Pharmacological effect of Gastrodin

Introduction

Gastrodia elata Blume (Figure 1) is a well-known traditional Chinese medicine that is mainly used to treat diseases related to the nervous system, such as stroke, epilepsy, and headache. 4-Hydroxybenzyl alcohol 4-O-β-D-glucoside, commonly known as gastrodin, has a chemical formula of C13H18O7 and a molecular weight of 286.278Da, and it is the main bioactive component of Gastrodia elata Blume.[1] In terms of solubility, gastrodin demonstrates a hierarchal dissolution pattern in organic solvents that can be arranged as ethyl acetate>acetone>ethanol>cyclohexane, a solubility that increases in line with temperature elevation. Gastrodin was found to be used in the management of various diseases, encompassing neurological, cardiovascular, endocrine, and liver diseases. Gastrodin has multiple biological properties, including neuroprotective, anti-inflammatory, antioxidant, lipid-modulating, and vasoprotective effects, which collectively contribute to its therapeutic efficacy against these diseases.[2]

Pharmacological effects of Gastrodin

The neuroprotective effects of gastrodin

Current studies show that gastrodin has a wide range of neuroprotective effects, and this compound is expected to be useful for the treatment or improvement of a variety of nervous system diseases, including neurodegenerative diseases,neuroinflammation, epilepsy, neuropathic pain, stroke, and cognitive impairment. Further studies have shown that the neuroprotective effects of gastrodin are closely related to the inhibition of oxidative stress, inflammation, and neuronal apoptosis. Additionally, gastrodin can inhibit the abnormal discharge of neurons, promote the expression of neurotrophic factors, and inhibit the accumulation of Aβ, which are the key points at which gastrodin exerts neuroprotection.[1]

Reducing nervous system inflammation

Current research shows that gastrodin can inhibit inflammation of the nervous system by regulating multiple signaling pathways, including the nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and Notch-1 signaling pathways. Inhibition of the NF-κB and MAPK signaling pathways.Further research showed that gastrodin(10–100 µM) inhibited the renin–angiotensin system, thus inhibiting the activation of the Notch-1 signaling pathway and reducing the expression of TNF-α and IL-1β in LPS induced BV-2 microglia. In conclusion, these studies show that gastrodin can inhibit the expression of proinflammatory factors by regulating multiple inflammatory signaling pathways, thus inhibiting the inflammation of the nervous system. Because many nervous system diseases are closely related to inflammation, the anti-neuroinflammatory activity of gastrodin makes it promising for the treatment of various nervous system diseases.[1]

Mitigating nervous system damage caused by oxidative stress

When brain tissue is damaged, the oxidative balance is broken, and a large number of reactive oxygen species (ROS) are produced and accumulate. ROS are the key factor inactivating mitochondrial apoptosis, so gastrodin can improve neuronal apoptosis by clearing ROS. Further research shows that this is related to activating the NFE2-related factor 2 (Nrf2) signaling pathway and promoting the expression of various endogenous antioxidant proteins.  Cell experiments show that activation of the Nrf2 signaling pathway is the key for gastrodin to improve the oxidative stress of the nervous system. Animal experiments further confirmed that gastrodin can mitigate oxidative stress in the nervous system.

Neurotrophic effects of gastrodin and Inhibiting neuronal autophagy

Many studies have shown that gastrodin can promote neuronal repair and inhibit neuronal apoptosis by promoting the expression of various neurotrophic factors. Gastrodin (1-100µM) inhibited autophagy in LPS-induced mouse astrocytes by activating the PI3K/protein kinase B(AKT)/mammalian target of rapamycin (mTOR) signaling pathway and reducing the expression of LC3-II, P62, andBeclin-1.[1]

According to the above research results, gastrodin is beneficial to the following Neurological diseases, including Parkinson's disease,Alzheimer's disease,Tourette's syndrome,Depression,Epilepsy,Stroke,Vascular dementia,Cerebral ischemia-reperfusion (I/R) injury and Glaucoma, etc.[2]

Cardioprotective effect

Clinical studies have confirmed that gastrodin relieves angina pectoris in patients diagnosed with coronary artery disease, and exerts a cardioprotective effect in patients subjected to cardiac surgical procedures utilizing cardiopulmonary bypass. Considering the pivotal role of autophagy at the juncture of multiple injury mechanisms associated with myocardial ischemia-reperfusion injury (MIRI), there was a study had explores the first target of gastrodin on the regulation of autophagy in MIRI, or the cross-linking of multiple effects, which may be the key to the protective effect of gastrodin on myocardium. Therefore, gastrodin may attenuate myocardial damage and enhance cardiac function by modulating autophagic and mitophagic processes during the event of MIRI.

Male C57BL/6 mice and H9C2 cells were subjected to I/R and hypoxia-reoxygenation (H/R) injury after gastrodin administration, respectively, to assess the impact of gastrodin on cardiomyocyte phenotypes, heart, and mitochondrial structure and function. The effect of gastrodin on cardiac function and mitochondrial structure inpatients undergoing cardiac surgery has been observed in clinical practice.Methods: The effects of gastrodin on cardiac structure and function, mitochondrial structure, and expression of related molecules in an animal model of MIRI were evaluated using immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy, western blotting, and gene sequencing. Its effects on the morphological, molecular, and functional phenotypes of cardiomyocytes undergoing H/R were observed using immunohistochemical staining, real-time quantitative PCR, and western blotting. Gastrodin significantly reduces myocardial infarct size and improves cardiac function in MIRI mice in animal models and increases cardiomyocyte viability and reduces cardiomyocyte damage in cellular models. In clinical practice, myocardial injury was alleviated with better cardiac function in patients undergoing cardiac surgery after the application of gastrodin; improvements in mitochondria and autophagy activation were also observed. Gastrodin primarily exerts cardioprotective effects through activation of the PINK1/Parkin pathway, which promotes mitochondrial autophagy to clear damaged mitochondria. Gastrodin can promote mitophagy and preserve mitochondria through PINK1/Parkin, thus indicating its tremendous potential as an effective perioperative myocardial protective agent.[3]

In addtion,gastrodin also exerts protective effects against brain, liver, lung and kidney I/R,etc.[2-3] 

References

1.Xiao G, Tang R, Yang N, Chen Y. Review on pharmacological effects of gastrodin. Arch Pharm Res. 2023;46(9-10):744-770. doi:10.1007/s12272-023-01463-0

2.Wang Y, Bai M, Wang X, et al. Gastrodin: a comprehensive pharmacological review. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(6):3781-3802. doi:10.1007/s00210-023-02920-9

3.Chen L, Lv Y, Wu H, et al. Gastrodin exerts perioperative myocardial protection by improving mitophagy through the PINK1/Parkin pathway to reduce myocardial ischemia-reperfusion injury. Phytomedicine. 2024;133:155900. doi:10.1016/j.phymed.2024.155900

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