Animal models and natural products to investigate in vivo and in vitro antidiabetic activity

Diabetes mellitus is a chronic disease which has high prevalence. The deficiency in insulin production or impaired insulin function is the underlying cause of this disease. Utilization of plant sources as a cure of diabetes has rich evidence in the history. Recently, the traditional medicinal plants have been investigated scientifically to understand the underlying mechanism behind antidiabetic potential. In this regard, a substantial number of in vivo and in vitro models have been introduced for investigating the bottom-line mechanism of the antidiabetic effect. A good number of methods have been reported to be used successfully to determine antidiabetic effects of plant extracts or isolated compounds. This review encompasses all the possible methods with a list of medicinal plants which may contribute to discovering a novel drug to treat diabetes more efficaciously with the minimum or no side effects

Mimosa pudica L.: a comparative study via in vitro analysis and GC Q-TOF MS profiling on conventional and supercritical fluid extraction using food grade ethanol

The present study compared conventional (maceration) extraction (EtOHconv) and supercritical fluid extraction (SFE) methods as a mean of comparing conventional and green process for a weed namely Mimosa pudica L. to obtain a safe antidiabetic natural agent. In vitro analysis comprised of two different assays, antioxidant assay (determination of total phenolic content, total flavonoid content, and 2,2-diphenyl-1-picrylhydrazyl assay) and antidiabetic assay (inhibition of αamylase and α-glucosidase). GC Q-TOF MS profiling for both extracts was done after derivetisation to confirm the presence of bioactive compounds. SFE was performed at 40 MPa pressure, 60 °C temperature and 5 mL/min CO2 flow rate using 30 % ethanol (co-solvent) for 2 h. EtOHconv prepared using 95 % ethanol through conventional method (maceration) showed a good in vitro antioxidant potential and digestive enzymes inhibitory effect compared to supercritical fluid extract. α-amylase and α-glucosidase inhibitory activities for EtOHconv at 1 mg/mL were 30.08 % (±5.23) and 38.29 % (±2.52), whereas for standard acarbose it was 28.24 % (±13.66) and 36.93 % (±2.70), respectively. Supercritical fluid extract showed less potent in vitro antioxidant and digestive enzymes inhibitory effects (15.67±4.03- α-amylase, 28.36±2.01- α-glucosidase). GC Q-TOF MS analysis was done to confirm the presence of bioactive compounds in both the extracts. Although EtOHconv showed better results, SFE was found to contain more bioactive compounds associated with various pharmacological effects especially antioxidative as per GC Q-TOF MS results. SFE being a clean and green technology could be employed in future with more focus on method development and optimization to reproduce better and safe bioactive products from the neglected weed M. pudica

In vivo and in vitro antidiabetic studies of Pereskia bleo leaves

Background review Since ancient times, plants have been used as natural agents to treat diseases particularly diabetes whose prevalence is increasing worldwide. Leaves of Pereskia bleo (Jarum Tujuh Bilah) are traditionally used to treat diabetes in many countries including Malaysia, however, no scientific claim exists in literature. Objective To investigate in vivo and in vitro antidiabetic activity of P. bleo with respect to understand its role in the management of diabetes. Methods Freeze dried aqueous (AQ) and ethanol (ETOH) extracts of the leaves were examined for in vivo antidiabetic activity (alloxan induced diabetic adult albino male rats of Sprague Dawley strain) and in vitro activity (inhibition of alpha-glucosidase and alpha-amylase enzymes). Two doses (250 and 500 mg/kg body weight) of both extracts were administered orally to the normal and diabetic rats. The blood glucose level of the rats was measured by using glucometer at 0, 2, 4, 6, 8 and 24 h after administering both extracts. For in vitro method, the inhibitory activities of both extracts against α- amylase and α-glucosidase were evaluated at 5 different concentrations (i.e. 50, 100, 250, 500, and 1000 µg/ml). Toxicological study was also performed to know the safe nature of both extracts. Results and Conclusion The acute toxicity study revealed LD50 for the both AQ and ETOH extracts above 2500 mg/kg b.w. Both extracts exhibited a significant antihyperglycemic effect in diabetic rats after 24 h treatment of the extracts without showing hypoglycemic effect in normal rats. The highest blood glucose reduction (from 28.3 to 9.0 mmol/l) in diabetic rats was seen in ETOH extract at 250 mg/kg b.w. after 24 h. For in vitro antidiabetic study, both extracts showed high inhibitory activity against α-amylase. The highest inhibition (99.23%) was seen at 1000 µg/mL by AQ extract. On the other hand, AQ extract did not show inhibitory activity against α-glucosidase and ETOH showed a moderate inhibition (15.46%) against α-glucosidase at 1000 µg/mL. The results from this study further justify the traditional claims of P. bleo in the management of diabetes in Malaysia

