The Effects of Pycnogenol® as Add‐on Drug to Metformin Therapy in Diabetic Rats

The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio‐protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add‐on drug to metformin therapy in streptozotocin (STZ)‐induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin‐dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy. Copyright © 2016 John Wiley & Sons, Ltd.     

Inhibitory Effects of French Pine Bark Extract,Pycnogenol®, on Alveolar Bone Resorption and on the Osteoclast Differentiation

Pycnogenol^® (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non‐infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate‐resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1–100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis. Copyright © 2014 John Wiley & Sons, Ltd.     

Pycnogenol® in Metabolic Syndrome and Related Disorders

The present review provides an update of the biological actions of Pycnogenol® in the treatment of metabolic syndrome and related disorders such as obesity, dyslipidaemia, diabetes and hypertension. Pycnogenol® is a French maritime pine bark extract produced from the outer bark of Pinus pinaster Ait. Subsp. atlantica. Its strong antioxidant, antiinflammatory, endothelium‐dependent vasodilator activity, and also its anti‐thrombotic effects make it appropriate for targeting the multifaceted pathophysiology of metabolic syndrome. Clinical studies have shown that it can reduce blood glucose levels in people with diabetes, blood pressure in mild to moderate hypertensive patients, and waist circumference, and improve lipid profile, renal and endothelial functions in metabolic syndrome. This review highlights the pathophysiology of metabolic syndrome and related clinical research findings on the safety and efficacy of Pycnogenol®. The results of clinical research studies performed with Pycnogenol® are discussed using an evidence‐based, target‐oriented approach following the pathophysiology of individual components as well as in metabolic syndrome overall. Copyright © 2015 John Wiley & Sons, Ltd.     

Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen‐induced hepatotoxicity in rats

Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen‐induced acute liver injury in rats. The effect of PYC on acetaminophen‐induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. The best antioxidant properties were demonstrated in methanolic extracts. Seven‐day pretreatment with PYC suppressed elevation of CYP2E1 protein expression induced by administration of toxic dose of acetaminophen. PYC at 50 mg/kg showed the ability to significantly decrease malondialdehyde (MDA) level compared with the group received acetaminophen. Xanthine oxidase (XOD) enzyme activity was significantly elevated in acetaminophen‐treated group compared with control, whereas concomitant administration of PYC in a dose of 50 mg/kg significantly reduced activity of this enzyme. Significant decrease of glutathione (GSH) hepatic content in acetaminophen‐intoxicated rats compared with the control rats was improved by concomitant administration of PYC at 50 mg/kg. Protective effect of PYC on acetaminophen‐induced acute liver injury in rats has showed the best in vitro antioxidant potential expressed in methanolic extract and consequent histological assessment and oxidative status in liver homogenates.     

Improved effect of Pycnogenol® on impaired spatial memory function in partial androgen deficiency rat model

The improved effect of Pycnogenol^® on impaired spatial memory function was studied in orchidectomized rats. Endogenous testosterone levels were decreased by approximately one‐half for 3 months after castration. In the radial arm maze, castration significantly impaired working and reference memory function without lowering motor function. Pycnogenol^® increased the NGF content in the hippocampus and cortex, and improved the spatial memory impairment. These observations confirmed that diagnostic accuracy can be improved by Pycnogenol^® in androgen‐deficient rats. Copyright © 2009 John Wiley & Sons, Ltd.     

