Antidiabetic and Toxicity Studies of the Extract of Four Nigerian Medicinal Plants

Aims: To evaluate the anti-hyperglycaemic efficacy and safety of the methanol extract of the combination of Senecio biafrae leaf, Xylopia aethiopica fruit, Carica papaya seed and Spondias mombin stem bark mixed together in ratio 1:1:1:1 Study Design: Extract of medicinal plants was assayed using glucose and streptozotocin-induced herperglycaemic rats model. Place and Duration of Study: Department of Pharmacognosy, Obafemi Awolowo University, IleIfe, Nigeria, between May, 2019 and January, 2022. Methodology: The extract of the combined plant parts was tested for toxicity in rats while its effects on glucose level, blood and biochemical components were also assessed. Its in-vitro anti-hyperglycaemic activity was assayed in ?-amylase and ?-glucosidase inhibitory models while its in-vivo effects were tested in glucose and streptozotocin-induced hyperglycaemic rats. The antioxidant activity of the extract was also carried out. Results: The extract did not show any adverse effects on blood sugar levels, haematological and biochemical parameters in normal rats in sub acute toxicity tests. The extract gave comparable (p > 0.05) ?-amylase and ?-glucosidase inhibitory effects to acarbose. In glucose-induced hyperglycaemic rats, its 100 mg/kg was the most effective dose with 19, 40, 43, and 57% activity that was significantly higher (p < 0.05) than the 10, 18, 24, and 40% activity given by glibenclamide (5 mg/kg) at the same time points. In streptozotocin-induced diabetic assay, its 50 mg/kg showed 31, 85, 85 and 82 % effects on days 4, 7, 10 and 14, respectively that was significantly higher than its 100 mg/kg and glibenclamide on days 7 and 10. The extract also elicited high free radical scavenging effects in all the antioxidant assays. Conclusion: The extract of the combination of four Nigerian antidiabetic plants mixed together in equal ratio gave significantly better antidiabetic activity at low doses than the individual plants without toxic effects.

Anti-hyperglycaemic Effects of the Ashes of Some Nigerian Anti-diabetic Ethnomedicinal Plants

Aims: To evaluate blood glucose-lowering ability of leaf ashes and compare anti-hyperglycaemic activities of Annona muricata leaf extract and ash. Study Design: Ashes and extract of medicinal plants were assayed using glucose-loaded rats model. Place and Duration of Study: Department of Pharmacognosy, Obafemi Awolowo University, Ile-Ife, Nigeria, between March 2017 and February 2020. Methodology: Adequately prepared ashes of seven plants and A. muricata methanol extract were assayed for anti-hyperglycaemic potentials, using glucose-loaded (10 g/kg, p.o.) Wistar rats that were hyperglycaemic [blood glucose levels ? 7.0 mmol/L] thirty minutes thereafter (T0.0). Groups of 5 rats each, were administered 100, 150, 200 mg/kg of different ashes and A. muricata extract (200 mg/kg). Normal saline and glibenclamide (5 mg/kg) were negative and positive controls, respectively. Their blood glucose levels were determined at 0-4 hours post-extract/ash/drug administration; results analysed using ANOVA followed by the Student-Newman-Keuls’ and Dunnett post-hoc tests. P ? .05 was considered significantly different. Results: 100 mg/kg of Momordica charantia, Azadirachta indica and Eugenia malaccensis leaf ashes was their most active dose, indicating significantly higher extrapancreatic activity. 32, 37, 54, 59 and 36, 43, 50, 48 % reductions elicited by Chromolaena odorata (COLA) and A. muricata (AMLA) ashes (200 mg/kg) at 0.5, 1, 2 and 4 hours, respectively made them the most active ashes. Also, blood glucose levels in glibenclamide (5 mg/kg)-, COLA-, AMLA- and its extract (200 mg/kg)-treated rats were comparable (P > .05) and their anti-hyperglycaemic activity was suggested to be due to the pancreatic (insulinotropic) and extra-pancreatic actions of their constituents. Conclusion: Study justified anti-diabetic ethnomedicinal use of plant-ashes in Nigeria, while doses were recommended for the optimum folkloric usage of these leaf ashes in managing diabetes in the rural areas of Nigeria. The leaf ashes may contain elements with glucose postprandial tolerance factor and insulin stimulating properties.

