Neuroprotective and Neurorescue Mode of Action of Bacopa monnieri (L.) Wettst in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson's Disease: An In Silico and In Vivo Study.

Ethnopharmacological Relevance: Parkinson's disease (PD) is characterized by progressive death of dopaminergic neurons. The presently used medicines only tackle the symptoms of PD, but none makes a dent on the processes that underpin the disease's development. Herbal medicines have attracted considerable attention in recent years. Bacopa monnieri (L.) Wettst (Brahmi) has been used in Indian Ayurvedic medicine to enhance memory and intelligence. Herein, we assessed the neuroprotective role of Bacopa monnieri (L.) Wettst on Parkinson's disease. Aim of the Study: Bacopa monnieri (L.) Wettst, a medicinal herb, is widely used as a brain tonic. We investigated the neuroprotective and neurorescue properties of Bacopa monnieri (L.) Wettst extract (BME) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of PD. Materials and Methods: The mice model of MPTP-induced PD is used in the study. In the neuroprotective (BME + MPTP) and neurorescue (MPTP + BME) experiments, the animals were administered 40 mg/kg body weight BME orally before and after MPTP administration, respectively. Effect of BME treatment was evaluated by accessing neurobehavioral parameters and levels of dopamine, glutathione, lipid peroxide, and nitrites. An in silico study was performed using AutoDock Tools 1.5.6 (ADT). Results: A significant recovery in behavioral parameters, dopamine level, glutathione level, lipid peroxides, and nitrite level was observed in BME-treated mice. Treatment with BME before or after MPTP administration has a protective effect on dopaminergic neurons, as evidenced by a significant decrease in GFAP immunostaining and expression of inducible nitric oxide synthase (iNOS) in the substantia nigra region; however, the degree of improvement was more prominent in mice receiving BME treatment before MPTP administration. Moreover, the in silico study revealed that the constituents of BM, including bacosides, bacopasides, and bacosaponins, can inactivate the enzyme monoamine oxidase B, thus preventing the breakdown of MPTP to MPP+. Conclusion: Our results showed that BME exerts both neuroprotective and neurorescue effects against MPTP-induced degeneration of the nigrostriatal dopaminergic neurons. Moreover, BME may slow down the disease progression and delay the onset of neurodegeneration in PD.

Genistein Prevents Hypoxia-Induced Cognitive Dysfunctions by Ameliorating Oxidative Stress and Inflammation in the Hippocampus.

Genistein (GE), a plant-derived isoflavone, is a polyphenolic non-steroidal compound. Studies showed that GE possesses anti-cancer, anti-inflammatory, anti-microbial, anti-oxidant, and anti-apoptotic activities. However, the neuroprotective role of GE in amnesia has not been studied. This study aimed to evaluate the anti-amnesic potential of GE in a mice model of hypoxia-induced amnesia and to understand the underlying mechanism. Mice were exposed to hypoxia (10% O2) and administered vehicle or GE (10, 20, 30 mg/kg) orally for 28 days. Thereafter, Morris water maze (MWM), novel object recognition (NOR), and passive avoidance task (PAT) were performed to evaluate cognitive behavior. Next, we performed biochemical tests and gene expression analysis to uncover the mechanism underlying GE mode of action. Our results showed that GE-treatment ameliorated hypoxia-induced cognitive dysfunctions in mice. Further, GE-treatment suppressed the oxidative stress in the hippocampus of amnesic mice as evidenced by reduced lipid peroxidation, reduced nitrite and ROS levels, and increased levels of reduced glutathione (GSH) and increased total antioxidant capacity. GE treatment reduced the expression of pro-inflammatory cytokines TNFα, IL1ß, IL6, and MCP-1 and increased the expression of anti-inflammatory cytokine IL10 in the hippocampus of amnesic mice. Finally, GE treatment enhanced the expression of neuroprotective genes including BDNF, CREB, CBP, and IGF1 in the hippocampus of amnesic mice. Altogether, our results showed that GE treatment prevents hypoxia-induced cognitive dysfunction in mice by reducing oxidative stress and suppressing neuroinflammation while increasing the expression of neuroprotective genes in the hippocampus.

Neuroprotective effects of Bacopa monnieri in Parkinson's disease model.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra region and the presence of α-synuclein aggregates in the striatum and surrounding areas of brain. Evidences suggest that neuroinflammation plays a role in the progression of PD. We examined the neuro-protective effects of Bacopa monnieri (BM) in regulating neuroinflammation. Administration of BM suppressed the level of pro-inflammatory cytokines, decreased the levels of α-synuclein, and reduced reactive oxygen species (ROS) generation in PD animal model. Pre-treatment of BM showed more prominent results as compare to co- and post-treatment. Results suggest that Bacopa can limit inflammation in the different areas of brain, thus, offers a promising source of novel therapeutics for the treatment of many CNS disorders.