Directions: Take 1/8-1/4 tsp every 4-6 hours in coffee, water or fresh squeezed grapefruit juice. Check blood sugar upon waking, afternoon, before dinner and 2 hours after. Follow 22/2 one meal a day protocol.

*Fasting blood sugar should be between 70-90. Post meal blood sugar between 90-120 and quickly drop back under 100. Adjust dosage accordingly.

Pairs well with:

Jing Force, Thermo, Peel, Spice.

BEST ONE TOUCH GLUCOSE MONITOR TO BUY; zero mess or fuss takes 10 seconds. Check anywhere.

Featuring: Acanthopanax Senticosus (Rupr. Maxim.) Harms • Acer Nikoense Maxim. • Achyranthesbidentata Blume • Alchemilla Vulgaris Leaves And Flowers • Alisma Orientalis(Sam.)Juzep • Allium Cepa L. • Alstonia Macrophylla Wall. Ex G. Don. • Andrographis Paniculata (Burm. F.) Nees） • Anemarrhena Asphodeloides Bunge • Angelica Dahurica (Fisch.Ex Hoffm.) Benth. Et Hook.F. • Angelica Sinensis (Oliv.) Diels • Anthocyanin-Rich Berry- – Blueberry • Apigenin – Celery Seed • Apium Graveolens L. • Arbutus Unedo L. Roots Bark Aqueous • Arctium Lappa L • Asparagus Racemosus Willd • Astragalus Mongholicus Bunge • Astragaus Membrana- Ceus (Milkvetch Root) • Atractylodes Lancea( Thunb.)Dc. • Atractylodes Macrocephala Koidz. • Bauhinia Megalandra Leaves • Blackcurrant Polyphenols – Ribes Nigrum L • Cardamonin • Catalpol From Rehmannia Glutinosa (Chinese Foxglove Root • Chlorogenic Acid – Green Coffee Bean • Chrysin – Pinus Mon-Ticola Dougl. • Cinnamomum Cassia (Cassia Bark) • Cistanche Tubulosa • Citrus Maxima (Burm) Merr. • Citrus Medica Leaves • Coix Lachryma Jobi L. • Coptis Chinensis Franch. • Cordyceps Sinensis( Berk.)Sacc. • Cornus Officinalis (Asiatic Cornelian Cherry Fruit) • Crataegus Pin.Nati Fida Bge • Curcumin – Curcuma Longa L. • Cynodon Dactylon • Cytochalasin B – Drechslera Dematioidea • Daidzein – Soybean • Dendrobium Nobile Lindl • Egcg • Epicatechin • Epigallocatechin • Eriobotrya Japonica (Loquat Leaf) • Euonymus Alatus (Thunb.) Sieb. • Euphorbia Humifusa • Fenugreek (Trigonella Foenum-Graecum L. Seed) • Ficus Carica Linn • Fisetin – Cotinus Coggygria Scop. • Formononetin – Astragalus Mongholicus Bunge • Fructus Ligustri Lucidi • Fucoxanthin – Thallus Japonica • Ganoderma Lucidum（Leyss. Ex Fr.）Karst. • Gaultheria Phillyreifolia And G. Poeppigii Berries • Genistein – Glycine Max (Linn.) Merr • Glycyrrhiza Inflata • Gneyulins A And B From The Bark Of Gnetum Gnemonoides – Gnetum Gnemonoides • Gossypol – Cottonseed • Graviola (Annona Muricata) – Annona Muricata • Guava (Psidium Guajava) – Psidium Guajava • Gymnema Sylvestre (Retz.) Schult • Gynostemma Pentaphyllum • Helichrysum (Helichrysum Italicum) • Herba Fumariae • Honeybush (Cyclopia Genistoides) • Hordeurn Vulgare L. • Isoquercitrin • Kaempferol Galanga L • Kaempferol 3-O-Α-Rhamnoside Purified From Bauhinia Megalandra Leaves • Kurarinone From Sophora Flavescens Root • Lagerstroemia Speciosa • Laminaria Japonica • Lavandula Stoechas • Levisticum Officinale (Apiaceae) Leaf And Stem • Litchi Chinensis Sonn.Seed – Litchi Chinensis Sonn.Seed • Lonicera Japonica Thunb. (Honeysuckle Flower) • Lycium Barbarum L. Polysaccharide • Lycium Chinense Mill. • Maqui Berries (Aristotelia Chilensis) • Momordica Charantia L. • Morus Alba L Root And Peel • Mulberry Leaf • Myricetin – Myrica Rubra (Lour.) S. Et Zucc • Naringenin – Amacardi-Um Occidentale L. • Naringin – Citrus Grandis • Nelumbo Nucifera Gaertn • Nigella Sativa L. (Ranunculaceae) Seeds • Ophiopogon Japonicaus (Dwarf Lilyturf Tuber) • Oridonin – Rabdosia Rubescens • Oroxylum Indicum Seed • Paeonia Lactiflora Pall • Panax Ginseng C. A. Meye • Panax Notoginseng(Burk.)F.H.Chen • Pelargonidin-3-O-Glucoside Fragaria Virginiana • Persimmon Tannin • Phloretin – Bark Of Apple Trees • Phlorizin – Bark Of Apple Trees • Platycodon Grandifloru Seed And Root • Polygonatum Odoratum (Mill.) Druce • Polygonatum Sibiricum Delar. Ex Redoute • Polygonum Multiflorum (Fleeceflower Root) • Poria Cocos(Schw.)Wolf • Portulaca Oleracea L. • Prunella Vulgaris L. • Psidium Guajava Linn. Leaf • Pterocarpus Marsupium Roxb • Quercetin – • Quercetin-3-O-Glucoside – • Quercetin-4′-O-Glucoside (Q4′Glc) – Sophora Flavescens Ai • Quinidine (9S)-6′-Methoxycinchonan-9-Ol; • Radix Bupleuri • Ranawara (Cassia Auriculata) Dried Flowers • Resveratrol – Polygonum Cuspidatum Sieb.Et Zucc. • Rhodiola Rosea L • Rosa Laevigata Michx. • Salvia Miltiorrhiza Bge • Schisandrae Chinensis Fructus • Silybin – Silybum Marianum (L.) Gaertn. • Sophora Flavescens • Sophoraflavanone – Sophora Moorcroftiana, • Syzygium Aromaticum-Derived Triterpenes Oleanolic Acid (Oa) And Maslinic Acid (Ma) • Tangeretin – Citrus Reticulata Blanco Peel • Taraxacum Mongolicum Hand.-Mazz. • Thymus Praecox Subsp. Skorpilii Var. Skorpilii (Syn. Thymus Praecox Subsp. Jankae (Celak.) Jalas) • Tiliroside – Tribulus Terrestris L. • Trichosanthes Kirilowii Maxim. • Xanthohumol – Humulus Lupulus Linn. • Zea Mays L. • (+)-Cryptocaryone – Cryptocarya Concinna Hance • (+)-Pteryxin – Peucedanum Harry-Smithii Var. Subglabrum

SCIENCE:

sodium–glucose cotransporter 2 (SGLT2 ) inhibitors from natural products : discovery of next-generation antihyperglycemic agents

diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions , leading to the development of life-threatening complications . Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia , weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium –glucose cotransporter 2 (SGLT2 ) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes . Since the discovery of the first natural SGLT2 inhibitor , phlorizin , several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors , and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine .

“Plant‐derived glucose transport inhibitors with potential antitumor activity

glucose , a key nutrient utilized by human cells to provide cellular energy and a carbon source for biomass synthesis, is internalized in cells via glucose transporters that regulate glucose homeostasis throughout the human body . glucose transporters have been used as important targets for the discovery of new drugs to treat cancer, diabetes , and heart disease, owing to their abnormal expression during these disease conditions. Thus far, several glucose transport inhibitors have been used in clinical trials, and increasing numbers of natural products have been characterized as potential anticancer agents targeting glucose transport. The present review focuses on natural product glucose transport inhibitors of plant origin, including alkaloids, flavonoids and other phenolic compounds, and isoprenoids, with their potential antitumor properties also discussed.

SGLT2 inhibitors as calorie Restriction mimetics: Insights on longevity pathways and Age-related diseases

sodium–glucose cotransporter -2 (SGLT2 ) inhibitors induce glycosuria , reduce insulin levels , and promote fatty acid oxidation and ketogenesis. By promoting a nutrient deprivation state, SGLT2 inhibitors upregulate the energy deprivation sensors AMPK and SIRT1, inhibit the nutrient sensors mTOR and insulin /IGF1 , and modulate the closely linked hypoxia-inducible factor (HIF)-2α/HIF-1α pathways . Phosphorylation of AMPK and upregulation of adiponectin and PPAR-α favor a reversal of the metabolic syndrome which have been linked to suppression of chronic inflammation . downregulation of insulin /IGF1 pathways and mTOR signaling from a reduction in glucose and circulating amino acids promote cellular repair mechanisms, including autophagy and proteostasis which confer cellular stress resistance and attenuate cellular senescence. SIRT1, another energy sensor activated by NAD+ in nutrient-deficient states, is reciprocally activated by AMPK , and can deacetylate and activate transcription factors, such as PCG-1α, mitochondrial transcription factor A (TFAM), and nuclear factor E2-related factor (NRF)-2, that regulate mitochondrial biogenesis. FOXO3 transcription factor which target genes in stress resistance, is also activated by AMPK and SIRT1. Modulation of these pathways by SGLT2 inhibitors have been shown to alleviate metabolic diseases , attenuate vascular inflammation and arterial stiffness , improve mitochondrial function and reduce oxidative stress–induced tissue damage. Compared with other calorie restriction mimetic such as metformin, rapamycin, resveratrol, and NAD+ precursors, SGLT2 inhibitors appear to be the most promising in the treatment of aging –related diseases , due to their regulation of multiple longevity pathways that closely resembles that achieved by calorie restriction and their established efficacy in reducing cardiovascular events and all-cause mortality . Evidence is compelling for the role of SGLT2 inhibitors as a calorie restriction mimetic in anti-aging therapeutics.

flavonoids CAPABLE OF inhibitING glucose uptake in cells

flavonoids are a group of polyphenolic compounds ubiquitously found in plants including fruits, and vegetables. Broad ranges of the biological activities of flavonoids have been reported using in vitro studies. I report that several natural flavonoids blocked glucose uptake in myelocytic U937 cells. Although there were some variations in the blocking activity of individual flavonoids , approximately half of the glucose uptake was blocked by flavonoids at the concentrations of 8–50 μM. The decreasing order of the blocking activity was fisetin ≥ myricetin ≥ quercetin ≥ apigenin > genistein > cyanidin > daidzein ≥ hesperetin > naringenin > catechin. Fisetin showed approximately 50% inhibition of glucose uptake at a concentration of 8 μM. Similar patterns of the inhibition were observed in lymphocytic Jurkat cells. Fisetin and quercetin inhibited glucose transport in a competitive manner. K_i values for fisetin and quercetin were proximately 9 and 12 μM, respectively. This study showed that some types of natural flavonoids block glucose uptake in U937 cells and that natural flavonoids could be used as alternative blockers of glucose uptake in vitro.

organ protection by SGLT2 inhibitors : role of metabolic energy and water conservation

therapeutic inhibition of the sodium–glucose co-transporter 2 (SGLT2 ) leads to substantial loss of energy (in the form of glucose ) and additional solutes (in the form of Na+ and its accompanying anions) in urine. However, despite the continuously elevated solute excretion, long-term osmotic diuresis does not occur in humans with SGLT2 inhibition . Rather, patients on SGLT2 inhibitor therapy adjust to the reduction in energy availability and conserve water. The metabolic adaptations that are induced by SGLT2 inhibition are similar to those observed in aestivation—an evolutionarily conserved survival strategy that enables physiological adaptation to energy and water shortage. Aestivators exploit amino acids sfrom muscle to produce glucose and fatty acid fuels. This endogenous energy supply chain is coupled with nitrogen transfer for organic osmolyte production, which allows parallel water conservation. Moreover, this process is often accompanied by a reduction in metabolic rate. By comparing aestivation metabolism with the fuel switches that occur during therapeutic SGLT2 inhibition , we suggest that SGLT2 inhibitors induce aestivation-like metabolic patterns, which may contribute to the improve ments in cardiac and renal function observed with this class of therapeutics.

improve ment of skeletal muscle insulin sensitivity by 1 week of SGLT2 inhibitor use

Background and Aims:

It is currently unclear whether sodium–glucose co-transporter 2 (SGLT2 ) inhibitor administration can improve the insulin sensitivity as well as rapidly reduce plasma glucose concentrations in humans during the early phase of treatment initiation. This study aimed to investigate the effect of SGLT2 inhibitor on insulin sensitivity in the early phase of treatment initiation.

Methods and Results

This single-center, open label, and single-arm prospective study recruited 20 patients (14 men) with type 2 diabetes mellitus (T2DM). We examined the patients’ metabolic parameters before and 1 week after SGLT2 inhibitor (10 mg/day of empagliflozin) administration. The glucose infusion rate (GIR) was evaluated using the euglycemic hyperinsulin emic glucose clamp technique. Changes in laboratory and anthropometric parameters before and after SGLT2 inhibitor administration were analyzed according to the change in the GIR. The BMI, body fat amount, skeletal muscle amount, systolic blood pressure, and triglyceride level significantly decreased along with the treatment , while urinary glucose level and log GIR value significantly increased. Notably, changes in the GIR after SGLT2 inhibitor administration, which indicated improvement in peripheral insulin sensitivity , were negatively correlated with T2DM duration and positively with reduction in fluctuation of daily plasma glucose profiles before and after treatment .

Conclusion

SGLT2 inhibitor improved insulin sensitivity in the skeletal muscle independent of anthropometric changes. Patients with short duration of T2DM and insulin resistance can be good candidates for short-term SGLT2 inhibitor administration to improve insulin sensitivity in the skeletal muscle.

natural products as lead compounds for sodium glucose cotransporter (SGLT) inhibitors

glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption , gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporter s (SGLTs). The intestinal glucose absorption by endothelial cells is managed by SGLT1 , the transfer from them to the blood by GLUT2 . In the kidney SGLT2 and SGLT1 are responsible for reabsorption of filtered glucose from the primary urine, and GLUT2 and GLUT1 enable the transport of glucose from epithelial cells back into the blood stream.