大蒜素对2型糖尿病大鼠氧化应激反应的影响

目的观察大蒜素对2型糖尿病大鼠氧化应激反应的影响,并探讨其发生机制。方法取健康雄性Wistar大鼠40只,随机分为正常组10只和糖尿病造模组30只。以高热量饮食+链脲佐茵素法建立糖尿病大鼠模型,将造模成功的26只再随机分为2组,即单纯糖尿病组13只,糖尿病+大蒜素组13只。糖尿病+大蒜素组喂高脂高糖饲料加大蒜素3周。测定大鼠FPG、血清XOD、SOD、MDA和TNF-α、CRP、PAI-1及IL-6水平的变化,观察大蒜素对2型糖尿病大鼠氧化应激反应的干预作用。结果与正常组比较,糖尿病大鼠空腹血糖升高,血浆SOD活性降低而MDA、XOD含量增加,血浆TNF-α、PAI-1及IL-6水平升高,均具有显著性差异(P0.05或0.01)。服用大蒜素后,空腹血糖的升高、血浆SOD的减少和MDA、XOD含量的增加均受到一定程度抑制,血浆TNF-α、PAI-1及IL-6水平也有所降低,具有显著性差异(P0.05或0.01)。结论大蒜素对2型糖尿病大鼠有一定降血糖效应,其机制可能是通过抗氧化、抑制炎症反应而减轻氧化应激损伤的程度。     

黄连素对2型糖尿病神经病变大鼠神经传导速度的影响

目的观察不同剂量的黄连素(Ber)对2型糖尿病周围神经病变(DPN)大鼠空腹血糖(FBG)、痛阈及神经传导速度(NCV)的影响。方法采用高脂高果糖饲料喂养1个月再用小剂量链脲佐菌素(STZ)诱导的方法建立2型DPN大鼠模型,将实验动物随机分为4组。正常对照组不予任何处理,DPN对照组予磷酸盐缓冲液(PBS)1 mL/kg,低剂量组和高剂量组分别给予Ber 100 mg/kg、187.5 mg/kg灌胃,整个治疗持续8周。用血糖仪测FBG,用热板法测定大鼠痛阈,用BL-420生物功能信号采集记录系统测定NCV。结果低剂量组、高剂量组的FBG均较DPN对照组明显降低(P均<0.05),而DPN对照组大鼠FBG则维持在高血糖水平。DPN对照组大鼠痛阈值明显降低(P<0.05),而高剂量组的痛阈值较DPN对照组显著升高(P<0.01)。两剂量组均可加快NCV,高剂量组对NCV有更加显著的改善(P<0.001)。在用Ber治疗的后期能使明显消瘦的大鼠体质量回升。结论Ber可明显降低2型DPN大鼠的FBG,且大剂量Ber对2型DPN大鼠的周围神经病变有明显的改善作用。     

施今墨对药配方对2型糖尿病大鼠氧化应激的影响

目的 观察施今墨对药配方对2型糖尿病大鼠血糖、游离脂肪酸(FFA)和氧化应激的影响,初步探讨其作用机制.方法 随机选取6只Wistar大鼠作为正常组,余44只采用高脂高糖饲养+腹腔注射链脲佐菌素(35 mg/kg)方法制备2型糖尿病大鼠模型,将造模成功大鼠随机分为模型组、二甲双胍组及施今墨对药配方高、中、低剂量组,二甲...     

瑞格列奈对2型糖尿病胰岛素分泌和氧化应激作用的研究

目的研究瑞格列奈对2型糖尿病胰岛素分泌和氧化应激的作用。方法将80例2型糖尿病患者随机分成2组:治疗组42例口服瑞格列奈,同时辅以饮食控制或二甲双胍口服;对照组38例单用饮食控制或二甲双胍口服。治疗2个月后,抽肘静脉血查胰岛素分泌时相(FPIS和SPIS)、血清丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果瑞格列奈只增加FPIS而不影响SPIS和总胰岛素分泌;治疗组治疗后血清MDA含量降低(P<0.05),血清SOD活性显著增加(P<0.001)。结论瑞格列奈只增加FPIS,可良好控制餐后血糖,显著改善氧化应激指标。     

瑞格列奈对2型糖尿病胰岛素分泌和氧化应激作用的研究

目的研究瑞格列奈对2型糖尿病胰岛素分泌和氧化应激的作用。方法将80例2型糖尿病患者随机分成2组：治疗组42例口服瑞格列奈，同时辅以饮食控制或二甲双胍口服；对照组38例单用饮食控制或二甲双胍口服。治疗2个月后，抽肘静脉血查胰岛素分泌时相（FPIS和SPIS）、血清丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性。结果瑞格列奈只增加FPIS而不影响SPIS和总胰岛素分泌；治疗组治疗后血清MDA含量降低（P〈0．05），血清SOD活性显著增加（P〈0．001）。结论瑞格列奈只增加FPIS，可良好控制餐后血糖，显著改善氧化应激指标。     

