Evaluation of the Antidiabetic and Insulin Releasing Effects of A. squamosa, Including Isolation and Characterization of Active Phytochemicals

Abstract

Annona squamosa is generally referred to as a ‘custard apple’. Antidiabetic actions of hot water extract of Annona squamosa (HWAS) leaves together with isolation of active insulinotropic compounds were studied. Insulin release, membrane potential and intracellular Ca2+ were determined using BRIN-BD11 cells and isolated mouse islets. 3T3L1 adipocytes and in vitro models were used to determine cellular glucose uptake, insulin action, starch digestion, glucose diffusion, DPP-IV activity and glycation. Glucose intolerant high-fat fed rats were used for in vivo studies. Active compounds were isolated and characterized by HPLC, LCMS and NMR. HWAS stimulated insulin release from clonal β-cells and mouse islets. Using fluorescent indicator dyes and modulators of insulin secretion, effects could be attributed to depolarization of β-cells and influx of Ca2+. Secretion was stimulated by isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, indicating additional non-KATP dependent pathways. Extract stimulated cellular glucose uptake and insulin action and inhibited starch digestion, protein glycation, DPP-IV enzyme activity and glucose diffusion. Oral HWAS improved glucose tolerance and plasma insulin in high-fat fed obese rats. Treatment for 9 days with HWAS (250 mg/5 mL/kg), partially normalised energy intake, body weight, pancreatic insulin content, and both islet size and beta cell mass. This was associated with improved oral glucose tolerance, increased plasma insulin and inhibition of plasma DPP-IV activity. Isolated insulinotropic compounds, including rutin (C27H30O16), recapitulated the positive actions of HWAS on beta cells and in vivo glucose tolerance and plasma insulin responses. Annona squamosa is attractive as a dietary adjunct in treatment of T2DM and as a source of potential antidiabetic agents including rutin.

Anti-hyperglycaemic and insulin-releasing effects of Camellia sinensis leaves and isolation and characterisation of active compounds

“…In order to elucidate the secretory pathway activated by C. sinensis, these studies included assessment of the effects of established insulin secretion modulators including diazoxide (K ATP -channel opener), tolbutamide (sulphonylurea and K ATP -channel blocker), verapamil (voltage-dependent Ca 2þ channel blocker), isobutylmethylxanthine (phosphodiesterase inhibitor), 30 mM KCl and 10 mM alanine, both of which depolarise the plasma membrane and cause Ca 2þ influx. This is primarily accomplished by alanine through co-transport of the amino acid with Na þ plus metabolism and the production of ATP (28) .…”

“…To evaluate effects of the extract of C. sinensis leaves (250 mg/ 5 ml per kg) and the isolated phytochemical (isoquercitrin) (100 mg/kg) on glycaemic control, oral glucose tolerance tests (18 mmol/kg) were conducted using 6 or 12 h fasted HFF rats or mice in both acute or chronic studies (6 d) as described previously (28) . Blood was collected at times indicated in Figs.…”

“…Glucose tolerance (18 mmol/kg) was evaluated after 6 d of treatment. At the end of the study, pancreatic tissues were collected to measure islet morphology and pancreatic insulin content (28) .…”

Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools

“…The liver is essential for maintaining appropriate glucose homeostasis, as it delivers glucose during fasting and stores glucose afterward. However, these hepatic processes are dysregulated in diabetes mellitus, and this imbalance contributes to hyperglycemia in the fasted and postprandial states which is consistent with the decreased glycogen level in the liver of the DBC group [ 25 ]. The significant decrease of creatinine levels is an indication of protective effect of HKEx in diabetic nephropathy.…”

A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes

“…This herb is well known for its various medicinal properties, which include antioxidant, anti-diabetic, and hepatoprotective effects [ 95 ]. Hot water extract of A. squamosa was recently reported to promote cellular glucose absorption and the secretion/action of insulin, and to suppress DPP-4 activity [ 96 ].…”