Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation

Abstract

BBR attenuated cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB signaling pathway, and by retarding oxidative stress and neuro-inflammation.

Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review

“…Furthermore, intracerebral administration of STZ led to features characteristic of AD, including cognitive impairment and ACh homeostasis disturbances [160], which could be alleviated by insulin sensitizers [15,161]. Our literature survey indicated that berberine directly protects the brain cells against damages associated with dementia [27,29,32,34,39], possibly via antioxidative and anti-inflammatory effects [28,35,37,42], and also by reducing A levels [31,38]. Berberine was able to promote cognitive functions [38,40], through enhancing cholinergic neurotransmission [30,33,36,41].…”

“…Potential benefits were demonstrated in 16 nondiabetic studies (Table 1) and in 9 studies using diabetic models (Table 2). In nondiabetic models, berberine protected learning and memory in heavy metal-induced AD [28], Aβ-induced memory deficits model [34], familial AD models [29,35,38] and D-galactose-induced brain damage [40,145]. In the rat VaD model induced by chronic cerebral hypoperfusion, berberine protected hippocampal calyculin A1 (CA1) neurons and prevented memory deficit [27].…”

“…In the rat VaD model induced by chronic cerebral hypoperfusion, berberine protected hippocampal calyculin A1 (CA1) neurons and prevented memory deficit [27]. Mechanistically, berberine reduced oxidative stress in the brain by increasing the levels of antioxidants, including glutathione, glutathione peroxidase and superoxide dismutase (SOD) [28,35,37], reduced AChE expression levels [28] and AChE activity at as low as 0.44-6 µmol/L half maximal inhibitory concentration [30,33,36,41] and uncompetitively inhibited indoleamine 2,3-dioxygenase [32], the first rate-limiting enzyme of kynurenine pathway, thereby potentially reducing the accumulation of neurotoxic metabolites involved in AD pathogenesis [146][147][148]. Berberine reduced Aβ generation in Swedish mutant amyloid precursor (APP)-expressing cells [31] and suppressed the Aβ-induced inflammatory response in microglia [42].…”

“…Although bioavailability of berberine is relatively low, it crosses the blood brain barrier and stably distributes in the brain tissue, compared to other organs [162], suggesting that berberine could prevent dementia through direct actions in the brain. As a whole, berberine could protect brain functions via a number of mechanisms: neuroprotection [55,62], reducing oxidative stress [28,35,37,43], suppressing brain inflammation [51,53], reducing the generation of Aβ, hyperphosphorylated tau and APP [29,31,39,146], enhancing ACh signaling [28,30,33,36,41,45], and possibly reducing the accumulation of neurotoxic metabolites [32], suggesting that berberine is an effective therapy against dementia including AD and VaD.…”

Berberine: A potential adjunct for the treatment of gastrointestinal cancers?

“…[2][3][4][5][6][7][8] Moreover, a growing preclinical literature suggests that BBR has a broad number of antinfective activities, [9][10][11] and it could also exert some protective effects against neurodegenerative processes. 12 Also, recent data have shown that BBR could also exert some gastroprotective effects. 13 BBR has poor water solubility and its oral bioavailability is less than 5% and bowel P-glycoprotein contributes to this, actively expelling the alkaloid from the lumen mucosal cells.…”