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Effects of gastrodin injection on blood pressure and vasoactive substances in treatment of old patients with refractory hypertension: A randomized controlled trial
Abstract
To examine and determine the contents of endothelin (ET) and nitric oxide (NO) in plasma, and to observe the effects of gastrodin injection on blood pressure, ET and NO levels in old patients with refractory hypertension.
A total of 63 old patients with refractory hypertension, 30 patients with common hypertension and 30 healthy people were included. The contents of ET and NO in plasma of patients in different groups and healthy people were examined and analyzed. The old patients with refractory hypertension were randomly divided into two groups: gastrodin-treated and routine treatment groups. Besides conventional hypotensive drugs, intravenous drip infusion of 1 000 mg gastrodin was administered to the patients in gastrodin-treated group for two courses (4 weeks), while the patients in routine treatment group were treated only with conventional hypotensive drugs. The changes of blood pressure, ET and NO levels before and after treatment in different groups were measured.
The plasma level of ET in refractory hypertension group was higher than that in common hypertension group (t=3.27, P=0.008), while the level of NO was lower (t=-3.81, P=0.002). The systolic pressure and pulse pressure difference in gastrodin-treated group were decreased significantly after one course of treatment (t=1.85, P=0.03; t=1.74, P=0.04). The level of ET in gastrodin-treated group decreased gradually after treatment, but there were no significant difference between before treatment and two courses of treatment, while the level of NO in gastrodin-treated group was increased after treatment (t=-2.70; P=0.04).
Gastrodin injection is beneficial to old patients with refractory hypertension, and can improve the balance of ET and NO levels in plasma.
... In recent years, gastrodin injections have been used for the treatment of hypertension in China (Liu et al. 2018;Qiao et al. 2021;Lai et al. 2022;Zhou et al. 2022). Gastrodin has been shown to reduce blood pressure in both hypertensive patients and spontaneously hypertensive rats (SHRs) (Zhang et al. 2008;Liu et al. 2015;Qian et al. 2020). Moreover, gastrodin injections can reduce plasma endothelin levels and increase plasma nitric oxide levels in hypertensive patients (Zhang et al. 2008;Qian et al. 2020). ...
... Gastrodin has been shown to reduce blood pressure in both hypertensive patients and spontaneously hypertensive rats (SHRs) (Zhang et al. 2008;Liu et al. 2015;Qian et al. 2020). Moreover, gastrodin injections can reduce plasma endothelin levels and increase plasma nitric oxide levels in hypertensive patients (Zhang et al. 2008;Qian et al. 2020). However, the regulatory mechanisms underlying the effects of gastrodin have yet to be fully elucidated. ...
... Gastrodin is a natural compound extracted from Gastrodia elata. Extensive studies of the pharmacological properties of gastrodin have demonstrated a therapeutic effect on reducing blood pressure in patients from Chinese populations (Zhang et al. 2008;Qian et al. 2020). Moreover, gastrodin has been shown to inhibit the RAAS and PPARc and decrease SBP in SHRs . ...
Context
Gastrodin has been used as antihypertension therapy in China; however, the mechanisms underlying the effects of gastrodin have yet to be fully elucidated.
Objective
To explore the therapeutic efficiency of gastrodin as an antihypertensive and determine the mechanisms underlying this effect.
Materials and methods
C57BL/6 mice were continuously administered angiotensin II (Ang II) (500 ng/kg/min) to induce hypertension. Mice were randomly divided into control, Ang II and Ang II + gastrodin groups. Mice received intragastric administration of gastrodin (5 mg/kg) or double distilled water once a day for 4 weeks. Blood pressure, pulse wave velocity (PWV), thickness of the abdominal aorta, pathological morphology and differential expression transcripts (DETs) were assessed. Abdominal aorta rings and primary isolated vascular smooth muscle cells were subjected to Ang II stimulation to induce hypertension as ex vivo and in vitro models, respectively. Vascular ring tension, release of Ca²⁺ and levels of proteins involved in the myosin light chain kinase (MLCK)/phospho-myosin light chain 2 (p-MLC2) pathway were determined.
