Oleanane Triterpenoids from the Leaves of Gymnema inodorum and Their Insulin Mimetic Activities.

During an effort to find insulin mimetic compounds, the leaves of Gymnema inodorum were shown to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation on a 70% ethanol extract of G. inodorum was applied to yield two new (1 and 2) and two known (8 and 9) oleanane triterpenoids with a methyl anthranilate moiety together with five further new oleanane triterpenoids (3-7). The chemical structures of all isolates were determined based on their spectroscopic data, including IR, UV, NMR, and mass spectrometric analysis. The isolated compounds (1-9) were determined for their stimulatory activities on glucose uptake in differentiated 3T3-L1 adipocyte cells using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent-tagged glucose probe. Three compounds (3, 5, and 9) showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Chemicals with a methyl anthranilate moiety have been considered as crucial contributors of flavor odor in foods, and quantitative analysis showed the content of compound 8 to be 0.90 ± 0.01 mg/g of the total extract. These results suggest that the leaves of G. inodorum have the potential to be used as an antidiabetic functional food or tea.

Participants with pharmacologically impaired taste function seek out more intense, higher calorie stimuli.

OBJECTIVE: Research suggests a weaker sense of taste in people with obesity, with the assumption that a debilitated taste response increases the desire for more intensely tasting stimuli to compensate for decreased taste input. However, empirical testing of this supposition remains largely absent. METHOD: In a randomized, repeated measures design, 51 healthy subjects were treated with varying concentrations of a tea containing Gymnema sylvestre (GS), to temporarily and selectively diminish sweet taste perception, or a control tea. Following treatment in the four testing sessions, taste intensity ratings for various sweet stimuli were captured on the generalized Labeled Magnitude Scale (gLMS), liking for real foods assessed on the hedonic gLMS, and optimal level of sweetness quantified via an ad-libitum mixing task. Data were analyzed with mixed models assessing both treatment condition and each subject's resultant sweet response with various taste-related outcomes, controlling for covariates. RESULTS: GS treatment diminished sweet intensity perception (p < 0.001), reduced liking for sweet foods (p < 0.001), and increased the desired sucrose content of these foods (p < 0.001). Regression modeling revealed a 1% reduction in sweet taste response was associated with a 0.40 g/L increase in optimal concentration of sucrose (p < 0.001). DISCUSSION: Our results show that an attenuation in the perceived taste intensity of sweeteners correlates with shifted preference and altered hedonic response to select sweet foods. This suggests that those with a diminished sense of taste may desire more intense stimuli to attain a satisfactory level of reward, potentially influencing eating habits to compensate for a lower gustatory input.

Hepatoprotective benzofurans and furanolignans from Gymnema tingens.

Two new benzofurans, gymnefuranols A (1) and B (2), together with six known furanolignans (3-8), were isolated from Gymnema tingens. The structures of the new compounds were elucidated by comprehensive analysis of the NMR and HR-MS data. Compounds 1, 2, 6, and 7 showed hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.

Hepatoprotective phenolic glycosides from Gymnema tingens.

Six new phenolic diglycosides, named gymnetinosides A-F (1-6), were isolated from the ethanolic extract of Gymnema tingens, together with three known diglycosides, sequinoside K (7), khaephuoside B (8), and albibrissinoside A (9). The structures of the new compounds were determined by spectroscopic techniques including 1D-, 2D NMR, mass spectroscopy, and circular dichroism. Compounds 1, 5, and 6 showed hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.

Extraction of gymnemic acid from Gymnema inodorum (Lour.) Decne. leaves and production of dry powder extract using maltodextrin.

The aim of the present study was to maximize the extraction of gymnemic acid (GA) from Phak Chiang Da (PCD) leaves, an indigenous medicinal plant used for diabetic treatment in Northern Thailand. The goal was to overcome the low concentration of GA in the leaves, which limits its applications among a larger population and develop a process to produce GA-enriched PCD extract powder. The solvent extraction method was employed to extract GA from PCD leaves. The effect of ethanol concentration and extraction temperature were investigated to determine the optimum extraction conditions. A process was developed to produce GA-enriched PCD extract powder, and its properties were characterized. In addition, color analysis (L*, a*, and b*) was performed to evaluate the overall appearance of the PCD extract powder. Antioxidant activity assay was conducted to assess the ability of the PCD extract powder to neutralize DPPH free radicals. The results showed that the concentration of 50% (v/v) ethanol at 70 °C for 2 h resulted in a higher GA concentration of 8307 mg/kg from dried PCD leaves. During the drying process, the use of maltodextrin at a concentration of 0.5% (w/v) was found to produce PCD extract powder with the maximum GA concentration. The color analysis revealed that the PCD extract powder had a dark greenish tint mixed with yellow. The antioxidant activity assay showed that 0.1 g of PCD extract powder was able to neutralize 75.8% of DPPH free radicals. The results concluded that PCD extract powder could potentially be used as a source of nutraceuticals or as a functional food ingredient. These findings suggest the potential value of GA-rich PCD extract powder in various applications in the pharmaceutical, nutraceutical, or food industries.

