In vivo and in vitro antidiabetic effect of Cistus laurifolius L. and detection of major phenolic compounds by UPLC–TOF-MS analysis

Ethnopharmacological relevance

In Turkish folk medicine, various parts of Cistus laurifolius L. are used to treat gastric ulcer and various types of pains. Additionally the tea prepared from the leaves is used to decrease symptoms of diabetes.

Materials and methods

In the present study, the hypoglycemic effects of aqueous and ethanol extracts of Cistus laurifolius were investigated in normal, glucose loaded hyperglycemic and streptozocin (STZ)-induced diabetic rats. α-Glucosidase and α-amylase enzyme inhibitory effects were determined to evaluate the mechanism of action. Total phenolic content of the extracts were determined by using Folin–Ciocalteu reagent and Ultra Performance Liquid Chromatography–Time of Flight Mass Spectrometer (UPLC–TOF-MS) was used to detect the major phenolic compounds in the extract.

Results

Results indicated that blood glucose levels of the STZ-induced diabetic rats were decreased by ethanol extract at of 250 and 500 mg/kg doses as compared to control group (16%–34%). In glucose loaded animals, extracts have shown a weak hypoglycemic effect (11%–20%). Additionally, the ethanol extract of Cistus laurifolius is found to be a potent inhibitor of α-glucosidase and α-amylase, possibly due to several polyphenolic compounds present within the extract. Twelve major flavonoids (apigenin, quercetin, kaempferol, naringenin, quercitrin and their derivatives), gallic, ellagic and chlorogenic acid in chromatographic fingerprint were analyzed by the on-line UPLC–TOF-MS system.

Conclusions

Due to having inhibitory effect on blood glucose level and carbohydrate digesting enzymes (α-glucosidase and α-amylase), Cistus laurifolius leaves might be beneficial for diabetic patients.     

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.     

Vitexin and isovitexin from the Leaves of Ficus deltoidea with in-vivo α-glucosidase inhibition

Ethnopharmacological relevance

The leaves of Ficus deltoidea are used as a traditional medicine by diabetes patients in Malaysia.

Aim of the study

The objective of the study is to identify and evaluate bioactive constituents with in vivo α-glucosidase inhibition.

Materials and Methods

The partitioned extracts, subfractions and pure bioactive constituents were subjected to α-glucosidase inhibition assay. The identified bioactive constituents were administered orally to sucrose loaded normoglycemic mice and induced diabetic rats. The postprandial blood glucose levels were monitored at 30 min interval. Acute toxicity was evaluated in both normoglycemic mice and induced diabetic rats.

Results

Bioactivity guided fractionation led to the isolation of both vitexin (1) and isovitexin (2). Oral administration of 1 mg/kg of either vitexin (1) or isovitexin (2) significantly (p<0.05) reduced the postprandial blood glucose level in sucrose loaded normoglycemic mice at 30 min. The percentage of postprandial blood glucose reduction was highest in sucrose loaded induced diabetic rats administered orally with 200 mg/kg of vitexin (1) or 100 mg/kg of isovitexin (2). Both vitexin (1) and isovitexin (2) did not exert any signs of toxicity at the highest dose of 2 g/kg administered orally to normoglycemic mice and induced diabetic rats.

Conclusion

Both the C-glycosyl bioflavonoids, namely, vitexin (1) and isovitexin (2) exhibited in vivo α-glucosidase inhibition.     

Berberine improves neurogenic contractile response of bladder detrusor muscle in streptozotocin-induced diabetic rats

Ethnopharmacological relevance

Coptidis Rhizoma has been used to treat diabetes mellitus for more than 1400 years in China. Berberine, one of the main alkaloids of Coptidis Rhizoma, is a principal antidiabetic component of Coptidis Rhizoma. To investigate the effects of berberine on impaired neurogenic contractility of detrusor muscle from urinary bladder of rats with early stage diabetes.

Materials and methods

The detrusor muscle strips were isolated from urinary bladders of streptozotocin-induced diabetic rats, 5% sucrose-induced diuretic rats or normal rats, and were placed in organ bath. The contractions induced by electrical field stimulation (EFS), carbachol, KCl, adenosine triphosphate, and the effects of berberine on those contractions were measured.