Inhibitory potentials and kinetics of the inhibition of carbohydrate-hydrolysing enzymes by the pod and seed extracts of Lessertia montana (Fabaceae) E. Phillips & R.A. Dyer

The study evaluated the effect of extracts of the seeds and pod parts of Lessertia montana on diabetes and freeradicals. Free radical scavenging activities of the extracts was tested against 1,1-diphenyl-2-picrylhydrazyl (DPPH),nitric oxide, 2,2-azinobis (3-ethylbenzothiazoline-6) sulphonic acid (ABTS), hydroxyl radical and reducing power,metal chelating assays, while the antidiabetic activity was assessed via the inhibition and kinetics of α-amylase andα-glucosidase. The pod decoction extract revealed the best radical scavenging activities in DPPH, ABTS, and metalchelating (with IC50 values 1,371, 730, and 798 µg/ml, respectively) compared with other extracts and control havingan IC50 (3,094, 4,125, and 523 µg/ml, respectively) values. While the aqueous ethanolic extract for both parts exhibitedthe highest reducing capabilities of 2.969 (pod) and 3.457 (seeds) at 1 mg/ml, the aqueous extract of the seed showedthe best inhibitory activities in two of the six tested assays, namely, hydroxyl radical (717 µg/ml) and metal chelating(59 µg/ml). The kinetics of inhibition of α-amylase and α-glucosidase by aqueous ethanolic extract of the pod wascompetitive and non-competitive, respectively, while the two enzymes were uncompetitively inhibited by ethanolicextract of the seed. The investigation corroborated the antioxidative and antidiabetic potentials of the leaf as previouslyestablished from our group.

A comparative study of antihyperglycemic effect of Gymnema sylvestre and metformin in streptozotocin induced diabetic rats

Background: Diabetes mellitus (DM) is a metabolic disorder that has the phenotype of hyperglycemia. According to World Health Organization (WHO) there were 65.1 million diabetics in India in 2013, International Diabetes Federation estimates this to increase to 190 million by 2035. Although a number of drugs are available for treatment of DM, their cost and safety profile are major concern. Medicinal plants are used by clinicians for treatment of diabetes. Gymnema sylvestre (GS) extract has been reported to increase insulin levels in diabetic rats. This study was designed to compare the antihyperglycemic effect of Gymnema sylvestre with metformin.Methods: Diabetes was induced in Sprague-Dawley rats using streptozotocin 45mg/kg. Methanolic extract of Gymnema sylvestre 120mg/kg p.o. prepared using Soxhlet apparatus.Results: GS extract reduced blood glucose levels but not statistically significant. GS extract increased HDL and triglycerides, reduced both serum ALT and AST but no statistical significance seen. Metformin significantly increased serum urea, which was not seen in GS extract group. GS extract showed regenerative changes in pancreas, liver and kidney.Conclusions: The study investigation demonstrates that methanolic extract of GS possesses antihyperglycemic and hypolipidaemic activity and so it can be considered as a promising natural remedy in a prediabetic state and in mild hyperlipidaemia to prevent its progression. Increase in ? cell regeneration activity could be a probable mechanism of action. However, further long term clinical studies are recommended to define its possible role in diabetes mellitus and hyperlipidaemia. Role of GS as a potential hepatoprotective agent also needs further evaluation.

Cytotoxic, kinetics of inhibition of carbohydrate-hydrolysing enzymes and oxidative stress mitigation by flavonoids roots extract of Dicoma anomala (Sond.)