Insulin-mimetic activity of 23-glycosyl oleanane triterpenoids isolated from Gymnema latifolium.

Chemical investigation of the plant Gymnema latifolium led to the isolation of seven undescribed 23-glycosyl oleanane triterpenoids, gymlatinosides GLF1-GLF7, and two known compounds, gymnemosides D and E. The structures of the isolated compounds were elucidated using diverse spectroscopic methods. The extract of G. latifolium and all isolated compounds significantly enhanced 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) uptake into 3T3-L1 adipocytes at 20 µM. Among them, gymlatinosides GLF2 and gymlatinosides GLF4 showed particularly potent stimulatory effects on glucose uptake in a dose-dependent manner. Further investigation revealed that gymlatinosides GLF2 at 20 µM upregulated the expression of phosphorylated AMPK (p-AMPK). The results suggested that gymlatinosides GLF2 may enhance glucose uptake via regulating the AMPK signaling pathway.

Phytochemical profiling, human insulin stability and alpha glucosidase inhibition of Gymnema latifolium leaves aqueous extract: Exploring through experimental and in silico approach.

Diabetes mellitus Type 2 (DM2T) is a rapidly expanding metabolic endocrine disorder worldwide. It is caused due to inadequate insulin secretion by pancreatic beta cells as well as development of insulin resistance. This study aimed to investigate the anti-α-glucosidase, insulin stabilization effect, and non-cytotoxic nature of Gymnema latifolium leaf aqueous extract (GLAE). FTIR analysis revealed the functional groups of compounds present in GLAE. Through LC/ESI-MS/MS analysis, about 12 compounds which belongs to different classes, triterpene glycosides, flavonoids, phenolics, stilbene glycosides and chlorophenolic glycosides were identified. GLAE showed in vitro antioxidant activity. GLAE stabilized insulin by increasing its α-helical content. GLAE inhibited the mammalian α-glucosidase (IC50 = 144 µg/mL) activity through competitive mode (Ki = 61.30 µg/mL). GLAE did not affect the viability of normal cell line (Vero cell line) which shows its non-toxic nature. Molecular docking of phytocompounds identified in GLAE was done with human α-glucosidase and insulin. The top 2 compounds [Gymnema saponin V (GSV) and quercetin 3-(2-galloylglucoside) (QGG) with α-glucosidase; GSV and Z)-resveratrol 3,4'-diglucoside (RDG) with human insulin] with low binding free energy were subjected to 100 ns molecular dynamics simulation to ascertain the stable binding of ligand with protein. The MM/GBSA analysis revealed binding free energy of GSV/α-glucosidase and QGG /α-glucosidase to be - 20.9935 and, - 30.9461 kcal/mol, respectively. Altogether GLAE is valuable source of anti-α-glucosidase inhibitors and insulin stabilizing compounds, suggesting potential lead for further exploration as complementary medicine against DM2T.

The Effect of a 14-Day gymnema sylvestre Intervention to Reduce Sugar Cravings in Adults.

