Maternal hyperglycemia is associated with increased risk of adverse outcomes for both mother and offspring. Insulin is the standard treatment of hyperglycemia with the aim to reduce risks of complications, however, due to several restrictions, the search for more effective drugs from traditional medicinal plants continues. The antidiabetic effects of Orthosiphon stamineus (O . stamineus ) in non-pregnant and pregnant streptozotocin-induced Sprague Dawley rats were identified. The effect of different concentrations of O. stamineouson insulin level using isolated pancreatic islets in response to low and high concentrations of glucose was identified. Oral glucose tolerance test was performed in both pregnant and non-pregnant rats prior to and after treatment with O. stamineus (0.1 g/100 g of body weight). O. stamineus was given orally daily for 2 weeks in non-pregnant and 10 days in pregnant rats. Oral glucose tolerance test indicated that treatment with O. stamineus in non-pregnant and pregnant rats significantly reduced blood glucose level and stimulated glucose-induced insulin secretion. No mortality was recorded throughout the study and no signs of toxicity during the experimental period including in both mother and foetus. For plasma analysis, the interactions of peptides such as GLP-1 and ghrelin level might contribute to the glucose lowering effect by O. stamineus via stimulation of insulin. The incubation of islets showed that O . stamineussignificantly stimulated insulin release in response to high glucose. O. stamineus could be a potential source of a specific oral hypoglycaemic agent to treat glucose intolerance in pregnancy.

Aims. To evaluate the antidiabetic effects of Gynostemma pentaphyllum (GP) in Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, and to investigate the mechanisms of insulin release. Methods. Oral glucose tolerance test was performed and plasma insulin levels were measured. Results. An oral treatment with GP (0.3g/kg of body weight daily) for two weeks in GK rats improved glucose tolerance versus placebo group (). Plasma insulin levels were significantly increased in the GP-treated group. The insulin release from GP-treated GK rats was 1.9-fold higher as compared to the control group (). GP stimulated insulin release in isolated GK rat islets at high glucose. Opening of ATP-sensitive potassium (K-ATP) channels by diazoxide and inhibition of calcium channels by nifedipine significantly decreased insulin response to GP. Furthermore, the protein kinase A (PKA) inhibitor H89 decreased the insulin response to GP (). In addition, GP-induced insulin secretion was decreased after preincubation of GK islets with pertussis toxin to inhibit exocytotic proteins (). Conclusion. The antidiabetic effect of GP is associated with the stimulation of insulin release from the islets. GP-induced insulin release is partly mediated via K-ATP and L-type Ca2

Introduction: The beneficial effects of resistant starch (RS) consumption on health in terms of reducing postprandial hyperglycaemia are evident. However, the potential of local Sarawak sago RS in regulating glucose has not been extensively studied. Objectives: This study aims to identify glucose-lowering effects of Sarawak sago RS, namely native (RS2) and chemically modified (RS4). Methodology: An oral glucose tolerance test (OGTT) was performed before and after 1 month treatment with sago RS2 and RS4 in spontaneously type 2 diabetes (T2D), Goto-Kakizaki (GK) rat. The mechanisms involved were further explored by screening the in vitro inhibitory activities of α-glucosidase and dipeptidyl peptidase (DPP)-IV. Histopathology examination for pancreas, kidney and liver tissues was done in response to sago RS intake using haematoxylin and eosin (H&E) staining. Results and discussion: The incremental area under the curve (iAUC) for blood glucose in RS-treated groups was decreased and significant in RS2-treated group ( p < 0.05). Improved iAUC for insulin and higher glucagon-like peptide (GLP-1) levels were observed in all RS-treated groups ( p < 0.05). Both sago RS may have potential roles in regulating glucose via α- glucosidase and DPP-IV inhibitory activities by reducing intestinal glucose absorption. For histopathology, although insignificant, sago RS2 and RS4 attenuated lesion scores of pancreatic tissue whereas the liver and kidney tissues significantly showed lesser lesion scores compared to the control diabetic group suggesting the potential of RS in reducing cell degeneration. Conclusion: Findings of this study indicates that RS2 showed greater glucose-lowering effect when compared to RS4, thus the therapeutic potential in the T2D management should be further explored.

Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called ‘ubi gadong’. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method. Treatment of D.hispida caused mortality when dosage above 2000 mg/kg b.w. was given to pregnant rats. The PCR array showed that several genes were significantly up and down-regulated upon treatment with D.hispida. Treatment of D.hispida at 2000 mg/kg b.w leads to significant upregulation of several genes such as Btg2, Gsr, L2hgdn, S100a8, Slc17a3, Bhmt, Cd68, Cyp1a2 whereas several genes were downregulated such as Abcb1a, Aldoa, Cdc14b, Icam1, Krt18, Hpn and Maob. The consumption of D.hispida extract when taken at lower dosage of 2000 mg/kg may not be harmful to rats. D.hispida extract given at the highest dosage to pregnant rats caused alterations of several genes categorized in different hepatotoxic group functions such as necrosis, cholestasis and phospholipodisis.

The beneficial effects of resistant starch (RS) consumption on health in terms of reducing postprandial hyperglycemia are evident. However, the potential of local Sarawak sago RS in regulating glucose has not been extensively studied. This study aims to identify glucose lowering effects of Sarawak sago RS namely, native unmodified (RS2) and chemically modified (RS4). An oral glucose tolerance test was performed before and after one-month treatment with sago RS2 and RS4 in spontaneously type 2 diabetes, goto kakizaki rat. The mechanisms involved were further explored by screening the in vitro inhibitory activities of α-Glucosidase and DPP-IV. Histopathology examination for pancreas, kidney and liver tissues was performed in response to sago RS treatment using hematoxylin and eosin (H&E) staining.The blood glucose area under the curve (AUC) in RS-treated groups was decreased and significant in RS2-treated group (p<0.05). Improved insulin AUC and higher glucagon like peptide (GLP-1) levels were observed in all RS-treated groups (p<0.05). Sago RS2 and RS4 might have potential roles in regulating glucose via α-Glucosidase and DPP-IV inhibitory activities by reducing glucose absorption in the intestine. For histopathology study, although insignificant, sago RS2 and RS4 attenuated lesion scores of pancreatic tissue whereas the liver and kidney tissues significantly showed lesser lesion scores as compared to the control diabetic group suggesting the potential of RS in reducing cell degeneration which indeed requires further validation.Findings of this study suggests the therapeutic potential of sago RS in the T2D management which may justify further investigation to be done.

Background Type 3c diabetes mellitus (T3cDM) is a subtype that develops following pancreatic diseases, such as pancreatitis, impairing both exocrine and endocrine functions. Its management is challenging owing to exocrine enzyme deficiencies. Although plants have long been used for diabetes treatment, research on their role in T3cDM, particularly in exocrine enzymes, remains limited. The exact mechanisms by which enzymes and hormones interact remain unclear. Thus, this study aims to explore the role of Orthosiphon stamineus (OS) in glucose regulation by exploring both pancreatic endocrine and exocrine functions in the T3cDM Wistar Bonn/Kobori (WBN/Kob) pancreatitis rat model. Methods This protocol describes a planned, single-blind, randomized, controlled study conducted on animals to determine the efficacy of OS in regulating exocrine and endocrine pancreatic functions in a pancreatitis-induced WBN/Kob rat model. The groups will consist of control and different treatment groups. The duration of treatment is one month. A glucose tolerance test will be conducted orally before and after OS treatment. Blood glucose and insulin levels will be collected at different time points. Exocrine enzymes (amylase, lipase, and trypsinogen) and endocrine hormones (insulin, glucagon, ghrelin, pancreatic polypeptide, and somatostatin) will be measured in the serum. Hemoglobin A1c and lipid-soluble vitamins will also be evaluated. Results This pre-clinical study aims to explore pancreatic endocrine hormones and exocrine functions in response to OS treatment in rats with T3cDM pancreatitis. Body weight, diarrhea, and any adverse effects will be assessed as the secondary outcomes. Statistical analysis will be conducted to determine the significance of differences between the two groups. Conclusion This study protocol examines the efficacy of OS in addressing both exocrine and endocrine pancreatic dysfunction, ultimately aiding in blood glucose regulation. The findings of this study may help improve the health strategies of T3cDM patients and enhance patient outcomes.