid chromatography–tandem mass spectrometry

Among marine toxins, tetrodotoxin (TTX) and paralytic shellfish poisons (PSPs) are known as notorious neurotoxins that induce serious food poisoning incidents in the Southeast Asia region. The aim of this study was to investigate whether TTX and PSP toxins are important issues of seafood safety. Paralytic toxicity was observed in mice exposed to 34 specimens from five species of gastropods using a PSP bioassay. Five species of gastropods, Natica vitellus, Natica tumidus, Oliva hirasei, Oliva lignaria, and Oliva annulata, were collected from the coastal seawaters in Nha Trang City, Vietnam, between August 2007 and October 2007. The average lethal potency of gastropod specimens was 90 ± 40 (mean ± standard deviation) mouse units (MU) for N. vitellus, 64 ± 19 MU for N. tumidus, 42 ± 28 MU for O. hirasei, 51 ± 17 MU for O. lignaria, and 39 ± 18 MU for O. annulata. All toxic extracts from the sample species were clarified using a C18 Sep-Pak solid-phase extraction column and a microcentrifuge filter prior to analysis. High-performance liquid chromatography coupled with fluorescence detection indicated that the toxins of the olive shell (O. hirasei, O. lignaria, and O. annulata) were mainly composed of saxitoxin (STX) (73–82%), gonyautoxin (GTX) 2, 3 (12–22%), and minor levels of TTX (5–6%). The toxins of N. vitellus and N. tumidus were mainly composed of STX (76–81%) and GTX 1, 4 (19–24%). Furthermore, liquid chromatography–tandem mass spectrometry analysis was used to verify the identity of the PSPs and TTX. Our evidence shows that these gastropods have novel toxin profiles.     

Systematic Evaluation of Parameters Important for Production of Native Toxin A and Toxin B from Clostridioides difficile

In the attempt to improve the purification yield of native toxin A (TcdA) and toxin B (TcdB) from Clostridioides difficile (C. difficile), we systematically evaluated culture parameters for their influence on toxin production. In this study, we showed that culturing C. difficile in a tryptone-yeast extract medium buffered in PBS (pH 7.5) that contained 5 mM ZnCl₂ and 10 mM glucose supported the highest TcdB production, measured by the sandwich ELISA. These culture conditions were scalable into 5 L and 15 L dialysis tube cultures, and we were able to reach a TcdB concentration of 29.5 µg/mL of culture. Furthermore, we established a purification protocol for TcdA and TcdB using FPLC column chromatography, reaching purities of >99% for both toxins with a yield around 25% relative to the starting material. Finally, by screening the melting temperatures of TcdA and TcdB in various buffer conditions using differential scanning fluorimetry, we found optimal conditions for improving the protein stability during storage. The results of this study present a complete protocol for obtaining high amounts of highly purified native TcdA and TcdB from C. difficile.     

TAT-EGFP融合蛋白对小鼠生物膜穿透性的研究

探讨TAT-穿透生物膜的效应,为临床上应用生物大分子药物进入组织细胞内发挥治疗作用提供实验基础。按分子克隆常规操作构建pET28a-TAT-EGFP重组表达载体,转导入宿主菌BL21后用IPTG诱导TAT-EGFP融合蛋白表达,经镍金属鳌合层析柱纯化获得融合蛋白。通过腹腔注射到小鼠体内,观察TAT-EGFP融合蛋白穿透各组织生物膜及达到各组织的时间、浓度。腹腔注射TAT-EGFP,30 min后各主要脏器经检测均有荧光出现,4 h各组织荧光强度达最大值。证明在生物大分子的N-末端加上TAT具有穿透力的蛋白转导区肽段形成的融合蛋白可有效穿透细胞膜到达各组织。     

Pharmacokinetic performance of the nitrendipine intravenous submicron emulsion in rats

To compare pharmacokinetic behaviors of nitrendipine submicron emulsion with nitrendipine solution following intravenous administration in rats. The plasma concentrations were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry detection (UPLC–MS/MS) through a new validated method. The pharmacokinetic parameters of the nitrendipine submicron emulsion and nitrendipine solution were as follows: AUC_0–t 900.76 ± 186.59 versus 687.08 ± 66.24 ng h/ml, C_max 854.54 ± 159.48 versus 610.59 ± 235.99 ng/ml, t_1/2 2.37 ± 1.99 versus 2.80 ± 2.69 h. The relative bioavailability of nitrendipine submicron emulsion to nitrendipine solution was 131.4 ± 11.3%. The developed methods could meet the requirements of bioanalysis. Compared to the solution injection, intravenous submicron emulsion presents higher systematic exposure which can help to improve the therapeutic efficacy.     

