Abstract
Ethnopharmacological Relevance. The medicinal use of Gastrodia elata BI., a dry tuber of the orchid family, has a long history. Gastrodia elata BI. has the functions of calming the liver, relieving muscle spasms, and dispelling gas. Aim of this Review. To review the traditional uses, botany, phytochemistry, pharmacology, and pharmacokinetics of Gastrodia elata BI. In addition, we discuss the future development and research prospects of this plant in detail. Materials and Methods. This article collects information from relevant documents, including scientific papers, books, and dissertations concerning Gastrodia elata BI. Results. To date, research on Gastrodia elata BI. has identified about 100 active compounds. Many compounds in Gastrodia elata BI. have biological activities, such as sedation and hypnosis, anticonvulsion, improvement of learning and memory, protection of neurons, antidepressive effects, lowering of blood pressure, promotion of angiogenesis, protection of cardiomyocytes, antiplatelet aggregation, anti-inflammatory activity, and amelioration of labor pains. Conclusion. Although many traditional uses of this plant have been confirmed, it is necessary to continue to study the relationship between its structure and function, clarify the mechanisms of pharmacological effects, and explore new clinical applications so as to better delineate the quality control standards for Gastrodia elata BI.
1. Introduction
As a traditional Chinese medicine, Gastrodia elata BI. (GB) has a long history, being recorded in many ancient books. The plant is mainly grown in Hubei, Sichuan, Yunnan, Guizhou, and Shaanxi [1]. There are nine preparations listed in the Pharmacopoeia of the People’s Republic of China [2], namely, Tianma Pills, Tianma Headache Tablets, Tianma Gouteng Granules, Tianma Shouwu Tablets, Tianma Qufeng Patches, Tianma Xingnao Capsules, Bantian Ma Pills, Quan Tianma Capsules, and Strong Tianma Duzhong Pills. These preparations are used to treat headaches, chills, and nasal congestion, as well as dizziness, tinnitus, vertigo, tremor, insomnia, loss of memory, slow response, backache, epilepsy, convulsions, sore mouth, dry throat, hair loss, gray hair, chills, cold limbs, numbness, and other ailments. From the research on GB, about 100 active compounds have been isolated, and phenolic compounds, organic acids, steroids, polysaccharides, furan aldehydes, adenosines, and amino acids have been isolated and identified from the plant [3]. Moreover, many researchers have found that GB has a wide range of pharmacological activities, including static and hypnotic effects, anti-inflammatory and antioxidant effects, lowering of blood pressure, lowering blood lipids, and antiaging and antitumor effects.
This article collects information from relevant documents, including scientific papers, books, and dissertations concerning GB. Some dissertations and scientific databases were used, including Baidu Scholars, Science Net, Weipu, Wanfang, and CNKI. We have systematically summarized many studies concerning GB, including its traditional uses, botany, phytochemistry, pharmacology, and pharmacokinetics. Finally, the problems and research directions of the GB Research Institute are discussed. The article summary chart is shown in Figure 1.
2. Traditional Application
GB is also known as Chijian, Dingfengcao, Guiduyou, and other names. The names are different in various historical periods. The earliest record is in the “Shennong’s Classic of Materia Medica” [4], with “Chijian” as the correct name, also known as Limu or Guiduyou. The plants were used to kill ghosts, as a poison, in long-term service to benefit vitality, and for light body growth. In the Wei-Jin period, “WuPu Ben Cao” [5], Guiduyou was used as the correct name, with aliases Shencao and Yan Gouji. The plant was recorded in “Baopuzi” with Du Yaozhi as the correct name [6]. The earliest ancient book that mentions the name “GB” is “Mingyi Bielu” [7] in the late Han Dynasty, which says, “Wumuma, a name of Gastrodia.” During the Northern and Southern Dynasties, Lei Wei [5] first used GB as the correct name. At the end of the Sui Dynasty and the beginning of the Tang Dynasty, “Yao xinglun” [8] listed two items of Chijian and Chijianzhi, saying “Chijian, a GB, also known as Dingfengcao”, and the names in “Xinxiu Bencao” and “Shennong’s Classic of Materia Medica” are consistent. The 2020 edition of “The Pharmacopoeia of the People’s Republic of China” records that GB has the effects of dispelling wind and relieving spasms, suppressing liver yang, and dredging collaterals. It is used to treat convulsions in children, epilepsy, tetanus, headache, dizziness, hand and foot problems, numbness of the limbs, and rheumatic arthralgia.
