Anti-neuroinflammatory Potential of Natural Products in Attenuation of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder associated with dementia and cognitive impairment most common in elderly population. Various pathophysiological mechanisms have been proposed by numerous researcher, although, exact mechanism is not yet elucidated. Several studies have been indicated that neuroinflammation associated with deposition of amyloid- beta (Aβ) in brain is a major hallmark toward the pathology of neurodegenerative diseases. So, there is a need to unravel the link of inflammatory process in neurodegeneration. Increased microglial activation, expression of cytokines, reactive oxygen species (ROS), and nuclear factor kappa B (NF-κB) participate in inflammatory process of AD. This review mainly concentrates on involvement of neuroinflammation and the molecular mechanisms adapted by various natural compounds, phytochemicals and herbal formulations in various signaling pathways involved in neuroprotection. Currently, pharmacologically active natural products, having anti-neuroinflammatory potential are being focused which makes them potential candidate to cure AD. A number of preclinical and clinical trials have been done on nutritional and botanical agents. Analysis of anti-inflammatory and neuroprotective phytochemicals such as terpenoids, phenolic derivatives, alkaloids, glycosides, and steroidal saponins displays therapeutic potential toward amelioration and prevention of devastating neurodegeneration observed in AD.

Keywords: Alzheimer's disease; herbal formulation; natural products; neuroinflammation; neuroprotection; phytochemicals.

Figure 1

Schematic representation of role of glial cells in pathophysiology of Alzheimer's disease. Numerous stimuli such as Aβ peptides, neurotoxin and proinflammatory mediators activates microglial cells and astrocytes. Activated microglial cells and astrocytes results in increased production of proinflammatory cytokines and intracellular Aβ and Tau aggregation resulting in synaptic loss and neuronal death (Morales et al., 2014).

Figure 2

Schematic representation of natural products involved in neuroprotection against Alzheimer's disease. External stimulus binds to Trk receptor activating PI3K/AKT, Ras/MAPK, and PL-Cγ pathways. LPS binds to TLRs activating NF-κB and JNK signaling. External stimulus releases Nrf2 from Nrf2-KEAP-1 complex and activates ARE. Trk, tyrosine kinase receptor; LPS, lipopolysaccharide; TLRs, toll-like receptors; PI3K, phosphatidylinsoitol-3-kinase; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; ERK, extracellular signal-regulated kinases; Nrf2, nuclear factor e2-related factor 2; KEAP-1, Kelch-like ECH-associated protein-1; MEK, mitogen-activated protein kinase; PL-Cγ, phospholipase Cγ; NF-κB, nuclear factor-kappa B; PKC, protein kinase C; JNK, c-Jun N-terminal kinase; ARE, Antioxidant response element; CREB, cyclic adenosine monophosphate response element binding protein; IκB, inhibitory kappa B; CaMKII/IV, Ca2+-calmodulin kinase II/IV; GSK3β, glucose synthase kinase-3β. Diosgenin, Prosapogenin III, Quercetin, Apigenin, Ginsenoside Rg3, Rosmarinic acid, Ginkgolide B, Limonoid, Quinic acid, Curcumin, Resverstrol, Berberine, 6- Shagoal, Ligraminol E4-O-β-d-xyloside, Huperzine A, Sophocarpidine, Naringenin, Epigallocatechin-3-galate (EGCG), Oxyresveratrol, α-Mangostin, Galantamine.

Figure 3

Chemical Structures of natural compounds.