Gymnemic-acids (GA) block lingual sweet taste receptors, thereby reducing pleasantness and intake of sweet food. Objective: To examine whether a 14-day gymnema-based intervention can reduce sweet foods and discretionary sugar intake in free-living adults. Healthy adults (n = 58) were randomly allocated to either the intervention group (INT) or control group (CON). The intervention comprised of consuming 4 mg of Gymnema sylvestre containing 75% gymnema acids, a fibre and vitamin supplement, and an associated healthy-eating guide for 14 days; participants in the CON group followed the same protocol, replacing the GA with a placebo mint. Amount of chocolate bars eaten and sensory testing were conducted before and after the 14-day intervention (post-GA or placebo dosing on days zero and 15, respectively). Food frequency questionnaires were conducted on days zero, 15 and after a 28-day maintenance period to examine any changes in intake of sweet foods. A range of statistical procedures were used to analyse the data including Chi square, t-test and two-way analysis of variance. Post dosing, INT consumed fewer chocolates (2.65 ± 0.21 bars) at day zero than CON (3.15 ± 0.24 bars; p = 0.02); there were no differences between groups at day 15 (INT = 2.77 ± 0.22 bars; CON = 2.78 ± 0.22 bars; p = 0.81). At both visits, a small substantive effect (r < 0.3) was observed in the change in pleasantness and desire ratings, with INT showing a slight increase while CON showed a small decrease over the 14-day period. No differences were found in the intake of 9 food categories between groups at any timepoint. There were no differences in consumption of low sugar healthy foods between visits, or by group. The 14-day behavioural intervention reduced pleasantness and intake of chocolate in a laboratory setting. There was no habituation to the mint over the 14-day period. This study is the first to investigate the effect of longer-term gymnema acid consumption on sweet food consumption outside of a laboratory setting; further research is needed to assess how long the effect of the 14-day intervention persists.

Recent developments made in the assessment of the antidiabetic potential of gymnema species - From 2016 to 2020.

BACKGROUND: In traditional herbal medicine, the Gymnema species has been well known for various therapeutic activities such as anti-diabetic, anti-inflammatory, anti-bacterial, anti-arthritic, anti-hyperlipidemic, cytotoxic, and immunostimulatory activities. This review is an effort to analyse all the recent studies done to explore the anti-diabetic potential of traditional Gymnema species. Gymnema sylvestre (Retz.) R.Br. ex Sm. is an important member of the Apocynaceae family that has been used to treat a variety of diseases, the most studied of which is diabetes. This action is mostly due to the pharmacologically active phytoconstituents present in its extract, which include gymnemic acids, triterpenoid saponin glycosides, and so on. Numerous other Gymnema species have also demonstrated a similar pharmacological action. INTRODUCTION: The goal of this study is to give a critical overview of the available data on Gymnema species that are used to treat diabetes. The major goal of this study is to give up-to-date knowledge on ethnopharmacology, botany, pharmacology, and structure-activity relationships of Gymnemaspecies from 2016 to 2020, as well as potential future research. The potential of using medicinal plants for alleviating symptoms of diabetes is recently being recognized. This review aims to summarize the available data and highlight both the potential and shortcomings of using Gymnema therapeutically. This knowledge can further be used to develop more therapeutically effective drugs derived from Gymnema. MATERIALS AND METHODS: Data for Gymnema species was obtained using a mix of several search terms from online databases such as PubMed, SCOPUS, and Europe PMC. Other literature surveys relevant to traditional knowledge, phytochemistry, pharmacology, or structure-activity relationship activity were also used as reference. Several methods by which Gymnema species extracts exert their effects have been investigated, and a summary of the newly discovered chemicals isolated from the plant in the previous five years has been provided. RESULTS: SAR based evaluation has been carried out for a total of 27 pharmacologically active compounds belonging to three species of Gymnema genus (Gymnema sylvestre, Gymnema latifolium, and Gymnema inodorum).These compounds demonstrated the critical significance of plant medicines for diabetes management. Numerous heterocyclic compounds have anti-diabetic action and may serve as a starting point for the design and identification of new diabetes inhibitors. CONCLUSIONS: This study aims to provide researchers with a better understanding of the antidiabetic potential Gymnema species, as well as an outline of prospective future developments. It was concluded after studying the evaluation done in the last 5 years that although extracts of Gymnema have shown good antidiabetic potential, further modifications in the structures could result in the development of more potent and safer compounds.

Four new pregnane glycosides from Gymnema latifolium and their α-glucosidase and α-amylase inhibitory activities.

Four new pregnane glycosides, gymlatifosides A - D (1 - 4) and one known pregnane glycoside, verticilloside J (5) were isolated from the leaves of Gymnema latifolium Wall. ex Wight. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR, HR-ESI-MS, and in comparison with the reported data. All these compounds were tested for α-glucosidase and α-amylase inhibitory activities. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 37.8 ± 1.5% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 7.0 to 30.1%. In addition, all compounds 1-5 showed moderate/weak anti α-amylase activity in the investigated test.

Pregnane glycosides from Gymnema inodorum and their α-glucosidase inhibitory activity.