Regarding whether GB and Chijian are the same thing, different generations of doctors held their own opinions. “Yaoxing Lun”, “Kaibao Bencao” in the Song Dynasty [9], “Jiayou Ben” [10], “Bencao Yanyi” [11], “Bencao Pinhui Jingyao” [12], and “Ben Cao Meng Yun” [13] believed that Chijian and Gastrodia were not the same thing. “Mengxi Bi Tan” [14], “Bencao Gangmu” [15], “Bencao Tongxuan” [16], and “Benzao Hui” [17] believed that the red arrow and GB were synonymous and were the same medicinal material.
At present, GB has a wide range of clinical uses. It is commonly used to treat infantile convulsions, epileptic convulsions, tetanus, headaches, dizziness, hand and foot problems, numbness of the limbs, and rheumatic arthralgia. The classic clinical prescriptions Tianma Alisma Decoction, Banxia Baizhu Tianma Decoction, and Tianma Gouteng Decoction can treat a variety of illnesses, including migraine, hypertension, atherosclerosis, and insufficient cerebral blood supply [4, 18].
It can be seen that the clinical application of GB is very extensive, and there are many prescriptions recorded in ancient Chinese literature. As shown in Table 1, the dosage forms include decoctions, pills, tablets, capsules, and granules. The extremely high nutritional value of GB makes its application in the beverage and health industry unique. The beverages and foods made with it have significant nourishing and strengthening effects [21–25].
3. Botany
GB is a saprophytic herb in the Orchidaceae Gastrodia genus, with a plant height of about 2 m. There are no roots and no leaves; only the above-ground flower stems and underground tubers that cannot conduct photosynthesis. The growth process requires fungal infection to provide nutrition. [26] The picture of GB is shown in Figure 2.
(a)
(b)
(c)
3.1. Tubers
According to the characteristics of different developmental stages, GB tubers can be divided into a protocorm, a vegetative propagation stem, a rice hemp, a white hemp, and a sisal hemp.
Protocorms are bulbs formed by the symbiotic germination of GB seeds, Mycena osmundicola Lange, M. orchidicola Fanet Guo, and other small mushrooms, with an average length of 0.4–0.7 mm and a diameter of 0.3–0.5 mm.
Vegetative propagation stems are formed by the differentiation and growth of protocorms, and these can also germinate through asexual reproduction of the white hemp and rice hemp [27–29].
Rice hemp refers to small tubers with a length of less than 2 cm formed by the growth of the apical or lateral buds of the vegetative propagation stem through sexual or vegetative propagation. Because it resembles a grain of rice, it is also called hemp, and is most suitable for asexual propagation and expansion [30].
White hemp refers to underground tubers with strong snow-white top buds. Small and medium white hemp can only be used for hemp seed cultivation and cannot be used as a medicine. Large white hemp can be used for both cultivation and as a medicine.
Sisal refers to the tubers of GB with terminal flower buds formed by the growth and reproduction of white hemp. It has the three characteristics of terminal flower stalk bud, tail umbilicus, and ring pattern around the body. It has a high content of active ingredients and is mostly harvested as commercial GB. [31].
3.2. Flower Stems and Flowers
The top bud of the sisal sprouts and grows to form a GB tuber. Its height is 0.5–1.3 m; the diameter is 1–1.5 cm, and there are generally 5–7 nodes. There are sheath-like phimosis membranous scales alternating on the nodes. The early stage of the flower stem is fleshy and solid, and the fruit is mature. The flower stem becomes hollow and the color becomes darker. The inflorescences of GB are racemes, which are mostly formed in the winter of the first year. The inflorescences are drawn out and bloom in the second year. Generally, each plant can have 30 to 70 flowers. The flowers are bisexual and symmetrical. The ovary and pedicel are composed of several parts, with various flower colors. Under natural conditions, GB relies on insect pollination. Both self-pollination and cross-pollination can produce fruits [32, 33].
3.3. Fruits and Seeds
The fruit of GB is a long oval capsule with a length of 1.5 to 1.7 cm and a diameter of 0.9 cm. It has six longitudinal ridges and is similar in color to the stem. Each fruit contains 10,000 to 50,000 seeds [31]. The seeds of GB are small and powdery. Under the microscope, the mature seeds are spindle-shaped, with a length of 0.8 mm and a width of 0.15–0.2 mm. The seeds have no endosperm and are composed of embryos and seed coats. The seed coats are white and translucent and are composed of parenchyma cells. The embryo is oval, light brown, or dark brown [32, 33].