The flavonoid phlorizin was isolated from the bark of apple trees and shown to cause glucosuria . phlorizin is an inhibitor of SGLT1 and SGLT2 . With phlorizin as lead compound, specific inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of type 2 diabetes . inhibition of SGLT2 eliminates excess glucose via the urine. In recent times, the dual SGLT1 /SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities.

Besides phlorizin , also some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels which can be helpful in the prevention and supplementary treatment especially of type 2 diabetes .

inhibition of the intestinal glucose transporter GLUT2 by flavonoids

We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited by intestinal luminal compounds that are inefficiently absorbed and naturally present in foods. Because of their abundance in fruits and vegetables, flavonoids were selected as model compounds. Robust inhibition of glucose and fructose transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its glucoside precursor isoquercitrin. IC₅₀s for quercetin, myricetin, and isoquercitrin were ∼200‐ to 1000‐fold less than glucose or fructose concentrations , and noncompetitive inhibition was observed. The two other major intestinal sugar transporters , GLUT5 and SGLT1 , were unaffected by flavonoids . sugar transport by GLUT2 overexpressed in pituitary cells and naturally present in Caco‐2E intestinal cells was similarly inhibited by quercetin. GLUT2 was detected on the apical side of Caco‐2E cells, indicating that GLUT2 was in the correct orientation to be inhibited by luminal compounds. Quercetin itself was not transported by the three major intestinal glucose transporters . Because the flavonoid quercetin, a food component with an excellent pharmacology safety profile, might act as a potent luminal inhibitor of sugar absorption independent of its own transport, flavonols show promise as new pharmacologic agents in the obesity epidemic.

Development of glucose transporter (GLUT) inhibitors

The discovery of novel compound classes endowed with biological activity is at the heart of chemical biology and medicinal chemistry research. This enables novel biological insights and inspires new approaches to the treatment of diseases . cancer cells frequently exhibit altered glycolysis and glucose metabolism and an increased glucose demand. Thus, targeting glucose uptake and metabolism may open up novel opportunities for the discovery of compounds that differentiate between normal and malignant cells. This review discusses the different chemical approaches to the development of novel inhibitors of glucose uptake through facilitative glucose transporters (GLUTs), and focusses on the most advanced and potent inhibitor classes known to date. GLUT inhibitors may find application not only in the treatment of cancer, but also of other proliferative diseases that exhibit glucose addiction

glucose control by the kidney : an emerging target in diabetes

The full significance of the kidney‘s role in glucose homeostasis is now well recognized. For example, it is now known that renal gluconeogenesis contributes substantially to total-body glucose release in the postabsorptive state. The kidney contributes to glucose homeostasis by filtering and reabsorbing glucose . Under normal circumstances, glucose filtered by glomeruli is completely reabsorbed , but glucosuria may occur under conditions of hyperglycemia or reduced reabsorptive capacity. The sodium–glucose cotransporter SGLT2 (encoded by the SLC5A2 gene), which is expressed almost exclusively in proximal tubules, mediates approximately 90% of active renal glucose reabsorption . This transporter can be block ed by SGLT2 inhibitors , a class of compound that may prove effective in managing type 2 diabetes . The glucosuria induced by these compounds has a naturally occurring parallel in familial renal glucosuria (FRG), a condition in which SGLT2 mutations reduce renal reabsorptive capacity. Interestingly, the chronic glucosuria of patients with FRG does not appear to be associated with other pathological changes, and patients with FRG are mostly asymptomatic. This suggests that glucosuria is not intrinsically detrimental. Selective SGLT2 inhibitors are currently in clinical trials.

INGREDIENTS:

Acanthopanax senticosus (Rupr. Maxim.) Harms extract

Fundamental studies on the inhibitory action of Acanthopanax senticosus Harms on glucose absorption

Aim of the study

Acanthopanax senticosus Harms extract (ASE) is used as an ingredient of over-the-counter drugs and function al foods, such as health supplements, in Japan. ASE exhibits a hypoglycemic effect; however, the mechanism of the hypoglycemic effect is not clear. In the present study, we investigated whether ASE has a glucose absorption inhibitory action .
Materials and methods

We examined the effects of ASE on α-amylase and α-glucosidase activities, and on glucose uptake in Caco-2 cells. We also examined the effects of ASE oral administration on glucose tolerance in type 2 diabetes mellitus model db/db mice.
Results

The addition of ASE inhibited α-glucosidase activity but not α-amylase activity . The α-glucosidase inhibitory activity of ASE was approximately 1/13 of that of acarbose. The addition of ASE inhibited 2′-deoxy-d-glucose (DG) uptake in human intestinal Caco-2 cells, and the inhibitory activity of ASE was approximately 1/40 of that of phloretin. Kinetic analysis of glucose uptake indicated that ASE has no effects on DG uptake through passive diffusion, but that ASE inhibits intracellular DG uptake chiefly by inhibiting transport via a glucose transporter . In the glucose tolerance study, db/db mice orally administered ASE for 3 days showed significantly lower plasma glucose level than the control group 30 min after sucrose loading, without affecting plasma insulin levels . In addition, ASE oral administration significantly inhibited α-glucosidase activity in the small intestine mucosa extirpated from the mice.
Conclusion

These findings indicate that ASE may be useful as an ingredient of functional foods to improve postprandial hyperglycemia and prevent type II diabetes mellitus .
Graphical abstract

Acanthopanax senticosus Harms extract (ASE) suppressed glucide absorption by the inhibition of intestinal α-glucosidase activity and glucose uptake . ASE is expected to inhibit the rapid rise in blood glucose level immediately after a meal and to improve impaired glucose tolerance in type II diabetes mellitus .

Acer nikoense

Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer nikoense

Two cyclic diarylheptanoids, acerogenins A (1) and B (2) have been isolated from the bark of Acer nikoense as inhibitors of Na⁺–glucose cotransporter (SGLT). Acerogenins A (1) and B (2) inhibited both isoforms, SGLT1 and SGLT2 . Structure–activity relationship of acerogenin derivatives on inhibitory activity of SGLT as well as conformational analysis of 1 and 2 on the basis of J-resolved HMBC spectra and X-ray analysis were discussed.

Graphical abstract

Two cyclic diarylheptanoids, acerogenins A (1) and B (2) have been isolated from the bark of Acer nikoense as inhibitors of Na⁺–glucose cotransporter (SGLT). Acerogenins A (1) and B (2) inhibited both isoforms, SGLT1 and SGLT2 . Structure–activity relationship of acerogenin derivatives on inhibitory activity of SGLT as well as conformational analysis of 1 and 2 on the basis of J-resolved HMBC spectra and X-ray analysis were discussed.

Achyranthes bidentata Bl.root extract

Unexplored Potential of traditional Chinese medicine in diabetes mellitus

diabetes is one of the most prevalent disease worldwide and is associ–ated with one of the highest morbidities and mortality rates associated. Like the western and conventional medicines, traditional Chinese medicine (TCM ) has promising results in the ailment of diabetes and its associated complications . But still the use of TCM is refrained for further explorations due to inadequate knowledge of active pharmaceutical ingredient and its isolation. Thus, this review will highlight some of the key concepts and rational behind the therapeutic regimen of TCM aiming towards diabetes treatment . A detailed study of all the articles including research as well as reviews, which were available on the world wide web was performed. The review includes MEDLINE and EMBASE databases using keywords alone or in combinations, such as diabetes , diabetic complications , Chi–nese therapy, traditional chinese medicine , diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic complications , α-amylase and several others. TCM collectively is an effective and comparatively safe in the treatment of diabetes mellitus and its associated complications . Sig–nificant results are seen in monotherapy and in combination therapy with current conventional drugs. The effects include controlling glycemic levels along with the mitigation of diabetes associated complications . Focus on clinical trials and further investigations might help in concluding TCM as one of the most effective and safe treatment therapies . TCM holds enor–mous potential by virtue of its mechanism of action by maintaining the homeostasis in the body and thereby exhibiting pharmacological action .

