INTRODUCTION:

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin secretion, insulin action, or both¹. Over the past three decades, diabetes prevalence has increased significantly, with South Asia projected to see a >150% rise in type 2 DM cases between 2000 and 2035². Key contributors include sedentary lifestyles and unhealthy diets, which lead to elevated reactive oxygen species (ROS), oxidative stress, and subsequent cellular damage^3,4. One therapeutic strategy to manage postprandial hyperglycemia (PPHG) involves inhibiting carbohydrate-hydrolyzing enzymes—α-amylase and α-glucosidase. These enzymes facilitate starch breakdown into glucose, and their inhibition slows glucose absorption, effectively lowering blood glucose levels^5–7. While synthetic inhibitors like acarbose, voglibose, and miglitol are commonly used, they often cause adverse side effects^6,8.

This has increased interest in plant-based alternatives, as many medicinal plants exhibit antidiabetic activity due to their rich content of bioactive secondary metabolites⁹.

Manihot esculenta Crantz (cassava), a perennial shrub native to South America and widely cultivated in India and Malaysia, is known for its edible leaves and roots^10,11. Traditional and scientific studies have highlighted its diverse biological activities, including its potential for diabetes management¹², antioxidant¹³, anticancer¹⁴, hepatoprotective¹⁵, anti-inflammatory^16,17, analgesic¹⁸, and antimicrobial effects¹⁹. Naturally occurring compounds present in various plant species have been widely explored for their potential in drug discovery, with few investigations carried out on Manihot esculenta^20-21. The leaves of M. esculenta are particularly rich in phenolic compounds²², including polyphenols like flavonoids and tannins, which have demonstrated inhibitory effects on α-amylase and α-glucosidase^23–25, making it a promising candidate for managing PPHG.

Despite its potential, limited research exists on the antidiabetic properties of M. esculenta. Therefore, this study aims to evaluate the α-amylase and α-glucosidase inhibitory activities of M. esculenta leaf extract and assess its antidiabetic effects in streptozotocin (STZ)-induced diabetic albino mice.

MATERIALS AND METHODS:

Plant Material:

Leaves of Manihot esculenta were collected from Mirza and Boko (Kamrup Rural District, Assam, India) and authenticated by the Botanical Survey of India (Voucher Specimen No.: BSI/ERC/Tech/2023-24/1191).

Preparation and administration of extract:

Dried leaf powder was macerated in methanol (1:10 w/v) for 48hours at room temperature. The filtrate was concentrated using a rotary evaporator to obtain a semi-solid extract. Mice were orally administered with the extract at doses of 250 and 500mg/kg body weight using a 5 mm orogastric tube for 21 days²⁶.

In vitro alpha amylase inhibitory assay:

Inhibition of porcine α-amylase was determined using DNS method²⁷. The absorbance was measured at 540 nm. The % alpha amylase inhibition was calculated by the formula:

Absorbance of Control – Absorbance of sample

% Inhibition of α - amtylase activity = -------------------- X 100

Absorbance of Control

IC₅₀ values were determined from inhibition curves.

In vitro alpha glucosidase inhibitory assay:

α-glucosidase inhibitory activity was evaluated a slightly modified method²⁸. The α-glucosidase inhibition percentage was calculated by the following equation:

Absorbance of Control – Absorbance of sample

% Inhibition of α – glucosidase activity = ----------------- X 100

Absorbance of Control

IC₅₀ values were determined from inhibition curves.

Acute oral toxicity study:

Acute oral toxicity studies were performed as per Organisation for Economic Co-operation and Development (OECD) 423 guidelines with slight modifications²⁹. Five female albino mice (n=5) selected by random sampling were fed with the methanolic leaf extract at different concentrations (5, 50, 300, 2,000 mg/kg body weight and 5,000mg/kg body weight) and were continuously monitored for 1h, 4h and 24hrs for signs of toxicity for 15 days.

Selection of dose:

On the basis of toxicity evaluation, 1/10^th of highest dose was considered to be the threshold dose i.e. 500 mg/kg body weight and a lower dose 250mg/kg body weight was selected for administration to the animals¹⁵.

Determination of Body weight:

The body weight of the animal was continuously measured on 1^st, 7^th, 14^th, 21^stday of the experiment.

Determination of Blood glucose level:

The blood glucose level was determined using Accuchek active glucometer using glucose strips by collecting blood from tail vein.

Oral glucose tolerance test (OGTT):

OGTT was performed by selecting five animals randomly from each group. The animals were fasted overnight before the test. OGTT was performed at baseline and then glucose was administered (2 g/kg body weight) orally. Blood glucose levels were measured at 30, 60, 90- and 120-minutes post glucose administration³⁰.

Estimation of serum lipid parameters:

All the parameters were measured using commercially available kits.

