Gastrodin, a Promising Natural Small Molecule for the Treatment of Central Nervous System Disorders, and Its Recent Progress in Synthesis, Pharmacology and Pharmacokinetics

Abstract

Gastrodia elata Blume is a traditional medicinal and food homology substance that has been used for thousands of years, is mainly distributed in China and other Asian countries, and has always been distinguished as a superior class of herbs. Gastrodin is the main active ingredient of G. elata Blume and has attracted increasing attention because of its extensive pharmacological activities. In addition to extraction and isolation from the original plant, gastrodin can also be obtained via chemical synthesis and biosynthesis. Gastrodin has significant pharmacological effects on the central nervous system, such as sedation and improvement of sleep. It can also improve epilepsy, neurodegenerative diseases, emotional disorders and cognitive impairment to a certain extent. Gastrodin is rapidly absorbed and widely distributed in the body and can also penetrate the blood-brain barrier. In brief, gastrodin is a promising natural small molecule with significant potential in the treatment of brain diseases. In this review, we summarised studies on the synthesis, pharmacological effects and pharmacokinetic characteristics of gastrodin, with emphasis on its effects on central nervous system disorders and the possible mechanisms, in order to find potential therapeutic applications and provide favourable information for the research and development of gastodin.

Keywords: gastrodin; pharmacokinetics; pharmacology; research progress; synthesis.

Figure 1

Chemical structure of gastrodin.

Scheme 1

The first chemical synthesis method of gastrodin [31]. (A) The chemical synthesis of intermediate 4-formylphenyl 2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranoside. (B) Three methods for the reduction in 4-formylphenyl 2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranoside to gastrodin.

Scheme 2

The second chemical synthesis method of gastrodin [32].

Scheme 3

The biological synthesis methods of gastrodin [35,36,38]. (A) The biotransformation from p-hydroxybenzaldehyde to gastrodin by Datura titular L. cells. (B) The biotransformation from p-hydroxybenzaldehyde to gastrodin by Rhizopus chinensis S_AITO AS 3.1165. (C) The artificial pathway to gastrodin from glucose constructed in E. coli. AroG*, feedback-resistant mutant of AroG; CAR, carboxylic acid reductase; ADH, alcohol dehydrogenase; UGT, uridine sugar glycosyltransferase.

Figure 2

Pharmacological activities and molecular mechanisms of gastrodin in the central nervous system. The red arrows indicate up-regulation of expression, and blue arrows indicate down-regulation of expression. GABA, γ-aminobutyric acid; 5-HT, 5-hydroxytryptamine; IL-1β, interleukin-1beta; BCL-2, B-cell lymphoma-2; IL-6, interleukin-6; ERK, extracellular regulated protein kinases; TLR4, toll-like receptor 4; NF-κB, nuclear factor kappa-B; Nrf2, nuclear factor erythroid 2-related factor 2; AMPK, adenosine 5′-monophosphate-activated protein kinase; PPARα, peroxisome proliferators-activated receptor α; BDNF, brain-derived neurotrophic factor; NGF, nerve growth factor; MAPK, mitogen-activated protein kinase; AKT, protein kinase B; SOD, superoxide dismutase; GSH, glutathione; GPX, glutathione peroxidase; HO-1, homoxygenase-1; IGF-1, insulin-like growth factor-1; Bax, BCL-2-associated X protein; CAT, catalase; mTOR, mammalian target of rapamycin; PKA, protein kinase A; CREB, cAMP-response element binding protein; IL-18, interleukin-18; TNF-α, tumor necrosis factor-alpha; iNOS, nitric oxide synthase; COX-2, cyclooxygenase-2; MDA, malondialdehyde; ROS, reactive oxygen species; Aβ, amyloid-beta protein; NLRP3, NOD-like receptor thermal protein domain associated protein 3.

Figure 3

The synthesis, CNS effects and pharmacokinetics of gastrodin. CNS, central nervous system; STLG1, sodium-dependent glucose transporter 1; BBB, blood–brain barrier; HBA, p-hydroxybenzyl alcohol.