Fruit of the jambolan tree (Eugenia jambolana Lam.) and experimental diabetes

The fruit of Indian Eugenia jambolana have been shown to have therapeutic properties, but because the therapeutic potential of a plant is related to the geographic region in which the plant was grown and to the part of the plant used, we investigated Brazilian Eugenia jambolana fruit using the same preparation and experimental methods as have been used in India. The well-established metabolic cage model was used to evaluate the physiological and metabolic parameters associated with streptozotocin-induced diabetes in rats (n=10) which had been administered, by gavage, 50 mg per day of lyophilised Eugenia jambolana fruit-pulp extract for 41 days. We found that, compared to untreated controls, rats treated with the lyophilised fruit-pulp showed no observable difference in body weight, food or water intake, urine volume, glycaemia, urinary urea and glucose, hepatic glycogen, or on serum levels of total cholesterol, HDL cholesterol or triglycerides. No change was observed in the masses of epididymal or retroperitoneal adipose tissue or of soleus or extensor digitorum longus muscles. This lack of any apparent effect on the diabetes may be attributable to the regional ecosystem where the fruit was collected and/or to the severity of the induced diabetes.     

Anti-hyperglycemic effect of Eugenia jambolana and Tinospora cordifolia in experimental diabetes and their effects on key metabolic enzymes involved in carbohydrate metabolism

In India, the decoction of kernels of Eugenia jambolana (EJ) and extracts of Tinospora cordifolia (TC) are used as a household remedy for diabetes. These also form constituents of many herbal formulations for diabetes that are marketed in this country. The anti-hyperglycemic effect of aqueous and alcoholic extracts as well as lyophilized powder of these two plants was evaluated in diabetic animals using different doses of diabetogenic agents for varying duration (21-120 days) so as to assess their effect in mild (plasma sugar>180 mg/dl, duration 21 days), moderate (plasma sugar>280 mg/dl, duration 120 days) and severe (plasma sugar>400 mg/dl, duration 60 days) diabetes mellitus. In the pilot study (mild diabetes), maximum reduction of 73.51 and 70.37% in glucose levels was seen in animals receiving 200 mg/kg per day of lyophilized powder of EJ and 400 mg/kg per day of aqueous extract of TC after 3 and 15 weeks of treatment, respectively. There percent reduction in glucose decreased significantly in the moderate and severe diabetes; 55.62 and 17.72% for EJ and 48.81 and 0% for TC at the similar time intervals. The alteration in hepatic and skeletal muscle glycogen content and hepatic glucokinase, hexokinase, glucose-6-phosphate and phosphofructokinase levels in diabetic mice were partially restored by EJ but not by TC. The mechanism of action of EJ and TC is discussed.     

Antifertility effect in male rats of oleanolic acid, a triterpene from Eugenia jambolana flowers

The antifertility activity of oleanolic acid (C30H48O3), isolated from the flowers of Eugenia jambolana, was evaluated in male albino rats. The administration of the compound for 60 days decreased the fertilizing capacity of the animals without any significant changes in body weight or reproductive organ weights. The compound produced arrest of spermatogenesis but did not cause any abnormality to spermatogenic cells, Leydig interstitial cells and Sertoli cells. Oleanolic acid may prove to be a promising antifertility agent devoid of undesirable side effects.     

Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits

The hypoglycaemic and hypolipidemic effect of ethanolic extract obtained from seeds of E. jambolana was investigated in alloxan-induced diabetic rabbits. Hypoglycaemic activity was assessed by reduction in fasting blood glucose (FBG) at 90min and also fall in peak blood glucose during glucose tolerance test (GTT) in sub-diabetic and mild diabetic (MD) rabbits, but in severe diabetic (SD) rabbits by reduction in FBG at 90min. Ethanolic extract (100mg/kg body weight) when given orally to sub-diabetic (AR) for 1 day, MD for 7 days and SD for 15 days showed significant fall in FBG at 90min (12% AR, 18.9% MD and 29% SD) and also produced 16.9% fall in peak blood glucose in AR and 21% in MD rabbits during GTT. When administered daily for 15 days to MD and SD rabbits, significant fall in FBG (41.3% MD, 31.6% SD) and glycosylated haemoglobin (GHb) levels (23.3% MD, 26.6% SD) were observed, while serum insulin level showed significant increase (32.8% MD, 26.9% SD). Liver and muscle glycogen content also increased. The ethanolic extract of seeds also exhibited significant hypolipidemic effect as evident from fall in total serum cholesterol (TC)/high density lipoprotein cholesterol (HDL-c) ratio, serum low density lipoprotein cholesterol (LDL-c) levels and decreased activity of HMG-CoA reductase. The histopathological studies of liver, pancreas and aorta in alcoholic extract treated diabetic groups revealed almost normal appearance.     

