Kartika Rahma, Erni Hernawati Purwaningsih, Yetty Ramli, Aulanniam Aulanniam
Insulin resistance in the brain contributes to metabolic and neurodegenerative disorders. Existing ones have a limited efficacy and a long-term safety profile for traditional therapy, mainly represented by metformin. Hence, there is an urgent necessity for a safe alternative using plant-based medications. One such candidate, Tinospora crispa (T. crispa), has shown antidiabetic properties, but there is no scientific study focusing on its effectiveness in alleviating brain insulin resistance. This study aims to evaluate the potential of T. crispa for brain insulin resistance via modulation of the PI3K/Akt pathway. Six-week-old Wistar rats were randomly assigned to seven different groups for the study. These included a normal control group (N), a high-fat high-fructose group (HFHF), a group treated with metformin (MET), groups receiving T. crispa extract at doses of 200 mg/kgBW (TC200) and 400 mg/kgBW (TC400) combinations of T. crispa with metformin (TC200MET, TC400MET). The rats were fed a high-fat, high-fructose (HFHF) diet for 16 weeks, with treatments beginning at week 8 after confirming insulin resistance. Body weight, glucose and insulin levels were measured at week 0, 8 and 16. Lipid profiles were assessed using colorimetry, whilebrain PI3K/Akt expressions were measured using qRT-PCR. Both were conducted at the end of the study. Results shows that A 16-week HFHF diet did not affect body weight or induce obesity in mice but led to insulin resistance, elevated fasting blood glucose and altered lipid profiles. Treatment with T. crispa extract or its combination with metformin improved insulin resistance, glucose homeostasis and lipid levels. Notably, increased expression of IRS, PI3K and AKT was observed only in the TC400 and TC400MET groups. These findings suggest that T. crispa extract exhibits neuroprotective effects as an insulin sensitizer via the PI3K/Akt pathway, both as a monotherapy and in combination with metformin. © 2026, Walailak University. All rights reserved.
Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; Department of Pharmacy, Faculty of Health Science and Technology, Universitas Binawan, Jakarta, 13630, Indonesia; Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; Department of Neurology, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia; Department of Chemistry, Faculty of Science, Universitas Brawijaya, Malang, 65145, Indonesia