Ameliorative Effects of Pine Bark Extract on Spermatotoxicity by α‐Chlorohydrin in Rats

We investigated the protective effects of pine bark extract (Pycnogenol®, PYC, Horphag Research Ltd., Route de Belis, France) against α‐chlorohydrin (ACH)‐induced spermatotoxicity in rats. Rats were orally administered ACH (30 mg/kg/day) with or without PYC (20 mg/kg/day) for 7 days. Administration of ACH significantly decreased sperm motility. α‐Chlorohydrin also caused histopathological alterations and apoptotic changes in caput epididymides. An increased malondialdehyde concentration and decreased glutathione content, as well as catalase and glutathione peroxidase activities were also found. In contrast, PYC treatment significantly prevented ACH‐induced spermatotoxicity, including decreased sperm motility, histopathological lesions, and apoptotic changes in the caput epididymis. Pycnogenol® also had an antioxidant benefit by decreasing malondialdehyde and increasing levels of the antioxidant glutathione and the activities of the antioxidant enzymes catalase and peroxidase in epididymal tissues. These results indicate that PYC treatment attenuated ACH‐induced spermatotoxicity through antioxidant and antiapoptotic effects. Copyright © 2013 John Wiley & Sons, Ltd.     

Effect of Cichorium intybus seeds supplementation on the markers of glycemic control,oxidative stress,inflammation, and lipid profile in type 2 diabetes mellitus: A randomized,double‐blind placebo study

Diabetes mellitus is associated with increased levels of inflammation and oxidative stress in patients. The aim of the present study was to test the hypothesis that aqueous extract of Cichorium intybus seeds (AECIS) would have add‐on beneficial effect in type 2 diabetes mellitus (T2DM). In this double‐blind randomized clinical study, 150 subjects were enrolled to assess the add‐on efficacy and safety of AECIS in T2DM patients. The subjects were randomized (1:1) to the AECIS (n = 51) and placebo (n = 49) groups. The subjects in both groups continued to take prescribed doses of metformin. The standardization of AECIS was carried out by liquid chromatography–mass spectrometry and phytochemical analysis. The mean hemoglobin A1c (HbA1c) level in the AECIS and placebo groups at baseline was 8.6% and 8.5%, respectively. Mean values of HbA1c at the end of 12 weeks of intervention were 7.42% in the AECIS group (a reduction of 1.18% from baseline) and 8.4% in the placebo group (mean reduction of 0.1% from baseline). Besides, significant reduction in inflammation, oxidative stress, and hypertriglyceridemia was seen in the AECIS group (p < .05). The study shows for the first time that AECIS supplementation ameliorates the disease progression and it is beneficial as a potential adjunct dietary supplement for the management of T2DM.     

糖末宁对糖尿病大鼠神经传导速度和红细胞山梨醇的影响

目的:观察中药复方糖末宁对糖尿病大鼠神经传导速度、红细胞山梨醇(RBC-S)含量等指标的影响,探讨其防治糖尿病周围神经病变的机制.方法:采用链脲佐菌素糖尿病大鼠模型,给予糖末宁灌胃(2.95、5 90、11.80g·kg-1,i.g)连续3周,以甲钴胺作为阳性对照组,并设正常对照组及模型对照组,观察治疗前后对糖尿病大鼠神经传导速度、RBC-S含量的影响.结果:糖末宁治疗后,与模型组和治疗前相比,中剂量组和大剂量组对尾神经传导速度减慢有显著增加作用(P＜0.05);治疗后,糖末宁及甲钴胺组RBC-S含量明显下降(P＜0.01),中剂量组RBC-S含量低于模型组(P＜0.05).结论:糖末宁对糖尿病神经病变的治疗作用,可能与纠正多元醇代谢异常作用有关.     