4. Phytochemistry
4.1. Phenolic Compounds and Their Glycosides
4.1.1. Phenolic Compounds Containing a Benzene Ring
There are more than 40 phenolic compounds isolated from GB. The phenolic compounds containing a benzene ring are shown in Table 2 and the chemical structure is shown in Figure 3.
4.1.2. Phenolic Compounds Containing Two or More Benzene Rings
Phenolic compounds containing two or more benzene rings are shown in Table 3 and the chemical structure is shown in Figure 4.
4.2. Organic Acids and Lipids
The organic acids separated from Gastrodia are tabulated in Table 4 and the chemical structure is shown in Figure 5.
4.3. Steroids and Their Glycosides
Five steroids have been isolated and identified from GB, as shown in Table 5 and the chemical structure is shown in Figure 6.
4.4. Other Categories
In addition to phenols, organic acids, and steroids, Gastrodia contains other compounds, including polysaccharides, furan aldehydes, adenosines, amino acids, and peptides. The specific ingredients are shown in Table 6 and the chemical structure is shown in Figure 7.
(a)
(b)
(c)
5. Pharmacology
GB has a wide range of effects, including the central nervous system, cardiovascular system, skeletal system, digestive system, endocrine system, urinary system, and respiratory system. This is shown in Table 7, Figure 8.
5.1. The Effect of GB on the Central Nervous System
5.1.1. Hypnosis and Sedation
GB has hypnotic and sedative effects [57]. Studies have shown that the main effect of fresh GB on sleep depends on the chemical composition of phenols [40], and gastrodin has a prominent effect among the phenols [59, 85]. The memory improvement caused by Gastrodia can ameliorate oxidative stress and boost neurotransmitter levels. The mechanism may be related to the up-regulation of central dopamine (DA) system activity, the regulation of dopamine receptor 2(D2)-mediated signaling pathways, and the regulation of monoamine neurotransmitters in the hypothalamus and hippocampus.
5.1.2. Anti-Parkinson’s Disease
GB also has significant effects on Parkinson’s disease (PD), slowing the pathological process of Alzheimer’s disease(AD) to a certain extent, reducing the deposition of beta-amyloid (Aβ), and improving learning and memory ability in AD dementia mouse models [60]. Studies have shown that GB extract can significantly improve the behavior of Parkinson’s disease model mice [61], and Gastrodia extract can improve the cognitive dysfunction of PD rats [50, 61]. The decoctions had a therapeutic effect on transgenic Parkinson’s mice [63]. The mechanism may be related to the enhancement of the human body’s antioxidant capacity, protection of DA neurons in the brain, regulation of the level of monoamines in the brain, inhibition of a variety of apoptosis-related signaling pathways, activation of Wnt signaling pathways [65, 92], regulation of the Kelch-like epoxylopropylamine-related protein 1 (keap1)-nuclear factor E2 related factor2(Nrf2)/heme oxygenase-1(HO-1) pathway, or enhancement of the expression of downstream antioxidant genes and Superoxide dismutase(SOD) enzyme activity [66]. In addition, through studying the changes in the intestinal flora, three probiotics, Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus murine, were found in high doses of GB decoctions, each of which can help prevent and delay Alzheimer’s disease. These findings present new ideas and methods [67].
5.1.3. Antidepressant
Gastrodia extract has antidepressant effects [69]. Studies have shown that gastrodin can alleviate depression-like behavior in chronic unpredictable stress model (CUMS)-induced depressed rats. Gastrodin injection has also been used to treat patients with schizophrenia and immune dysfunction [70]. The antidepressant mechanism involves an increase in the monoamine neurotransmitters in the central nervous system, anti-inflammatory effects, increases in the number of new neurons, the rearrangement of the nerve cytoskeleton, and regulation of the expression of T helper cell 17 (Th17) and related inflammatory factors [71].
5.1.4. Anticonvulsant
GB has anticonvulsant effects, and GB stalks and seeds also have good anticonvulsant effects [73, 102]. The mechanism of action is similar to that of carbamazepine.