Two new pregnane glycosides, gyminosides A and B (1 and 2) and three known, tinctoroside B (3), tinctoroside C (4), and gymnepregoside F (5) were isolated from the leaves of Gymnema inodorum (Lour.) Decne. Their structures were elucidated by physical and chemical methods and comparing with those reported in the literature. All these compounds were evaluated for α-glucosidase assay. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 63.7 ± 3.9% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 40.0 to 52.1%.

Inhibitory effects of Gymnema inodorum (Lour.) Decne leaf extracts and its triterpene saponin on carbohydrate digestion and intestinal glucose absorption.

ETHNOPHARMACOLOGICAL RELEVANCE: Chiang-Da, Gymnema inodorum (Lour.) Decne. (GI), is an ethnomedicinal plant that has been used for diabetic treatment since ancient times. One of the anti-diabetic mechanisms is possibly related to the actions of triterpene glycoside, (3ß, 16ß)-16,28-dihydroxyolean-12-en-3-yl-O-ß-D-glucopyranosyl-ß-D-glucopyranosiduronic acid (GIA1) in decreasing carbohydrate digestive enzymes and intestinal glucose absorption in the gut system. AIMS OF THE STUDY: To observe the amount of GIA1 in GI leaf extracts obtained from different ethanol concentrations and to investigate the anti-hyperglycemic mechanisms of the extracts and GIA1. MATERIALS AND METHODS: The crude extracts were prepared using 50%v/v to 95%v/v ethanol solutions and used for GIA1 isolation. The anti-hyperglycemic models included in our study examined the inhibitory activities of α-amylase/α-glucosidase and intestinal glucose absorption related to sodium glucose cotransporter type 1 (SGLT1) using Caco-2 cells. RESULTS: GIA1 was found about 8%w/w to 18%w/w in the GI extract depending on ethanol concentrations. The GI extracts and GIA1 showed less inhibitory activities on α-amylase. The extracts from 75%v/v and 95%v/v ethanol and GIA1 significantly delayed the glycemic absorption by lowering α-glucosidase activity and glucose transportation of SGLT1. However, the 50%v/v ethanolic extract markedly decreased the α-glucosidase activity than the SGLT1 function. CONCLUSION: Differences in the GIA1 contents and anti-glycemic properties of the GI leaf extract was dependent on ethanol concentrations. Furthermore, the inhibitory effects of the 75%v/v and 95%v/v ethanolic extracts on α-glucosidase and SGLT1 were relevant to GIA1 content.

Gymnema inodorum (Lour.) Decne. Extract Alleviates Oxidative Stress and Inflammatory Mediators Produced by RAW264.7 Macrophages.

Gymnema inodorum (Lour.) Decne. (G. inodorum) is widely used in Northern Thai cuisine as local vegetables and commercial herb tea products. In the present study, G. inodorum extract (GIE) was evaluated for its antioxidant and anti-inflammatory effects in LPS plus IFN-γ-induced RAW264.7 cells. Major compounds in GIE were evaluated using GC-MS and found 16 volatile compounds presenting in the extract. GIE exhibited antioxidant activity by scavenging the intracellular reactive oxygen species (ROS) production and increasing superoxide dismutase 2 (SOD2) mRNA expression in LPS plus IFN-γ-induced RAW264.7 cells. GIE showed anti-inflammatory activity through suppressing nitric oxide (NO), proinflammatory cytokine production interleukin 6 (IL-6) and also downregulation of the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6 mRNA levels in LPS plus IFN-γ-induced RAW264.7 cells. Mechanism studies showed that GIE suppressed the NF-κB p65 nuclear translocation and slightly decreased the phosphorylation of NF-κB p65 (p-NF-κB p65) protein. Our studies applied the synchrotron radiation-based FTIR microspectroscopy (SR-FTIR), supported by multivariate analysis, to identify the FTIR spectral changes based on macromolecule alterations occurring in RAW264.7 cells. SR-FTIR results demonstrated that the presence of LPS plus IFN-γ in RAW264.7 cells associated with the increase of amide I/amide II ratio (contributing to the alteration of secondary protein structure) and lipid content, whereas glycogen and other carbohydrate content were decreased. These findings lead us to believe that GIE may prevent oxidative damage by scavenging intracellular ROS production and activating the antioxidant gene, SOD2, expression. Therefore, it is possible that the antioxidant properties of GIE could modulate the inflammation process by regulating the ROS levels, which lead to the suppression of proinflammatory cytokines and genes. Therefore, GIE could be developed into a novel antioxidant and anti-inflammatory agent to treat and prevent diseases related to oxidative stress and inflammation.