Enrichment, in vitro, and quantification study of antidiabetic compounds from neglected weed Mimosa pudica using supercritical CO2 and CO2-Soxhlet

Supercritical fluid extraction (SFE) using carbon dioxide (CO2) and liquid CO2 using Soxhlet (CO2-Soxhlet) extraction were employed to extract three (3) antidiabetic compounds viz. stigmasterol, quercetin, and avicularin from Mimosa pudica. Various extraction parameters were studied. Extracts were analyzed pharmacologically, qualitatively and quantitatively to ascertain enrichment levels. All three antidiabetic compounds were effectively enriched under optimized conditions of temperature 60°C, pressure 40 MPa, co-solvent ratio 30%, and CO2 flow rate of 5 ml min−1. SFE was found to be the better method for enrichment of the antidiabetic compounds than the CO2-Soxhlet method. Extraction conditions were seen to affect the enrichment of desired compounds

Turning weeds into drugs: The prospect of Mimosa pudica for Diabetes mellitus in-vitro

In our quest with respect to proposing alternative medicinal source against the global threat diabetes mellitus, a weed i.e. Mimosa pudica has been studied for its anti-diabetic potential. This study aimed to investigate in vitro inhibitory activity against diabetic enzymes (i.e. α-amylase & α-glucosidase) to evaluate potency of the weed against diabetes mellitus as well as to perform thorough chemical profiling using GCMS-Q-TOF, both done for first time for this weed, to assess the probable compounds present that could be linked to antidiabetic activity. Total phenolic and flavonoid contents along with DPPH radical scavenging assays were also done on five different extracts and fractions of M. pudica. Chemical class identification followed by derivetisation of the samples to analyse through GCMS was also done. Results showed good inhibitory activity against both the enzymes as compared to standard i.e. acarbose. At 1mg/mL, the MeOHi and EtOAc extracts showed two and three fold higher activity then the standard, respectively. Chemical profiling of all the extracts through GCMS- Q-TOF analysis identified organic acids, quinolone, quinone, phenolic compounds and dodecaborane as major constituents. Presence of highly radical scavenging dodecaborane is being reported for the 1st time in M. pudica. This study revealed that extracts of M. pudica is a rich source of phenolic compounds, dodecaborane, and organic acids and showed considerable high enzyme inhibitory activity. Extracts of M. pudica could be further subjected to isolation to identify the active principles responsible for its antidiabetic activity

Weeds as alternative useful medicinal source: Mimosa pudica Linn. on diabetes mellitus and its complications

