Bacopa monnieri inhibits apoptosis and senescence through mitophagy in human astrocytes

Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

“…Again, in in vitro and in vivo models of mitochondrial toxin-induced PD, phytochemicals such as kaempferol and baicalein provide anti-apoptotic and antioxidant neuroprotective effects through the enhancement of mitochondrial turnover by autophagy, which is abolished when autophagy is pharmacologically inhibited [ 52 , 55 ]. These effects are also reported for bacosides/bacopasides, which induce Parkin-dependent mitophagy to exert anti-senescence and anti-apoptotic effects [ 71 ]. While inducing mitophagy, Parkin-dependent ubiquitination also triggers the degradation of the pro-apoptotic protein Bax [ 179 ].…”

“…Similar to polyphenols, terpenes are classified into many categories based on the number of carbon atoms and iso-prene residues present in their structure, ranging from monoterpenes to polyterpenes [ 108 ]. As some triterpenes are steroidal in nature, they are known as triterpenoid saponins, among which bacosides/bacopasides and withanolides represent two major bioactive compounds of nootropic and neuroprotective plant extracts [ 3 , 71 , 109 , 110 , 111 , 112 , 113 ]. Within the tetraterpenoid group, carotenoids (such as α-/β carotene, lutein, zeaxanthin, and fucoxanthin) occurring widely in orange fruits and vegetables, are worth citing for their neuroprotective effects in various experimental models of neurodegeneration, especially AMD [ 7 , 114 , 115 ].…”

“…As shown in various experimental models of neurodegeneration, a failure in the autophagy machinery may predispose to neuronal injury due to extreme oxidative damage intermingling with protein overload and neuroinflammation, while rescuing autophagy may confer protection to grant cell survival [ 7 , 10 , 21 , 24 , 28 , 29 ]. It is remarkable that a wide variety of phytochemicals, including phenolic compounds such as anthocyanins, stilbenes (resveratrol), monophenols (caffeic acid, gallic acid), glucosides and flavonoids (catechin, epicatechin, quercetin, myricetin), and also nitrogen-containing compounds (berberine and spermine), are capable of stimulating autophagy to confer neuroprotection through either Akt/mTOR inhibition or AMPK/SIRT1 or TFEB activation [ 3 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Thus, in the next section, we discuss evidence bridging the antioxidant effects of these compounds with autophagy-related neuroprotection.…”

“…In this frame, it is remarkable that the common neuroprotective, antioxidant, and anti-inflammatory effects produced by several phytochemicals are associated with rescuing autophagy, meanwhile counteracting behavioral alterations, mitochondrial damage as well as intracellular accumulation and release of potentially detrimental substrates [ 3 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. As recently reviewed, the neuroprotective effects of phytochemicals involve also a double-faceted, yet controversial modulation of the proteasome pathway, which will not be discussed in detail herewith [ 9 ].…”

Natural Products for Neurocognitive Disorders

“…Furthermore, studies on APP/PS1 mice have shown that Bacopia monnieri extracts can reduce plaque load and enhance plaque clearance, possibly via phagocytosis (20). Bacopa monnieri prevents senescence and has an anti-apoptotic effect in brain astrocytes and, therefore, is thought to combat brain pollution and age-related neurological disorders (21). Taken together, the neuroprotective actions and positive effects of bacoside A on memory, mental, and intellectual functions can be largely attributed to its ability to reduce beta amyloid aggregation and toxicity (22), lower inflammation in the brain, scavenge ROS, and increase cerebral blood flow (23,24).…”