Alchemilla vulgaris

Phytochemical Screening of Alchemilla Vulgaris, Sophora Japonica , Crataegus Azarolus, and Their inhibitory activity on Lipase and α-amylase

Phytochemical screening of Alchemilla Vulgaris(leaves and flowers) ,Sophora Japonica , and Crataegus Azarolus (leaves and fruits ) , have been determined, and the results showed that the different plant parts of the studied plants contained the following compounds: phenols, carbohydrates, , flavonoids , , saponins, , tannins, and glycosides. While it has shown the absence of alkaloids and cardinols , except the leaves ofCrataegus Azarolus that contained alkolois.The effect of Alchemilla Vulgaris (leaves and flowers),Sophora Japonica , and Crata egus Azarolus (leaves and fruits ) on lipase activity and α –amylase activity were screened by used different extracts[MeOH; MeOH 70% EtOH ; EtOH70% ; Hexane ; Chloroform]. to test their anti-obesity activity using porcine pancreatic lipase inhibitory assay, and porcine pancreatic α –amylase . The results showedthat the extract obtained withpolarsolvents have a good inhibitory activity , and the highest effect on lipase activity was in the MeOH extractsbut the highest effect onα –amylase activity was in the MeOH 70% extracts,on the contrary the non-polar solvents (Hexane ; Chloroform) have avery weak effect on lipase and α –amylase activity ,also we showed that the polar extracts of Alchimalla Vulgaris (leaves and flowers) have the highest effect on lipase activity and α –amylase activity comparative with the extracts of Sophora Japonica , and Crata egus Azarolus (leaves and fruits)These results suggest that the chemical content of polar extracts of these plants might be of therapeutic interest with respect to the treatment of obesity . International Journal of Ac ademic Scientific Research

Alisma orientalis(Sam.)Juzep extract

Chemical constituents from Alisma orientalis extracts with hypoglycemic effect / 中草药

Objective:
To study the chemical constituents in Alisma orientalis extracts with hypoglycemic effect.
Methods:
To study the in vivo hypoglycemic effects of A. orientalis extracts, high fat diet (HFD)-induced insulin resistance male C57BL/6J mice were treated with water and ethanol extracts of A. orientalis in diet, and glucose tolerance test was carried out following the intervention. Silica gel, ODS, and preparative HPLC were used to isolate the compounds. Their chemical structures were elucidated on the basis of NMR and MS spectral data.
Results:
Sixteen compounds were identified as sitosterol (1), palmitic acid (2), heptadecanoic acid (3), eicosanoic acid (4), 11-deoxy-alisol B (5), 23-acetate alisol B (6), 23-acetate alisol C (7), alisol B (8), 24-acetate alisol A (9), alisol G (10), 24-acetate alisol F (11), alisol L (12), alisol C (13), alisol F (14), alisol A (15), and 16-oxo-24-acetate alisol A (16), and nine of the triterpenes could improve glucose uptake in HepG2 cells.
Conclusion:
Compounds 3 and 4 are isolated from A. orientalis for the first time. The water and ethanol extracts of A. orientalis could improve glucose tolerance test. Triterpenes may be one of the therapeutic material basis in hypoglycemic activities in A. orientalis.

Allium cepa L.extract

Extracts and flavonoid s from onion inhibit the intestinal sodium-coupled glucose transporter 1 (SGLT1 ) in vitro but show no anti-hyperglycaemic effects in vivo in normoglycaemic mice and human volunteers

Extracts and flavonoids from onion are described as having anti-diabetic activities. We here demonstrate that an onion extract and individual flavonoids thereof diminish glucose uptake mediated by the intestinal glucose transporter SGLT1 when expressed in oocytes and studied in mouse intestinal segments in vitro. Strongest inhibition of SGLT1 was observed for quercetin-4′-O-glucoside (Q4′glc) in oocytes but with only moderate inhibition in jejunal segments of mice. An oral glucose tolerance test (OGTT) performed in obese/hyperglycaemic mice revealed that the onion extract to reduce blood glucose increases significantly. However, an OGTT performed in healthy volunteers after administration of the onion extract failed to reveal an effect on glucose and insulin levels . Despite its capability to inhibit intestinal glucose uptake via SGLT1 in vitro and in mice in vivo, the onion extract did not alter blood glucose levels during an OGTT in human volunteers and this may predominantly be due to a dosing effect.

Alstonia macrophylla

Alstiphyllanines E–H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter

Three new picraline-type alkaloids, alstiphyllanines E–G (1–3) and a new ajmaline-type alkaloid, alstiphyllanine H (4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids (5–20). Structures and stereochemistry of 1–4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F (1 and 2) showed moderate Na⁺–glucose cotransporter (SGLT1 and SGLT2 ) inhibitory activity . A series of a hydroxy substituted derivatives 21–28 at C-17 of the picraline-type alkaloids have been derived as having potent SGLT inhibitory activity . 10-Methoxy-N(1)-methylburnamine-17-O-veratrate (6) exhibited potent inhibitory activity , suggesting that the presence of an ester side chain at C-17 may be important to show SGLT inhibitory activity . Structure activity relationship of alstiphyllanines on inhibitory activity of SGLT was discussed.

Andrographis paniculata Nees

Mechanistic understanding of PtyroneTM: A plant based natural anti diabetic product

Objective

To investigate the combinatorial effect of hydroalcoholic extracts of Andrographis paniculata Nees. and Pterocarpus marsupium Roxb. plants prospective to diabetes management.

Methods

Taking a lead from the scientific literature, in silico studies have also been designed for the screening of anti-diabetic targets against andrographolide and pterostilbene compounds followed by in vivo studies from Andrographis paniculata Nees. and Pterocarpus marsupium Roxb. Furthermore, the diabetes was induced by STZ model and the impact of Andrographis paniculata Nees. and Pterocarpus marsupium Roxb. have been conformed by relative expression studies by qPCR.

Results

Our results have shown that andrographolide and pterostilbene are SGLT2 inhibitors and selective PPARγ agonists in in silico studies. Later, during in vivo mRNA expression studies confirming the same pattern. The findings of the study has shown to overcome the common knowledge of the only C–glycoside based molecules inhibiting the SGLT2 .

Conclusions

The possible mechanism for Ptyrone^TM in the management of diabetes could be a selective PPARγ agonist, GLUT4 translocation and SGLT2 inhibition molecule.

Anemarrhena asphodeloides Bunge extract

antidiabetic activity of a xanthone compound, mangiferin

Mangiferin (MF) isolated from Anemarrhena asphodeloides Bunge rhizome, was tested for antidiabetic activity in KK-Ay mice, an animal model of type-2 diabetes . MF lowered the blood glucose level of KK-Ay mice 3 weeks after oral administration (p < 0.01). However, no effect on the blood glucose level in normal mice was seen, indicating that MF could be useful in treating type-2 diabetes . In addition, MF improve d hyperinsulin emia and, on insulin tolerance test, reduced blood glucose levels of KK-Ay mice. From these findings, it seems likely that MF exerts its antidiabetic activity by decreasing insulin resistance.

