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.     

Antidiabetic effect of total flavonoids from Sanguis draxonis in type 2 diabetic rats

Ethnopharmacological relevance

Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated ( 33 and 37), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats.

Materials and methods

T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35 mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200 mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF.

Results

SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP).

Conclusions

This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF.     

Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats

Ethnopharmacological relevance

The seed of Entada phaseoloides (L.) Merr. (Entada phaseoloides) has been long used as an effective herb for the treatment of Diabetes mellitus by Dai people, one of the Chinese ethnic minorities. Saponin is an abundant type of secondary metabolic products in the seed of this plant. The aim of this study is to evaluate the potential therapeutic effects of total saponins from Entada phaseoloides (TSEP) in experimental type 2 Diabetes mellitus (T2DM) rats.

Materials and methods

T2DM rats were induced by high-fat diet and low-dose streptozotocin (STZ). Then different oral doses of TSEP (25, 50 and 100 mg/kg) were administrated to T2DM rats for 21 days. For comparison, a standard antidiabetic drug, metformin (200 mg/kg), was used as a positive control drug. Then the relative biochemical analysis and histopathological examination were made to evaluate the antidiabetic effect of TSEP.

Results

TSEP dramatically reduced fasted blood glucose and serum insulin levels and alleviates hyperglycemia associated oxidative stress in T2DM rats. Moreover, a significantly hypolipidemic effect and an improvement in tissue steatosis could be observed after TSEP administration. Further investigations revealed a possible anti-inflammation effect of TSEP by examining serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). The effects of TSEP exhibited a dose-dependent manner and were comparable to metformin.

Conclusion

Our present study demonstrates both hypoglycemic and hypolipidemic activities of TSEP in T2DM rats, which support its antidiabetic property. This work also implies a possibility that TSEP exerts its therapeutic effect through repressing chronic inflammation responses.     

The leaf and seed aqueous extract of Phyllanthus amarus improves insulin resistance diabetes in experimental animal studies

Ethnopharmacological relevance

Amongst the Yoruba tribe (Southwest Nigeria), water decoction of the leaf and seed of Phyllanthus amarus Schum. and Thonn. is reputably used for the local management of diabetes mellitus, obesity and hyperlipidemia.

Aim of the study

The present study seeks to evaluate the effectiveness and elucidate mechanism(s) of action of the aqueous leaf and seed extract of Phyllanthus amarus (PAE) in normal and 10% sucrose-induced hyperglycemia and dyslipidemia as an experimental model of insulin resistance diabetes mellitus.

Materials and methods

In this study, the repeated oral antihyperglycemic action of 150–600 mg/kg/day of PAE was evaluated in normal and 10% sucrose-induced insulin resistance rats using indicators such as fasting blood glucose (FBG), insulin and insulin resistance indices. The extract's weight losing, antihyperlipidemic and anti-atherogenic effects were also evaluated by measuring the effect of the extract on the body weight, plasma levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and atherogenic indices.

Results

In normal rats, PAE caused significant (p<0.05, p<0.01 and p<0.001) and dose related decreases in body weight, FBG, TG, TC, LDL-c, and atherogenic indices. Repeated oral treatment with 10% sucrose drink for 30 days was associated with significant (p<0.001) weight gain, hyperglycemia, insulin resistance indices, hyperlipidemia and atherogenic indices. However, pre-treatment with PAE significantly (p<0.05, p<0.01 and p<0.001) and dose-dependently attenuated increase in any of these measured parameters.

Conclusions

Overall, results of this study showed PAE to effectively control insulin resistance DM which was mediated via improvement in insulin resistance, thus, validating its ethnomedical use in the local management of DM.     

Pharmacological characterization of different fractions of Calotropis procera (Asclepiadaceae) in streptozotocin induced experimental model of diabetic neuropathy

Ethnopharmacological relevance

Calotropis procera (Ait.) R.Br. is one of an ancient traditional shrub, which has been used for the treatment of diabetes, pain and inflammation for thousands of years in India. The root extract of Calotropis procera has been widely used by the tribal?s of district Udaipur, Rajasthan (India) for treatment of diabetes mellitus and its associated complications like diabetic neuropathy. The present study was performed to explore the protective effect of root, stem and leaf extracts of Calotropis procera in diabetes and diabetic neuropathy against tactile allodynia, mechanical hyperalgesia and thermal hyperalgesia in streptozotocin induced diabetic rats.

