Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs

Abstract

Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as "dementia", "Alzheimer's," "traditional medicine," "ethnopharmacology," "ethnobotany," "herbs," "medicinal plants" or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking.

Keywords: Alzheimer's disease; amyloid fibrils; dementia; ethnopharmacology; herbal drugs; β-amyloid.

Figure 1

Overview of mechanisms linking mitochondrial activity with dementia: (1) Mitochondria are crucially important for activating apoptosis (Wang and Youle, 2009); (2) Mitochondria regulate calcium signaling pathway (Walsh et al., 2009); (3) Oxidative phosphorylation occurs in electron transport chain of mitochondria; (4) Calcium signaling induces apoptosis (Hajnoczky et al., 2003); (5) Calcium and neuroinflammatory signaling pathways interact with each other (Sama and Norris, 2013); (6) Cell cycle requires calcium signaling (Berridge, 1995); (7) Mitochondrial oxidative phosphorylation is one of the main sources of reactive oxygen species (Dai et al., 2014); (8) Oxidative phosphorylation and reactive oxygen species regulate cell cycle (Antico Arciuch et al., 2012); (9) Oxidative stress and neuroinflammation are highly interconnected processes (Gao et al., 2014); (10) Neuronal apoptosis (LeBlanc, ; Favaloro et al., 2012); (11) Impaired calcium signaling (Berridge, ; Nimmrich and Eckert, 2013); (12) Changes in cell cycle (Raina et al., ; Katsel et al., 2013); (13) Presence of neuroinflammation (Pasqualetti et al., 2015); (14) Increased oxidative stress (Bennett et al., ; Kumar and Singh, 2015); (15) Changes in mitochondrial morphology and functions (Spano et al., ; Hung et al., 2018).

Figure 2

Chemical structure and targeted mechanisms of galantamine (Gal) against AD and dementia. The major biological effects of Gal lead to significant neuroprotection via dual AChE inhibition and allosteric stimulation of nAChRs.

Figure 3

Most prominent phytochemical constituents found in Gingko biloba (Gb).

Figure 4

Neuroprotective effects of Gingko biloba L.

Figure 5

Phytochemical constituents of ginseng.

Figure 6

Chemical structures of curcuminoids.

Figure 7

Tautomerism of curcumin: (A) Diketo and 1,3-keto-enol equilibrium form of curcumin with its biologically relevant structural units. (B) Hydrogen transfer in the most stable enol form.

Figure 8

Neuroprotective effects of curcumin.

Figure 9

Chemical structures of the major phytoconstituents of Glycyrrhiza glabra.

Figure 10

A simplified representation of the neuroprotective effects of licorice for dementia treatment.

Figure 11

Chemical structures of the nootropic drug L-Theanine and its proteinogenic amino acid analogs.