Antihyperglycemic activity of 14-deoxy, 11, 12-didehydro andrographolide on streptozotocin-nicotinamide induced type

Nagalakshmi Kamaraj1, Kadhirmathiyan Velumani2, Ajay Guru3

  • 1Department of Biotechnology, Karpaga Vinayaga College of Engineering and Technology, Padalam, Chengalpattu, Tamil Nadu, 603308, India.

Molecular Biology Reports
|October 19, 2023
PubMed
Abstract

Insights

This study shows that 14-deoxy, 11, 12-didehydro andrographolide effectively lowers blood glucose in diabetic rats. The compound modulates key insulin signaling pathways, offering potential as an antihyperglycemic agent.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Endocrinology

Background:

  • Diabetic Mellitus (DM) is a metabolic disorder characterized by insulin deficiency or resistance.
  • Type 2 diabetes was induced in rats using streptozotocin and nicotinamide.
  • This study investigates the potential of 14-deoxy, 11, 12-didehydro andrographolide in managing hyperglycemia.

Purpose of the Study:

  • To evaluate the antihyperglycemic effects of 14-deoxy, 11, 12-didehydro andrographolide.
  • To assess the impact of the compound on insulin signaling pathways.
  • To determine the efficacy in a rodent model of type 2 diabetes.

Main Methods:

  • Rats with induced type 2 diabetes were treated with varying doses of 14-deoxy, 11, 12-didehydro andrographolide.
  • Blood glucose levels, body weight, and pancreatic histopathology were monitored.
  • Insulin signaling cascade gene and protein expression was analyzed using qPCR and Western blotting.

Main Results:

  • 14-deoxy, 11, 12-didehydro andrographolide significantly reduced blood glucose levels in diabetic rats.
  • The compound improved lipid profiles, decreasing the atherogenic index and cholesterol ratio.
  • Upregulation of insulin receptor tyrosine kinase (IRTK), insulin receptor beta (IR-β), and glucose transporter type 4 (GLUT4) was observed.

Conclusions:

  • 14-deoxy, 11, 12-didehydro andrographolide demonstrates significant antihyperglycemic activity.
  • The compound acts by modulating the expression of crucial insulin signaling molecules.
  • These findings suggest its potential as a therapeutic agent for type 2 diabetes.

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
212
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
160
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
184
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
192
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
334
Oral Hypoglycemic Agents: Sulfonylureas01:17

Oral Hypoglycemic Agents: Sulfonylureas

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
215