Materials and methods

Diabetes and peripheral neuropathy were induced in Wistar rats by injection of streptozotocin (45 mg/kg/intraperitoneally). The roots, stem and leaves of Calotropis procera were sequentially extracted with petroleum ether, chloroform, ethyl acetate and methanol. All the extracts were assessed by oral administration at 100 and 250 mg/kg in streptozotocin diabetic rats. The following compounds were used as positive controls: insulin NPH (1 IU/kg/day), metformin (500 mg/kg/day), glibenclamide (2.5 mg/kg/day) and a combination of acarbose (20 mg/kg/day) with methylcobalamine (500 µg/kg/day). In contrast, the streptozotocin induced untreated diabetic rats termed as negative control. Thermal hyperalgesia, mechanical hyperalgesia and tactile allodynia were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy by Eddy?s hot plate, tail immersion, Randall–Selitto and Von Frey hair tests. The basal nociceptive thresholds were assessed in week 4 of post streptozotocin injection. All groups received their treatment on a regular basis from 28 to 42 days following a confirmation of diabetic neuropathy. The nociceptive thresholds were assessed in all groups in week 5 and 6. The histopathology of pancreas and biochemical estimations of plasma insulin and glycosylated haemoglobin (HbA₁C%) levels were also performed in week 6 of post streptozotocin injection.

Results

The negative control rats developed diabetes and diabetic neuropathy after 6 week of streptozotocin administration distinguished by significant (p<0.01) hyperalgesia and tactile allodynia with enhanced HbA₁C% level compared to normoglycemic rats. Chronic administration of root methanol, stem methanol and leaf ethyl-acetate extracts of Calotropis procera for 2 weeks at 100 and 250 mg/kg doses significantly (p<0.01) attenuated the diabetes induced mechanical hyperalgesia, thermal hyperalgesia, tactile allodynia and HbA₁C% level in streptozotocin diabetic rats as compared to negative control rats. Further, the root methanol extract of Calotropis procera in 100 mg/kg dose showed the regeneration capability of β cells in the histology of pancreas with significant (p<0.01) improvement in plasma insulin level in streptozotocin diabetic rats compared to negative control rats.

Conclusion

Root methanol extract of Calotropis procera (100 mg/kg) has shown ameliorative effect in diabetic neuropathy which may be attributed by its multiple actions including potent hypoglycemic and antioxidant.     

Evaluation of hypoglycemic activity of total lignans from Fructus Arctii in the spontaneously diabetic Goto-Kakizaki rats

Ethnopharmacological relevance

Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity.

Materials and methods

Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50 mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated.

Results

TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats.

Conclusion

The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.     

Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats

Ethnopharmacological relevance

The use of an aqueous extract of coriander (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan traditional treatment of diabetes remains to be experimentally validated.

Aim of the study

The study aim was to investigate potential hypoglycemic (and hypolipidemic) activity of CS-extract after a single oral dose and after daily dosing for 30 days (sub-chronic study) in normal and obese-hyperglycemic-hyperlipidemic (OHH) Meriones shawi rats.

Materials and methods

After a single oral dose of CS-extract (20 mg/kg; predetermined as optimum), plasma glucose, insulin, total cholesterol (TC), and triglycerides (TG) were measured in normal and OHH rats (hypercaloric diet and forced limited physical activity); glibenclamide (GLB; 2.5 mg/kg) was used as reference. In the sub-chronic study, the effect of CS-extract and GLB (at the above doses) on body weight (BW), plasma glucose, insulin, TC, LDL-cholesterol, HDL-cholesterol, TG, urea and creatinine was determined in normal and OHH rats; insulin resistance (IR as HOMA-IR), atherosclerotic and cardioprotective indices were calculated.