Results

The EFS- or KCl-induced contraction of detrusor muscle was significantly decreased in diabetic rats as compared with diuretic or normal rats. Atropine and suramin inhibited EFS-induced contraction. In diabetic rats, the atropine sensitive components were decreased in EFS-induced contraction of detrusor muscle, and the adenosine triphosphate-induced contraction was significantly increased. The carbachol-induced contrations were not different among groups. Berberine significantly potentiated EFS-induced contractions of detrusor muscle both from normal and diabetic rats, but the potentiated effect of BBR was more sensitive to atropine in diabetic rats. Berberine also potentiated adenosine triphosphate-induced contraction of detrusor muscle, but did not change carbachol- or KCl-induced contraction.

Conclusion

The neurogenic contraction of urinary bladder detrusor muscle is decreased while purinergic contraction of bladder detrusor muscle is increased in rats with early stage diabetes. Berberine increases the neurogenic contractile response to EFS possibly via both presynaptic increasing neurotransmitters release and postsynaptic potentiation of purinergic transmitter-regulated response in rat urinary bladder detrusor; and in diabetic rats, berberine increases neurogenic contractile response mainly via the presynaptic increasing acetylcholine release.     

Regulation effects on abnormal glucose and lipid metabolism of TZQ-F,a new kind of Traditional Chinese Medicine

Aim of the study

Based on the recipe of the traditional anti-diabetic formula TZQ, we developed TZQ-F, a new formula including 8 fractions isolated from Red Paeony root, Mulberry leaf, Lotus leaf, Danshen root and Hawthorn leaf with a good quality assurance. The study was aimed at fraction preparation and effects of the fractions on abnormal glucose and lipid metabolism.

Materials and methods

The active fractions were obtained by macroporous resin, ion-exchange resin and polyamide resin column chromatographies. HPLC analyses were used for quality control. In vitro mechanism study included DPPH radical scavenging, AGEs formation inhibition, α-glucosidase inhibition and lipase inhibition, and rats on high-fat diet were used for in vivo study.

Results

In vitro mechanism study showed that among the 8 fractions, three of them had inhibition effects on intestinal disaccharase, three with inhibition effects on lipase, and five with effects of free radical scavenging. In vivo study showed that after 4 weeks of treatment, TZQ-F significantly decreased the levels of serum total cholesterol, TG, glucose, LDL-C and HDL-C in rats on high-fat diet. Consistent with the in vitro and in vivo results, histology study demonstrated that TZQ-F alleviated hepatic steatosis induced by high-fat diet.

Conclusions

TZQ-F possesses the potential regulation effects on abnormal glucose and lipid metabolism.     

Hepatoprotective effects of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced acute liver hepatotoxicity in rats

Aim of the study

Coptidis rhizoma (CR, Chinese name is Huanglian) has been used in treating infectious and inflammatory diseases for two thousand years in Traditional Chinese Medicine (TCM). Its related pharmacological basis for the therapeutics has been studied intensively, but CR can also be used for vomiting of “dampness-heat type or acid regurgitation” due to “liver-fire attacking stomach” in TCM, whose symptoms seem to link the hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. To clarify this ethnopharmacological relevance, hepatoprotective effect of Coptidis rhizoma aqueous extract (CRAE) and its possible mechanism were studied in rats intoxicated with carbon tetrachloride (CCl₄) in the present study.

Materials and methods

Sprague–Dawley (SD) rats aged 7 weeks old were intraperitoneally injected with CCl₄ at a dose of 1.0 ml/kg as a 50% olive oil solution. The rats were orally given the CRAE at doses of 400, 600, 800 mg/kg and 120 mg/kg berberine body weight (BW) after 6 h of CCl₄ treatment. At 24 h after CCl₄ injection, samples of blood and liver were collected and then biochemical parameters and histological studies were carried out.

Results

The results showed that CRAE and berberine inhibited significantly the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increased the activity of superoxide dismutase (SOD). Observation on the hepatoprotective effect of berberine was consistent to that of CRAE.

Conclusion

The study is the first time to demonstrate that CRAE has hepatoprotective effect on acute liver injuries induced by CCl₄, and the results suggest that the effect of CRAE against CCl₄-induced liver damage is related to antioxidant property.     

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.     

Interaction of baicalin with berberine for glucose uptake in 3T3-L1 adipocytes and HepG2 hepatocytes

Ethnopharmacological relevance

Baicalin and berberine are important coexisting constituents of the combination of Radix Scutellariae and Rhizoma Coptidis, known as scutellaria–coptis herb couple (SC), which has heat clearing and detoxifying effects. The aims of the present study were to investigate the effects of the combination of baicalin+berberine on glucose uptake in 3T3-L1 adipocytes or HepG2 cells.