Angelica dahurica (Fisch.ex Hoffm.) Benth. et Hook.f.extract

Phellopterin isolated from Angelica dahurica reduces blood glucose level in diabetic mice

insulin resistance is the critical condition for the development of metabolic syndrome s including type II diabetes and heart disease. To investigate the active components of Angelica dahurica root which is known to increase insulin sensitivity , its methanol extract was subfraction ated. The ethyl acetate (EtOAc) fraction of the Angelica dahurica root extract significantly promote d adipocyte differentiation in 3T3-L1 preadipocyte cells. Among the three compounds isolated from the EtOAc extract (bergapten (1), imperatorin (2) and phellopterin (3)), phellopterin (3) induced the highest adipocyte differentiation at 25 and 50 μg/mL. In addition, treatment with imperatorin (2) and phellopterin (3) increased the mRNA expression of peroxisome proliferator-activated receptors γ (PPARγ). In diabetic animal model induced by high-fat diets (HFD) and streptozotocin (STZ), administration of phellopterin ((3), 1 mg/kg and 2 mg/kg) significantly reduced the levels of blood glucose , triglycerides and total cholesterol. Taken together, these results indicate that phellopterin (3) enhances adipocytes differentiation in 3T3-L1 preadipocytes, phellopterin (3) significantly prevents HFD/STZ-induced type Ⅱ diabetes . The present study also provides phellopterin (3) may be a valuable therapeutic alternative for enhancing insulin sensitivity through promotion of adipocyte differentiation and by increasing mRNA expression levels of PPARγ, which is a major mediator of insulin sensitivity .

Angelica sinensis extract

chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice

This study aimed to investigate the therapeutic effects of Angelica sinensis polysaccharide (ASP), an active component derived from a water extract of Angelica sinensis, in high-fat diet (HFD)-fed BALB/c mice. The potential mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters were evaluated and key proteins involved in the lipid/glucose metabolism were analyzed. Long-term feeding with a HFD induced severe fatty liver and hyperglycemia . Histological examination clearly showed that ASP reduced lipid accumulation in the liver and attenuate d hepatic steatosis in HFD-fed mice. In addition, ASP markedly alleviated serum and liver lipid disorders and fatty liver via the upregulation of PPARγ expression and the activation of adiponectin-SIRT1-AMPK signaling. Furthermore, ASP also significantly relieved severe oxidative stress , demonstrating that ASP might attenuate nonalcoholic fatty liver disease via a “two-hit” mechanism. In addition, ASP reduced blood glucose levels and ameliorated insulin resistance via the regulation of related metabolic enzymes and by activating the PI3K/Akt pathway in HFD-fed mice. Our findings revealed that ASP might be used as an alternative dietary supplement or health care product to ameliorate metabolic syndrome in populations that consistently consume HFDs.

anthocyanin-rich berry-extract

Regulation of glucose transporter Expression in Human intestinal Caco-2 Cells following Exposure to an Anthocyanin-Rich Berry Extract

Polyphenols contained within plant tissues are consumed in significant amounts in the human diet and are known to influence a number of biological processes. This study investigated the effects of an anthocyanin-rich berry-extract on glucose uptake by human intestinal Caco-2 cells. Acute exposure (15 min) to berry extract (0.125%, w/v) significantly decreased both sodium-dependent (Total uptake ) and sodium-independent (facilitated uptake ) ³H-D-glucose uptake . In longer-term studies, SGLT1 mRNA and GLUT2 mRNA expression were reduced significantly. Polyphenols are known to interact directly with glucose transporters to regulate the rate of glucose absorption . Our in vitro data support this mechanism and also suggest that berry flavonoids may modulate post-prandial glycaemia by decreasing glucose transporter expression. Further studies are warranted to investigate the longer term effects of berry flavonoids on the management of glycaemia in human volunteers.

apigenin

glucose _transporter .14.aspx”>Apigenin Inhibits the GLUT-1 glucose transporter and the Phosphoinositide 3-Kinase/Akt Pathway in Human Pancreatic cancer cells

Objectives:

The antiproliferative mechanisms of flavonoid drugs inpancreatic cancer cells remain unclear. In this study, we evaluated the effects of the flavonoid apigenin on glucose uptake , on the expression of the glucose transporter 1 (GLUT-1), and on the phosphoinositide 3-kinase (PI3K)/Akt pathway in human pancreatic cancer cells .
Methods:

Human pancreatic cancer cells were treated with apigenin and then underwent glucose uptake assays. Real-time reverse transcription-polymerase chain reaction and Western blot analysis were conducted to evaluate GLUT-1 and pAkt expression in CD18 and S2-013 human pancreatic cancer cells after treatment with apigenin or PI3K inhibitors (LY294002 and wortmannin).
Results:

Apigenin (0-100 μM) significantly inhibited, in a dose-dependent fashion, glucose uptake in CD18 and S2-013 human pancreatic cancer cell lines. Apigenin inhibited both GLUT-1 mRNA and protein expression in a concentration- and time-dependent fashion. The PI3K inhibitors , like apigenin, downregulated both GLUT-1 mRNA and protein expression.
Conclusions:

Our results demonstrate that the flavonoid apigenin decreases glucose uptake and downregulates the GLUT-1 glucose transporter in human pancreatic cancer cells . In addition, the inhibitory effects of apigenin and the PI3K inhibitors on GLUT-1 are similar, indicating that the PI3K/Akt pathway is involved in mediating apigenin’s effects on downstream targets such as GLUT-1.

Unraveling the inhibition of intestinal glucose Transport by Dietary Phenolics: A Review

Background: glucose transport across the intestinal brush border membrane plays a key role in metabolic regulation. Depending on the luminal glucose concentration, glucose is mainly transported by the sodium-dependent glucose transporter (SGLT1 ) and the facilitated-transporter glucose transporter (GLUT2 ). SGLT1 is apical membrane-constitutive and it is active at a low luminal glucose concentration, while at concentrations higher than 50 mM, glucose is mainly transported by GLUT2 (recruited from the basolateral membrane). Dietary phenolic compounds can modulate glucose homeostasis by decreasing the postprandial glucose response through the inhibition of SGLT1 and GLUT2 .

Methods: Phenolic inhibition of intestinal glucose transport has been examined using brush border membrane vesicles from rats, pigs or rabbits, Xenopus oocytes and more recently Caco-2 cells, which are the most promising for harmonizing in vitro experiments.

Results: Phenolic concentrations above 100 μM has been proved to successfully inhibit the glucose transport. Generally, the aglycones quercetin, myricetin, fisetin or apigenin have been reported to strongly inhibit GLUT2 , while quercetin-3-O-glycoside has been demonstrated to be more effective in SGLT1 . Additionally, epigallocatechin as well as epicatechin and epigallocatechin gallates were observed to be inhibited on both SGLT1 and GLUT2 .

Conclusion: Although, valuable information regarding the phenolic glucose transport inhibition is known, however, there are some disagreements about which flavonoid glycosides and aglycones exert significant inhibition , and also the inhibition of phenolic acids remains unclear. This review aims to collect, compare and discuss the available information and controversies about the phenolic inhibition of glucose transporters . A detailed discussion on the physicochemical mechanisms involved in phenolics-glucose transporters interaction s is also included.

