Phytochemicals as Micronutrients: What Is their Therapeutic Promise in the Management of Traumatic Brain Injury?

Abstract

Traumatic brain injury (TBI) is one of the key causes of deaths and disabilities worldwide. TBI progresses in two phases. The primary phase of injury is the direct result of the physical damage caused by the external force applied to the brain while the secondary injury takes place minutes to days after the primary injury. The secondary phase of TBI is marked by a series of pathological events that start following the initial mechanical impact. The mechanisms underlying TBI pathogenesis in the secondary phase are intricate and include metabolic alterations, excitotoxicity, oxidative stress, and neuroinflammation, among others; all culminating in neuronal cell damage and death. Currently, there is no FDA-licensed drug that targets TBI. Hence, the search for novel therapeutic agents that can target one or more of the mechanisms underlying the pathology of the secondary phase of TBI is warranted. Such novel therapeutic agents are expected to ameliorate the adverse consequences of TBI. Over the years, evidence has accumulated regarding the role of phytochemicals as novel agents in the management of TBI. Phytochemicals are a class of micronutrients composed of herbal or plant secondary metabolites. Phytochemicals offer appropriate candidates for the treatment of TBI since their use can warrant the inhibition of the progression of the secondary injury and the activation of major neuroprotective signaling pathways following TBI. In this regards, phytochemicals have been acknowledged to cause a significant decrease in neuronal injury through different mechanisms including the activation of the Nrf2 transcription factor leading to activation of several antioxidant enzyme systems such as superoxide dismutase, inhibition of NADPH oxidases (NOX) enzymes, suppression of nuclear factor kappa B (NF-κB) activity and reduction of the release of inflammatory mediators, suppression of the NLRP3 inflammasome, stimulation of neurogenesis by activating neurotrophic factors (BDNF), among others. As such, the chapter aims to evaluate the neuroprotective effects of phytochemicals in TBI by reviewing the available literature. In this chapter, we introduce TBI and the mechanisms that underlie its pathology. Also, we overview the current conventional strategies that are being used to manage TBI. Then, we overview phytochemicals and explore their use in the management of diseases with a special focus on their use in the treatment of neurological diseases. Finally, we discuss the therapeutic potentials of phytochemicals in the management of TBI by focusing on six phytochemicals: ginseng, curcumin, coumarin, genistein, apocynin, and baicalein. We review the available literature on the use of these phytochemicals in the context of TBI. In addition, we document the recent studies aimed that discuss the in vitro and in vivo experimental evidence on the cellular and molecular mechanisms of neuroprotection by these phytochemicals. We conclude that all of the studied phytochemicals have shown experimental preclinical promise. But, well-designed and controlled clinical trials are urgently needed to demonstrate their safety and efficacy in order to realize their benefits in human TBI patients.