Materials and methods

Insulin-resistant adipocytes and hepatocytes models were established. Glucose consumption was assayed to evaluate the effects of berberine, baicalin, and berberine+baicalin on glucose uptake, and the interaction of baicalin with berberine for glucose uptake was evaluated in 3T3-L1 adipocytes or HepG2 cells. Moreover, the effects of baicalin on the dose–effect relationship of berberine for glucose uptake was also evaluated in 3T3-L1 adipocytes.

Results

The results of the present study demonstrated that berberine increased glucose consumption in 3T3-L1 adipocytes and HepG2 hepatocytes in a dose-dependent manner. In contrast, statistical analyses indicated that baicalin (in doses up to 100 μmol/L) produced no obvious effect. The effect of berberine+baicalin on glucose uptake was better than that of berberine or baicalin alone, which indicated that berberine and baicalin had the trend of synergetic effect on glucose uptake. Furthermore, these results showed that the synergistic effect occurred in a specific dose range, while the antagonistic effect was present in another dose range in the presence of 10 μmol/L baicalin. Interestingly, the entire dose–response curves of berberine shifted down in the presence of 100 μmol/L baicalin, and baicalin antagonised the effect of berberine on glucose uptake in 3T3-L1 adipocytes.

Conclusions

The results of the present study showed that berberine dose-dependently increased glucose consumption in 3T3-L1 adipocytes and HepG2 hepatocytes. Furthermore, interaction of baicalin with berberine was additive at low doses of baicalin and antagonistic at higher baicalin doses. Thus, it is possible that baicalin is a partial agonist. These results provided a basis for the study of the TCM compatibility mechanism and a new insight into the application for Gegen Qinlian Decoction (GGQLD) or SC in the clinic.     

Nigella sativa inhibits intestinal glucose absorption and improves glucose tolerance in rats

Aim of the study

Nigella sativa L. (Ranunculaceae) seeds have been used traditionally for centuries, notably for treating diabetes.

Materials and methods

We studied the effects of the crude aqueous extract of Nigella sativa seeds on intestinal glucose absorption in vitro using a short-circuit current technique and in vivo using an oral glucose tolerance test.

Results

The aqueous extract of Nigella sativa (0.1 pg/ml to 100 ng/ml) exerted dose-dependent inhibition of sodium-dependent glucose transport across isolated rat jejunum. Maximal inhibition exceeded 80% and IC₅₀ was close to 10 pg/ml. An oral glucose tolerance test was carried out in rats after the initial dose and after a 6-week treatment of Nigella sativa (2 g/(kg day)), and compared to metformin (300 mg/(kg day)). Chronic Nigella sativa treatment improved glucose tolerance as efficiently as metformin. Nigella sativa and metformin also reduced body weight without any toxic effect.

Conclusions

To our knowledge, this is the first demonstration that Nigella sativa directly inhibits the electrogenic intestinal absorption of glucose in vitro. Together with the observed improvement of glucose tolerance and body weight in rats after chronic oral administration in vivo, these effects further validate the traditional use of Nigella sativa seeds against diabetes.     

Antidiabetic effects of Justicia spicigera Schltdl (Acanthaceae)

Ethnopharmacological importance

Justicia spicigera is a plant species used for the Teenak (Huesteca Potosina) and Mayan (Yucatan peninsula) indigenous for the empirical treatment of diabetes, infections and as stimulant.

Aim of the study

To evaluate the cytotoxicity, antioxidant and antidiabetic properties of J. spicigera.

Materials and methods

The effects of ethanolic extracts of J. spicigera (JSE) on the glucose uptake in insulin-sensitive and insulin-resistant murine 3T3-F442A and human subcutaneous adipocytes was evaluated. The antioxidant activities of the extract of JSE was determined by ABTS and DPPH methods. Additionally, it was evaluated the antidiabetic properties of JSE on T2DM model.

Results

JSE stimulated 2-NBDG uptake by insulin-sensitive and insulin-resistant human and murine adipocytes in a concentration-dependent manner with higher potency than rosiglitazone 1 mM. JSE showed antioxidant effects in vitro and induced glucose lowering effects in normoglycemic and STZ-induced diabetic rats.

Conclusion

The antidiabetic effects of administration of J. spicigera are related to the stimulation of glucose uptake in both insulin-sensitive and insulin-resistant murine and human adipocytes and this evidence justify its empirical use in Traditional Medicine. In addition, J. spicigera exerts glucose lowering effects in normoglycemic and STZ-induced diabetic rats.     