Objective:To investigate the free radical scavenging, antidiabetic, kinetics and cytotoxic potentials of flavonoids extract of Dicoma anomala root by using standard methods.Methods:Antioxidant activity of the flavonoids was investigated at scavenging free radicals such as 1,1- diphenyl-2-picrylhydrazyl, nitric oxide, hydroxyl radical, reducing capabilities, 2,2-azino- bis (3-ethylbenzothiazoline-6) sulfonic acid as well as metal chelating capability at different concentrations (0.125-1.000 mg/mL) while the antidiabetic activity was evaluated via the inhibition and kinetics of carbohydrate digestive enzymes including, alpha glucosidase, sucrase and maltase. Brine shrimp lethality assay was also employed to examine the cytotoxic effects of the extract by using different range of concentrations (0.125-2.000 mg/mL).Results:The study revealed the best antioxidant activity of the extract in 1,1-diphenyl-2-picrylhydrazyl, 2,2-azino-bis (3-ethylbenzothiazoline-6) sulfonic acid and nitric oxide having ICConclusions:The results obtained from this study are suggestive of the antioxidative, antidiabetic and cytotoxic potentials of flavonoids root extract of Dicoma anomala.

Cytotoxic, kinetics of inhibition of carbohydrate-hydrolysing enzymes and oxidative stress mitigation by flavonoids roots extract of Dicoma anomala (Sond.)

Objective: To investigate the free radical scavenging, antidiabetic, kinetics and cytotoxic potentials of flavonoids extract of Dicoma anomala root by using standard methods. Methods: Antioxidant activity of the flavonoids was investigated at scavenging free radicals such as 1,1- diphenyl-2-picrylhydrazyl, nitric oxide, hydroxyl radical, reducing capabilities, 2,2-azinobis (3-ethylbenzothiazoline-6) sulfonic acid as well as metal chelating capability at different concentrations (0.125-1.000 mg/mL) while the antidiabetic activity was evaluated via the inhibition and kinetics of carbohydrate digestive enzymes including, alpha glucosidase, sucrase and maltase. Brine shrimp lethality assay was also employed to examine the cytotoxic effects of the extract by using different range of concentrations (0.125-2.000 mg/mL). Results: The study revealed the best antioxidant activity of the extract in 1,1-diphenyl-2-picrylhydrazyl, 2,2-azino-bis (3-ethylbenzothiazoline-6) sulfonic acid and nitric oxide having IC50 values of (386.90±4.91), (736.00±38.12), (629.30±9.62) g/mL respectively compared with quercetin (standard) with IC50 [(522.20±12.38), (1 021.00±15.61) and (1 075.00±29.35) g/mL] respective values while it was insignificantly (P>0.05) at par with quercetin for reducing power. Similarly, the extract exhibited a moderate inhibition of alpha glucosidase (43.1%), sucrase (33.4%) and maltase (29.9%) activities which were significantly (P<0.05) better than acarbose (18.4%, 12.7% and 24.9% respectively) although acarbose (46.1%) inhibited the higher activity of alpha amylase than the extract (13.7%). The kinetics of mode of inhibition of alpha amylase, alpha glucosidase, sucrase and maltase by flavonoids extract of Dicoma anomala revealed an uncompetitive, non-competitive, competitive and non-competitive inhibition respectively. The result of the lethality assay showed a potent cytotoxic effect of the flavonoids with LC50 value 0.510 mg/mL. Conclusions: The results obtained from this study are suggestive of the antioxidative, antidiabetic and cytotoxic potentials of flavonoids root extract of Dicoma anomala.

The Ethanolic Leaf Extract of Alchornea cordifolia (Schum. & Thonn.) Muell. Arg Inhibits the Development of Dyslipidaemia and Hyperglycaemia in Dexamethasone-Induced Diabetic Rats.

