Standardized Extracts of Bacopa monniera Protect Against MPP+- and Paraquat-Induced Toxicity by Modulating Mitochondrial Activities, Proteasomal Functions, and Redox Pathways

Abstract

Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases and affects millions of people worldwide. Strong evidence supports the role of free radicals, oxidative stress, mitochondrial, and proteasomal dysfunctions underlying neuronal death in PD. Environmental factors, especially pesticides, represent one of the primary classes of neurotoxic agents associated with PD, and several epidemiological studies have identified the exposure of the herbicide paraquat (PQ) as a potential risk factor for the onset of PD. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of Bacopa monniera (BM) against PQ-induced and 1-methyl-4-phenyl-pyridinium iodide (MPP(+))-induced toxicities and to elucidate the mechanisms underlying this protection. Our results show that a pretreatment with the BM extract from 50 μg/ml protected the dopaminergic SK-N-SH cell line against MPP(+)- and PQ-induced toxicities in various cell survival assays. We demonstrate that BM pretreatment prevented the depletion of glutathione (GSH) besides preserving the mitochondrial membrane potential and maintaining the mitochondrial complex I activity. BM pretreatment from 10.0 μg/ml also prevented the generation of intracellular reactive oxygen species and decreased the mitochondrial superoxide level. BM treatment activated the nuclear factor erythroid 2-related factor 2 pathway by modulating the expression of Keap1, thereby upregulating the endogenous GSH synthesis. The effect of BM on the phosphorylation of Akt further strengthens its role in the promotion of cell survival. By preserving the cellular redox homeostasis and mitochondrial activities and by promoting cell survival pathways, BM extract may have therapeutic uses in various age-related neurodegenerative diseases such as PD.

A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats

“…Pennell [family: Scrophulariaceae ] has been considered as a reputable nootropic medicine and is traditionally used for memory enhancing, rejuvenating, increasing longevity and promoting progeny [4]. Experimental studies have shown that Bacopa monnieri possesses anti-dementia [5], cognitive enhancing [6, 7], antidepressant [8], anti-anxiety [9], antiepileptic [10–12], antiparkinson [13, 14], anti-amnesic [15–17], antibacterial [18], antidiabetic [19], anti-inflammatory [20–22], anti-arthritis [23], antihypertensive [24], anticancer [25], anti-asthmatic [26], spasmolytic [27], antiulcer [28, 29], analgesic [30–32], anti-aging [33], antifungal [34], antioxidant [35–37], adaptogenic [38, 39], anti-addictive [40, 41], lessened narcotics-induced toxicity [42], neuroprotective [35, 43–45], antiemetic [46, 47], cardioprotective [48, 49], hepatoprotective [50–53] and nephroprotective [53, 54] properties. Clinical trials have shown that Bacopa monnieri has both acute [55, 56] and chronic [55–59] cognitive enhancing effects and improves memory performance in older persons [60, 61] and patients with Alzheimer’s disease [62].…”

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

“…Paraquat toxicity also is known to involve mitochondrial dysfunction, excessive NMDA activity, oxidative stress, elevated in�ammatory cytokines and elevated NF-B activity [142][143][144][145][146][147], raising a possible role for all of these NO/ONOO − cycle elements in the generation of paraquatdependent PAH.…”

Comparative evaluation of four triterpenoid glycoside saponins of bacoside A in alleviating sub-cellular oxidative stress of N2a neuroblastoma cells

“…The antioxidant properties of bacoside A are attributed to their ability to regulate the activities of antioxidant enzymes viz . superoxide dismutase, catalase and glutathione peroxidases in the neuronal cells . Bacosides‐rich extracts were evaluated for their anti‐apoptotic and cytoprotective properties on neuronal and lung epithelial cell lines .…”

“…superoxide dismutase, catalase and glutathione peroxidases in the neuronal cells. [16,17] Bacosides-rich extracts were evaluated for their anti-apoptotic and cytoprotective properties on neuronal and lung epithelial cell lines. [18,19] Existing studies had provided extensive documents on nootropic properties of B. monnieri but lack information on the role of four different bacoside A components in alleviating progression of neuronal diseases.…”