Title : Neuroprotective effect of andrographolide combination with piperine against streptozotocin induced alzheimer’s disease
Abstract:
Streptozotocin (STZ) is a widely used neurotoxin in experimental models of Alzheimer’s disease (AD) due to its ability to induce cognitive dysfunction and neurodegeneration. STZ administration leads to the accumulation of amyloid-beta (Aβ) plaques and the development of AD-like symptoms, including memory impairment and neuroinfammation. Andrographolide (ANDRO), a bioactive compound derived from Andrographis paniculata, and Piperine from Piper nigrum has demonstrated antioxidant, anti-inflammatory, and neuroprotective effects. This study aimed to evaluate the neuroprotective effects of ANDRO in combination with Piperine in a rat model of STZ-induced AD. The study utilized male Wistar rats weighing 180–220 g (48 rats; n = 8/group). Stereotactic injections of STZ (3 mg/kg) were administered bilaterally to induce AD-like symptoms. After 7 days, rats showing cognitive impairments, as indicated by performance deficits in the Morris water maze, were selected for treatment. Rats were treated for 14 days with three different doses of ANDRO (15, 30, 60 mg/kg, p.o.) in combination with Piperine (5, 10, 20 mg/kg, p.o.) or donepezil (5 mg/kg, p.o.) as the standard treatment. Behavioral assessments were conducted weekly, and on day 21, rats were euthanized under deep anesthesia (pentobarbital, 100 mg/kg) for biochemical and neurochemical analysis. Brain tissues were isolated for evaluation of oxidative stress markers, neuroinfammatory mediators, neurotransmitters, and Aβ1–42 and phosphorylated tau (p-tau) levels. Treatment with ANDRO in combination with Piperine significantly improved cognitive function, as evidenced by behavioral tests, and reduced oxidative stress, as indicated by decreased malondialdehyde (MDA) and increased glutathione (GSH) levels. The combination treatment also attenuated neuroinfammation by reducing proinfammatory cytokines (IL-1β, TNF-α, and IL-16) and restored neurotransmitter levels, including glutamate and GABA. Additionally, ANDRO and Piperine treatment significantly decreased the hippocampal levels of Aβ1–42 and p- tau compared to the disease control group. The standard treatment with donepezil showed improvements in cognitive performance but had less impact on biochemical and molecular markers.