Effect of Crude Extract of Eugenia jambolana Lam. on Human Cytochrome P450 Enzymes

The fruit of Eugenia jambolana Lam. is very popular for its anti‐diabetic property. Previous studies on the crude extract of E. jambolana (EJE) have successfully explored the scientific basis for some of its traditional medicinal uses. Considering its wide use and consumption as a seasonal fruit, the present study investigates the ability of E. jambolana to interact with cytochrome P450 enzymes. The standardized EJE was incubated with pooled human liver microsomes to assess the CYP2C9‐, CYP2D6‐, and CYP3A4‐mediated metabolism of diclofenac, dextromethorphan, and testosterone, respectively. The metabolites formed after the enzymatic reactions were quantified by high performance liquid chromatography. EJE showed differential effect on cytochrome P450 activities with an order of inhibitory potential as CYP2C9 > CYP3A4 > CYP2D6 having IC₅₀ of 76.69, 359.02, and 493.05 µg/mL, respectively. The selectivity of EJE for CYP2C9 rather than CYP3A4 and CYP2D6 led to perform the enzyme kinetics to explicate the mechanism underlying the inhibition of CYP2C9‐mediated diclofenac 4′‐hydroxylation. EJE was notably potent in inhibiting the reaction in a non‐competitive manner with K_i of 84.85 ± 5.27 µg/mL. The results revealed the CYP2C9 inhibitory potential of EJE with lower K_i value suggesting that EJE should be examined for its potential pharmacokinetic and pharmacodynamic interactions when concomitantly administered with other drugs. Copyright © 2014 John Wiley & Sons, Ltd.     

Treatment with extracts of Momordica charantia and Eugenia jambolana prevents hyperglycemia and hyperinsulinemia in fructose fed rats

Insulin resistance has been implicated as a major contributor to the development of hyperglycemia in NIIDM patients. Herbal extracts of Momordica charantia (MC) and Eugenia jambolana (EJ) have been shown to reduce hyperglycemia in diabetic animal models and human patients. However, no work has been done so far to assess their effect on insulin resistance. This study was undertaken to study the effects of different doses (100,200 and 400 mg per day) of alcoholic and aqueous extracts of MC and EJ on the metabolic parameters (body weight and serum glucose, insulin and triglycerides levels) of fructose fed rats. Fructose feeding for 15 days increased serum glucose and insulin levels markedly and triglycerides levels marginally vs. control (75.46+/-2.41 vs. 55.59+/-2.89 mg/dl, 6.26+/-1.27 vs. 15.04+/-2.43 mg/dl and 50.93+/-3.30 vs.41.1+/-3.33 mg/dl, respectively). Treatment with 400 mg per day of aqueous extracts of MC and EJ for 15 days substantially prevented hyperglycemia and hyperinsulinemia induced by a diet high in fructose (63.52+/-2.9 and 66.46+/-2.2 vs. 75.46+/-2.4, respectively).     

