This preprint investigated the neuroprotective effects of berberine pretreatment in a rat model of Parkinson’s disease.
Key Points:
Berberine supplementation displayed therapeutic benefits for managing Parkinson’s disease symptoms:
- Improved motor function and coordination
- Reduced oxidative stress and enhanced antioxidant defenses
- Restored mitochondrial function
- Decreased neuroinflammation and apoptosis
- Effects were mediated through the Nrf2 pathway
Study Investigated Oral Berberine’s Mechanism and Protection Against Parkinson’s Disease
Researchers divided rats into groups to assess effectiveness of Berberine pretreatment on rotenone-induced Parkinson’s disease symptoms. They also assessed if Berberine works by affecting a key protein (Nrf2) involved in the antioxidant defense system.
- Control: Healthy, normal mice; no treatment
- Rotenone: Induced Parkinson’s disease model, no other treatment
- Berberine (30 mg/kg) + Rotenone
- Berberine (100 mg/kg) + Rotenone
- Nrf2 blocker + Berberine (30 mg/kg) + Rotenone
- Nrf2 blocker + Berberine (100 mg/kg) + Rotenone
Berberine was administered orally 60 minutes prior to rotenone, which was administered subcutaneously. Nrf2 blocker was administered via injection 30 minutes prior to Berberine.
Motor function and biomarkers were assessed 21 days after treatment.
“Rotenone administration resulted in significant reductions in body weight, locomotor activity, rotarod performance, grip strength, and motor coordination in rats, indicative of neurotoxicity and clinical Parkinson’s Disease symptoms.”
Berberine Pretreatment Improved Motor Function and Coordination
Berberine treatment significantly reduced:
- Impairments in locomotor activity
- Rotarod performance
- Grip strength
It also improved limb movement and motor coordination in the beam-crossing task.
When the key antioxidant protein (Nrf2) was blocked, the rats did not experience these benefits.
“[Berberine] treatment significantly attenuated rotenone-induced reduction in locomotor activity, latency to fall, and grip strength score, as well as the increase in the latency to remove from the bar, number of slips, and the time taken to cross the beam.”
Berberine Improved Markers of Oxidative Stress
Berberine prevented damage induced by Rotenone:
- Markers of oxidative stress were lower (nitrate, lipid peroxidation)
- Increased markers of regenerative capacity (glutathione, superoxide dismutase, and catalase)
The Nrf2 blocker negated berberine’s effects on these markers.
“Our study highlights the therapeutic potential of BBR in treating PD using an animal model. We propose that BBR exerts its neuroprotective effects through anti-oxidative, mitochondrial dysfunction prevention, anti-neuroinflammatory, and anti-apoptotic pathways, possibly mediated by the Nrf2 signaling pathway.”
Berberine Restored Mitochondrial Function
Mitochondrial dysfunction, a hallmark of Parkinson’s Disease, was evident in rotenone-treated rats.
Berberine administration restored mitochondrial function, an effect that was eliminated by the Nrf2 blocker.
“Berberine significantly alleviated rotenone-induced striatal mitochondrial dysfunction; the diminished levels of superoxide dismutase, total ATPase, NADH-cytochrome C reductase, and succinate-cytochrome C reductase in rotenone groups were significantly elevated by Berberine treatment”
Decreased Brain Inflammation
Berberine significantly reduced neuroinflammatory molecules (TNF-α, IL-1β, IL-6) and markers of cell death (apoptotic marker caspase-3).
This effect was eliminated when the key antioxidant protein, Nrf2, was blocked.
Conclusion:
Berberine exerted neuroprotective effects in a rotenone-induced rat model of Parkinson’s disease, improving motor function, reducing oxidative stress, restoring mitochondrial function, and decreasing neuroinflammation and apoptosis.
“Berberine treatment mitigated most of the rotenone-induced motor impairments, implicating the Nrf2-mediated pathway in its neuroprotective effects. However, co-administration of an NRF2 blocker significantly attenuated the protective effects of BBR on behavioral outcomes.”