Apium graveolens L. extract

The effects of celery leaf (apium graveolens L.) treatment on blood glucose and insulin level s in elderly pre-diabetic s

Objectives:

To analyze the effect of celery leaf extract on blood glucose and plasma insulin levels in elderly pre-diabetics.
Methods:

This study was conducted between March and November 2014 at the Faculty of medicine , Syiah Kuala University, Banda Aceh, Indonesia. A quasi-experimental pretest-posttest with a control group was conducted with elderly pre-diabetic volunteers. The subjects included 16 elderly pre-diabetics older than 60 (6 males and 10 females). The subjects were randomly divided into 2 groups: a control group (placebo-treated) and a treatment group (celery-treated). The treatment consisted of celery leaf extract capsules at the dose of 250 mg, 3 times per day (morning, afternoon and evening), 30 minutes before a meal, for 12 days. Data analysis was performed using the t-test (p<0.05).
Results:

There was a significant decrease in pre-prandial plasma glucose levels (p=0.01) and post-prandial plasma glucose levels (p=0.00), but no significant increase in plasma insulin levels (p=0.15) after celery leaf treatment in elderly pre-diabetics.
Conclusion:

Celery was effective at reducing blood glucose levels , but there was a lack of association between blood glucose levels and plasma insulin levels in elderly pre-diabetics.

Arbutus unedo L. roots bark

Arbutus unedo L., (Ericaceae) inhibits intestinal glucose absorption and improves glucose tolerance in rodents

Ethnopharmacological relevance

Arbutus unedo L., (Ericaceae) is one of the most traditional plants commonly used to treat diabetes in people living in Eastern Morocco region particularly in Taza and Beni Mellal.
Aim of the study

The aim of the study was to find if there is a scientific support to the ethnopharmacological relevance use of Arbutus unedo L., roots bark (AU) to treat diabetes .
Materials and methods

We studied the effects of crude aqueous extract of AU on intestinal glucose absorption using short-circuit current technique in vitro and oral glucose tolerance test in vivo.
Results

The aqueous extract of AU (10 µg/mL to 1 mg/mL) induced concentration-dependent inhibition of sodium -dependent glucose transport across isolated mouse jejunum. The maximal inhibition was obtained with 1 mg/mL, which exhibited more than 80% of the Phloridzin inhibition with an IC50 close to 216 µg/mL. A 6-week AU ingestion (2 g/(kg day)), improved oral glucose tolerance as efficiently as metformin (300 mg/(kg day)). Arbutus unedo L. and metformin also reduced body weight.
Conclusions

Arbutus unedo L. roots bark aqueous extract directly inhibited the electrogenic intestinal absorption of glucose in vitro. In addition it improved oral glucose tolerance and lowered body weight in rats after chronic oral administration in vivo. These results add a scientific support to the ethnopharmacological relevance use of Arbutus unedo L. roots bark to treat diabetes .

Arctium lappa L extract

Arctium lappa contributes to the management of type 2 diabetes mellitus by regulating glucose homeostasis and improving oxidative stress : A critical review of in vitro and in vivo animal-based studies

diabetes is a metabolic disease highly widespread worldwide, and the most common form is the type 2 diabetes mellitus (T2DM). A large number of synthetic drugs are currently available for the treatment of diabetes ; however, they present various side effects and, for this reason, people are increasingly inclined to search natural alternative treatments . Among these, Arctium lappa (A. lappa) has interesting anti-diabetic activities, exerted by improving glucose homeostasis and reducing insulin -resistance. In addition, A. lappa exerts a marked antioxidant activity , an effect known to play a pivotal role in the treatment of T2DM. The purpose of this review is to analyse scientific evidence in order to evaluate the role of A. lappa and its bioactive compounds in management of T2DM. The literature search performed provided only in vitro and animal-based studies. No clinical studies have been conducted in order to investigate the effect of A. lappa on T2DM patients. However, available literature provides evidence for further clinical trials in order to confirm these claimed activities on humans .

Asparagus Racemosus

>Antihyperglycaemic activity of Asparagus racemosus roots is partly mediated by inhibition of carbohydrate digestion and absorption , and enhancement of cellular insulin action

Asparagus racemosus roots have been shown to enhance insulin secretion in perfused pancreas and isolated islets. The present study investigated the effects of ethanol extracts of A. racemosus roots on glucose homeostasis in diabetic rats, together with the effects on insulin action in 3T3 adipocytes. When administered orally together with glucose , A. racemosus extract improved glucose tolerance in normal as well as in two types of diabetic rats. To investigate the possible effects on carbohydrate absorption , the sucrose content of the gastrointestinal tract was examined in 12 h fasted rats after an oral sucrose load (2·5 g/kg body weight). The extract significantly suppressed postprandial hyperglycaemia after sucrose ingestion and reversibly increased unabsorbed sucrose content throughout the gut. The extract also significantly inhibited the absorption of glucose during in situ gut perfusion with glucose . Furthermore, the extract enhanced glucose transport and insulin action in 3T3-L1 adipocytes. Daily administration of A. racemosus to type 2 diabetic rats for 28 d decreased serum glucose , increased pancreatic insulin , plasma insulin , liver glycogen and total oxidant status. These findings indicate that antihyperglycaemic activity of A. racemosus is partly mediated by inhibition of carbohydrate digestion and absorption , together with enhancement of insulin secretion and action in the peripheral tissue. Asparagus racemosus may be useful as a source of novel antidiabetic compounds or a dietary adjunct for the management of diabetes .

Astragaus membrana

Meta-analysis of the clinical value of Astragalus membranaceus in diabetic nephropathy

Aim of study

Nowadays diabetic nephropathy (DN) has become a serious problem. Astragalus membranaceus is a traditional herb used for thousands of years in China and East Asia for kidney disease. In modern medicine , Astragalus shows significant renal protective effect in DN. We aimed to systematically review the randomized and semi-randomized control trials to ascertain its role in the treatment of DN.

Materials and methods

PUBMED, MEDLINE, Chinese journal full-test database (CJFD), Chinese biological and medical database were searched by computer and manual searching. Two assessors independently reviewed each trial. 25 studies comprising 21 RCTs and 4 CCTs were involved including 1804 patients (945 in treatment group and 859 in control group).

Results and conclusions

Astragalus injection had more therapeutic effect in DN patients including renal protective effect (BUN, SCr, CCr and urine protein) and systemic state improve ment (serum albumin level ) compared with the control group.

Ethnopharmacological relevance

This study investigates the effect of Astragalus in DN patients. It suggests that although of unknown bioactive ingredients and mechanism of renal protection , the role of Astragalus in the treatment of DN can be disclosed and of profound significance.