Diabetes mellitus is one of the major reasons for mortality worldwide and numerous scientific studies are going on to find plausible solutions to overcome and manage diabetes and its related infirmities. Traditional medicines use medicinal plants as anti-diabetic agents and despite being a disturbing weed to farming land Mimosa pudica Linn. has a high traditional usage for various purposes including anti-diabetic complications. The objective of this article is to accumulate and organise literatures based on traditional claims and correlate those with current findings on the use of M. pudica in the management of diabetes mellitus. M. pudica is a creeping perennial shrub which is a common weed widely distributed in Southeast Asia specially in India, Bangladesh, Malaysia, China, Philippine etc. This plant has various species of which M. pudica is a well recognised plant of medicinal origin which has been traditionally used as folk medicine in India, Bangladesh and Philippine, Chinese, herbal and siddha medicines. It has wound healing, antidiabetic, anti-diarrhoeal, antimicrobial, anti-cancer, anti-infections, anti-worm, anti-proliferative, anti-snake venom, anti-depressant and anxiolytic etc. activities. The objective of this article is to provide up-to-date information on the traditional and scientific studies based on this plant on the frontier of diabetes mellitus. The methodology followed was to methodically collect, organise and chart the recent advances in the use of M. pudica in diabetes and its related complications like vascular complications, diabetic wound, hyperlipidemia etc. Various scientific studies and traditional literatures clearly support the use of M. pudica as an anti-diabetic agent among other uses. So far, the anti-diabetic compounds have not been isolated from this plant and this can be a good scientific study for the future anti-diabetic implications

Enriched extracts of anti-diabetic compounds from neglected weed M. Pudica using supercritical and subcritical carbon dioxide extractions and the corresponding in vitro study for diabetes mellitus

Medicinal plants and various extracts are traditionally used to treat ailments, disease and infections. Traditionally, organic solvents, water and oil were and are still used for the extraction of herbal medicine and often boiling (percolation) and vigorous techniques to separate the bioactive compounds were employed. Along with the advent of green technology and extraction methods, organic solvent-free extract preparation is on the rise. The current study aimed to undergo enrichment of chosen pre-isolated anti-diabetic compounds from M. pudica. The current study was employed using supercritical CO2 extraction (SFE) and subcritical CO2 Soxhlet by studying parameters of temperature, pressure, modifier or co-solvent and flow rate of CO2. It was found that the SFE and CO2-Soxhlet can be utilized to collect extract enriched with anti-diabetic compounds, which are stigmasterol, quercetin and avicularin from M. pudica in a clean and healthier method for future anti-diabetic implications

Phytochemical and in vitro antidiabetic investigations of stems of Tetracera Indica Merr., a Malaysian traditional medicinal plant

Tetracera indica Merr. (Family: DILLENIACEAE) is a large, woody, rain forest climber of Malaysia which is commonly known as Mempelas paya or sand paper plant. Different parts of T. indica are traditionally used to treat various ailments including diabetes. Four flavonoids (MHQ1-Wogonin, MHQ2-Norwogonin, MHQ3-Quercetin, MHQ4-Techtochrysin) and two terpenoids (MHQ5-Stigmasterol, MHQ6-Betulinic acid) were isolated from the stems ethanol extract of T. indica and subjected to cytotoxicity test against 3T3-L1 adipocytes with regard to evaluate their antidiabetic potential. All the compounds were isolated and purified through silica gel and sephadex LH-20 column chromatography and recrystallization with ethanol and their structures were elucidated through 1D and 2D 1H- and 13C-NMR spectroscopy and their spectral data were compared with the previously reported data of the same compounds. Cytotoxicity test was performed by MTT assay on 3T3-L1 pre-adipocytes to determine the safe dose of all isolated compounds. MHQ1 and MHQ4 showed IC50 below 100 µg/ml whereas rest of the compounds found to be safe up to 100 µg/ml. MHQ1, MHQ2, MHQ3 and MHQ4 were further subjected to adipogenesis to investigate insulin like activity or insulin sensitizing activity for the purpose of evaluating antidiabetic activity. All compounds were introduced to the cells in different safe concentrations as well as in different adipogenic cocktails. The adipogenic cocktails were modified by the compounds and rosiglitazone in the presence or absence of insulin. Results showed that MHQ-1, MHQ-2 and MHQ-4 induced adipogenesis like insulin and enhanced adipogenesis like rosiglitazone significantly. Furthermore, MHQ1 and MHQ2 as well as rosiglitazone as positive control were subjected to fluorescence glucose uptake test by 2-NBDG (fluorescent glucose analog) on mature adipocytes. Results suggested significant glucose uptake activity by MHQ1 and MHQ2. It is suggested that further study on the isolated compounds might help to discover a new safe compound with strong antidiabetic activity