Therapeutic roles of natural remedies in combating hereditary ataxia: A systematic review

Abstract

Background: Hereditary ataxia (HA) represents a group of genetically heterogeneous neurodegenerative diseases caused by dysfunction of the cerebellum or disruption of the connection between the cerebellum and other areas of the central nervous system. Phenotypic manifestation of HA includes unsteadiness of stance and gait, dysarthria, nystagmus, dysmetria and complaints of clumsiness. There are no specific treatments for HA. Management strategies provide supportive treatment to reduce symptoms.

Objectives: This systematic review aimed to identify, evaluate and summarise the published literature on the therapeutic roles of natural remedies in the treatment of HA to provide evidence for clinical practice.

Methods: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed and Science Direct Scopus were thoroughly searched for relevant published articles from June 2007 to July 2020.

Results: Ten pre-clinical and two clinical studies were eligible for inclusion in this systematic review. We identified the therapeutic roles of medicinal plants Brassica napus, Gardenia jasminoides, Gastrodia elata, Ginkgo biloba, Glycyrrhiza inflata, Paeonia lactiflora, Pueraria lobata and Rehmannia glutinosa; herbal formulations Shaoyao Gancao Tang and Zhengan Xifeng Tang; and medicinal mushroom Hericium erinaceus in the treatment of HA. In this review, we evaluated the mode of actions contributing to their therapeutic effects, including activation of the ubiquitin-proteasome system, activation of antioxidant pathways, maintenance of intracellular calcium homeostasis and regulation of chaperones. We also briefly highlighted the integral cellular signalling pathways responsible for orchestrating the mode of actions.

Conclusion: We reviewed the therapeutic roles of natural remedies in improving or halting the progression of HA, which warrant further study for applications into clinical practice.

Keywords: Herbal formulation; Hereditary ataxia; Medicinal mushroom; Medicinal plant; Natural remedy.

Fig. 1

PRISMA flowchart for identification of relevant studies

Fig. 2

Chemical structures of the identified compounds with bioactive effects against HA

Fig. 3

Schematic diagram of the activation of UPS by natural remedies against polyQ-induced SCA. ATP adenosine triphosphate, cAMP cyclic adenosine monophosphate, PKA protein kinase, PolyQ polyglutamine, BAX BCL-2-associated X, BCL B-cell lymphoma

Fig. 4

Schematic diagram of the activation of the antioxidant signalling pathway by natural remedies against polyQ-induced SCA. PGC-1α peroxisome proliferator-activated receptor γ, NRF2 nuclear factor erythroid 2-related factor 2, ARE antioxidant response element, CYCS cytochrome c, NQO1 NAD(P)H Quinone Dehydrogenase 1, GCLC glutamate-cysteine ligase catalytic subunit, GSTP1 glutathione S-transferase pi 1, SOD2 superoxide dismutase 2, PolyQ polyglutamine, ROS reactive oxygen species

Fig. 5

Schematic diagram of the maintenance of intracellular calcium homeostasis by natural remedies against polyQ-induced SCA. BAX BCL-2 associated X, PARP poly (adenosine diphosphate-ribose) polymerase

Fig. 6

Schematic diagram of the regulation of chaperones by natural remedies against polyQ-induced SCA. HSF1 heat shock transcription factor 1, HSPA5 heat shock 70 kDa protein 5, HSP70 heat shock protein 70