5.1.5. Antivertigo
Gastrodin injection has antivertigo effects and can effectively control acute vertigo [103]. It is effective in the treatment of post-traumatic vertigo [75]. Gastrodin had a significant effect on the treatment of middle-aged and elderly patients with vertigo [76].
5.1.6. Analgesia
Gastrodin can effectively reduce pain and reduce the levels of serum inflammatory factors. Its mechanism of action may be related to the significant downregulation of c-fos gene expression in spinal dorsal horn tissue [72].
5.1.7. Antiepileptic
Gastrodia has antiepileptic effects. Studies have confirmed that gastrodin can prolong the incubation period of generalized tonic-clonic seizure (GTCS) and minimal clonic seizure (MCS) in rats with pentylenetetrazole-induced epilepsy and improve cognitive function. The mechanism may be through regulating the abnormal expression of COX-2 [78], regulating the Nrf2/HO-1 classical antioxidant signal pathway, thereby reducing the expression of inflammatory factors iNOS [79], and regulating the level of monoamines in the brain to exert its antiepileptic effect [104], improve rat cognitive impairment, and protect nerves. Gastrodia can reduce the expression of serine-threonine protein kinase (p-AKT) and caspase 3 protein to resist the effect of resistance, thus triggering the model to play a protective role [80]. Gastrodin protected the brain of rats with pilocarpine-induced epilepsy by inhibiting the TLR4/NF-κB signaling pathway [81]. Gastrodin injection inhibited the levels of proapoptotic factors in the cerebral cortex of rats with epileptic seizures after ischemic stroke, increased the levels of antiapoptotic factors, and reduced the level of p38 protein kinase in the body. It has the effect of protecting brain nerves and appears to be safe [50].
5.1.8. Protects Nerve Cells
Gastrodia has a protective effect on nerve cells. An experiment compared the protective effects of GB powder and flour on nerve cells. The results showed that GB had a strong effect, and its mechanism of action may be related to the levels of 7-Aminobutyrate transaminase(GABA-T) mRNA and protein expression in the rat hippocampus [82].
5.2. Pharmacological Effects of Gastrodia on the Cardiovascular System
5.2.1. Protects Cardiomyocytes
The effect of Gastrodia in protecting cardiomyocytes is mainly related to gastrodin. Gastrodin can inhibit the opening of mitochondrial permeability transition pore (mPTP) when cardiomyocytes undergo oxidative stress damage and thereby reduce apoptosis and reduce oxidative stress damage [83]. Gastrodin can also reduce autophagy, improve the clearance of autophagosomes, and reduce cell apoptosis [74]. Gastrodin upregulated the expression of 14-3-3η protein, inhibited cardiomyocyte oxidative damage [105], downregulated the degree of cardiomyocyte oxidative stress, reduced cell apoptosis, and acted as an anti-inflammatory [84]. These effects functioned to protect cardiomyocytes.
5.2.2. Antihypertension
Gastrodia can effectively reduce hypertension caused by various factors, including essential hypertension [106], senile refractory hypertension [101], and spontaneous hypertension. The mechanism may be related to the inhibition of the release of vascular inflammatory substances s [20]. The results of a meta-analysis indicated that the blood pressure-lowering mechanism of gastrodin may be related to the involvement of 19 key target genes in 15 biological processes by influencing 14 hypertension pathways [107].
5.2.3. Antiplatelet Aggregation and Antihrombosis
Gastrodia extract G2 had the effect of inhibiting platelet aggregation induced by adenosine diphosphate (ADP). In vitro experiments in rabbits demonstrated that the extract inhibited platelet activating factor (PAF)-induced platelet aggregation, confirming the antiplatelet aggregation effect of Gastrodia extract [86]. Experiments have examined the in vitro and in vivo activated partial thromboplastin timing and platelet aggregation rate induced by adenosine diphosphate as indicators to analyze the antiplatelet aggregation and antithrombotic effects of the drug, confirming that gastrodin can reduce platelet aggregation and thrombosis within a certain range [87]. The possible anticoagulant mechanism of gastrodin is related to its interference with the knob-hole interaction between fibrin molecules, which effectively inhibits the formation of blood clots and reduces the risk of thrombosis [88]. The ethyl acetate extract of Gastrodia significantly stimulated plasmin activity [108]. At the same time, phenolic compounds isolated from the methanol extract of Gastrodia had a strong inhibitory effect on platelet aggregation induced by U46619 [109].