Results
Gastrodin treatment attenuated increases in blood pressure, PWV and thickness of the abdominal aorta. Treatment with gastrodin resulted in 2785 DETs and the enrichment of vascular contraction and calcium signalling pathways. Gastrodin treatment attenuated Ang II-induced vasoconstriction, produced a norepinephrine-precontracted vasodilation effect (attenuated by verapamil), and reduced intracellular Ca²⁺ release. Furthermore, gastrodin suppressed activation of the MLCK/p-MLC2 pathway in vivo and in vitro.
Conclusions
Gastrodin treatment lowers blood pressure, suppresses Ang II-induced vascular contraction and MLCK/p-MLC2 pathway activation, thereby demonstrating the mechanisms underlying the therapeutic efficacy of gastrodin as an antihypertensive.
... [12][13][14][15] It can also antagonize the vasoconstriction effect of catecholamine transmitters, non-competitively antagonize the potential dependent calcium channels and receptor-operated calcium channels and prevent the influx and release of Ca 2+ , leading to vasodilation and lowering BP. [14] In the past decades, numerous clinical studies using GI as a supplementary treatment to cure hypertension reported good effects. [12,[16][17][18][19][20][21][22][23][24][25][26][27] However, there were differences in the results of related clinical trials. We collected all relevant available studies to carry out the meta-analysis. ...
... Systolic blood pressure (SBP, mm Hg). Nine studies [12,[16][17][18][19][20]24,26,27] involving 992 participants reported the results of SBP in patients with hypertension. Six of them [12,[16][17][18][19]24] found GI plus conventional treatment had a significant decrease of SBP in patients with hypertension while the remaining 3 of them [20,26,27] reported non-significant association. ...
... Nine studies [12,[16][17][18][19][20]24,26,27] involving 992 participants reported the results of SBP in patients with hypertension. Six of them [12,[16][17][18][19]24] found GI plus conventional treatment had a significant decrease of SBP in patients with hypertension while the remaining 3 of them [20,26,27] reported non-significant association. The metaanalysis indicated that GI combined with conventional therapy had a significant reduction of SBP compared with using conventional therapy alone in patients with hypertension (WMD À6.67, 95% CI: À10.30, À3.04. ...
Background:
Hypertension is a common chronic disease and poses a huge burden to health care systems. Recent studies have shown that gastrodin injection (GI) has a potential supplementary therapeutic effect on hypertension.
Objectives:
To systematically assess the efficacy and safety of GI in treatment of hypertension.
Methods:
Systematic search was conducted on 7 databases (PubMed, Cochrane Library, Embase, Wanfang database, China biomedical literature service system, VIP Chinese Sci-tech journal database and China national knowledge internet). The retrieval time was from the establishment of database to February 15, 2020. Two researchers independently selected literature, extracted data and evaluated the risk of bias in the study. The methodological quality was evaluated with Cochrane handbook. The meta-analysis was performed with Stata 14.0 software.
Results:
Thirteen studies were included in this study involving 1525 patients. Compared with using conventional therapy alone, GI combined with conventional therapy can decrease systolic blood pressure (weighted mean difference [WMD] -6.67, 95% confidence interval [CI]: -10.30, -3.04. number of estimates [k] = 9, I = 89.3%), diastolic blood pressure (WMD -4.52, 95% CI: -7.79, -1.26. k = 9, I = 92.3%), and improve the clinical efficacy (relative risk [RR] 1.18, 95% CI: 1.10, 1.26. k = 6, I = 12.6%).
Conclusions:
The current evidence showed that GI combined with conventional therapy can improve systolic blood pressure, diastolic blood pressure and clinical efficacy. GI can become a supplementary treatment for hypertension.
... The add-on effect of CHM is still considered to be effective if BP finally attains normal range, no matter how many/what kinds of antihypertensive drugs have already been used before [32]. This add-on design is widely used in TCM clinical studies currently [33]. ...