Results

A single dose of CS-extract or GLB suppressed hyperglycemia in OHH rats, and normo-glycemia was achieved at 6-h post-dose; there was no effect on lipids, TG or insulin, but IR decreased significantly. The hypoglycemic effect was lower in normal rats. In the sub-chronic study in OHH rats, the test substances (CS-extract > GLB) reduced plasma glucose (normoglycemia on Day 21), insulin and IR, TC, LDL-cholesterol, and TG. Atherosclerotic index decreased while cardioprotective indices increased only by CS-extract, with no effect on BW, urea or creatinine.

Conclusion

Sub-chronic administration of CS-extract in OHH Meriones shawi rats normalized glycemia and decreased the elevated levels of insulin, IR, TC, LDL-cholesterol and TG. Since, the CS-extract decreased several components of the metabolic syndrome and decreased atherosclerotic and increased cardioprotective indices, CS-extract may have cardiovascular protective effect. The present study validates the traditional use of coriander in diabetes.     

Further evaluation of antihyperglycaemic activity of Hunteria umbellata (K. Schum) Hallier f. seed extract in experimental diabetes

Ethnopharmacological relevance

In African traditional medicine, water decoction made from the dry seeds of Hunteria umbellata (K. Schum) Hallier f. is highly valued in the management of diabetes mellitus.

Aim

In the present study, the antihyperglycaemic activity of the seed aqueous extract of Hunteria umbellate (K. Schum) Hallier f. (HU) was investigated in alloxan-induced, high fructose- and dexamethasone-induced hyperglycaemic rats.

Materials and methods

Alloxan-induced, dexamethasone-induced and high fructose-induced hyperglycaemic rats were treated with single, daily oral administration of 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in Groups III, IV, V and VI, for 14 days, 21 days and 8 weeks, respectively. The effects of these drugs on FBG, free plasma insulin levels, HbA_1c, serum TG and TC, and insulin resistance indices were investigated.

Results

Data generated in the current study showed that glibenclamide and graded oral doses of HU caused significant dose related (p < 0.05, <0.01 and <0.001) reductions in FBG when compared to the values obtained for the model control (Group II) rats. Similarly, daily oral administration of 66.7 g/kg fructose to rats for 8 weeks was associated with significant (p < 0.001) hyperglycaemia, elevations in plasma HbA_1c, free insulin, fasting insulin resistance indices, serum TG, and cholesterol. However, concomitant oral treatments with 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg, and 200 mg/kg of HU extract significantly and dose dependently (p < 0.05, <0.01 and <0.001) attenuated development of hyperglycaemia, decreased levels of plasma HbA_1c, free insulin, and serum triglyceride and cholesterol, in the Groups III, IV, V and VI rats, respectively, when compared to fructose-induced hyperglycaemic (Group II) rats. Similar effect was also recorded in the dexamethasone-induced hyperglycaemic rats.

Conclusion

Results of this study suggest that the hypoglycaemic and antihyperlipidaemic effects of HU are mediated via enhanced peripheral glucose uptake and improvements in hyperinsulinaemia.     

Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats

Ethnopharmacological relevance

Berberis aristata DC root is used in traditional medicine for a number of ailments including metabolic disorders.

Aim of the study

The aim of the present study was to explore the antihyperglycemic and antioxidant potential of 50% aqueous ethanolic root extract of Berberis aristata (BA) in alloxan induced diabetic rats.

Materials and methods

BA root extract (250 mg/kg) was administered to diabetic rats and standard drug glybenclamide (0.6 mg/kg) to group serving as positive control. Effect of extract on antioxidant and carbohydrate metabolism regulating enzymes of liver was studied in diabetic rats along with its safety parameters.

Results

The main constituents of root were identified as berberine, berbamine and palmatine through HPTLC. The extract besides being safe, lowered the blood glucose significantly without any hypoglycemic effect on their control counterparts. It increased CAT, SOD, GPx, GR activity significantly and reduced lipid peroxidation (41.6%) and protein carbonylation (30.15%). It also increased the glucokinase and glucose-6-phosphate dehydrogenase activities and decreased glucose-6-phosphatase activity in diabetic rats which play a critical role in glucose homeostasis.

Conclusion

Thus, the extract of Berberis sristata (root) has strong potential to regulate glucose homeostasis through decreased gluconeogenesis and oxidative stress.     