Antihyperglycaemic activity of aqueous leaf extract of Combretum micranthum (Combretaceae) in normal and alloxan-induced diabetic rats

Aim of the study

To investigate antidiabetic effect of the leaves of Combretum micranthum G. Don, a medicinal plant used for treating diabetes in Northwestern Nigeria.

Materials and methods

Three doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the aqueous leaf extract of Combretum micranthum were administered to normal glucose loaded, subdiabetic and diabetic rats.

Results

Of the doses tested, 100 mg/kg of the extract was the most effective. It produces a significant hypoglycaemic and antidiabetic activity comparable to the effect of standard drug (0.6 mg/kg glibenclemide).

Conclusion

This study demonstrated the potential antidiabetic property of aqueous leaf extract of Combretum micranthum thus justifying its traditional usage.     

Antidiabetic activities of Tecoma stans (L.) Juss. ex Kunth

Ethnopharmacological relevance

Tecoma stans aqueous extract (TAE) is widely used as a traditional antidiabetic remedy in Mexico; its rational use is controversial. We provide evidence of its main antidiabetic activities.

Aim of the study

To evaluate in vivo and in vitro intestinal α-glucosidases inhibition as the possible mode of action of TAE on type 2 diabetes mellitus (DM2) animal models, and to test the effects of its sub-chronic administration on lipids and glucose blood levels.

Materials and methods

In healthy and streptozotocin (STZ)-induced diabetic male Sprague–Dawley rats, glucose or cornstarch was administered after an oral dose of TAE, acarbose, tolbutamide or vehicle, in order to build starch and glucose tolerance curves (STC and GTC). An intestinal brush border preparation was used to evaluate the TAE α-glucosidases inhibitory activity. Moreover, in STZ-induced diabetic rats TAE, tolbutamide or vehicle was administered for 21 days for evaluate their effects on fasting glucose cholesterol and triglycerides. Also, TAE total phenolic compounds were quantified.

Results

In STC, TAE decreased hyperglycemic peak values in both healthy and STZ-treated rats, in a magnitude similar to that of acarbose. The in vitro preparation showed a dose-dependent inhibition of glucose release from starch. Sub-chronic administration of TAE significantly reduced cholesterol and triglycerides levels. Moreover, we confirmed that acute and sub-chronic administration of TAE (500 mg/kg) in both rat models did not diminish fasting glucose and did not modify the GTC.

Conclusions

The study present evidence that the main antidiabetic effect of TAE is due to intestinal α-glucosidase inhibition by decreasing the postprandial hyper-glycaemia peak; in addition, TAE sub-chronic administration reduces triglycerides and cholesterol, without modifying fasting glucose.     

Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations

Ethnopharmacological relevance

Coptidis Rhizoma (Huanglian) and its major component, berberine, have drawn extensive attention toward their antineoplastic effects in the recent years. The antineoplastic effects are related to the Chinese Medicine (CM) properties of Huangliang in treating diseases by removing damp-heat and purging fire and counteracting toxicity.

Aim of the review

To trace the long history of the traditional use of Huanglian from folk medicines, especially from Chinese medicine, to recent pharmacological studies of Huanglian and berberine, with an emphasis on their antineoplastic effects and the promise as novel antineoplastic agents.

Methods

A total of seven databases were extensively searched for literature research. The terms and keywords for searching included Huanglian, berberine, Coptis, Coptidis Rhizoma, anticancer, anti-invasion, antimatastasis and mechanism. The papers including ours with studies on anticancer and mechanism, pharmacology and toxicology of Huanglian and/or berberine were focused.

Results

In view of traditional use, the anticancer effects of Huanglian can be ascribed to its CM trait by removing damp-heat, fire and toxicity. From modern biomedical studies, anticancer effects have been demonstrated in both Huanglian and berberine. The underlying molecular mechanisms involve cell-cycle arrest, apoptosis induction and anti-inflammation. Berberine is an essential anticancer compound in Huanglian. In some studies, the use of Huanglian was shown to be more effective and beneficial than the use of berberine alone. The presence of other protoberberine-type alkaloids in Huanglian might give synergistic effects for the anticancer effects. Berberine also demonstrates effects of antiangiogenesis, anti-invasion and anti-metastasis in some cancer cell lines, however, more investigations are required to unravel the underlying mechanisms involved.

Conclusions

The modern evidences of treating cancer with Huanglian and berberine have a strong linkage with traditional concept and rules of using Huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as Huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of Huanglian and berberine. The clinical application of berberine or Huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms.     