... Ultimately, five eligible studies were included. [30][31][32][33][34] All trials were conducted in China and published in Chinese. ...
... We Ultimately, five eligible studies were included. [30][31][32][33][34] All trials were conducted in China and published in Chinese. ...
... The add-on effect of CHM is still considered to be effective if BP finally attains normal range, no matter how many/what kinds of antihypertensive drugs have already been used before [32]. This add-on design is widely used in TCM clinical studies currently [33]. ...
... Ultimately, five eligible studies were included. [30][31][32][33][34] All trials were conducted in China and published in Chinese. ...
... We Ultimately, five eligible studies were included. [30][31][32][33][34] All trials were conducted in China and published in Chinese. ...
Objectives This study aimed to summarise the current evidence from randomised control trials (RCTs) concerning treatment of patients with resistant hypertension with Chinese herbal medicine (CHM).
Design Seven databases, including the Cochrane Library, PubMed, EMBASE, CNKI, VIP, CBM and Wanfang, were systematically searched from their inception to March 2014 for RCTs investigating treatment of resistant hypertension in which CHM was used either as a monotherapy or in combination with conventional medicine versus placebo, no intervention or conventional medicine.
Results Five trials containing 446 hypertensive patients were identified. The methodological quality of most trials was evaluated as generally low. All included trials compared CHM plus antihypertensive drugs with antihypertensive drugs alone for resistant hypertension. Formulations of CHM included tablet, decoction and injection. It was found that, compared with antihypertensive drugs alone, CHM (tablet) plus antihypertensive drugs resulted in clinically, but not statistically, significant reductions in systolic blood pressure (SBP; weighted mean difference (WMD)=−10.32 mm Hg; 95% CI −21.10 to 0.46; p=0.06) and diastolic blood pressure (DBP; WMD=−3.30 mm Hg; 95% CI −7.66 to 1.06; p=0.14). CHM (decoction) plus antihypertensive drugs also produced a clinically meaningful, but not statistically significant, reduction in SBP (WMD=−12.56 mm Hg; 95% CI −26.83 to 1.71; p=0.08), and did significantly decrease DBP (WMD=−7.89 mm Hg; 95% CI −11.74 to −4.04; p<0.0001). There were no significant differences in SBP (WMD=−3.50 mm Hg; 95% CI −8.95 to 1.95; p=0.21) and DBP (WMD=1.00 mm Hg; 95% CI −1.39 to 3.39; p=0.41) between CHM (injection) plus the antihypertensive drugs group and antihypertensive drugs alone. The safety of CHM remained uncertain.
Conclusions No definite conclusions about the effectiveness and safety of CHM for resistant hypertension could be drawn. More rigorously designed trials are warranted.
... The result as shown in gure 3 further revealed a signi cant weight gain in rats fed with high salt diet by 54.50% (p < 0.05) when compared with the animals on normal rat chow (51.19%) after 8weeks. The observed pathological weight gain (p < 0.05) is in agreement with the report of Dobrian et al., 2003, in which a proclamation of an increase in the size of adipocytes with a concomitant twofold increase in loss of leptin hormone responsiveness, and corresponding anabolism of fatty molecules via activated endoplasmic reticulum stress and phospholipase 2 [44] in salt-sensitive animal model, were reported as the metabolic etiologies. However, group orally co-treated with 75, 100 and 150mg/kg/body weight of terpenoid-rich fraction exhibited dose dependent weight recuperation potential comparatively to the control group (51.19%). ...
... Nephrotoxicity, endothelial hardening, and pro-oxidant proliferation along the intima, and arterioles degradation via augmentation of lipid pro le peroxidation, were also intimated by Boegehold (2013). Others include, an in amed endoplasmic reticulum and ribosome in the cytoplasm of hepatocytes [44], activation of liver enzymes leading to fatty liver [6], decrease in antioxidant kinetics of catalase (CAT), glutathione along the mitochondrial respiratory chain, and proliferating oxidative marker product malondialdehyde (MDA) [58]; [59] were also intimated. More so, the integration of adiposity by a concomitant twofold increase in loss of leptin hormone responses [60], was also accounted by [61] and [62]. ...