Anti-obesity and antihyperlipidaemic effect of Hunteria umbellata seed extract in experimental hyperlipidaemia

Aim of the study

In Nigerian folk medicine, water infusion of the dried seeds of Hunteria umbellata (K. Schum.) Hallier f. has a reputation for the local management of obesity and hyperlipidaemia. The present study is aimed at evaluating the anti-obesity and antihyperlipidaemic activities as well as the underlying mechanisms of action of the aqueous seed extract of Hunteria umbellata (HU) in normal, triton-induced, and olive oil-induced hyperlipidaemic rats.

Materials and methods

Normal and olive oil-induced hyperlipidaemic, and triton-induced hyperlipidaemic rats were pre-treated with single, daily oral administration of 10 ml/kg of distilled water, 20 mg/kg of simvastatin, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in 10 ml/kg of distilled water for 28 days and 24 h. The effects of these drugs on % body weight change, feeding pattern, serum lipids, coronary artery risk index (CRI) and atherogenic index (AI) and Lee's index (LI) were investigated.

Results

Oral pre-treatment with simvastatin and graded oral doses of HU significantly (p < 0.05) reduced the weight gain pattern and caused dose related (p < 0.05, p < 0.01 and p < 0.001) reductions in the serum lipids, CRI, AI and LI. Also, HU pre-treatment significantly improved triton-induced hepatic histological lesions.

Conclusions

Results of this study showed that HU has both anti-obesity and antihyperlipidaemic effects which may partly be mediated via inhibition of intestinal lipid absorption and de novo biosynthesis of cholesterol. Thus, the results justify the ethnopharmacological use of the extract in the management of obesity and hyperlipidaemia.     

The hypoglycemic activity of Lithocarpus polystachyus Rehd. leaves in the experimental hyperglycemic rats

Ethnopharmacological relevance

Leaves of Lithocarpus polystachyus Rehd. are used for the treatment of disorders such as diabetes, hypertension, and epilepsy in folk medicine of South China. The possible antidiabetic effects of the leaves were investigated in experimental type 2 and type 1 diabetic rats.

Materials and methods

Type 2 diabetic rats received orally three different extracts of Lithocarpus polystachyus Rehd. leaves for 4 weeks (aqueous extract [ST-1], ethanol extract [ST-2], flavonoid-rich fraction [ST-3]). At the end of the experiment biochemical parameters were tested and livers and pancreases were excised for histological study. After the comparison of the pharmacological test results of the three extracts, the one which showed the best bioactivity was further studied to confirm its antidiabetes effect on both type 2 and type 1 diabetic rats.

Results

Compared to ST-1 and ST-2, ST-3 had better effects on regulation of blood glucose, glycosylated serum protein, cholesterol, triglyceride, malondialdehyde, superoxide dismutase and attenuation of liver injury in type 2 diabetic rats (p < 0.01 or p < 0.05). ST-3 administration for four weeks also significantly reduced the fasting serum insulin and C-peptide level and improved the insulin tolerance (p < 0.05). In type 1 diabetic rats, ST-3 supplement for three weeks caused significant reduction in fasting blood glucose, total cholesterol, triglyceride, urea nitrogen, creatinine and liver mass, along with significantly inhibiting the decline of insulin level compared to diabetic control (p < 0.05 or p < 0.01).

Conclusion

The flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves (ST-3) had better beneficial effect than that of the ethanol or aqueous extract in experimental diabetic rats, which means that the bioactivity of the herbal leaves is probably due to the presence of flavonoids. The results also strongly suggest that the antidiabetic effect of ST-3 was possibly through multiple mechanisms of action including blood lipid and antioxidant mediation. The results indicated that the aqueous flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves possessed significant protective activity in type 2 and type 1 diabetes.     

Isolation and characterization of a novel antihyperglycemic protein from the fruits of Momordica cymbalaria

Aim of the study

A new antihyperglycemic protein was identified in the aqueous extract of fruits of Momordica cymbalaria by bioassay-guided fractionation. The study was aimed at isolation and characterization of this protein.

Materials and methods

The active principle was purified to homogeneity by ammonium sulphate precipitation, gel filtration column chromatography on Sephadex G-50 followed by reverse phase HPLC. Its N-terminal amino acid sequence was identified and compared in the protein data bank. Optimum dose and route of administration of the active principle was determined in STZ induced diabetic rats.