慢性应激对实验性2型糖尿病倾向大鼠血浆去甲肾上臁素、肾上腺素含量影响的实验研究

[目的]从糖尿病多因素致病角度出发,探讨情志因素对2型糖尿病发病的作用机制——气机失调证,以及具有理气降逆散结功效的复方中药心身5号方的调节作用。【方法】采用旋转、拥挤、限制3种情志刺激结合腹腔注射少量链脲佐菌素（s眩）的实验方法,制作了2型糖尿病倾向大鼠模型,实验动物分为正常组、应激组、STZ组、应激＋STZ组和中药组。检测血浆去甲肾上腺素（NE）、肾上腺素（E）含量,同时观察具有理气降逆散结功效的复方中药心身5号方的调节作用。【结果】慢性情志应激可促使STZ鼠血浆NE、E含量升高,其中肾上腺素在应激＋STZ组有极显著性差异（P〈0．01）,中药可降低血浆E含量。【结论】慢性情志刺激引起实验性2型糖尿病倾向大鼠血浆NE、E含量升高是糖尿病发病机制之一,同时具有理气降逆散结功效的复方中药心身5号方有明显调节作用。     

Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat

The effect of chronic silymarin (SM) treatment on hyperalgesia, sciatic motor nerve conduction velocity (MNCV) and oxidative stress in streptozotocin (STZ)‐diabetic neuropathic rat was evaluated. Rats were divided into control, diabetic, SM‐treated control and diabetic, and sodium salisylate (SS)‐treated control and diabetic. SM was administered daily at a dose of 100 mg/kg for two months. Finally, hyperalgesia and sciatic MNCV and oxidative stress markers were assessed. Diabetic rats showed a significant deficit in MNCV and markedly exhibited chemical and thermal hyperalgesia, indicating development of diabetic neuropathy. Antioxidant enzyme superoxide dismutase (SOD) level significantly reduced and malondialdehyde (MDA) level significantly increased in diabetic rats compared to control rats; SM treatment significantly ameliorated the alteration in MNCV, hyperalgesia, MDA level and antioxidant enzyme SOD in diabetic rats. These results clearly suggest the potential effect of SM in prevention and treatment of diabetic neuropathy. Copyright © 2009 John Wiley & Sons, Ltd.     

糖络宁对STZ诱导糖尿病大鼠坐骨神经传导速度及病理学的影响

目的:观察中药复方糖络宁对糖尿病大鼠坐骨神经传导速度及病理的影响。方法:采用链脲佐菌素糖尿病大鼠模型,造模成功后随机分为模型组、西药组、糖络宁高、中、低剂量组给药,共给药12周,给药结束后,观察糖络宁对糖尿病大鼠坐骨神经传导速度及病理的影响。结果:组间比较,与正常组比较,模型组在2、4、8、12周时的神经传导速度均有明显减慢(P<0.01);与模型组比较,西药组在4、8、12周可以明显改善神经传导速度(P<0.05或P<0.01);与模型组比较,低、中、高剂量组在各周均能明显改善神经传导速度的作用(P<0.05或P<0.01);与西药组比较,高剂量组在12周时有更加明显的改善效果(P<0.05)。与模型组比较,各用药组的神经纤维变性及断裂均明显减少,其中中剂量组改善最为明显,神经纤维断裂及变性均很少,基本恢复至正常组水平;其次是低剂量组与高剂量组;最后是西药组,虽然与模型组比较有所改善,但仍出现不少神经断裂及变性;结论:糖络宁可以有效提高糖尿病大鼠坐骨神经传导速度,改善神经病理形态学改变。     

慢性应激对实验性2型糖尿病倾向大鼠血浆去甲肾上腺素、肾上腺素含量影响的实验研究

[目的]从糖尿病多因素致病角度出发,探讨情志因素对2型糖尿病发病的作用机制——气机失调证,以及具有理气降逆散结功效的复方中药心身5号方的调节作用.[方法]采用旋转、拥挤、限制3种情志刺激结合腹腔注射少量链脲佐菌素(STZ)的实验方法,制作了2型糖尿病倾向大鼠模型,实验动物分为正常组、应激组、STZ组、应激+STZ组和中药组.检测血浆去甲肾上腺素(NE)、肾上腺素(E)含量,同时观察具有理气降逆散结功效的复方中药心身5号方的调节作用.[结果]慢性情志应激可促使STZ鼠血浆NE、E含量升高,其中肾上腺素在应激+STZ组有极显著性差异(P＜0.01),中药可降低血浆E含量.[结论]慢性情志刺激引起实验性2型糖尿病倾向大鼠血浆NE、E含量升高是糖尿病发病机制之一,同时具有理气降逆散结功效的复方中药心身5号方有明显调节作用.     