Astragalus mongholicus Bunge extract

Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK

Aim:

To establish the mechanism underlying the improve ment of glucose toxicity by Astragalus polysaccharide (APS), which occurred via an AMP activated protein kinase (AMPK )-dependent pathway.
Methods:

In vivo and in vitro effects of APS on glucose homeostasis were examined in a type 2 diabetes mellitus (T2DM) rat model. The T2DM rat model was duplicated by a high-fat diet (58% fat, 25.6% carbohydrate, and 16.4% protein) and a small dose of streptozotocin (STZ, 25 mg/kg, ip). After APS therapy (700 mg·kg−1·d−1, ig) for 8 weeks, blood glucose , glycosylated hemoglobin, and serum insulin were measured. insulin sensitivity was evaluated by the comprehensive analysis of oral glucose tolerance tests (OGTT) and HOMA IR index. Hepatic glycogen was observed by the PAS staining method. The expression and activity of skeletal muscle AMPK α and acetyl-CoA carboxylase (ACC), and the phosphorylation of hepatic glycogen synthase (GS), the glycogen synthase (GS),were measured by Western blotting. glucose uptake was measured with the 2-deoxy-[3H]-D-glucose method in C2C12 cells.
Results:

The hyperglycemia status, insulin sensitivity , glucose uptake , and activation level of AMPK in diabetic rats were improve d in response to APS administration. APS could also alleviate glucose toxicity in cultured mouse cells by the activation of AMPK .
Conclusion:

APS can alleviate glucose toxicity by increasing liver glycogen synthesis and skeletal muscle glucose translocation in the T2DM rat model, via activation of AMPK .

Atractylodes lancea( Thunb.)DC.extract

Effects of Atractylodes lancea on plasma glucose and Lipid Profile in Streptozotocin Induced diabetic Rats

The purpose of this study was to examine the effects of Atractylodes lancea (A.l.) in a dose-dependent manner on lipid levels and plasma glucose in diabetic rats induced with streptozotocin (STZ). The Sprague-Dawley rats were randomly classified into five groups: normal, STZ-control and three experimental groups [A.l.-1, diabetic treated with ethanolic extract of A.l. (1 g/kg b.w.), A.l.-2, diabetic administered with ethanolic extract of A.l. (2 g/kg b.w.), and A.l.-3, diabetic administered with ethanolic extract of A.l. (3 g/kg b.w.)]. The normal and STZ-control group were fed an AIN-93 diet and the three experimental groups were administered with A.l. extract at doses of 1, 2, and 3 g/kg b.w./day, respectively, for 14 days. The plasma glucose levels in all the experimental groups were significantly lower than the STZ-control group after 14 days of treatment . The total cholesterol of the A.l.-3 and triglyceride levels , atherogenic index (AI) of all three experimental groups were significantly lower than the STZ-control group. The ALT and AST activities at A.l.-2, A.l.-3 were significantly lower than the STZ-control group. This result that demonstrate the administration of Atractylodes lancea can reduce hyperglycemia and hyperlipidemia risk in diabetic rats.

Atractylodes macrocephala Koidz.extract

[Studies on physico-chemical properties and hypoglycemic activity of complex polysaccharide AMP-B from Atractylodes macrocephala Koidz].

AIM: To isolate a complex polysaccharide (AMP-B) from Atractylodes macrocephala Koidz and study its phtsico-chemical properties and hypoglycemic activity . METHODS: The root of Atractylodes macrocephala K. was extracted with water and precipitated with ethanol, dialyzed against water and freeze-dried to get the crude polysaccharides (AMP). A complex polysaccharide (AMP-B) was isolated and purified on DEAE-cellulose column. The model of diabetes rats was established with alloxan injection through the tail vein. Male rats were divided into 5 groups: the normal group, the control group, and three AMP-B-fed groups. Measuring the blood glucose , water and food consumption, thymus and pancreas index, and studying cut sections of pancreas tissues. RESULTS: AMP-B is a complex-polysaccharide, elemental analysis of AMP-B shown C 32.84%, H 5.68%, and N 1.79%. The neutral polysaccharide content of AMP-B was 50.3%, uronic acid was 40.4%, and protein was 11.5%. Monosaccharide composition of AMP-B was determined by GC, AMP-B composed of Glc, Gal, Man, Ara and Rha in a molar ratio of 3.0:2.5:1.3:3.5:1.0. AMP-B was found to reduce blood glucose level in alloxan-diabetic rats markedly at doses of 50, 100 and 200 mg.kg-1 by ig, but no effect in normal rat. AMP-B was found to decrease the consumption of water and food, recover pancreas damage of diabetic rats obviously, inhibited the atrophy of thymus and pancreas of the diabetic rats induced by alloxan. CONCLUSION: AMP-B showed significant hypoglycemic effect on the experimental hyperglycemia s rats induced by alloxan.

Bauhinia megalandra leaves

Effects of Bauhinia megalandra aqueous leaf extract on intestinal glucose absorption and uptake by enterocyte brush border membrane vesicles

Aqueous extract of Bauhinia megalandra leaves was able to inhibit the intestinal glucose absorption in a concentration-dependent way and additive to phlorizine. Moreover, B. megalandra leaf extract drastically reduced the ¹⁴C-glucose uptake by enterocyte brush border membrane vesicles. The B. megalandra leaf extract administrated orally, simultaneously with glucose improve d the glucose tolerance with a significant reduction of the 30-min peak. The extract did not have an effect on the glucose tolerance when glucose was administrated subcutaneously.

blackcurrant polyphenols

Apple and blackcurrant polyphenol-rich drinks decrease postprandial glucose , insulin and incretin response to a high-carbohydrate meal in healthy men and women

Postprandial glycemic responses to meals are inhibited by polyphenol-rich plant foods. Combinations of polyphenols may be particularly effective through complementary mechanisms. A randomized, controlled, double-blinded cross-over trial was conducted in healthy volunteers to test the hypothesis that apple and blackcurrant polyphenol-rich drinks would reduce postprandial blood glucose concentrations . Secondary outcomes included insulin and glucose -dependent insulin otropic polypeptide (GIP) secretion. Twenty men (mean age 26 y, SD 8) and 5 postmenopausal women (mean age 57 y, SD 3) consumed a placebo drink (CON) and 2 polyphenol-rich drinks containing fruit extracts: either 1200 mg apple polyphenols (AE), or 600 mg apple polyphenols+600 mg blackcurrant anthocyanins (AE+BE), in random order with a starch and sucrose meal. Incremental areas under the curve (iAUC) for plasma glucose concentrations were lower following AE+BE over 0–30 and 0–120 min compared with CON; mean differences (95% CI) −32 mmol/L·min (−41, −22, P<.0005) and −52 mmol/L min (−94, −9, P<.05), respectively. AE significantly reduced iAUC 0–30 min (mean difference −26 mmol/L min, −35, −18, P<.0005) compared with CON, but the difference over 120 min was not significant. Postprandial insulin , C-peptide and GIP concentrations were significantly reduced relative to CON. A dose response inhibition of glucose transport was demonstrated in Caco-2 cells, including total and GLUT-mediated transport, and SGLT1 -mediated glucose transport was strongly inhibited at all doses in Xenopus oocytes, following 10 min incubation with 0.125–4 mg apple polyphenols/ml. In conclusion, ingestion of apple and blackcurrant polyphenols decreased postprandial glycemia, which may be partly related to inhibition of intestinal glucose transport.

cardamonin

inhibitory Effect of Tangeretin and Cardamonin on Human intestinal SGLT1 activity In Vitro and blood glucose levels in Mice In Vivo

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases , such as type II diabetes . The absorption of food-derived glucose is primarily mediated by sodium /glucose cotransporter 1 (SGLT1 ). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases . In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity . Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity . Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake , suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter , whereas that of cardamonin was specific to SGLT1 . Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in V_max and an increase in K_m, whereas suppression by cardamonin was associated with a reduction in V_max and no change in K_m. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels . In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.