Poor lipid and glucose regulation increases the risk for the development of major cardiovascular diseases and other organ damage. The study evaluated the serum glucose and lipid lowering effects of the 70% (v/v) ethanolic leaf extract of Alchornea cordifolia (ALC) using the dexamethasone-induced diabetic rat model. Thirty six female Sprague-Dawley rats (180-200g; n=6) were rendered hyperglycaemic with dexamethasone (10 mg/kg, sc) once daily for 8 days except the normal control. Each group received either normal saline 0.5 ml/rat, ALC (250 mg/kg, p.o. or 500 mg/kg, p.o.), glibenclamide (5 mg/kg, p.o.) or atorvastatin (5mg/kg, p.o.) as treatment once daily for 8 days. Fasting blood glucose (FBS) readings were recorded at baseline, day 4, 6 and 9. Blood was collected for the estimation of serum triglycerides (TG), total cholesterol (TC), low density lipoproteins (LDL), very low density lipoproteins (VLDL) and high density lipoprotein (HDL) on day 9. The diabetic control group had significantly raised FBS levels (8.20 ± 1.04 mmol/l; ***p<0.001). Glibenclamide (5.20 ± 0.29; ***p<0.001) and the extracts [(ALC 250 mg/kg, p.o.; (5.35 ± 0.95 mmol/l); *p<0.05); ALC 500 mg/kg, p.o.; (5.98 ± 1.12 mmol/l); *p<0.05)] prevented an increase in FBS level. The herbal extracts also reduced the level of serum lipids of rats treated. The 70% (v/v) ethanolic leaf extract of Alchornea cordifolia has some potential for use in lipid and glucose control.

Antihperglycaemic and Antihyperlipidaemic Activities of Aqueous Ethanol Root Extract of Pseudocedrela Kotschyi on Alloxan-Induced Diabetic Rats.

Aim: To evaluate the antihyperglycaemic and antihyperlipidaemic properties of Pseudocedrela kotschyi in alloxan induced diabetic rats. Materials and Methods: Fasting blood glucose (FBG) was conducted by first inducing diabetes through intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight) (bwt). The diabetic rats, 5 per group received graded extract doses (100, 250 and 500 mg/kg) or glibenclamide (10 mg/kg) or 0.5mL acacia solution (2 %w/v) for 15 days. Blood was collected on days 0, 3, 5, 7, 9, 11, 13, 15 for glucose estimation. In postprandial test, three extract groups (100, 250 and 500 mg/kg) and the control were arranged, each comprised of 5 rats. Each animal was administered orally with glucose at a dose of 2g/kg bwt followed by extract administration 30min later. Blood glucose was monitored at 30, 60 and 120 min intervals. In hypoglycaemic study, the extract was administered at doses of 100, 250 and 500 mg/kg bwt. Lipid profile was analyzed by modified enzymatic procedure and glycated haemoglobin (HbA1C) by standard protocol. Results: The diabetic rats treated with the extract/glibenclamide showed weight gain. They also experienced dose (250 and 500 mg/kg bwt) dependent decrease in glycaemia with maximum decrease of 259.1±3.0 (24.9%) and 266.1±2.9 (25.3%) respectively while glibenclamide, 227.0±3.8 (36.0%). The postprandial test showed that the extract induced lower blood glucose level after 60 min. The extract also showed to have good hypoglycaemic activity at doses of 250 and 500 mg/kg bwt respectively. The pancreatic tissue analysis from the rats treated with the root extract indicated substantial beta cells survivor. An appreciable decrease in HbA1C level was found in the extract and glibenclamide treated compared to the negative control. In lipid profile study, Pseudocedrela kotschyi extract was observed to have ameliorated dyslipidaemia. Conclusion: The extract showed efficacy in attenuating hyperglycaemia, inducing hypoglycaemia and ameliorating dyslipidaemia.

Evaluaton of hypoglycaemic and wound healing activities of Tiliacora acuminata.

Natural products particularly plant origin have played a vital role in prevention and mitigation of human diseases. The present study was carried to evaluate the antihyperglycaemic and wound healing activity of the leaf Extracts of Tiliacora acuminate (Lam) on rats, the aqueous leaf extract was found to produce significant reduction of blood glucose concentration between 2-4 h of administration in alloxan induced hyperglycaemic rats at tested dose levels. However, in normoglycaemic animals, the extract at 400mg/kg produced significant reduction of blood glucose between 2-4 h of administration. In the wound healing studies, the leaf juice was found to be more active than the extract.

In vitro Antioxidant, Antihyperglycaemic and Antihyperlipidaemic Activities of Ethanol Extract of Lawsonia inermis Leaves.