5.2.4. Promotes Angiogenesis
Gastrodiol components increased the expression of Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2), α-SMA, and Smad-3 and reduce the expression of Ang-2 in the brain of middle cerebral artery occlusion/reper-fusion (MCAO/R) rats and promoted angiogenesis and maturation after cerebral ischemia [89]. Angiogenesis experiments with microvessels-deficient zebrafish showed that gastrodin significantly promoted angiogenesis [90]. Gastrodin promoted Vascular endothelial growth factor-A(VEGF-A) secreted by M2 macrophages to activate vascular endothelial cells and promote angiogenesis [110]. Experiments have shown that the ethanol extract of Gastrodia increased angiogenesis in a mouse lower limb ischemia model, and its mechanism may be related to the promotion of the expression of the pro-angiogenesis factor VEGF-A and its receptors VEGFR-2 and Angpt2 [35].
5.3. Skeletal System
Gastrodin can increase the proliferation of primary osteoblasts, activate the Nrf2/Keapl signaling pathway, reduce mitochondrial oxidative stress damage, maintain the steady state of mitochondrial membrane potential and the normal production of ATP to inhibit cell apoptosis, and promote the formation of osteogenic calcium nodules. These effects promote osteogenic differentiation and improve osteoporosis. The antioxidant capacity of rats was improved through treatment with different doses of gastrodin; the oxidative stress products and fluorine content of the body were reduced, and the damage of fluoride to bone and dentin was reduced to a certain extent. [100].
5.4. Digestive System
Gastrodia has a certain protective effect on the gastric mucosa [91], and at the same time, it has a relaxing effect on the smooth muscle of the ileum [45]. Gastrodin can prevent the loss of liver cell mitochondrial membrane potential caused by alcohol, reduce the release of cytochrome C in mitochondria, and inhibit the activation of caspase-3 in liver cells, thereby inhibiting liver cell apoptosis and returning abnormal liver function to normal. It can also effectively improve the pathological changes of the liver [92]. These studies show that Gastrodia can be used as an effective drug for the treatment of liver disease [93].
5.5. Endocrine System
Studies have shown that Gastrodia extract can improve glucose metabolism, lipid metabolism, and insulin resistance [94]. In type 2 diabetic rat animal models, Gastrodia significantly improved hypothalamic insulin signaling, enhanced insulin sensitivity, and reduced hepatic glycogen output in a hyper insulinemic state [95]. In addition, gastrodin (100 µmol/L intervention for 24 h) had an inhibitory effect on human retinal endothelial cell damage induced by high glucose, and its mechanism may be related to the regulation of the Silent Information Regulator 1 (SIRT1)/TLR4/NF-κBp65 signaling pathway [64].
5.6. Urinary System
Gastrodia can effectively improve the contractility of bladder smooth muscle [97]. Studies have shown that gastrodin can reduce the levels of renal inflammatory factors and also inhibit oxidative stress by regulating Nrf2-mediated antioxidant signals and by activating AMPK. In addition, gastrodin inactivates the receptors of advanced glycation end products and the high mobility group box-1 (HMGB1) pathway and inhibits the activation of TLR, NF-κB, and transforming growth factor-β (TGF-β). This suggests that gastrodin can inhibit carbon tetrachloride-induced renal inflammation and fibrosis through the AMPK/Nrf2/HMGB1 pathway [44].
5.7. Respiratory System
In IgE-mediated guinea pig asthma animal models, phenolic compounds extracted from Gastrodia (intervened at a dose of 12.5 mg/kg for 24 h) significantly inhibited the airway resistance in the acute and remission phases of asthma and effectively inhibited the recruitment of white blood cells, reduced histamine release, and inhibited eosinophil peroxidase (EPO) and phospholipase A activities. This suggests that Gastrodia extract may have certain clinical applications in the treatment of asthma [98].
5.8. Strengthens Immunity
Both the polysaccharides and water extracts of Gastrodia could promote the increase of mouse immunoglobulin levels and increase thymus and spleen indexes. In addition, Gastrodia injection improved the function of mouse phagocytes and serum lysozyme activity, enhanced the immune response and nonspecific effects of mouse T cells, and promoted the formation of specific antibodies, indicating that Gastrodia can enhance immunity [99].