CCN2 protein is an announcing marker for cardiac remodeling following STZ-induced moderate hyperglycemia in mice

Diabetes causes changes in the myocardium, which are often called diabetic cardiomyopathy. This condition has been extensively investigated in animal models with high glucose levels. Nevertheless, it has not been investigated whether moderate hyperglycemia, in the absence of other features of metabolic syndrome, may also cause similar changes in the heart. The aim of the study was to assess changes in the myocardium in an animal model of mild type 1 diabetes. Moderate hyperglycemia was induced in 8- to 10-week-old male C57BL6J mice by 5 intraperitoneal injections of streptozotocin (40 mg/kg). After 16 weeks, they were sacrificed, and left ventricle (LV) dimensions and extent of cardiac fibrosis were assessed by morphometry. The abundance of CCN proteins in LVsamples was assessed using western blotting, while activity of metalloproteinase 2 was established in zymography. Real time PCR was used to investigate the expression of transforming growth factor β1 (TGFβ1) and atrial natriuretic peptide. Mice with moderate hyperglycemia presented comparable cardiac dimensions with fibrosis and hypertrophy parameters as the non-diabetic controls. However, the abundance of profibrotic CCN2 protein was significantly increased in hyperglycemic animals (1.67 ± 0.28 vs. 1 ± 0.47, p < 0.05). Interestingly, this change was independent from the TGFβ1 expression, as its RNAabundance was similar in both groups. Moderate hyperglycemia also caused an increase in the activity of the metalloproteinase 2 (1.21 ± 0.17 vs. 1 ± 0.07, p < 0.05).Despite diabetes, no profound changes in cardiac morphology were found. In our animal model, moderate hyperglycemia caused activation of a profibrotic gene expression program, which was counterbalanced by the increase of metalloproteinase activity.     

麦芽糖注射液对2型糖尿病糖脂代谢和胰岛素分泌影响的研究

目的探讨麦芽糖注射液对2型糖尿病血糖、脂质代谢及胰岛素分泌的影响,并评价其供能的有效性。方法59例2型糖尿病患者随机分为麦牙糖组和氯化钠组,分别静脉输注10%麦芽糖注射液或0.9%氯化钠注射液各500 ml。观察输注前后血糖(BG)、血C肽、血游离脂肪酸(FFA)、血酮体、尿糖及尿酮变化。结果①麦芽糖组(A组)用药后1、2、3、5h静脉血糖均较用药前有所增加,其增量分别为(0.04±0.82)mmol/L、(0.39±1.19)mmol/L、(0.50±1.37)mmol/L、(0.14±1.24)mmo1/L,氯化钠组(B组)则较用药前有所下降,其血糖下降值各为(0.93±1.05)mmol/L、(1.12±1.05)mmol/L、(1.28±1.05)mmol/L、(1.66±1.20)mmol/L,两组比较差异有统计学意义(P<0.01);②两组用药后5 h内血浆游离脂肪酸(FFA)及血酮体均有下降,但氯化钠组下降不如麦芽糖果组明显,两组比较差异有统计学意义;③麦芽糖组用药后C肽及尿糖水平有所增加,尿酮治疗前后变化两组差异无统计学意义(P>0.05)。结论麦芽糖注射液用于2型糖尿病患者,在提供能量时未引起血、尿酮体升高,还能降低血FFA浓度,虽然开始治疗5h内血糖水平有所提高,但其升值幅度不大,故在监测血糖情况下,使用是安全的。     

Potential antidiabetic effect of the Semecarpus anacardium in a type 2 diabetic rat model

Semecarpus anacardium Linn. nut milk extract (SA) was evaluated for its antidiabetic role in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding high-fat diet for 2 weeks followed by single intraperitoneal injection of streptozotocin 35 mg/kg body weight. Diabetic rats were treated with SA orally at a dosage of 200 mg/kg body weight daily for 30 days. Metformin (500 mg/kg body weight, orally) was used as a reference drug. SA significantly (p < 0.05) reduced the blood glucose levels and decreased the levels of HbA1c and the glucose intolerance. SA treatment significantly (p < 0.05) decreased the increase in lipid profile. The levels of urea, uric acid and creatinine were restored to near normal levels when compared with control diabetic rats. The histopathological abnormalities were also found to be normalized after treatment with SA nut milk extract. The potential antihyperglycemic action of SA is plausibly due to its underlying antioxidant role.     

