Herbal Therapeutics for Alzheimer's Disease: Ancient Indian Medicine System from the Modern Viewpoint

Abstract

Alzheimer's is a chronic neurodegenerative disease where amyloid-beta (Aβ) plaques and neurofibrillary tangles are formed inside the brain. It is also characterized by progressive memory loss, depression, neuroinflammation, and derangement of other neurotransmitters. Due to its complex etiopathology, current drugs have failed to completely cure the disease. Natural compounds have been investigated as an alternative therapy for their ability to treat Alzheimer's disease (AD). Traditional herbs and formulations which are used in the Indian ayurvedic system are rich sources of antioxidant, anti-amyloidogenic, neuroprotective, and anti-inflammatory compounds. They promote quality of life by improving cognitive memory and rejuvenating brain functioning through neurogenesis. A rich knowledge base of traditional herbal plants (Turmeric, Gingko, Ashwagandha, Shankhpushpi, Giloy, Gotu kola, Garlic, Tulsi, Ginger, and Cinnamon) combined with modern science could suggest new functional leads for Alzheimer's drug discovery. In this article Ayurveda, the ancient Indian herbal medicine system based on multiple clinical and experimental, evidence have been reviewed for treating AD and improving brain functioning. This article presents a modern perspective on the herbs available in the ancient Indian medicine system as well as their possible mechanisms of action for AD treatment. The main objective of this research is to provide a systematic review of herbal drugs that are easily accessible and effective for the treatment of AD.

Keywords: Alzheimer's; Aβ plaques; cognitive memory; medicinal herbs; neurodegenerative; neurofibrillary tangles.

Fig. (1)

The amyloid precursor protein (APP) is a transmembrane protein, and during normal physiological condition, 90% of the APP is cleaved through α and γ-secretase and forms soluble p3 and APP intracellular domain (AICD) fragments. When a small percentage of APP molecules enter the β-secretase route, APP is cleaved by β-secretase. It results in the formation of β-APPs and membrane-bound C99 peptides. The γ-secretase cleaves the C-terminal membrane-bound C99 peptide within the transmembrane domain to produce two primary isoforms of Αβ with 40 and 42 amino acid lengths which are responsible for Αβ plaques formation.

Fig. (2)

The phytochemically active chemical structure of curcumin (a) ar-Tumerone, and (b) curcumin.

Fig. (3)

This flowchart shows the diverse mechanisms of action by which curcumin provides neuroprotection against Alzheimer’s disease. The active compounds inhibit the development and neurotoxicity of Aβ and hyperphosphorylated tau, which are two histology hallmarks of Alzheimer’s disease.

Fig. (4)

The bioactive chemical structure of Gingko biloba extract Egb761.

Fig. (5)

The several mechanisms by which Ginkgo extract provides neuroprotection in Alzheimer’s disease.

Fig. (6)

The chemical structure of Withaferin A. It is a lactone produced from Withania somnifera with anti-inflammatory, immunomodulatory, anti-metastasis, and anti-carcinogenic activities.

Fig. (7)

The chemical structure of Ayapanin isolated from the sources of Shankhpushpi. It improves scopolamine-induced spatial memory impairment.

Fig. (8)

The chemical structure of Tinosporide extracted from the stem of T. Cordifolia.

Fig. (9)

The bioactive chemical structure of Asiaticoside isolated from Centella asiatica extract.

Fig. (10)

The bioactive chemical structures isolated from Allium sativum. (a) S-allyl-L-cysteine (SAC), and (b) di-allyl-disulfide (DAD).

Fig. (11)

There are several mechanisms by which S-allyl-cysteine (SAC) provides neuroprotection against Alzheimer’s disease.

Fig. (12)

The bioactive chemical structures isolated from Ocimum sanctum. (a) Apigenin, and (b) Rosmarinic acid.

Fig. (13)

The bioactive chemical compound gingerol is isolated from ginger.

Fig. (14)

The phytochemically active chemical structure of (a) epigallocatechin gallate, and (b) Catechin isolated from Cinnamon.