5.9. Other Effects
5.9.1. Antioxidant
The antioxidant capacity of rats was improved through treatment with different doses of gastrodin. The oxidative stress products and fluorine content of the body were reduced, and the damage of fluoride to bone and dentin was reduced to a certain extent. Reference [100]GB polysaccharides have a certain scavenging effect on ferrous ions, ABTS free radicals, hydroxyl free radicals, and DPPH free radicals. The scavenging effect is in the order of hydroxyl free radicals > DPPH free radicals > ABTS free radicals > metal ion free radicals [35]. Gastrodin has antioxidant and antiapoptotic effects in H2O2-induced oxidative stress damage. Gastrodin inhibits H2O2-induced oxidative damage and apoptosis of LSECs by activating the p38 MAPK/Nrf2/HO-1 pathway; it can reduce liver ischemia-reperfusion injury in mice through anti-inflammatory, antioxidant, and antiapoptotic effects [52]. Gastrodia extract can effectively improve the antioxidant capacity of rats, improve the level of oxidative stress-related indicators in rats, and thereby improve the hypoxia capacity of the rat body [53].
5.9.2. Treatment of Deafness and Tinnitus
Gastrodin acupoint injection for sudden deafness accompanied by tinnitus can not only promote the disappearance of tinnitus but also improve the clinical effect [77]. Gastrodin injection is also used in the clinical treatment of patients with vertigo and tinnitus, with significant curative effect [101].
5.9.3. Antitumor
Vascular dementia rats as experimental subjects were injected with GB extract, and the extract had a significant effect on improving the learning and memory of the mice. The main mechanism of action may be related to reducing oxidative damage in the hippocampus and scavenging free radicals [111]. Gastrodin significantly reduced the cerebral infarction volume and edema volume of rats with transient middle cerebral artery occlusion and significantly improved the neurological functions of patients [112]. In addition, gastrodin also inhibited neuronal apoptosis caused by glutamate and hypoxic-ischemic sugar and reduced the levels of nitric oxide and calcium ions in extracellular glutamate. Gastrodin also had an effect on the expression of aging-related genes in the brain tissue of rapidly aging mice. The antiaging effect of gastrodin is mainly through regulating the expression levels of some aging-related genes. The effective phenolic components in Gastrodia can reduce the area of infarcts in the whole brain and cortex, improve the distribution of neurons in the hippocampus and cortex of mice, reduce the activity of caspase-3, and enhance the expression of Bcl-2, confirming that gastrodin’s neuroprotective effect is related to its mechanism of weakening the apoptotic pathway.
5.9.4. Whitening
Gastrodia extract significantly reduced the melanin content in normal human melanocytes without obvious cytotoxicity. In addition, zebrafish in vivo experiments showed that Gastrodia extract effectively reduced melanin production without adverse side effects and no obvious cytotoxicity. This suggests that the extract of GB has a powerful whitening effect [113, 114].
6. Pharmacokinetics
In recent years, many domestic and foreign scholars have studied the pharmacokinetics of GB. The pharmacokinetics of gastrodin was studied by intragastric administration of gastrodin (100 mg/kg). The results showed that gastrodin could be detected in plasma at 4.98 minutes after administration. Tmax was (0.42 ± 0.14) h, and t1/2 was (1.13 ± 0.06) h [115]. The measured half-life differs in different species (The t1/2 of intravenous injection in rats, rabbits and dogs is 8.41 h, 38.4 h, 105 min respectively) [19]. Gastrodin can pass through the blood-brain barrier [116], and can also be metabolized to 4-hydroxy-benzyl alcohol to enter the blood-brain barrier to exert an effect on the central system [117], and finally be excreted through the bile [118]. The Tmax of 4-hydroxy-benzyl alcohol was 15 min, and the Cmax of plasma, bile, and brain were 109 ng/mg, 77.7 ng/mg, and 34.7 ng/mg [118]. Parishin is one of the active ingredients proven to have clinical efficacy. It is completely metabolized into gastrodin, 4-hydroxy-benzyl alcohol, parishin B and parishin C within 5 minutes in the body. Four metabolites are rapidly eliminated in the body [119]. N6-(4-hydroxybenzyl)-adenosine has obvious neuroprotective effect, Tmax is 69 min, t1/2 is 7.75 h [120]. 4-hydroxybenzaldehyde has protective effect on cerebral ischemia/reperfusion injury, in Rapid in vivo absorption, short half-life and low absolute bioavailability [121]. 4-Methoxybenzyl alcohol has a good brain protection effect, with a short half-life (t1/2 0.317 ± 0.094 h) [122]. GB extracts are mostly indexed by gastrodin and p-hydroxybenzyl alcohol. Other components in GB extract cause gastrodin and p-hydroxybenzyl alcohol to accumulate in tissues, with slow absorption and prolonged action. The Tmax of gastrodin is 70 min [123].