南瓜多糖的分离、纯化及其降血脂作用

目的 :研究南瓜多糖对正常及糖尿病模型小鼠血脂的影响。方法 :南瓜经甲醇回流、热水提取、弃蛋白、透析、乙醇沉淀 ,再经SephadexG1 0 0柱层析纯化 ,得南瓜多糖 (PP)。聚丙烯酰胺凝胶电泳证明其为均一体。PP的分子量为 1 .6× 1 0 4。经纸层析表明由D 葡萄糖、D 半乳糖、L 阿拉伯糖、木糖和D 葡萄糖醛酸组成。其摩尔比分别为 6∶3∶2∶1∶6。结果 :PP水溶液 2 0 0、5 0 0mg/kg经腹腔注入正常及糖尿病模型小鼠后 ,两者总胆固醇、低密度脂蛋白下降 ,高密度脂蛋白增加。结论 :PP是较理想的能改善脂类代谢的食疗剂。     

Antihyperglycemic,antihyperlipidemic and antioxidant activities of polysaccharides from Catathelasma ventricosum in streptozotocin-induced diabetic mice

It is the first time to extract polysaccharides (CVPs) from Catathelasma ventricosum. The antihyperglycemic and antioxidant activity of CVPs in streptozotocin-induced diabetic mice were examined. Compared with untreated diabetic mice, the administration of CVPs for 30 days caused a significant decrease in the concentrations of blood glucose, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C) and maleic dialdehyde (MDA), and a significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C) and the activities of antioxidant enzymes. Specially, when normal mice were treated with CVPs, all detection indexes and pathologic morphologies of liver, kidney and pancreas are similar to untreated normal mice, which indicated CVPs are safe for normal mice. In addition, the average molecular weight of CVPs was estimated to be from 3.7 × 10³ to 1.7 × 10⁷ Da and they were mainly composed of glucose (93.5%) with the conformation of α-d-Glucopyranose.     

重组人胰高血糖素样肽-1对实验性糖尿病大鼠血糖的影响

目的观察重组人胰高血糖素样肽 1[rhGLP 1(7 36 )NH2 和rhGLP 1(7 37) ]对实验性糖尿病大鼠模型血糖和血浆胰岛素水平的影响。方法正常SD大鼠按 3.2 4g/kg腹腔注射 5 0 %葡萄糖 ,诱发暂时性高血糖动物模型。腹腔注射不同剂量 (2 0、4 0、80 μg/kg)rhGLP 1(7 36 )NH2 和rhGLP 1(7 37) ,间隔取血测定血糖与血浆胰岛素水平。正常SD大鼠按 6 0mg/kg腹腔注射链脲佐菌素 ,建立实验性 1型糖尿病大鼠模型。静脉输注rhGLP 1(7 36 )NH2 [4.0ng/(kg·min) ]12 0min并观察血糖变化。结果腹腔注射 4 0、80 μg/kgrhGLP 1(7 36 )NH2 和rhGLP 1(7 37)处理组大鼠的血糖、血浆胰岛素水平与对照组之间的差别具有非常显著性意义 (P <0 .0 0 1) ,且呈现一定的量效关系。二者之间促胰岛素分泌和降血糖活性差异无显著性。静脉输注rhGLP 1(7 36 )NH2 6 0min后 ,血糖水平 (17.0 4± 1.31)mmol/L(P <0 .0 5 ) ,12 0min后血糖水平 (11.98± 1.0 5 )mmol/L(P <0 .0 0 1)。结论rhGLP 1能显著改善实验性糖尿病大鼠的血糖水平 ,这与其促胰岛素分泌活性有关。     

