Phytochemicals as Micronutrients: What Is their Therapeutic Promise in the Management of Alzheimer’s Disease?

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease with devastating outcomes to patients and exhaustive burdens to healthcare systems. Alzheimer’s disease has always been the focus of extensive research since its discovery in the early 1900s; however, AD continues to wreak havoc among the elderly population. Unfortunately, until now AD is still without any defined treatment that can curb its otherwise insidious progression. In the wake of this crisis and in the absence of a restorative cure, alternative approaches to AD management have been sought. In this regard, phytochemicals—a class of micronutrients composed of herbal or plant secondary metabolites— have shown potential as novel agents in the management of several diseases including cancer, hyperlipidemia, cardiovascular diseases, hyperglycemia, and neurodegenerative disorders including AD. Phytochemicals therapeutic abilities can be attributed to their ability to protect against several AD pathologic events such as inflammation, oxidative stress, protein misfolding, aggregation, and several more. In this chapter, we overview AD and its progression to pathology. Next, we highlight the available conventional treatments currently used to mitigate symptoms of AD. Then, we expose phytochemicals and their known therapeutic potential in several diseases including neurodegenerative disorders. Lastly, we explore the available literature concerning the use of phytochemicals in the management of AD. Specifically, light is shed on the possible curative capacity of certain plant phytochemicals—namely those of Ginkgo biloba, Piper nigrum, Withania somnifera, Lavandula angustifolia, Olea europaea, Nigella sativa, Ficus carica, and Panax ginseng—in the management of AD. Mechanisms by which extracts of these plants exert their neuroprotective effects are discussed alongside other aspects pertaining to the efficacy, safety, and druggability of some of these phytochemicals. We conclude that phytochemicals have shown promise in the management of AD. However, clinical trials remain lacking in this area and extensive efforts need to be exerted to determine the safety, efficacy, and exact modes of action of phytochemicals in human AD patients

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

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

Crosstalk between Microglia and Neurons in Neurotrauma: An Overview of the Underlying Mechanisms.

Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation. However, sustained microglial activation initiates a chronic neuroinflammatory response which can disturb neuronal health and disrupt communications between neurons and microglia. Thus, microglia-neuron crosstalk is critical in a healthy brain as well as during states of injury or disease. As most studies focus on how neurons and microglia act in isolation during neurotrauma, there is a need to understand the interplay between these cells in brain pathophysiology. This review highlights how neurons and microglia reciprocally communicate under physiological conditions and during brain injury and disease. Furthermore, the modes of microglia-neuron communication are exposed, focusing on cell-contact dependent signaling and communication by the secretion of soluble factors like cytokines and growth factors. In addition, how microglia-neuron interactions could exert either beneficial neurotrophic effects or pathologic proinflammatory responses are discussed. We further explore how aberrations in microglia-neuron crosstalk may be involved in central nervous system (CNS) anomalies, namely: traumatic brain injury (TBI), neurodegeneration, and ischemic stroke. A clear understanding of how the microglia-neuron crosstalk contributes to the pathogenesis of brain pathologies may offer novel therapeutic avenues of brain trauma treatment

High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury

AimsTraumatic brain injury (TBI) constitutes a serious public health concern. Although TBI targets the brain, it can exert several systemic effects which can worsen the complications observed in TBI subjects. Currently, there is no FDA-approved therapy available for its treatment. Thus, there has been an increasing need to understand other factors that could modulate TBI outcomes. Among the factors involved are diet and lifestyle. High-fat diets (HFD), rich in saturated fat, have been associated with adverse effects on brain health. Main methodsTo study this phenomenon, an experimental mouse model of open head injury, induced by the controlled cortical impact was used along with high-fat feeding to evaluate the impact of HFD on brain injury outcomes. Mice were fed HFD for a period of two months where several neurological, behavioral, and molecular outcomes were assessed to investigate the impact on chronic consequences of the injury 30 days post-TBI. Key findingsTwo months of HFD feeding, together with TBI, led to a notable metabolic, neurological, and behavioral impairment. HFD was associated with increased blood glucose and fat-to-lean ratio. Spatial learning and memory, as well as motor coordination, were all significantly impaired. Notably, HFD aggravated neuroinflammation, oxidative stress, and neurodegeneration. Also, cell proliferation post-TBI was repressed by HFD, which was accompanied by an increased lesion volume. SignificanceOur research indicated that chronic HFD feeding can worsen functional outcomes, predispose to neurodegeneration, and decrease brain recovery post-TBI. This sheds light on the clinical impact of HFD on TBI pathophysiology and rehabilitation as well.This work was funded by grants from the Science, Technology and Innovation Funding Authority to AFE (45912) and American University of Beirut Faculty of Medicine, Medical Practice Plan (AUB-FM MPP) to FK (320112). We thank the members of Dr. Ahmed El-Yazbi lab. (Nahed Mogharbil & Dr. Rana Alaaeddine) for their sincere help in conducting the cardiovascular experiments. We thank Leila Nasrallah and Yara Yehya for their help in the neurological experiments. We thank Dr. Gerry Shaw, the CEO of EnCor Biotechnology Inc. Gainesville, Fl, USA for helping us with the antibodies

Western and ketogenic diets in neurological disorders: can you tell the difference?

The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.Funding. This work has been funded by an American University of Beirut Faculty of Medicine grant to F.H.K. via the Medical Practice Plan (MPP), titled “Impact of metabolic stress-induced neuroinflammation on molecular and behavioral outcomes post-traumatic brain injury.” The funding agency had no role in the writing of the manuscript or the decision to submit it for publicatio