红参对糖尿病视网膜神经节细胞的神经保护作用

目的通过观察糖尿病(diabetes mellitus,DM)大鼠视网膜神经节细胞(retinal ganglion cells,RGCs)凋亡及对凋亡相关基因和神经营养因子表达的检测,探讨红参对RGCs的神经保护作用.方法链脲佐菌素诱导实验性DM大鼠模型.治疗组每日红参粉末灌胃给药1次.TUNEL法检测RGCs凋亡并记数RGCs凋亡数量.LSAB法检测bcl-2、Bax、bFGF在RGCs层的表达,图象分析仪检测免疫组化的显色强度并进行定量分析.结果DM大鼠RGCs凋亡数量显著增加,治疗组RGCs凋亡数量明显减少.LSAB法标记染色的bcl-2、Bax、bFGF在DM大鼠视网膜RGCs层表达增强,bcl-2、bFGF在治疗组表达增强,Bax表达减弱.bcl-2、bFGF表达与RGCs凋亡数呈负相关,Bax表达与RGCs凋亡数呈正相关.结论红参能促进bcl-2和bFGF的表达,抑制bax的表达,减少DM RGCs的凋亡,对RGCs具有神经保护作用.     

实验性糖尿病动物模型的建立

糖尿病是一种具有遗传倾向的葡萄糖代谢和内分泌障碍继而引起全身性代谢紊乱的临床综合征。目前建立糖尿病动物模型的方法很多，但由于种种原因成功率以及重复率并不是很高，为糖尿病的研究造成很大困难，为此笔者2002年3—11月在糖尿病的动物模型方面做了大量的实验，经反复摸索，找到了成功率高、重复性强的造模方法，现报道如下。     

实验性衰老糖尿病大鼠模型研究

目的:进行人工诱导衰老糖尿病大鼠模型的初筛。方法:选用Wistar雌性大鼠,采用腹腔注射D-半乳糖后,给予不同周期高脂高糖饲料喂养,再配以不同剂量的链脲佐菌素(STZ)素腹腔注射,制备模型大鼠。检测空腹血糖(FBG)、超氧化物歧化酶(SOD)、丙二醛(MDA),并取胰腺组织行HE染色常规病理切片,以初筛实验性衰老糖尿病大鼠模型。结果:①各组成模率之间差异无显著性;②衰老糖尿病各组大鼠FBG升高,SOD下降,MDA升高;③胰腺病理切片显示:衰老糖尿病各组胰岛细胞团为正常对照组的22.93%-44.51%(P0.01),且胰岛边界不清,岛内细胞排列不规则,细胞空泡化,细胞数目明显减少。结论:①不同造模法均可达到较高成模率。②采用腹腔注射D-半乳糖42d+高脂高糖6周+腹腔注射STZ(25mg/体质量.体表面积,2次)法所构建的实验性衰老糖尿病模型较为理想。     

Antihyperglycemic and hypolipidemic activity of aqueous extract of Cassia auriculata L. leaves in experimental diabetes

Ethnopharmacological relevance

Cassia auriculata L. (Caesalpiniaceae) is widely used from ancient period to treat diabetes mellitus. The leaves of Cassia auriculata are having potential in the development of drug for diabetes due to its antihyperglycemic and lipid-lowering activity.

Aim of the study

The present study was to evaluate antihyperglycemic and hypolipidemic activity of aqueous extract of Cassia auriculata leaves (CLEt) in streptozotocin (STZ)-induced mild diabetic (MD) and severe diabetic (SD) rats.

Materials and methods

Male Albino rats were rendered diabetic by STZ (45 mg/kg, intraperitoneally). CLEt was orally administered to MD and SD rats at 100, 200 and 400 mg/kg doses for 1 day to determine antihyperglycemic activity. The 400 mg/kg dose was administered daily for 3 weeks to assess glycemic control and hypolipidemic effect.

Results

CLEt showed dose dependant fall in fasting blood glucose (FBG). After 5 h of extract administration at 400 mg/kg dose, FBG was reduced by 13.9% and 17.4% in MD and SD rats respectively. After 3 weeks treatment, CLEt produced significant reduction in FBG and glycosylated haemoglobin (GHb) in both MD and SD rats. Serum lipid levels were reversed towards normal in extract fed MD and SD rats.

Conclusions

The results demonstrate that CLEt possesses potent antihyperglycemic and hypolipidemic activity in both MD and SD rats.     

Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats

The antihyperglycemic action of puerarin, purified from the roots of Pueraria lobata, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Bolus intravenous injection of puerarin decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Similar treatment with puerarin also decreased the plasma glucose in normal rats, although the effect was not as great as that in STZ-diabetic rats. Puerarin at the effective dose (15.0 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. In the isolated soleus muscle of STZ-diabetic rats, puerarin enhanced the uptake of radioactive glucose in a concentration-dependent manner. Moreover, the mRNA and protein levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle were increased after repeated intravenous administration of puerarin in STZ-diabetic rats for 3 days. These results suggest that puerarin can increase the glucose utilization to lower plasma glucose in diabetic rats lacking insulin.     

Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats

The antihyperglycemic effect of syringaldehyde (1), purified from the stems of Hibiscus taiwanensis, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) showing type-1 like diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 7.2 mg/kg of 1 attenuated significantly the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. A glucose uptake test showed that 1 exhibits an increase of glucose uptake activity in a concentration-related manner. Moreover, an effect by 1 was shown for insulin sensitivity in STZ-diabetic rats. The compound was found to increase insulin sensitivity in STZ-diabetic rats. These results suggest that syringaldehyde (1) can increase glucose utilization and insulin sensitivity to lower plasma glucose in diabetic rats.     

克糖症治疗2型糖尿病的临床观察

目的 :观察克糖症治疗 2型糖尿病的临床疗效。方法 :治疗组予克糖症水煎液 5 0 m L/次 ,分别于早、晚饭前半小时服用 ,治疗 3个月 ;对照组予一般口服降糖药物治疗。结果 :克糖症能有效改善疲软乏力等临床症状 ,降低餐后 2小时血糖水平 ,抗血管内皮氧化损伤 ,调节血管舒缩功能。结论 :克糖症具有较好的防治糖尿病及其血管并发症的作用。     

糖尿病石斛合剂序贯法的初步临床观察

目的：探索临床2型糖尿病中医药序贯疗法,为临床推广应用提供中西医结合理论和实践依据。方法：选用临床确诊的2型糖尿病患者经饮食、运动和口服降糖西药控制不良,且中医辨证属阴虚热盛、气阴两虚者为研究对象,加服石斛合剂序贯1、2、3方,每次循环后复查临床中医证候、空腹血糖（FBG）、餐后血糖（2hBG）、甘油三酯（TG）、总胆固醇（TC）、血压（BP）,2次循环后加测糖化血红蛋白（HbAlc）。结果：石斛合剂序贯疗法可明显改善2型糖尿病阴虚热盛、气阴两虚证者燥热、烦渴、盗汗等临床症状,且所有患者治疗后HbAlc和FBG或2hBG较治疗前至少下降10%以上,HOMA-IR、TC、TG、Bp均明显改善,与治疗前比较P均〈0.01。结论：2型糖尿病属本虚（阴虚气虚）标实（热瘀浊）疾病。石斛合剂序贯疗法（滋阴清热、益气活血,清肝泄浊）不仅可有效改善患者临床症状体征,而且具有显著降低患者血糖,改善血压、调整血脂作用,方法简单易行便于临床推广应用。     

Prevention of chemically induced diabetes mellitus in experimental animals by virgin argan oil

The argan tree plays an important socioeconomic and ecologic role in South Morocco. Moreover, there is much evidence for the beneficial effects of virgin argan oil (VAO) on human health. Thus, this study investigated whether administering VAO to rats can prevent the development of diabetes. VAO extracted by a traditional method from the almonds of Argania spinosa (2 mL/kg) was administered orally (for 7 consecutive days) to rats before and during intraperitoneal alloxan administration (75 mg/kg for 5 consecutive days). An alloxan diabetic‐induced untreated group and treated by table oil were used as control groups. Body mass, blood glucose and hepatic glycogen were evaluated. In the present study, subchronic treatment with VAO at a dose of 2 mL/kg, before the experimental induction of diabetes, prevented the body mass loss, induced a significant reduction of blood glucose and a significant increase of hepatic glycogen level (p < 0.001) compared with the untreated diabetic group. In conclusion, the present study shows that argan oil should be further investigated in a human study to clarify its possible role in reducing weight loss in diabetics, and even in inhibiting the development or progression of diabetes. This antidiabetic effect could be due to the richness of VAO in tocopherols, phenolic compounds and unsaturated fatty acids. Copyright © 2011 John Wiley & Sons, Ltd.     