Statistical Analysis:

The data are presented as mean±SEM (n=5). All the data were analyzed by Student’s t-test using SPSS ver. 21 for Windows. p-value less than 0.05(p<0.05) were considered statistically significant in this study.

RESULTS:

α-Amylase and α-glucosidase inhibitory activities:

The ability of M. esculenta leaf extract in methanol to inhibit α-amylase and α-glucosidase activities in the context of their antidiabetic potential was tested, with acarbose used as the positive control. The inhibitory effects of extract on α-amylase and α-glucosidase showed lower activity than acarbose, with IC50 values of 0.004 and 0.227 mg/ml (Table 1).

Body weight:

In this study, there was significant indication of obesity by the diabetic mice as compared to that of control group. However, it was seen that after 14 and 21 days of treatment, the groups treated with leaf extract (500 mg/kg body weight) (G4) as well as the standard drug treated group (G5) showed reduction in body weight of mice (Table 2).

Blood glucose level:

The fasting blood glucose level in normal and STZ induced diabetic mice are represented in Table 3. Initially blood glucose level was elevated in all STZ injected groups. Meanwhile, it was seen that after 14 and 21 days of treatment, treated groups showed significant reduction in their blood glucose level as compared to that of the untreated group.

Oral glucose tolerance test (OGTT):

The results of the oral glucose tolerance test (OGTT) conducted in mice revealed that groups G3, G4, and G5 exhibited significant fasting and postprandial hyperglycemia compared to G2 at the 16th week (Fig 1.).

Fig. 1: Oral Glucose tolerance test (OGTT) in normal and extract treated groups (*p<0.05 vs G2) (n=5, Mean±SEM).

Serum lipid parameters:

The serum lipid profile had shown elevated concentration of Total Cholesterol (TC), Triglyceride (TG), Very Low Density Lipoprotein (VLDL), Low Density Lipoprotein (LDL) but High Density Lipoprotein (HDL) showed a significant decrease in diabetic mice as compared to that of control group (G1). But after 7, 14 and 21 days of treatment the HDL level was significantly increased compared to the positive control group (G2). Similarly, TC, TG, VLDL, LDL also showed significant decrease in their concentrations after 14 and 21 days of treatment when compared with the positive control group (G2). The serum lipid parameter results have been presented in Tables 4 through 8.

Table 1: α-amylase and α-glucosidase inhibitory activity of methanolic extract of Manihot esculenta leaves and Acarbose

Sample	IC₅₀ values of alpha amylase (mg/ml)	IC₅₀ values of alpha glucosidase (mg/ml)
Methanolic Extract	0.367	0.351
Acarbose	0.004	0.227

*IC50- Inhibitory Concentration

Table 2: Body weight of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

Days	G1	G2	G3	G4	G5
0	33.04 ±0.88	33.52± 0.71	30.08±1.01	32±2.14	31.14±0.26*
7	31 ±1.38	33.26±0.67	28.44±0.57*	25.54±0.86**	31.06±0.22
14	31.24 ±1.35	32.66±0.98	28.36±0.68*	25.94±0.48**	31.1±0.32
21	31.76 ±1.11	32.72±0.86	31.06±0.53	26.3±0.73***	31.3±0.39

Table 3: Blood glucose level of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

Days	G1	G2	G3	G4	G5
0	96.8±7.98	218.2±12.26	276.6±33.71	257.2±16.2	260.4±31.39
7	96.2±7.73	222.8±13.87	255.4±30.86	228.4±18.87	194±14.75
14	98.4±3.78	234.8±20.48	214±13.91**	204±13.23**	166.2±8.63***
21	98.8±5.40	245.4±22.25	205.4±10.60**	185.8±6.31***	110.2±11.47***

*Blood glucose level of normal and STZ induced diabetic mice

Table 4: Showing total cholesterol (TC) level of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

TC (mg/dl)
Days	G1	G2	G3	G4	G5
7	101.4±4.611	270.4±17.811	194.6±7.600	171.2±7.303**	144.4±5.201**
14	99.92±10.563	273.4±17.310	188.2±9.666	169.2±5.927**	125.4±3.668***
21	108±13.509	288±8.080	125.2±6.077***	124±6.700***	116.8±3.652***

*TC-Total Cholesterol

Table 5: Showing triglyceride (TG) level of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

TG (mg/dl)
Days	G1	G2	`G3	G4	G5
7	126.4±2.712	274±13.464	254.2±6.902	256.4±8.744	226±21.154
14	123.2±8.339	293.4±23.686	221.8±8.230*	185.8±14.904**	158.4±12.151***
21	104±7.314	303.2±18.674	157.2±9.926***	155.2±12.113***	103±4.404***

*TG-Triglyceride

Table 6: Showing High density Lipoprotein (HDL) level of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