Purified Gymnemic Acids from Gymnema inodorum Tea Inhibit 3T3-L1 Cell Differentiation into Adipocytes.

Gymnema inodorum (GI) is an indigenous medicinal plant and functional food in Thailand that has recently helped to reduce plasma glucose levels in healthy humans. It is renowned for the medicinal properties of gymnemic acid and its ability to suppress glucose absorption. However, the effects of gymnemic acids on adipogenesis that contribute to the accumulation of adipose tissues associated with obesity remain unknown. The present study aimed to determine the effects of gymnemic acids derived from GI tea on adipogenesis. We purified and identified GiA-7 and stephanosides C and B from GI tea that inhibited adipocyte differentiation in 3T3-L1 cells. These compounds also suppressed the expression of peroxisome proliferator-activated receptor gamma (Pparγ)-dependent genes, indicating that they inhibit lipid accumulation and the early stage of 3T3-L1 preadipocyte differentiation. Only GiA-7 induced the expression of uncoupling protein 1 (Ucp1) and pparγ coactivator 1 alpha (Pgc1α), suggesting that GiA-7 induces mitochondrial activity and beige-like adipocytes. This is the first finding of stephanosides C and B in Gymnema inodorum. Our results suggested that GiA-7 and stephanosides C and B from GI tea could help to prevent obesity.

Oleanane hemiacetal glycosides from Gymnema latifolium and their inhibitory effects on protein tyrosine phosphatase 1B.

Gymnema sylvestre (Retz.) R. Br. ex Schult. has a long history to be used as an antidiabetic herbal medicine. Various varieties of G. sylvestre, have been studied intensively on their 3ß-hydroxy oleanane triterpenoid composition for hypoglycemic effects. It is also well-known that most species belonging to the same genus have similar chemical composition and biological activity. Thus, an extract of the Gymnema latifolium Wall. ex Wight, which showed considerable protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (>70% inhibition at 30 µg/mL), was studied intensively. Extensive chemical investigation on the 70% EtOH of G. latifolium led to the isolation of four previously undescribed oleanane hemiacetal glycosides, gymlatinosides GL1-GL4, three previously undescribed oleanane glycosides, gymlatinosides GL5-GL7, and two known 3ß-hydroxy oleanane analogs. The structures of the previously undescribed compounds were elucidated using diverse spectroscopic methods. The hemiacetal structure of the glycoside portion was further elaborated precisely by HMBC and J resolved proton NMR. Gymlatinosides GL2 and GL3 showed considerable PTP1B inhibitory effect.

Gymnema montanum H. protects against alloxan-induced oxidative stress and apoptosis in pancreatic beta-cells.

The present study evaluated the molecular mechanism of antidiabetic property of G. montanum leaf extract (GLEt) against alloxan-induced apoptotic cell death in rat insulinoma cells (RINm5F). The pre-treatment of GLEt (5 microg and 10 microg/ml) resulted in significant decrease in intracellular Ca(2+) concentration, nitric oxide (NO) production along with increase in mitochondrial membrane potential in alloxan (7mM/ml) treated cells. Further GLEt reduced apoptosis by inhibiting the release of cytochrome c and subsequent cleavage of PARP and caspase-3. The immunochemical staining of 8-hydroxydeoxyguanosine (8-OHdG) also evidenced the suppression of oxidative stress by GLEt. The cell cycle analysis, annexin-V labelling assay and TUNEL assay showed the suppression of apoptosis by the treatment of GLEt. Moreover, GLEt significantly increased the cellular antioxidant levels and decreased the lipid peroxides in alloxan-treated RINm5F cells. Taken together, these findings suggest that G. montanum protects pancreatic beta-cells against reactive oxygen species (ROS) by counteracting with mitochondrial membrane permeability and inhibition of the apoptotic pathway.

Complementary and alternative medicine for the treatment of type 2 diabetes.

OBJECTIVE: To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. QUALITY OF EVIDENCE: MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. MAIN MESSAGE: Chromium reduced glycosylated hemoglobin (HbA(1c)) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA(1c) levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA(1c) are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA(1c) or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. CONCLUSION: Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes.

Determination of Elements in Gymnema inodorum Lour by Particle Induced X-Ray Emission (PIXE).