Anti-diabetic activity of extract from Persea americana Mill. leaf via the activation of protein kinase B (PKB/Akt) in streptozotocin-induced diabetic rats

Ethnopharmacological relevance

The leaves of Persea americana Mill. (Lauraceae) have been popularly used in the treatment of diabetes in countries in Latin America and Africa.

Aim of the study

To investigate the hypoglycaemic properties and to determine the molecular mechanism by which the hydroalcoholic extract of the leaves of Persea americana reduce blood glucose levels in streptozotocin (STZ)-induced diabetes in rats via the enzymatic pathway of protein kinase B (PKB/Akt).

Methods

The hydroalcoholic extract of the leaves of Persea americana (0.15 and 0.3 g/kg/day), vehicle and metformin (0.5 g/kg/day) were administered orally to STZ-diabetic rats (n = 7/group) for 4 weeks. Changes in body weight, food and water intake, fasting glucose levels and oral glucose tolerance were evaluated. Phosphorylation and the expression of PKB in the liver and soleus muscle were determined by Western blot.

Results

The hydroalcoholic extract of the leaves of Persea americana reduced blood glucose levels and improved the metabolic state of the animals. Additionally, PKB activation was observed in the liver and skeletal muscle of treated rats when compared with untreated rats.

Conclusion

The results indicate that the hydroalcoholic extract of the leaves of Persea americana has anti-diabetic properties and possibly acts to regulate glucose uptake in liver and muscles by way of PKB/Akt activation, restoring the intracellular energy balance.     

Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats

Ethnopharmacological relevance

Cucumis trigonus Roxb. (Cucurbitaceae) fruit is used in the Indian traditional medicine for the treatment of diabetes. Based on a number of reports on the blood glucose level reduction and the other complications of diabetes associated with some Cucurbitaceae plants, the antidiabetic effect of Cucumis trigonus fruit was investigated.

Aim of the study

To investigate the antidiabetic action of the aqueous extract of Cucumis trigonus fruits in the different models of rats.

Materials and methods

The antidiabetic activity of aqueous extract of Cucumis trigonus fruit was evaluated by using normal and streptozotocin-induced-diabetic rats. The acute effect of aqueous extract was evaluated by administering 500 mg/kg p.o. to normoglycemic rats. In the chronic model, the aqueous extract was administered to normal and STZ-induced-diabetic rats at dose of 500 mg/kg p.o. per day for 21 days. Blood glucose levels and body weights were monitored at specific intervals and different biochemical parameters were also carried out.

Results

The statistical data indicated the significant increase in the body weight, liver glycogen and serum insulin level and decrease in the blood glucose, glycosylated hemoglobin levels, total cholesterol and serum triglycerides. HDL cholesterol level was significantly increased when treated with the extract.

Conclusion

The aqueous fruit extract of Cucumis trigonus has had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced-diabetic rats.     

Hypoglycaemic activity of four plant extracts traditionally used in South Africa for diabetes

Aim

To validate plant species for hypoglycaemic activity.

Materials and methods

Four plants were investigated for hypoglycaemic activity by evaluating inhibiting effects on carbohydrate-hydrolising enzymes: α-glucosidase and α-amylase. Acetone plant extracts were screened against C2C12 myocytes, 3T3-L1 preadipocytes and Chang liver cells by measuring glucose uptake. Cytotoxicity was done in preadipocytes and hepatocytes.

Results

Extract of Euclea undulata rootbark exhibited highest activity, displaying a glucose uptake of 162.2% by Chang liver cells at 50 μg/ml. An inhibition concentration of 50% for Euclea undulata was found to be 49.95 μg/ml for α-glucosidase and 2.8 μg/ml for α-amylase. No cytotoxicity was recorded for Euclea undulata, while Schkuhria pinnata and Elaeodendron transvaalense exhibited cytotoxicity at 12.5 μg/ml. α-Glucosidase and α-amylase assays showed inhibitory activity on enzymes for three plant extracts.

Conclusion

Euclea undulata, Schkuhria pinnata and Elaeodendron transvaalense showed in vitro hypoglycaemic activity. Schkuhria pinnata and Elaeodendron transvaalense indicated cytotoxicity on 3T3-L1 preadipocytes and Chang liver cells. Euclea undulata, Pteronia divaricata and Elaeodendron transvaalense inhibited α-glucosidase and α-amylase enzymes.

Ethnopharmacological relevance

Screening of plant extracts scientifically validated traditional use of Euclea undulata for treatment of diabetes. Cytotoxicity results revealed that acetone extracts of Schkuhria pinnata and Elaeodendron transvaalense are toxic and raise concern for chronic use.     