HDL (mg/dl)
Days	G1	G2	G3	G4	G5
7	36.18±0.539	27.66±0.555	45.86±0.421***	38.54±0.872***	31.42±0.688
14	34.16±0.791	26.74±0.402	45.42±0.793***	40.2±0.550***	55.94±0.989***
21	35.92±0.839	24.88±0.491	50.68±0.778***	50.12±0.503***	63.33±0.845***

*HDL-High Denisty Lipoprotein

Table 7: Showing Very Low Density Lipoprotein (VLDL-c) level of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

VLDL-c (mg/dl)
Days	G1	G2	G3	G4	G5
7	25.28±0.542	54.8±2.693	50.84±1.380	51.28±1.748	45.2±21.154
14	24.64±1.667	58.68±4.737	44.36±1.646	37.16±2.981	31.68±2.430**
21	20.8±1.462	60.64±3.734	31.44±1.985**	31.04±2.422**	20.6±0.880***

* VLDL-Very Low Density Lipoprotein

Table 8: Showing Low Density Lipoprotein (LDL-c) level of normal and STZ induced diabetic mice after 7, 14 and 21 days of treatment (All values are expressed as Mean±SEM (n=5). Significance level is at *p<0.05).

LDL (mg/dl)
Days	G1	G2	G3	G4	G5
7	19.54±6.82	187.94±14.56	97.89±5.79**	81.38±4.69**	67.78±0.28***
14	41.12±8.11	187.98±12.17	98.42±7.23**	91.84±2.39**	37.78±0.24***
21	51.28±11.20	202.48±3.85	43.08±3.31***	42.84±3.77***	32.86±1.92***

*LDL-Low Density Lipoprotein

DISCUSSION:

Inhibitors of alpha-amylase and alpha-glucosidase are commonly used in conventional diabetes management drugs. It has been observed that a number of plants block α-amylase and α-glucosidase and have antidiabetic, antihyperglycemic, and hypoglycemic properties. Plant extracts with similar inhibitory activity offer a natural and potentially safer alternative for controlling blood sugar levels. Our research has revealed a promising inhibitory effect of the methanolic leaf extract of Manihot esculenta. This effect could potentially be attributed to the abundance of phenolic compounds present in the extract³¹. These findings are consistent with research on the antidiabetic effects of other medicinal plant extracts^32-33.

There is a clear relationship between body weight and hyperglycemia, with obesity and excess body weight increasing the risk of insulin resistance and type 2 diabetes³⁴. In our study, we observed a significant improvement in body weight among animals treated with the extract compared to the diabetic animal group. This might be result of improved glycemic control. The induction of diabetes by streptozotocin is characterised by hyperglycemia, decrease insulin level, increase in level of total cholesterol, triglycerides, high density lipoprotein³⁵. An oral glucose tolerance test (OGTT) is used to assess how well the body regulates blood sugar levels after consuming a predetermined amount of glucose. Our study has provided evidence supporting the efficacy of the leaf extract in managing diabetes by reducing blood glucose levels. The lowering of blood glucose level after extract treatment were also reported by similar works on different plant extracts^36-40.

Diabetes mellitus is associated with alternations in carbohydrate, lipid and protein metabolism as decrease in insulin levels fails to activate enzyme lipase resulting in hyperglycemic state owing to metabolic abnormalities ^41-42. Dyslipidemia is often characterized by increase in TC, TG, LDL, VLDL and decrease in HDL levels. In the present study, the levels of TC, TG were markedly increased following induction of diabetes with Streptozotocin bridging the relationship between dyslipidemia and diabetes⁴³. The changed serum lipid profile in this study was reversed significantly following treatment with Manihot esculenta leaf extract after 14 and 21 days respectively. Similar findings were reported by different other researches^44-46.

CONCLUSION:

Plants have the ability to prevent diabetes because of a combination of phytochemicals or specific components found in plant extracts. Alkaloids, flavonoids, phenolic acids, glycosides, saponins, polysaccharides, stilbenes, and tannins are extensively studied for their potential to modulate blood glucose level. In the current study, the methanolic leaf extract of Manihot esculenta significantly reduced α-amylase and α-glucosidase activity. It also improved blood sugar control and fat levels in diabetic mice. These results suggest that M. esculenta leaves may be useful in treating diabetes and related fat disorders. Future research should be carried out focusing on isolating bioactive compounds and studying the molecular mechanisms involved.

ACKNOWLEDGMENT:

The authors are thankful to the Institutional Biotech Hub of B. Borooah College, Guwahati, Assam for allowing us to use the facilities available there.

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Received on 27.01.2025 Revised on 07.07.2025

Accepted on 20.10.2025 Published on 16.03.2026

Available online from March 18, 2026

Research J. Pharmacy and Technology. 2026;19(3):1080-1084.

DOI: 10.52711/0974-360X.2026.00153

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.