Aim: This present study investigated the free radical scavenging activities, antihperglycaemic and antihyperlipidaemic activities of ethanol extract of Lawsonia inermis leaves. Study Design: Twenty male rats were randomly and evenly distributed into four groups, and were subsequently exposed to the following treatments for twenty-one days: Group I (Control): Normal saline; Group II: Untreated Diabetic control; Group III: Diabetic rats treated with glibenclamide (600mg/Kg. b.wt); Group IV: Diabetic rats treated with ethanol extract of Lawsonia inermis (400mg/Kg b.wt). Place and Duration of Study: This work was carried out in the Department of Biochemistry, University of Lagos, Lagos, Nigeria between November 2012 and February 2013. Methodology: Phytochemical screening and the antioxidant activities of the plant extract were carried out. Brine shrimp lethality assay was also carried out on the plant extract for In vitro toxicity assay. Blood samples collected from the experimental rats were used for the determination of fasting blood sugar and biochemical profiles following the last oral treatment and an overnight fast. Results: Lawsonia inermis showed maximum inhibition of 77.39%, 50.78% and 83.18 % at 100μg/ml DPPH free radical scavenging activity, in vitro lipid peroxidation and nitric oxide respectively. Following twenty-one days of treatment with oral administration of ethanol extract of Lawsonia inermis leaves, fasting blood glucose was significantly reduced (P<0.001) compared to the untreated diabetic control. Activities of AST, ALT, and ALP were significantly decreased (P<0.001) in the diabetic rats treated with the extract compared to the untreated diabetic control rats. Diabetic rats treated with ethanolic leaf extract of Lawsonia inermis showed statistically significant decrease (P<0.001) in the levels of total cholesterol, total triglyceride and low density lipoprotein cholesterol when compared with untreated diabetic rats. Conclusion: The ethanol extract of Lawsonia inermis leaves showed antioxidant, antihyperglycaemic and antihyperlipidaemic activities.

Evaluation of antihyperglycaemic activity of Calotropis procera leaves extract on streptozotocin-induced diabetes in Wistar rats

Calotropis procera (Aiton) W.T.Aiton,Apocynaceae, popularly known as "algodão-de-seda", is a wild African bush, rich in bioactive substances that determine the medicinal potential of this species. Diabetes mellitus is a disease that affects about 10% of the population. This study aimed to evaluate the antihyperglycaemic activity of the hydroalcoholic extract of the leaves of C. procera of occurrence in coast of Pernambuco, Brazil. The hydroalcholic extract of the leaves of C. procera (300 and 600 mg/kg/day), vehicle, insulin (6U, s.c.) or metformin (500 mg/ kg/day) were administered orally to streptozotocin-induced diabetic rats (n = 7/group) for four weeks. Changes in body weight, food and water intake, biochemical markers, fasting glucose levels and oral glucose tolerance test were evaluated. The results showed that the C. procera dried extract (300 and 600 mg/kg) reduced significantly the level of blood glucose throughout the evaluation period and improved metabolic status of the animals and ameliorate the oral tolerance glucose test. The phytochemical screening revealed and quantified the presence of phenolic compounds and flavonoids in a percentage of 29.1 and 2.9%, respectively. Thus, we conclude that the extract of the leaves of C. procera has antihyperglycemic activity.

Antihyperglycaemic effect of flower of Phlogacanthus Thyrsiflorus Nees on streptozotocin induced diabetic mice

Objective: To study the anti hyperglycaemic effect of aqueous extract of the flower of Phlogacanthusthyrsiflorus Nees in streptozotocin (STZ) induced diabetic mice. Method: The flower extract of Phlogacanthus thyrsiflorus in doses 100 and 200 mg/kg b.w was administered for 21 days and blood glucose level, serum cholesterol, liver glycogen was estimated. Results: Treatment of the streptozotocin induced diabetic mice with the flower extract resulted in significant reduction of blood glucose level (P< 0.0001), serum cholesterol (P< 0.01) and increase in liver glycogen (P< 0.0001).Conclusions:The results suggest that the flower extract of P.thyrsiflorus possess anti hyperglycaemic effect in streptozotocin induced diabetic mice which justifies the traditional use of this plant as ethnomedicine in treatment of diabetes.

