Restoration of Brain Insulin Signaling by Tinospora crispa Extract via PI3K/AKT Pathway Modulation in HFHF-Fed Rats
DOI:
https://doi.org/10.48048/tis.2026.11597Keywords:
Insulin resistance, Tinospora crispa, PI3K, AKT, HFHF, Insulin resistance, Tinospora crispa, PI3K, AKT, HFHFAbstract
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.
HIGHLIGHTS
- The high consumption of fast food and high-sugar beverages, which disrupts sugar homeostasis, can also cause brain damage.
- Metformin, a blood sugar-lowering drug recently studied for its beneficial effects on brain function due to insulin resistance, can cause numerous side effects.
- Alternative plant-based drugs are needed as a substitute or adjuvant for metformin that can improve blood sugar levels, insulin resistance and mainly, the brain, which is still rarely studied.
- Unlike previous studies that primarily investigated Tinospora crispa in the context of peripheral glucose regulation, this work is the first to demonstrate its potential in reversing brain insulin resistance through restoration of PI3K/Akt signaling.
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