Background
It’s overwhelmingly accounted that there is high prevalence of high salt diet related adiposity and metabolic antioxidant infringement worldwide. The present study thus aimed to establish the folkloric use of Phyllantus amarus by traditional practitioners and compliment orthodox medicine in the management of high salt diet driven adiposity and vehemently associated with pro-oxidant cascades. The principal focus was to fractionate, evaluate the lethal dose of terpenoid rich concentrate of the Phyllanthus amarus (Schum and Thonn) whole plant using up and down method and investigate the in vivo antioxidant potential and antiobesity of the rich concentrate in healthy adult male Sprague-Dawley rats fed with 8% high salt diet for 8weeks.
Results
The results of the study revealed that there was a significant (p < 0.05) weight gained (54.50%) in the experimental group fed with a high salt diet when compared with rats fed with normal chow (51.19%). However, rats co-administered with High salt diet (8%) and terpenoid rich fraction (TRF) of the whole plant (75, 100, 150mg/kg/body weight), had a significant weight recuperation in dose-dependent manner (50.86%, 48.13%, 43.25%) in comparism to groups fed with normal rat chow (51.19%), with corresponding significant (p < 0.05) and dose-dependent decrease in the concentration of oxidative marker product malondialdehyde (MDA) (9.38 ± 0.22, 7.92 ± 0.11, 6.03 ± 0.18) and dose-dependent metabolic improvement of both the non-enzymatic reduced Glutathione (GSH) (40.15 ± 0.04, 46.21 ± 0.01, 51.22 ± 0.03) and enzymatic catalase (25.22 ± 0.01, 30.31 ± 0.05, 38.52 ± 0.03) activities.
Conclusion
Therefore, the terpenoid rich fraction of Phyllanthus amarus (Schum and Thonn) whole plant could therefore be applied as a recuperative agent against obesity and prooxidant proliferation in high salt diet related pathologies.
... Combined with antihypertensive drugs, GAS has been shown to be efficacious at lowering blood pressure among older patients with refractory hypertension. 5 Despite the fact that several studies have investigated the effect of GAS on the expression of individual genes in relation to hypertrophy, 678 little has been done to prove the effect of GAS on global gene expression changes in hypertrophy. Therefore, additional studies are needed to determine the unknown targets of GAS. ...
... 6 Additionally, GAS can lower blood pressure in patients with hypertension. 5 Other studies show that GAS can significantly inhibit the expression of notch signaling pathway members, including Notch-1, NICD, RBP-JK, and Hes-1. 26 GAS can also regulate glucose and lipid metabolism, as it activates AMP-activated protein kinase, inhibits liver steatosis, and reduces serum triglycerides (TG)/glucose. ...
Pathological cardiac hypertrophy is commonly associated with an upregulation of fetal genes, fibrosis, cardiac dysfunction, and heart failure. Previous studies have demonstrated that gastrodin (GAS) exerts cardioprotective action in the treatment of cardiac hypertrophy. However, the mechanism by which GAS protects against cardiac hypertrophy is yet to be elucidated. A mouse model of myocardial hypertrophy was established using an angiotensin II (Ang II) induction. GAS (5 or 50 mg/kg/d) was orally administered every day starting 7 days prior to the Ang II infusion combined with sham-operated controls. Heart samples from each group were collected for RNA sequencing. Using bioinformatics analysis, the key differentially expressed genes (DEGs) that are involved in reversing cardiac function were identified. Through bioinformatics analysis, the key DEGs that are involved in GAS’s inhibition of Ang II-induced abnormal gene expression within the heart were identified. This was further validated using quantitative real-time PCR and Western blotting in neonatal rat cardiomyocytes (NRCMs). Oral administration of GAS significantly suppressed the Ang II-induced increase in heart size and heart weight to body weight. Furthermore, pretreatment of the NRCMs with GAS led to a dose-dependent inhibition of Ang II-induced increases in Nppb mRNA expression. We identified 620 upregulated and 87 downregulated Ang II-induced DEGs II, among which the expression patterns of 58 and 146 genes were inverted by low-dose and high-dose GAS, respectively. These inverted DEGs were found to be mainly enriched in the biological processes of regulation of Ras protein signal transduction, heart contraction, covalent chromatin modification, glucose metabolism, and positive regulation of cell cycle. Among them, the insulin-like growth factor type 2 (Igf2) gene, which was found to be highly reversed and downregulated by GAS, served as a core gene linking energy metabolism, immune regulation, and systemic development. Subsequent functional verification demonstrated that IGF2, and its receptor IGF2R, is one of the targets of GAS that helps protect against cardiac hypertrophy. Taken together, we have identified, for the first time, IGF2/IGF2R as a potential target influenced by GAS in the prevention of cardiac hypertrophy.