Results

A 17 kDa protein with an isoelectric point of 5.0 was identified as the active principle of antidiabetic action present in the aqueous extract of fruits of MC. It is named as M.Cy protein and found to be a novel protein by comparing its N-terminal amino acid sequence with those in the protein data bank. It did not produce any hypoglycemia in either normal or diabetic rats.

Conclusions

The results suggest that ‘M.Cy protein’, present in the fruits of Momordica cymbalaria is an effective antihyperglycemic active principle in STZ induced diabetic rats at a dose of 2.5 mg/kg b.w.     

Costus spicatus tea failed to improve diabetic progression in C57BLKS/J db/db mice,a model of type 2 diabetes mellitus

Aim of the study

Costus spicatus Sw. (Costaceae) is a prominent medicinal herb used by Dominicans in the Dominican Republic and the United States for the treatment of diabetes, a growing epidemic in the Hispanic community. An ethnobotanical survey of the Dominican community in New York City revealed the popular use of a tea from the insulina plant to treat hyperglycemia. Insulina was identified as Costus spicatus. We tested the ability of a tea made from the leaves of Costus spicatus to alter glucose homeostasis in C57BLKS/J (KS) db/db mice, a model of obesity-induced hyperglycemia with progressive beta cell depletion.

Materials and methods

From 6 to 16 weeks of age, Experimental and Control animals (n = 6/5) were given ad lib access to Costus spicatus tea or water, respectively.

Results

Weight gain and progression of hyperglycemia and insulinopenia between the Experimental and Control groups were statistically indistinguishable. There was no difference between groups in average fed or fasting glucose and insulin concentrations. Intraperitoneal (IP) insulin tolerance testing after the 10-week study period showed that Costus spicatus tea consumption did not alter insulin sensitivity.

Conclusions

These data suggest that at the dose given, tea made from Costus spicatus leaves had no efficacy in the treatment of obesity-induced hyperglycemia. More investigation is needed to more fully explore dosages and the possible utility and biological activity of this common Dominican herbal remedy for the treatment of type 2 diabetes mellitus.     

Antihyperglycemic,antihyperlipidemic and antioxidant effects of ethanol and aqueous extracts of Cyclocarya paliurus leaves in type 2 diabetic rats

Ethnopharmacological relevance

Cyclocarya paliurus (CP) Batal., the sole species in its genus and native to China, is a herbal tea, which has been traditionally used in the folk medicine for the treatment of diabetes and hyperlipidemia in China. To evaluate the antihyperglycemic, antihyperlipidemic and antioxidant effects of ethanol and aqueous extracts from CP in high fat diet (HFD) and streptozotocin (STZ) induced diabetic rats.

Materials and methods

Type 2 diabetes was induced in 140 rats by feeding with HFD and high sugar water for 6 weeks and single injection of STZ (30 mg/kg, intraperitoneally). CP ethanol extract (CPEE) and aqueous extract (CPAE) at three doses at 2, 4 and 8 g/kg/day were orally administered once daily for four weeks. Blood glucose, serum insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), low density lipoprotein–cholesterol (LDL–C), high density lipoprotein–cholesterol (HDL–C), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), blood urea nitrogen (BUN), creatinine (CREA) and glycated serum protein (GSP) were examined. The content of total flavonoids and polysaccharides in CPEE and CPAE were assayed by ultraviolet spectrophotometry.

Results

Both CPEE and CPAE increased OGTT, ITT, HDL–C, SOD and GSH-Px, while they decreased FFA, TC, TG, LDL–C, MDA, BUN, CREA and GSP. The amount of total flavonoids was found in CPEE (30.41 mg/g extract), followed by CPAE (6.75 mg/g extract). Similarly, the polysaccharides content (4.13 mg/g extract) was observed in CPAE, while absent in CPEE.

Conclusions

The results suggested that CPEE and CPAE exhibited the similar antihyperglycemic, antihyperlipidemic and antioxidant effects in type 2 diabetic rats, and there were no significant differences between these two extracts.     

Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells

Ethnopharmacological relevance

Traditional Mongolian medicine (TMM) uses preparations from herbs as one form of medication for the treatment of a diversity of diseases including diabetes mellitus (DM). We evaluated the effect of extracts from the plant Leonurus sibiricus L. (LS), used in TMM to treat typical symptoms of type 2 DM, on insulin secretion, electrophysiological properties, intracellular calcium concentration and cell proliferation of INS-1E insulinoma cells under standard cell culture conditions (SCC; 11.1 mM glucose).

Materials and methods

Insulin secretion was measured by ELISA, electrical properties were assessed by whole cell patch clamping, intracellular calcium concentration (Ca_i) by Fluo-4 time lapse imaging, insulin receptor expression was verified by RT-PCR and cell proliferation assessed by CellTiter-Glo® cell viability assay.

Results

Insulin released from INS-1E cells into the culture medium over 24 h was significantly increased in presence of 500 mg/L aqueous LS extract (LS OWE) as well as methanolic LS extract (LS MeOH/H2O) but not in the presence of the butanol-soluble extract (LS MeOH/BuOH). Acute application of LS OWE resulted in a depolarization of the cell membrane potential paralleled by an initial increase and subsequent decline and silencing of action potential frequency, by KATP channel inhibition, persisting depolarization and an increase in Ca_i. The electrophysiological effects were comparable to those of 100 μM tolbutamide, which, however failed to elevate insulin secretion under SCC. Furthermore all LS extracts stimulated INS-1E cell proliferation.

Conclusions

The finding that extracts from Leonurus sibiricus L. enhance insulin secretion and/or foster cell proliferation may provide possible explanations for the underlying therapeutic principles in the empirical use of LS-containing formulations in DM and DM-related disorders as applied in TMM.     

Anti-hyperglycemic effect,inhibition of inflammatory cytokines expression,and histopathology profile in streptozotocin-induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts

Ethopharmacological relevance

Arracacia tolucensis is a medicinal plant used in northeast of Mexico as a remedy to treat people with Diabetes mellitus (DM); however, there are no scientific studies that support this information. Thus, we evaluated the anti-hyperglycemic effect of the hexane, ethyl acetate and ethanol extracts from aerial parts in streptozotocin-induced diabetic rats.

Materials and methods

DM was induced in Wistar male rats by single intraperitoneal injection of streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats were treated with all three extracts orally at a single dose (250 mg/kg) each 48 h for 21 days. Glibenclamide (1 mg/kg) was used as a reference drug. The fasting blood glucose levels, the hematic biometry and biochemical profiles, and the inhibition of inflammatory cytokines expression were estimated. Histopathology analysis of pancreas, liver, spleen, and kidney tissue was carried out.

Results

Ours results showed that ethyl acetate extract decreased blood glucose levels significantly (75%, p< 0.05) when compared to diabetic rats and controlled the body weight loss; the lipids level did not change, but the enzyme levels of aspartate aminotransferase and alanine aminotransferase decreased significantly (60.83% and 66.16%, respectively, p< 0.05) and inhibited the expression of inflammatory cytokines,with respect to diabetic rats. Histopathology injury was not observed; by contrast repair of islet of Langerhans was exhibited.

Conclusion

These results validate the use of Arracacia tolucensis as a treatment against DM and suggests it is suitable to continue studies for its safe therapeutic use.     

Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture

Aim of the study

The leaves of Costus pictus D. Don were used extensively for its antihyperglycemic activity by the people in Kerala, India. In the present study, the antihyperglycemic and insulin secretory activity of an aqueous extract of Costus pictus leaf extract was investigated in streptozotocin induced diabetic rats.

Materials and methods

Oral Glucose Tolerance Test was done to determine the effective dose of Costus pictus extract. Aqueous extract of Costus pictus leaves was given orally to the diabetic rats for 14 days. The insulin secretory action of the leaf extract was investigated using isolated pancreatic islets from rat. Liver glucose uptake activity was measured using d-[¹⁴C] glucose.

Results

The oral administration of an aqueous extract of Costus pictus at a dose of 250 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in diabetic rats at the end of 14 days treatment. The Costus pictus leaf extract significantly increased glucose induced insulin secretion at both 4 mM and 20 mM glucose concentrations which represents normal physiological and diabetic condition respectively. The decreased glucose uptake activity of the liver of diabetic rats was reverted to near normal levels after the treatment with Costus pictus leaf extract.