At present, Thailand uses medicinal plants to treat various diseases. Alternative medicine utilizes Gymnema inodorum Lour for antipyretic and anti-allergic purposes. There are also other research studies to treat diabetes mellitus, coronary artery disease, cataract, rheumatoid arthritis, gout, liver cancer, and stomach cancer. This study used particle-induced X-ray emission (PIXE) technique to analyze the elements in this plant. The advantage of this technique over other methods is the multi-elemental analysis and high sensitivity. The objective of this study was to determine the elemental compositions and to develop new standard methods for analyzing plant elemental compositions in Thailand. A 2-MeV proton beam was used to identify and characterize major and minor elements namely Mg, Al, Si, P, S, Cl, K, Ca, Ti, Mn, Fe, and Zn in Gymnema Inodorum Lour. Results have shown that these elements are present in varying concentrations in the selected parts: roots, stems, and leaves. The data of elemental analysis, applied in recommended quantities that are harmful to the body, describe the relationship between elements and efficacy of this plant in alternative medicine.

Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats and pigs: 1. Acute studies.

Rapid gastrointestinal absorption of refined carbohydrates (CHO) is linked to perturbed glucose-insulin metabolism that is, in turn, associated with many chronic health disorders. We assessed the ability of various natural substances, commonly referred to as "CHO blockers," to influence starch and sucrose absorption in vivo in ninety-six rats and two pigs. These natural enzyme inhibitors of amylase/sucrase reportedly lessen breakdown of starches and sucrose in the gastrointestinal tract, limiting their absorption. To estimate absorption, groups of nine SD rats were gavaged with water or water plus rice starch and/or sucrose; and circulating glucose was measured at timed intervals thereafter. For each variation in the protocol a total of at least nine different rats were studied with an equal number of internal controls on three different occasions. The pigs rapidly drank CHO and inhibitors in their drinking water. In rats, glucose elevations above baseline over four hours following rice starch challenge as estimated by area-under-curve (AUC) were 40%, 27%, and 85% of their internal control after ingesting bean extract, hibiscus extract, and l-arabinose respectively in addition to the rice starch. The former two were significantly different from control. L-Arabinose virtually eliminated the rising circulating glucose levels after sucrose challenge, whereas hibiscus and bean extracts were associated with lesser decreases than l-arabinose that were still significantly lower than control. The glucose elevations above baseline over four hours in rats receiving sucrose (AUC) were 51%, 43% and 2% of control for bean extract, hibiscus extract, and L-arabinose, respectively. Evidence for dose-response of bean and hibiscus extracts is reported. Giving the natural substances minus CHO challenge caused no significant changes in circulating glucose concentrations, indicating no major effects on overall metabolism. A formula combining these natural products significantly decreased both starch and sucrose absorption, even when the CHO were given simultaneously. These results support the hypothesis that the enzyme inhibitors examined here at reasonable doses can safely lower the glycemic loads starch and sucrose.

Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats 2. Subchronic studies.

Acute oral consumption of various natural inhibitors of amylase (bean and hibiscus extracts) and sucrase (L-arabinose) reduce absorption of starch and sucrose respectively in rats and pigs measured by lessened appearance of circulating glucose levels. The present subchronic study was designed to determine whether these selected inhibitors of gastrointestinal starch and sucrose absorption (so-called "carb blockers") remain effective with continued use and to assess their metabolic influences after prolonged intake. Sprague-Dawley rats were gavaged twice daily over nine weeks with either water or an equal volume of water containing a formula that included bean and hibiscus extracts and L-arabinose. To estimate CHO absorption, control and treated Sprague-Dawley rats were gavaged with either water alone or an equal volume of water containing glucose, rice starch, sucrose, or combined rice starch and sucrose. Circulating glucose was measured at timed intervals over four hours. The ability to decrease starch and sucrose absorption use. No toxic effects (hepatic, renal, hematologic) were evident. Blood chemistries revealed significantly lower circulating glucose levels and a trend toward decreased HbA1C in the nondiabetic rats receiving the natural formulation compared to control. Subchronic administration of enzyme inhibitors was also associated with many metabolic changes including lowered systolic blood pressure and altered fluid-electrolyte balance. We postulate that proper intake of natural amylase and sucrase inhibitors may be useful in the prevention and treatment of many chronic disorders associated with perturbations in glucose-insulin homeostasis secondary to the rapid absorption of refined CHO.