Catalpol from Rehmannia glutinosa

plasma glucose Lowering Mechanisms of Catalpol, an Active Principle from Roots of Rehmannia glutinosa, in Streptozotocin-Induced diabetic Rats

Catalpol is one of the active principles from roots of Rehmannia glutinosa Steud (Scrophulariaceae) that is widely used to treat diabetic disorders in Chinese traditional medicine using the name of Di-Huang, which is used to investigate the mechanisms for lowering of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats). Catalpol decreased plasma glucose in a dose-related manner, and this action was reduced by pretreatment with naloxone or naloxonazine. An increase of plasma β-endorphin by catalpol was also observed in parallel. The plasma glucose lowering action of catalpol was deleted in bilateral adrenalectomized rats. Moreover, catalpol enhanced β-endorphin release from the isolated adrenal medulla of STZ-diabetic rats. Otherwise, plasma glucose lowering action of catalpol failed to produce in opioid μ-receptor knockout mice. Also, repeated administration of catalpol for 3 days in STZ-diabetic rats resulted in a marked reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression in liver and an increased expression of glucose transporter subtype 4 (GLUT 4) in skeletal muscle. These effects were also reversed by blockade of opioid μ-receptors. Our results suggested that catalpol increased glucose utilization through increase of β-endorphin secretion from adrenal gland in STZ-diabetic rats.

Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism

The hypoglycemic and anti-diabetic effect of Rehmannia glutinosa oligosaccharide (ROS) in glucose -induced hyperglycemic and alloxan-induced diabetic rats and its mechanism was investigated in this paper. It was found that pretreatment of ROS in normal rats with 100 mg/kg for 3 days, i.p., induced a partial prevention of hyperglycemia caused by glucose (2 g/kg, i.p.), while when hyperglycemia was induced in adrenalectomized (ADX) rats, the preventive effect of ROS on hyperglycemia was lost. In alloxan-induced diabetic rats, ROS (100 mg/kg for 15 days, i.p.) showed a significant decrease in blood glucose level and hepatic glucose -6-phosphatase activity with an increase in hepatic glycogen content. Furthermore, ROS raised plasma insulin level and lowered plasma corticosterone level in alloxan-induced diabetic rats. The results indicated that oligosaccharide of Rehmannia glutinosa Libosch. exerted a significant hypoglycemic effect in normal and alloxan-induced diabetic rats. The regulatory mechanism of ROS on glucose metabolism was adrenal dependent and had a close relation with the neuroendocrine system.

Stachyose extract from Rehmannia glutinosa Libosch. to lower plasma glucose in normal and diabetic rats by oral administration

The hypoglycemic effects of water extract and stachyose extract (Part III) from Rehmannia glutinosa Libosch. were investigated in this paper by oral administration to normal, glucose – and adrenaline-induced hyperglycemic and alloxan-induced diabetic rats. The results showed that Part III had the effect of lowering fasted plasma glucose level and partially preventing hyperglycemia induced by glucose (2.5 g · kg⁻¹, i.p.) and adrenaline (300 μg · kg⁻¹, i.p.), respectively, but no obvious dose-dependent effect was found when it was administered at the doses of 100, 200 and 400 mg · kg⁻¹ for 6 days, i.g. In alloxan-induced diabetic rats, Part III (200 mg · kg⁻¹ for 15 days, i.g.) gave a significant decrease in blood glucose level . The results suggested that Part III, which is mainly composed of stachyose from Rehmannia glutinosa Libosch., had a significant hypoglycemic effect in glucose – and adrenaline-induced hyperglycemic and alloxan-induced diabetic rats.

[Hypoglycemic activity of polysaccharide fraction from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao and the effect on carbohydrate metabolism in normal mouse liver]

The ethanol precipitate fraction (RG-WP) obtained from the hot water extract from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao is mainly composed of pectin-like polysaccharide, and exhibited hypoglycemic activity in normal and streptozotocin-induced mice by intraperitoneal administration of the fraction . The results obtained after chemical modification and proteinase treatments of RG-WP suggest that the activity exists in the polysaccharide moiety. Furthermore, the effect of RG-WP on the activities of enzymes responsible for the glucose metabolism in the liver of normal mouse was studied to elucidate the mechanism of the hypoglycemic activity . Administration of RG-WP to normal mice significantly increased the activities of hepatic glucokinase and glucose -6-phosphatase dehydrogenase, but decreased those of hepatic glucose -6-phosphatase and phosphofructokinase. RG-WP stimulated the secretion of insulin and reduced the glycogen content in the liver of normal mouse.

chlorogenic acid

Chlorogenic acid reduces the plasma glucose peak in the oral glucose tolerance test: effects on hepatic glucose release and glycaemia

The effects of chlorogenic acid (CA) on hepatic glucose output, blood glucose levels and on glucose tolerance were analysed. Hepatic uptake of CA and its effects on hepatic catabolism of L-alanine and glucose -6-phosphatase (G-6-Pase) activity were also evaluated. CA (1 mM) inhibited about 40% of G-6-Pase activity (p < 0.05) in the microsomal fraction of hepatocytes, but no effect was observed on production of glucose from gluconeogenesis or on L-alanine catabolism, at various concentrations of CA (0.33, 0.5 and 1 mM), in liver perfusion experiments. Since there were indications of a lack of uptake of CA by the liver, it is possible that this compound did not reach sufficiently high intracellular levels to inhibit the target enzyme. Accordingly, intravenous administration of CA also failed to provoke a reduction in blood glucose levels . However, CA did promote a significant reduction (p < 0.05) in the plasma glucose peak at 10 and 15 min during the oral glucose tolerance test, probably by attenuating intestinal glucose absorption , suggesting a possible role for it as a glycaemic index lowering agent and highlighting it as a compound of interest for reducing the risk of developing type 2 diabetes .

Chlorogenic acid Maintains glucose homeostasis through Modulating the Expression of SGLT-1, GLUT-2, and PLG in Different intestinal Segments of Sprague-Dawley Rats Fed a High-Fat Diet

Objective

To reveal the effects and related mechanisms of chlorogenic acid (CGA) on intestinal glucose homeostasis .

Methods

Forty male Sprague-Dawley rats were randomly and equally divided into four groups: normal chow (NC), high-fat diet (HFD), HFD with low-dose CGA (20 mg/kg, HFD-LC), and HFD with high-dose CGA (90 mg/kg, HFD-HC). The oral glucose tolerance test was performed, and fast serum insulin (FSI) was detected using an enzyme-linked immunosorbent assay. The mRNA expression levels of glucose transporters (Sglt-1 and Glut-2) and proglucagon (Plg) in different intestinal segments (the duodenum, jejunum, ileum, and colon) were analyzed using quantitative real-time polymerase chain reaction . SGLT-1 protein and the morphology of epithelial cells in the duodenum and jejunum was localized by using immunofluorescence.

Results

At both doses, CGA ameliorated the HFD-induced body weight gain, maintained FSI, and increased postprandial 30-min glucagon-like peptide 1 secretion. High-dose CGA inhibited the HFD-induced elevation in Sglt-1 expression. Both CGA doses normalized the HFD-induced downregulation of Glut-2 and elevated the expression of Plg in all four intestinal segments.