7. Future Perspectives and Conclusions
In summary, GB is a traditional Chinese medicine with a long history of use, and it is frequently employed in clinical practice. At present, many chemical components have been isolated and identified from this plant. There is no doubt that GB is an important Chinese medicine, and because of this, many professions have made significant contributions to the research on GB. However, in the research on GB, new problems and challenges continue to appear, and we need further research and exploration to meet the requirements of clinical use.
First, as a traditional Chinese medicine, GB has been studied more intensely in recent years, with more research being conducted on phenolic compounds, other compounds rarely being reported. Second, there are few studies on GB kinetics and toxicology. This aspect should receive more attention from researchers, and in vivo verification studies should be conducted to ensure drug safety. In particular, GB is used as medicine and food by villagers. It is commonly used to stew chickens, for example. The proper amount, effects of long-term use, and whether it can be toxic still need in-depth research. Third, when the GB medicinal materials are sold, they will be advertised as having a tonic effect that may be related to the pharmacological effects of GB such as antivertigo and enhancement of immunity, but whether there is actually a tonic effect and the specific pharmacological conditions still need in-depth research. Fourth, in China the wild resources of GB are declining, and the market resources are not in high demand. There are many kinds of “GB” in the medicinal material market. It is necessary to analyze and identify the various “GB” according to market conditions and identify those that can be used for medicinal purposes and those that can be used as health food. There are also some artificially cultivated GB. In view of the fact that there are many types and different quality of GB on the market, research on medicinal materials should be strengthened to ensure their quality.
In general, GB as a commonly used traditional Chinese medicine requires further research. This article systematically introduces the research status of GB at home and abroad in recent years, including traditional applications, phytochemistry, pharmacology, and pharmacokinetics. Although significant progress has been made, there are still problems associated with various aspects of the plant. This article also proposes some suggestions for solving these problems. Therefore, to further develop and utilize this Chinese medicine, we need to make continuous efforts in the future.
Abbreviations
| ACL: | Areca catechu L |
| AD: | Alzheimer’s disease |
| ADP: | Adenosine diphosphate |
| AGS: | Acanthopanax gracilistylus W.W.Smith |
| AHFSVM: | Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.)Kitag |
| AKP: | Amomum kravanh Pierre ex Gagnep |
| AKR: | Aconitum kusnezoffii Reichb |
| ALD: | Aucklandia lappa Decne |
| ALL: | Arctium lappa L |
| AMBVM: | Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.)Hsiao |
| AMK: | Atractylodes macrocephala Koidz |
| APM: | Angelica pubescens Maxim.f. biserrata Shan et Yuan |
| ASD: | Angelica sinensis (Oliv.)Diels |
| ASG: | Aquilaria sinensis (Lour.)Gilg |
| AV: | Artemisia argyi Lévl. et Van |
| Aβ: | Beta-amyloid |
| BBL: | Bubalus bubalis Linnaeus |
| BCB: | Boswellia carterii Birdw |
| BCD: | Bupleurum chinense DC |
| BMK: | Buthus martensii Karsch |
| BML: | Bombyx mori Linnaeus |
| BOV: | Bovidae |
| BSF: | Beckmannia syzigachne (Steud.) Fern |
| BTDG: | Bos taurus domesticus Gmelin |
| BTM: | Bambusa textilis McClure |
| CAB: | Cuscuta australis R. Br |
| CAL: | Citrus aurantium L |
| CBJS: | Cibotium barometz(L.)J.Sm |