Antidiabetic effect of Ficus bengalensis aerial roots in experimental animals

Ethnopharmacological relevance

Herbal preparations of Ficus bengalensis had been considered as effective, economical and safe ethnomedicines for various ailments in Indian traditional system of medicine.

Aim of study

The present study was aimed to explore scientifically the antidiabetic potential of Ficus bengalensis aerial roots as its bark had already been reported to possess antidiabetic efficacy.

Materials and methods

Effect of variable doses of aqueous extract of Ficus bengalensis aerial roots on blood glucose level (BGL) of normal-, sub- and mild-diabetic models have been studied and the results were compared with the reference drug Glipizide and elemental Mg and Ca intake as glycemic elements.

Results

The dose of 300 mg kg⁻¹ showed the maximum fall of 43.8 and 40.7% in BGL during FBG and glucose tolerance test (GTT) studies of normal rats, respectively. The same dose showed a marked reduction in BGL of 54.3% in sub- and 51.7% in mild-diabetic rats during GTT. The concentration of Mg (1.02%) and Ca (0.85%) identified through laser induced breakdown spectroscopy (LIBS) in the most effective dose could be responsible for this high percentage fall in BGL as they take part in glucose metabolism.

Conclusion

The hypoglycemic effect in normoglycemic and antidiabetic effect in sub- and mild-diabetic models of aqueous extract of aerial roots of Ficus bengalensis are due to the presence of these glycemic elements in high concentration with respect to other elements.     

Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models

Ethnopharmacological relevance

Catharanthus roseus (L). Don (Catharanthus roseus) is a traditional anti-diabetic herb widely used in many countries, and the alkaloids of Catharanthus roseus are considered to possess hypoglycemic ability.

Aim of the study

To systematically investigate the potential anti-diabetic effects and the underlying anti-diabetic mechanisms of vindoline, one of the alkaloids in Catharanthus roseus.

Materials and methods

The regulation of vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2 diabetic rats) were used to evaluate the anti-diabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20 mg/kg) to diabetic mice/rats for 4 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test (OGTT) was performed after 4 weeks.

Results

Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC₅₀=50 μM). It was determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage-dependent outward potassium currents finally enhancing insulin secretion. It protected β-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20 mg/kg) treatment significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic rats, as reflected by its functions in increasing plasma insulin concentration, protecting the pancreatic β-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA_1c), improving OGTT and reducing plasma triglyceride (TG).

Conclusion

Our findings suggested that vindoline might contribute to the anti-diabetic effects of Catharanthus roseus, and this natural product may find its more applications in the improvement of β-cell dysfunction and further the potential treatment of type 2 diabetes.     

Ameliorative effect of Eucommia ulmoides Oliv. leaves extract (ELE) on insulin resistance and abnormal perivascular innervation in fructose-drinking rats

Aim of the study

Eucommia ulmoides Oliv. leaf is a traditional Chinese medicine that exhibits an anti-diabetic action. This study was designed to investigate whether long-term administration of Eucommia ulmoides Oliv. leaves extract (ELE) ameliorates pre-diabetic state of insulin resistance and abnormal perivascular innervation in the hyperinsulinemic state.

Materials and methods

ELE at doses of 500 and 1000 mg/kg was administered orally once daily for 4 weeks in fructose-drinking rats (FDRs). Plasma levels of insulin, blood glucose levels, and perivascular innervation were assessed using biochemical and immunohistochemical methods.

Results

FDR showed significant increase in plasma levels of insulin, an index for insulin resistance (Homeostasis Model Assessment ratio—HOMA-IR) and systolic blood pressure (SBP), but not blood glucose levels, as compared with control rats. Immunohistochemical study showed significantly greater density of tyrosine hydroxylase (TH)-like immunoreactivity (LI)-containing nerves and significantly lower density of calcitonin gene-related peptide (CGRP)-LI-containing nerves in mesenteric arteries of FDR than those in control. A 4-week treatment with ELE (500 and 1000 mg/kg, p.o.) significantly decreased plasma levels of insulin and HOMA-IR without affecting blood glucose levels and significantly lowered SBP in FDR. ELE treatment in FDR resulted in significant increase in CGRP-LI never fiber density and significant decrease in TH-LI never fiber density in mesenteric arteries of FDR.

Conclusions

These results suggest that long-term ELE treatment effectively prevents insulin resistance development and ameliorates abnormal perivascular innervation in FDR.