Anti-diabetic activity of an hexane extract of Prosthechea michuacana in streptozotocin-induced diabetic rats / Actividad antidiabética de un extracto de hexane de Prosthechea michuacana en ratas diabéticas inducidas por estreptozotocina

In this study we investigated the antihyperglycaemic, antihyperlipidaemic and antiglycation effects of some extracts of Prosthechea michuacana bulbs in normoglycemic and diabetic rats induced by streptozocin (STZ). Hexane, chloroform and methanol extracts of P. michuacana were screened for hypoglycemic activity, and biochemical parameters as serum triglycerides, total cholesterol, lipid peroxidation, liver glycogen, skeletal muscle glycogen levels, superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activity in diabetic rats. Additionally we determined Glucose 6 Phosphatase and glucokinase activities in liver, inhibition of insulin and protein glycation. Glucose levels in blood plasma were determined by using GOD-POD method. Administration of chloroform and methanol extracts showed no effect on STZ induced diabetic rats (SD). On the other hand, treatment with hexane extract at 200 and 400 mg/kg doses, resulted in a reversal of diabetes and its complications. Both doses significantly brought down blood glucose concentration (35.75 and 47.78 percent in diabetic rats, 50.64 and 57.10 percent in nondiabetic rats), increased glycogenesis and decreased glyconeogenesis bringing the glucose metabolism toward normalcy. These doses also reversed the hyperlipidemia by reducing cholesterol (41.56 percent, 46.08 percent) and triglycerides (37.5 percent, 46.27 percent) and improved hepatic antioxidant enzyme activities. Its effect was compared with that of glibenclamide and tolbutamide, as reference antidiabetic drugs. The hexane extract decreased the hyperinsulinemia by 24 percent in SD and showed a significant change on AGEs formation in vitro with IC50 values of 48.3 ug/ml comparable to inhibitory effect of aminoguanidine with IC50 values of 27.2 ug/ml. It reduced HbA1C levels by 6.4 percent in chronic STZ-diabetic rats. It is concluded that hexane extract of Prosthechea michuacana bulbs possesses anti-hyperglycemic and antihyperlipemic...

En este estudio se determinaron los efectos antidiabéticos, antihiperlipidemico y glicación (AGEs) de algunos extractos de Prosthechea michuacana (PM) en ratas normoglucémicas y con diabetes inducida por estreptozotocina (STZ). Se probó el efecto de los extractos de hexano, cloroformo, metanol de PM sobre la actividad hipoglucemiante, la carga de glucosa, los parámetros bioquímicos tales como triglicéridos, niveles de colesterol total, peroxidación lipídica, glucógeno del hígado, los niveles de glucógeno muscular, niveles de superoxide dismutase, catalasa, glutation reductasa and glutation peroxidasa en ratas normales y diabéticas. También se determinó la glucosa 6 Phosphatasa y las actividades de GK en el hígado, la inhibición de la insulina y la glicosilación de las proteínas. Los niveles de glucosa sanguínea se determinaron por el método de GOD-POD. La administración de los extractos de cloroformo y metanol no presentaron ningún efecto sobre la SD, en cambio el tratamiento con el extracto de hexano (PM) a dosis de 200 y 400 mg/kg, inhibió la diabetes y sus complicaciones. Ambas dosis redujeron significativamente los niveles de glucosa sanguínea (35.75 y 47.78 por ciento en las ratas diabéticas, 50.64 y 57.10 por ciento en las ratas diabéticas), el aumento de la glucogénesis y la disminución de la gluconeogénesis conduce el metabolismo de la glucosa hacia la normalidad. Estas dosis disminuyeron la hiperlipidemia reduciendo el colesterol (41.56 por ciento, 46.08 por ciento) y los triglicéridos (37.5 por ciento, 46.27 por ciento) así como también mejoran las actividades antioxidantes de las enzimas hepáticas. Su efecto se comparó con la glibenclamida y tolbutamida, fármacos usados como antidiabeticos. El extracto de hexano disminuyo la hiperinsulinemia en un 24 por ciento en SD. PM mostró un cambio significativo in vitro sobre la formación de los AGEs con valores de IC50 de 48.3 mg/ml comparable al efecto inhibidor de la aminoguanidina con valores de IC50 de...