罗格列酮治疗2型糖尿病疗效观察

目的观察胰岛素增敏剂马来酸罗格列酮(RSG)对2型糖尿病(T2DM)患者血糖、血压、血脂和胰岛素抵抗(IR)的影响,并检测治疗前后血清脂联素水平的变化。方法用计算机随机双盲法比较58例T2DM患者日服RSG 4 mg和安慰剂(1∶1)干预治疗12周后血糖、血脂、血压、IR、血清脂联素水平改变。结果罗格列酮治疗12周后,空腹血糖和餐后2 h(2 hPG)血糖、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、HOMA模型IR指数(HOMA-IR)、收缩压(SBP)、舒张压(DBP)、血清总胆固醇(TC)、三酰甘油(TG)均较治疗前降低(P<0.01和0.05);血清脂联素水平显著升高(P<0.01)。上述指标与安慰剂组比较均有显著性差异(P<0.05或0.01)。结论RSG可改善T2DM患者的血糖、血脂代谢,降低IR,降低血压并升高血清脂联素水平,有助于防治T2DM的血管并发症。     

针刺对NIDDM大鼠作用的形态学观察

目的 :探讨针刺对非胰岛素依赖型糖尿病 (NIDDM)大鼠胰岛素B细胞形态的影响。方法 :采用生化、放免等技术观察针刺对NIDDM大鼠空腹血糖 (FBS)、空腹胰岛素 (FINS)、C -肽 (C -P)、胰岛素敏感性指数 (IAI)的变化 ,同时用电子显微镜观察针刺对NIDDM大鼠胰岛B细胞形态学的改变。结果 :NIDDM大鼠B细胞体积增大 ,内分泌颗粒增多 ,苍白颗粒减少 ,芯颗粒与分泌颗粒的面积之比也明显增多 ,可见胰岛外分泌细胞可化生B细胞。针刺治疗后NIDDM大鼠FBS ,FINS ,C -P均显著下降 ,而IAI显著回升。与此同时 ,上述形态学的异常均出现逆转。结论 :上述变化是针刺治疗NIDDM良好效应的形态学依据     

Hypoglycemic effect of Opuntia ficus indica in non insulin-dependent diabetes mellitus patients

To assess whether Opuntia ficus indica stems, or their crude preparations have hypoglycemic effects, 8 patients with non insulin-dependent diabetes mellitus (NIDDM) were studied. Four different tests were carried out on each patient following the oral intake of 500 g of O. ficus indica. These were either: entire broiled; blended broiled; blended crude or blended crude and heated at 60°C. A control test was performed in each patient as well. Serum glucose levels were measured at 0, 30, 60, 120 and 180 min. Glycemia decreased in all the patients following ingestion of O. ficus indica, and reached statistically significant levels after 120 and 180 min (p < 0.01). The major hypoglycemic effect shown after O. ficus indica administration ranged from 23.3 ± 4.4 to 25.4 ± 14.3 mg/dL (mean ± SD) below the glucose levels at 0 min. No statistical differences in the hypoglycemic effects were observed between the Opuntia ficus indica preparations. Opuntia ficus indica exerts hypoglycemic effects in NIDDM patients independent of its heating or blending during preparation.     

Antihyperglycemic and antioxidative effects of a herbal formulation of Radix Astragali,Radix Codonopsis and Cortex Lycii in a mouse model of type 2 diabetes mellitus

There is emerging evidence that the generation of reactive oxygen species (ROS), which leads to dysfunction of pancreatic β‐cells, is a major factor in the development of type 2 diabetes mellitus. Antioxidation is one of the therapeutic strategies to overwhelm the imbalance in ROS production. In this study, a herbal formulation SR10, comprising Radix Astragali, Radix Codonopsis and Cortex Lycii, was examined for its antidiabetic and antioxidative effects using the diabetic +db/+db mouse model. The results showed that SR10 was effective in decreasing the blood glucose level in chronic treatment by improving β‐cell function. The activities and expression of antioxidant enzymes, catalase and superoxide dismutase, were up‐regulated when treated with SR10. Moreover, SR10 treatment did not exhibit any toxic effect to the host. Copyright © 2008 John Wiley & Sons, Ltd.