Conclusion

Our results suggest the glucose lowering effect of Costus pictus to be associated with the potentiation of insulin release from pancreatic islets and enhancement of peripheral utilization of glucose.     

Antidiabetic and antioxidant effect of various fractions of Phyllanthus simplex in alloxan diabetic rats

Aim of the study

To evaluate the antidiabetic and antioxidant effects of various fractions of Phyllanthus simplex on alloxan induced diabetes in rats.

Materials and methods

Hypoglycemic effect of Phyllanthus simplex fractions was evaluated in normal and diabetic rats. Diabetes was induced by intraperitoneal injection of alloxan monohydrate (120 mg/kg). Normal and diabetic rats were divided into different groups (six rats each group) and orally administered with petroleum ether (P.E.) (200 and 400 mg/kg), ethyl acetate (EtOAc) (100 and 200 mg/kg), methanol (125 and 250 mg/kg), water fraction (150 and 300 mg/kg) and glibenclamide (10 mg/kg) for 21 days. Blood samples were collected from overnight fasted normal rats on day 21, from overnight fasted diabetic rats at 7, 14 and 21 days of treatment and analyzed for blood glucose level. On day 22 blood samples were collected from diabetic rats to estimate biochemical parameters, rats were sacrificed by single stunning and tissues were excised to measure their antioxidant and glycogen status.

Results

In the normoglycemic rats, MeOH (125 and 250 mg/kg) and aqueous fractions (150 and 300 mg/kg) showed a significant (P < 0.05) hypoglycemic effect on day 21. In diabetic control rats, MeOH (125 and 250 mg/kg) and aqueous fractions (150 and 300 mg/kg) showed significant antihyperglycemic effect (P < 0.001). The active fractions (MeOH and aqueous) of Phyllanthus simplex also increased the body weight of diabetic rats significantly compared to the control group. The active fractions were able to normalize the marked alterations in antioxidant enzymes and antioxidant parameters levels in liver and kidney. Treatment with the active fractions also normalized the diabetic induced hyperlipidemia and liver glycogen.

Conclusions

These results demonstrate the antidiabetic and antioxidant potential of fractions of Phyllanthus simplex and suggests that the plant may have therapeutic value in diabetes and related complications.     

Treatment with Azadirachta indica in diabetic pregnant rats: Negative effects on maternal outcome

Ethnopharmacological relevance

The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD).

Materials and methods

Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0 mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0 mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed.

Results

Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats.

Conclusion

Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.     

Effect of Cydonia oblonga Mill. leaf extract on serum lipids and liver function in a rat model of hyperlipidaemia

Ethnopharmacological relevance

Cydonia oblonga Mill. leaves are traditionally used in Uyghur medicine to treat or prevent cardiovascular disease. Beyond a demonstrated effect on thrombosis, we tested it for an effect on dyslipidemia, in a rat model of hyperlipidemia.

Methods

Seventy healthy Sprague Dawley rats were randomly divided into 6 groups: normal controls, model controls, simvastatin, and low-, medium- and high-dose Cydonia oblonga Mill. leaf extracts (COM), orally for 56 days. The normal controls were fed a normal diet, all other groups a high fat diet. Rat weights were recorded over time. Total cholesterol (TC), triglycerides (TG), low and high-density lipoproteins (LDL, HDL), as well as AST, ALT and total protein (TP) were measured in serum at the end of the study. The antioxidant capacity of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA) was measured in liver samples, along with lipoprotein lipase (LPL), and hepatic lipase (HL). Liver pathology was described.

Results

COM dose-dependently reduced TC, TG, LDL-C and MDA, inhibited the activity of ALT, AST and LPS, increased HDL-C content, increased the activity of SOD, GSH-PX, LPL and HL, and reduced liver steatosis in hyperlipidaemia rats, which was significant at medium and high doses. The effect of COM was similar to that of simvastatin except for increased LPL and HL which were reduced by COM but not by simvastatin.

Conclusion

Cydonia oblonga Mill. leaf extracts have hypolipidaemic and hepatoprotective effects, probably related to increasing antioxidant capacity and lipoprotein metabolism in the liver, and inhibition of lipogenesis.