黄芪桂枝五物汤对奥沙利铂周围神经毒性大鼠神经传导速度的影响

目的探讨黄芪桂枝五物汤对奥沙利铂周围神经毒性大鼠坐骨神经传导速度的影响。方法将120只健康雌性W istar大鼠随机分成正常组（n=21）、模型组（n=24）、治疗组（n=24）、预防组（n=27）、防治组（n=24）,除正常组外,其余各组予以腹腔注射奥沙利铂（5m l/kg）造模。按不同分组用药干预治疗10天,分别观察造模后24h、48h及72h大鼠的一般情况并利用神经电生理仪检测坐骨神经传导速度、潜伏期、波幅等。结果与正常组比较,造模后24h,各组间大鼠神经传导速度、潜伏期无明显差异（P〉0.05）;造模后48h,模型组大鼠坐骨神经传导速度减慢、潜伏期延长,差异有统计学意义（P〈0.05）;造模后72h,模型组及治疗组大鼠神经传导速度减慢、潜伏期延长,差异有统计学意义（P〈0.05）。与模型组比较,造模后72h,预防组及防治组的的传导速度明显变快、潜伏期变短,且有显著差异（P〈0.05）。与预防组比较,造模后72h模型组与治疗组大鼠神经传导速度明显减慢、潜伏期延长,且有显著差异（P〈0.05）。结论在奥沙利铂治疗前运用黄芪桂枝五物汤能提高坐骨神经传导速度,缩短病变持续时间。     

Diuretic and antioxidant effects of Cacti‐Nea®, a dehydrated water extract from prickly pear fruit,in rats

Dehydrated extract of the prickly pear fruit Opuntia ficus indica, Cacti‐Nea^®, was evaluated for its chronic diuretic and antioxidant effects in Wistar rats. Cacti‐Nea^® was orally administered daily for seven days at the dose of 240 mg/kg/day. A positive group was orally treated with hydrochlorothiazide at the dose of 10 mg/kg/day and a control group with vehicle. Daily measurements of body weight, urine volume, and concentration of sodium, potassium and uric acid in urine were performed for each rat. At the end of the study, the blood globular level of glutathione peroxidase was determined. Cacti‐Nea^® significantly increased the urine volumes excreted by rats in comparison with the control group and it showed a trend to reduce significantly the body weight gain of rats. No significant differences were observed in the urine concentration of sodium, potassium and uric acid in comparison with the control group. The chronic diuretic effects of Cacti‐Nea^® were comparable with that of the standard drug hydrochlorothiazide. Chronic oral administration of Cacti‐Nea^® significantly increased the blood globular levels of glutathione peroxidase in comparison with control and hydrochlorothiazide groups. The prickly pear fruit extract Cacti‐Nea^® demonstrated chronic diuretic and antioxidant effects in Wistar rats with respect to the excretion of the metabolites. Copyright © 2009 John Wiley & Sons, Ltd.     

仙灵脾对2型糖尿病大鼠尿蛋白的影响

目的探讨仙灵脾对2型糖尿病(T2DM)大鼠肾脏的保护作用及作用机制。方法高脂高糖饲料加小剂量链脲佐菌素建立T2DM大鼠模型。将大鼠随机分为正常对照组(n=10)、模型组(n=16)、仙灵脾组(n=16)和二甲双胍组(n=12);8周处死大鼠,取血、尿、肾标本,检测血糖、肾功能、肾脏指数、TG、TC及24 h尿蛋白水平。结果与模型组比较,仙灵脾组的肾脏指数和24 h尿蛋白水平均明显降低(P均<0.05)。结论仙灵脾可能对糖尿病大鼠的肾脏有保护作用。