Neurohormetic phytochemicals: An evolutionary–bioenergetic perspective

Abstract

The impact of dietary factors on brain health and vulnerability to disease is increasingly appreciated. The results of epidemiological studies, and intervention trials in animal models suggest that diets rich in phytochemicals can enhance neuroplasticity and resistance to neurodegeneration. Here we describe how interactions of plants and animals during their co-evolution, and resulting reciprocal adaptations, have shaped the remarkable characteristics of phytochemicals and their effects on the physiology of animal cells in general, and neurons in particular. Survival advantages were conferred upon plants capable of producing noxious bitter-tasting chemicals, and on animals able to tolerate the phytochemicals and consume the plants as an energy source. The remarkably diverse array of phytochemicals present in modern fruits, vegetables spices, tea and coffee may have arisen, in part, from the acquisition of adaptive cellular stress responses and detoxification enzymes in animals that enabled them to consume plants containing potentially toxic chemicals. Interestingly, some of the same adaptive stress response mechanisms that protect neurons against noxious phytochemicals are also activated by dietary energy restriction and vigorous physical exertion, two environmental challenges that shaped brain evolution. In this perspective article, we describe some of the signaling pathways relevant to cellular energy metabolism that are modulated by ‘neurohormetic phytochemicals’ (potentially toxic chemicals produced by plants that have beneficial effects on animals when consumed in moderate amounts). We highlight the cellular bioenergetics-related sirtuin, adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 (IGF-1) pathways. The inclusion of dietary neurohormetic phytochemicals in an overall program for brain health that also includes exercise and energy restriction may find applications in the prevention and treatment of a range of neurological disorders.

Cellular stress response mechanisms as therapeutic targets of ginsenosides

“…Recently, it has been recognized that phytochemicals play a role in the chemical defense of plants, may act in a hormetic manner, and activate mildly evolutionarily conserved cellular stress response pathways at subtoxic doses after ingestion by humans. Moreover, such pathways may reduce the risk or enhance the tolerance to the insult of disorders, including neurodegenerative diseases, inflammatory and cardiovascular diseases, cancer, and inflammatory diseases . Thus, cellular stress response pathways may play a critical role in the therapeutic effects of hormetic phytochemicals.…”

Assessment of Antioxidant Activity and Neuroprotective Capacity on PC12 Cell Line of Frankenia thymifolia and Related Phenolic LC‐MS/MS Identification

“…Effects of these synthetic drugs have caught attention from research bases and industries towards natural herbal resources [2]. In addition to their antioxidant and several health promoting activities, natural bioactive compounds including phenolics, flavonoids, alkaloids, terpenoids, lignans, and saponins have potential properties to modulate neuronal function, protective mechanism against neurodegeneration, and memory enhancing properties and attenuate the damaging effects of reactive oxygen species (ROS).…”

Cellular membrane affinity chromatography (CMAC) in drug discovery from complex natural matrices

“…Plants use the array of phytochemicals that serve multiple purposes, for example: protection from abiotic stress, like excessive UV radiation (polyphenols, terpenes and terpenoids), attraction of pollinators (volatile terpenes), warding off herbivores (noxious phytochemicals, e.g. alkaloids), protection from bacterial or fungal infections (polyphenols, terpenoids, etc) [1][2][3][4]. Herbivores evolved different forms of biochemical changes, that protect them from the deleterious effects of some of the phytochemicals, for example: CYP450 superfamily of enzymes, transporter proteins and stress-response cellular signalling pathways [1][2][3][4].…”

“…alkaloids), protection from bacterial or fungal infections (polyphenols, terpenoids, etc) [1][2][3][4]. Herbivores evolved different forms of biochemical changes, that protect them from the deleterious effects of some of the phytochemicals, for example: CYP450 superfamily of enzymes, transporter proteins and stress-response cellular signalling pathways [1][2][3][4]. Many of these mechanisms are highly conserved adaptive stress response systems that humans share with simple herbivores.…”