A Systematic Review of the Neuroprotective Effects of a Polyherbal Formulation (Moringa oleifera, Phyllanthus niruri, Nigella sativa) on Cellular Injury Pathways Relevant to Ischemic Stroke Reperfusion and Trimethyltin-Induced Neurotoxicity

Abstract

Introduction: Ischemic stroke and the subsequent reperfusion injury trigger a devastating cascade of oxidative stress, neuroinflammation, and apoptosis, leading to neuronal death and significant neurological deficits. Polyherbal formulations represent a promising multi-target therapeutic strategy. This review systematically evaluates the neuroprotective potential of a combination of Moringa oleifera, Phyllanthus niruri, and Nigella sativa against the convergent cellular injury pathways central to both ischemia-reperfusion and Trimethyltin (TMT)-induced neurotoxicity.

Methods: A systematic search of PubMed, Google Scholar, Semanthic Scholar, Springer, Wiley Online Library was conducted for preclinical in vivo studies investigating the effects of M. oleifera, P. niruri, or N. sativa in animal models of cerebral ischemia (e.g., Middle Cerebral Artery Occlusion, MCAO) or TMT-induced neurotoxicity. Study selection followed PRISMA guidelines. Data on 17 key outcomes—including infarct volume, neurological scores, and biomarkers for oxidative stress, inflammation, and apoptosis—were extracted. Methodological quality was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool.

Results: A total of 16 preclinical studies met the inclusion criteria. The included studies demonstrated that extracts and active compounds from all three plants significantly mitigate cerebral injury. Key findings include a marked reduction in infarct volume and brain edema, improvement in neurological and motor function, and robust modulation of biochemical markers. Specifically, the interventions consistently reduced levels of malondialdehyde (MDA), increased the activity of endogenous antioxidants (Superoxide Dismutase, Catalase, Glutathione), suppressed pro-inflammatory mediators (TNF-α, IL-1β, IL-6, NF-κB), and inhibited apoptotic pathways by modulating the Bax/Bcl-2 ratio and Caspase-3 activity.

Discussion: The evidence strongly supports that the constituent herbs exert profound neuroprotective effects via a pleiotropic mechanism. Their primary antioxidant action quenches the initial burst of reactive oxygen species, thereby preventing the downstream activation of inflammatory and apoptotic cascades. The efficacy observed against both vascular (MCAO) and chemical (TMT) insults, which share common downstream cell death pathways, validates a robust, insult-independent cytoprotective mechanism. This suggests the polyherbal formulation targets fundamental processes of neuronal survival rather than merely vascular pathology.

Conclusion: The individual components of the proposed polyherbal formulation demonstrate significant neuroprotective activity against the core mechanisms of neuronal injury relevant to ischemic stroke. These findings provide a strong rationale for future preclinical research to validate the synergistic efficacy of the combined M. oleifera, P. niruri, and N. sativa formulation as a potential multi-target therapy for ischemic stroke.