Plants-Derived Neuroprotective Agents: Cutting the Cycle of Cell Death through Multiple Mechanisms

Abstract

Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer's, Parkinson's, and Huntington's diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features. Hence, several in vitro and in vivo study models specific to each disease have been employed to study NDs with the aim of understanding their underlying mechanisms and identifying new therapeutic strategies. Of the most prevalent drug development efforts employed in the past few decades, mechanisms implicated in the accumulation of protein-based deposits, oxidative stress, neuroinflammation, and certain neurotransmitter deficits such as acetylcholine and dopamine have been scrutinized in great detail. In this review, we presented classical examples of plant-derived neuroprotective agents by highlighting their structural class and specific mechanisms of action. Many of these natural products that have shown therapeutic efficacies appear to be working through the above-mentioned key multiple mechanisms of action.

Figure 1

Common phenolic compounds. Structures of aromatic acids and the flavonoid skeleton are shown.

Figure 2

Structures of some common neuroprotective phenolic acid esters and glycosides.

Figure 3

Structures of curcuminoids and resveratrol.

Figure 4

Examples of flavonoids with neuroprotective effects.

Figure 5

Bioactive phenolic compounds from Rosemary with potential neuroprotective effects.

Figure 6

Examples of alkaloids with neuroprotective effects.

Figure 7

Structures of ginsenosides and tenuigenin.

Figure 8

Structures of ginkgolides and related compounds.

Figure 9

Structures of selected neuroprotective sesquiterpenes.

Figure 10

The structure of the monoterpenoid, paeoniflorin.

Figure 11

Major targets for plant-derived neuroprotective agents. Cutting the cycle of neuronal cell death through general anti-inflammatory and antioxidant mechanisms has been shown to play the key role in neuroprotection by natural products. Ameliorating the deleterious effect of protein aggregation such as Aβ and reversing the transmitter deficit associated with NDs through multiple mechanisms have been well documented for many plant-derived neuroprotective agents.