... Gastrodin, a kind of glucopyranoside with hydroxyl functional groups, plays important roles in treatment of cardiovascular disease [34,35]. It has demonstrated efficacy as a calcium channel blocker and can inhibit intracellular Ca 2+ overload, raise the blood supply, increase arterial compliance, reduce blood viscosity, and improve microcirculation [35][36][37]. ...
... Gastrodin, a kind of glucopyranoside with hydroxyl functional groups, plays important roles in treatment of cardiovascular disease [34,35]. It has demonstrated efficacy as a calcium channel blocker and can inhibit intracellular Ca 2+ overload, raise the blood supply, increase arterial compliance, reduce blood viscosity, and improve microcirculation [35][36][37]. Gastrodin also exerts an anti-inflammatory effect that is used clinically [38][39][40]. The aforementioned activity of Gastrodin makes it an attractive small molecule for incorporation into biomaterials that seek to reduce thrombogenicity and inflammatory response. ...
Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels (<6 mm inner diameter). Here, polyurethane (PU) elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated. The films had inter-connected pores with porosities equal to or greater than 86% and pore sizes ranging from 250 to 400 μm. Incorporation of Gastrodin into PU films resulted in desirable mechanical properties, hydrophilicity, swelling ratios and degradation rates without collapse. The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability. The Gastrodin/PU had better anti-coagulation response (less observable BSA, fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood). Red blood cell compatibility, measured by hemolysis, was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups. Notably, Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs, correlated with decreasing pro-inflammatory cytokines TNF-α and IL-1β in RAW 264.7 cells. Upon implantation in a subcutaneous pocket, PU was encapsulated by an obvious fibrous capsule, concurrent with a large amount of inflammatory cell infiltration, while Gastrodin/PU induced a thinner fibrous capsule, especially 2Gastrodin/PU. Further, enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment, as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo. These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration, thus providing new insight into the development of clinically effective vascular grafts.
... Initially, GAS has been demonstrated to be a calcium channel blocker and can impede intracellular Ca 2+ overload [9,10]. In traditional medicine, GAS has been extensively used to treat cardiovascular and cerebrovascular diseases, such as stroke, dementia, and hypertension [11,12]. Recent studies have indicated that GAS possesses comprehensive pharmacological functions, including antioxidative effects, anti-inflammatory effects, neuroprotective effects, and hypoxia tolerance [13]. ...
... erefore, the prevention of AR after LT is beneficial for improving the survival rate of allografts [32,33]. Pharmaceutical research has found that GAS, extracted from Gastrodia elata, has various biological activities, such as scavenging oxygen free radicals, regulating immunity, preventing platelet aggregation, and protecting cell membranes [11][12][13]. In cardiac ischemia-reperfusion mice, it was found that GAS could regulate miR-21 and the PI3K/AKT pathway and inhibit the downstream NF-κB pathway to improve myocardial ischemia-reperfusion injury [34]. ...
Background:
Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT.
Methods:
Rat transplant models were established and divided into SHAM, LT, GAS-L (50 mg/kg GAS), and GAS-H (100 mg/kg GAS) groups. The liver function, inflammatory factors, liver histopathology, survival of rats, number of M2-type macrophages, liver cell apoptosis, and pathway proteins were assayed at 7 days and 14 days after the operations.