罗布麻提取物对STZ糖尿病大鼠肾损害的防护作用

本文探讨了罗布麻提取物 (AV) 对STZ大鼠糖尿病肾脏损害的防护作用及部分作用机制。采用链脲佐菌素 (STZ) 诱导大鼠糖尿病模型方法, 观察8周时大鼠血糖、肾功能、氧化应激等指标以及经AV治疗后的变化。结果显示, 糖尿病大鼠的血糖、血尿素氮、24 h尿蛋白含量、尿量、肾脏肥大指数、肾皮质MDA含量显著升高; 肾皮质SOD、GSH活性显著降低。AV干预治疗组的上述指标得到改善, 具有显著性差异。实验结果表明, AV对STZ大鼠糖尿病肾功能有明显的防护作用, 其作用可能与抑制肾脏氧化应激作用有关。     

The α-glucosidase inhibitory activity of avicularin and 4-O-methyl gallic acid isolated from Syzygium myrtifolium leaves

Diabetes Mellitus is the main cause of death on a global scale. In 2019, there were 463 million people with diabetes, and WHO predicts that by 2030, there will be 578 million. As an antidiabetic agent, α-glucosidase inhibitors are one of the methods employed to reduce the prevalence of diabetes. Diabetes is traditionally treated with Syzygium as a primary material, medicine, fruit, ornamental plant, and source of carpentry. This investigation aimed to examine the inhibitory effect of seven species of Syzygium against α-glucosidase enzyme using an in vitro assay and isolate active substances and ascertain their concentrations in each sample. As a solvent, ethanol was used in maceration to extract the substance. Afterward, the extract underwent a series of fractionation techniques, including liquid–liquid extraction, vacuum liquid chromatography, column chromatography, and preparative Thin Layer Chromatography (TLC) for purification and isolation. The compound's structures were elucidated using TLC, UV–Visible spectrophotometry, and nuclear magnetic resonance (NMR) spectroscopy. Based on concentrations of 100 and 200 µg/mL, Syzygium myrtifolium exhibited the most significant inhibitory effect, followed by other species of Syzygium. The proportion of ethyl acetate had the strongest activity (IC₅₀ 0.40 ± 0.02 µg/mL) contrasted to positive control acarbose (IC₅₀ 55.39 ± 0.67 g/mL) and quercitrin (IC₅₀ 6.47 ± 0.40 µg/mL). Avicularin and 4-O-methyl gallic acid were discovered in the ethyl acetate fraction of Syzygium myrtifolium with IC₅₀ values of 17.05 ± 0.75 µg/mL and 25.19 ± 0.21 µg/mL, respectively. As α-glucosidase inhibitory, the results of this study indicate Syzygium myrtifolium can be used as a dietary supplement to manage hyperglycemia.     

Antiarrhythmic effects and ionic mechanisms of allicin on myocardial injury of diabetic rats induced by streptozotocin

The aim of this study was to evaluate the antiarrhythmic effect of allicin (AL) on streptozotocin (STZ)-induced diabetic rats and explore the possible mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ treatment, the hyperglycemic rats (plasma glucose levels ≥16.7 mM) were administered with AL (4, 8, and 16 mg/kg) by intraperitoneal injection daily for 28 days. The fasting blood glucose levels were measured on every seventh day during the 28 days of treatment. The body weight and blood glucose levels were detected after 28 days. Antiarrhythmic effect of AL was observed in the diabetic rats induced by BaCl₂. To determine the ionic mechanism in rat ventricular myocytes of AL, action potential duration (APD), L-type calcium current (I_Ca-L), and inward rectifier potassium current (I_K1) were recorded by the whole cell-patch clamp technique. The expressions of L-type calcium channel protein α_1C mRNA and cell potassium channels protein Kir2.1 mRNA were studied by RT-PCR. AL normalized the RR interval and QT interval in diabetic rats. AL obviously delayed the onset of ventricular arrhythmia and reduced the score of arrhythmia induced by BaCl₂. Electrophysiological experiment revealed that AL could shorten APD through inhibition of I_Ca-L and enhancement of I_K1. RT-PCR analysis indicated that long-term treatment with AL could decrease the expression of α_1C mRNA and increase the expression of Kir2.1 mRNA. AL has antiarrhythmic effect in STZ-induced diabetic rats. It is tempting for the application of AL to be a useful therapeutic approach in diabetes with ventricular arrhythmia.