| CCLP: | Cinnamomum camphora(L.)Presl |
| CCO: | Clematis chinensis Osbeck |
| CCP: | Cinnamomum cassia Presl |
| CDM: | Cistanche deserticola Y. C. Ma |
| CGT: | Citrus grandis “Tomentosa” |
| CME: | Commiphora myrrha Engl |
| CMR: | Chrysanthemum morifolium Ramat |
| COP: | Coptis chinensis Franch |
| CRB: | Citrus reticulata Blanco |
| CRL: | Cyperus rotundus L |
| CSN: | Chaenomeles speciosa (Sweet)Nakai |
| CUMS: | Chronic unpredictable stress model |
| D2: | Dopamine receptor 2 |
| DA: | Dopamine |
| DDB: | Daemonorops draco Bl |
| ECT: | Eugenia caryophyllata Thunb |
| EPO: | Eosinophil peroxidase |
| ESS: | Ephedra sinica Stapf |
| ETC: | Elaphe taeniura Cope |
| EUO: | Eucommia ulmoides Oliv |
| GABA-T: | 7-Aminobutyrate transaminase |
| GB: | Gastrodia elata BI |
| GJE: | Gardenia jasminoides Ellis |
| GTCS: | Generalized tonic-clonic seizure |
| GUF: | Glycyrrhiza uralensis Fisch |
| HMGB1: | High mobility group box-1 |
| HO-1: | Heme oxygenase-1 |
| Kepa1: | Kelch-like epoxylopropylamine-related protein 1 |
| LCHSMB: | Ligusticum chuanxiong Hort. Salvia miltiorrhiza Bge |
| LSO: | Ligusticum sinense Oliv |
| MBF: | Moschus berezovskii Flerov |
| MCAO/R: | Middle cerebral artery occlusion/reper-fusion |
| MCS: | Minimal clonic seizure |
| MPTP: | Mitochondrial permeability transition pore |
| NTC: | Notopterygium incisum Ting ex H.T.Chang |
| PAE: | Pheretima aspergillum (E.Perrier) |
| PAF: | Platelet activating factor |
| p-AKT: | Serine-threonine protein kinase |
| PCP: | Picrorhiza scrophulariiflora Pennell |
| PCW: | Poria cocos(Schw.) Wolf |
| PD: | Parkinson’s disease |
| PGM: | Panax ginseng C. A. Mey |
| PKCH: | Polygonatum kingianum Coll.et Hemsl |
| PLO: | Pueraria lobata(Willd)Ohwi |
| PLP: | Paeonia lactiflora Pall |
| PMT: | Polygonum multiflorum Thunb |
| PNC: | Panax notoginseng (Burk.)F.H.Chen |
| PTT: | Pinellia ternata (Thunb.) |
| QIL: | Quisqualis indica L |
| RGL: | Rehmannia glutinosa Libosch |
| RPL: | Rheum palmatum L |
| SCB: | Schisandra chinensis(Turcz.)Baill |
| SDS: | Saposhnikovia divaricata (Turcz.) Schischk |
| SIRT1: | Silent Information Regulator 1 |
| SMB: | Salvia miltiorrhiza Bge |
| SNH: | Scrophularia ningpoensis Hemsl |
| SOD: | Superoxide dismutase |
| SSMK: | Scolopendra subspinipes mutilans L. Koch |
| STE: | Schizonepeta tenuifolia Eriq |
| STL: | Saiga tatarica Linnaeus |
| SUC: | Succinum |
| TGE: | Typhonium giganteum Engl |
| TGF-β: | transforming growth factor-β |
| Th17: | Thelper cell 17 |
| URMH: | Uncaria rhynchophylla (Miq.)Miq. ex Havil |
| VEGF-A: | Vascular endothelial growth factor-A |
| VEGFR-2: | Vascular Endothelial Growth Factor Receptor. |
Data Availability
The data that support the findings of this study are available from scientific papers, books, and dissertations concerning GB. Some dissertations and scientific databases were used, including Baidu Scholars, Science Net, Weipu, Wanfang, and CNKI.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
Authors’ Contributions
Ya-Nan Wu collated documents and wrote the manuscript; Si-Hua Wen helped to perform the arrangement of tables and pictures; Shang-Shang Yu and Wei Zhang Kai Yang polished the language; Kai Yang and Ding Liu helped to organize the literature; Chong-Bo Zhao and and Jing Sun contributed significantly to design, analysis, manuscript preparation, and revision.
Acknowledgments
This work was supported by Shaanxi Provincial Central Government Guided Local Science and Technology Development Project: Research on Comprehensive Development and Utilization of Zhashui Schisandra, Gastrodia elata BI. and other medicinal materials (Project No.: 2021-ZY2-CG-03); Shaanxi Provincial Innovative Talent Promotion Plan-Science and Technology Innovation Team (no. 2018TD-005).