Results:
With increasing GAS concentrations, liver function, expression of proinflammatory factors in the liver, and expression of M2-type molecules in macrophages were significantly improved, and the survival time of rats was significantly prolonged (P < 0.05). All rats treated with low or high doses of GAS were judged to have nondeterministic acute rejection. Flow cytometry showed that liver cell apoptosis was decreased significantly in the GAS-L and GAS-H groups after GAS administration compared with apoptosis and differentiation in the LT group (P < 0.05). Expression levels of Caspase-3, Bad, and Bax proteins were decreased, and the expression of the antiapoptotic protein Bcl-2 was increased in the GAS-L and GAS-H groups (P < 0.05). Mechanistically, the ERS-related IRE1α/TRAF2/NF-κB pathway was suppressed by GAS, and GAS acted mainly on intrahepatic macrophages to affect AR and reduce ROS production (P < 0.05).
Conclusion:
GAS ameliorated AR by inhibiting the IRE1α/TRAF2/NF-κB pathway in LT.
... There are other reports that show the beneficial cardiovascular effects of gastrodin, a major bioactive component of Gastordia elata Bl. For example, injection of gastrodin into elderly patients with refractory hypertension caused a decrease in systolic and pulse pressures (Zhang et al., 2008). Furthermore, this study showed that gastrodin increase NO levels while it simultaneously reduced endothelin levels (Zhang et al., 2008). ...
... For example, injection of gastrodin into elderly patients with refractory hypertension caused a decrease in systolic and pulse pressures (Zhang et al., 2008). Furthermore, this study showed that gastrodin increase NO levels while it simultaneously reduced endothelin levels (Zhang et al., 2008). Recently, the underlying mechanism for gastrodin's effects was elucidated. ...
Traditional medicine has a history extending back to thousands of years, and during the intervening time, man has identified the healing properties of a very broad range of plants. Globally, the use of herbal therapies to treat and manage cardiovascular disease (CVD) is on the rise. This is the second part of our comprehensive review where we discuss the mechanisms of plants and herbs used for the treatment and management of high blood pressure. Similar to the first part, PubMed and ScienceDirect databases were utilized, and the following keywords and phrases were used as inclusion criteria: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine, endothelial cells, nitric oxide (NO), vascular smooth muscle cell (VSMC) proliferation, hydrogen sulfide, nuclear factor kappa-B (NF-κB), oxidative stress, and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with plant or herb in question, and where possible with its constituent molecule(s). This part deals in particular with plants that are used, albeit less frequently, for the treatment and management of hypertension. We then discuss the interplay between herbs/prescription drugs and herbs/epigenetics in the context of this disease. The review then concludes with a recommendation for more rigorous, well-developed clinical trials to concretely determine the beneficial impact of herbs and plants on hypertension and a disease-free living.
... Gastrodin (PubChemCID:115067(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[4-(hydroxymethyl)phenoxy]oxane-3,4,5triol, Figure 1) is one of the major bioactive components extracted from the Chinese herb Gastrodia elata Bl. (Figure 1). Gastrodin injection has been extensively used to treat cardiovascular and cerebrovascular diseases in China and has a certain efficacy to lower blood pressure in hypertensive patients [5]. However, the related mechanisms still remain cryptic. ...
... Besides, gastrodin may improve microcirculation and cardiovascular compliance and promote fibrinolytic activity and anti-ischemic-reperfusion injury [12]. Additionally, gastrodin could also improve blood pressure, blood rheology, endothelin, and other indicators in patients with hypertension [5]. Some studies have shown that gastrodin inhibited cardiac hypertrophy and fibrosis through inhibiting ERK1/2 signaling pathway and activation of GATA-4 [6]. ...
Gastrodin is a bioactive compound extracted from traditional Chinese medicine,
Gastrodia elata
Bl. It has a definite effect on reducing blood pressure in hypertensive patients. However, the mechanisms of gastrodin in lowering blood pressure still remain unclear. In this study, 4 weeks of administration of gastrodin (100 mg/kg/d intraperitoneally injected) decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) (
190.2
±
8.9
versus
169.8
±
6.4
,
P
<
0.01
). Among SHRs receiving gastrodin treatment, angiotensin II (Ang II) and aldosterone (ALD) in serum were significantly decreased (
2022.1
±
53.0
versus
1528.7
±
93.9
,
213.33
±
35.17
versus
179.65
±
20.31
, and
P
<
0.01
,
P
<
0.05
, resp.) and dramatically downregulated expression of angiotensin type 1 receptor (AT1R) (
4.9
±
0.9
versus
2.6
±
0.9
,
P
<
0.05
) in myocardium in both mRNA and protein levels compared with their corresponding groups without gastrodin treatment. Additionally, gastrodin increased the mRNA expression (
0.18
±
0.07
versus
0.82
±
0.10
,
P
<
0.01
) and protein synthesis (
0.40
±
0.10
versus
0.34
±
0.10
,
P
<
0.01
) of peroxisome proliferator-activated receptor
γ
(PPAR
γ
) in myocardium tissues. Overall, our data demonstrated that gastrodin was able to decrease the SBP in SHR. Furthermore, this study showed that gastrodin intervened with the renin-angiotensin-aldosterone system (RAAS) and PPAR
γ
effectively, which indicates its antihypertensive mechanism.
... Gastrodin is also a potent antioxidant and free radical scavenger that decreases the levels of lipid peroxidation [24] and increases the expression of genes encoding antioxidant proteins [25]. In addition, gastrodin has been used in clinics as an effective and safe drug for preventing neurocognitive decline following cardiopulmonary bypass [26] and is beneficial to older patients with refractory hypertension by improving the balance of endothelin and nitric oxide in plasma [27], suggesting safe use in humans. However, studies evaluating the neuroprotective role of gastrodin in MPP + /MPTP PD experimental models have not been conducted. ...
... Moreover, gastrodin can cross the blood-brain barrier, enter the central nervous system, and protect against nerve lesions [60]. Gastrodin has been used as a safe and effective drug in the clinic for neurocognitive decline and refractory hypertension [26, 27]. Taken together, the similarities between the MPTP model and PD suggest that the neuroprotective effects of gastrodin could be useful against PD and it might be developed as a future clinical candidate for PD. ...
Gastrodia elata (GE) Blume is one of the most important traditional plants in Oriental countries and has been used for centuries to improve various conditions. The phenolic glucoside gastrodin is an active constituent of GE. The aim of this study was to investigate the neuroprotective role of gastrodin in 1-methyl-4-phenylpyridinium (MPP(+))/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) induced human dopaminergic SH-SY5Y cells and mouse model of Parkinson's disease (PD), respectively. Gastrodin significantly and dose dependently protected dopaminergic neurons against neurotoxicity through regulating free radicals, Bax/Bcl-2 mRNA, caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) in SH-SY5Y cells stressed with MPP(+). Gastrodin also showed neuroprotective effects in the subchronic MPTP mouse PD model by ameliorating bradykinesia and motor impairment in the pole and rotarod tests, respectively. Consistent with this finding, gastrodin prevented dopamine depletion and reduced reactive astrogliosis caused by MPTP as assessed by immunohistochemistry and immunoblotting in the substantiae nigrae and striatata of mice. Moreover, gastrodin was also effective in preventing neuronal apoptosis by attenuating antioxidant and antiapoptotic activities in these brain areas. These results strongly suggest that gastrodin has protective effects in experimental PD models and that it may be developed as a clinical candidate to ameliorate PD symptoms.
... Gastrodin, a glucopyranoside with hydroxyl functional groups, exhibits therapeutic potential for cardiovascular disease. [67,68] It acts by preventing intracellular Ca 2 + overload, increasing arterial compliance, reducing blood viscosity, improving blood supply, and enhancing microcirculation. Its efficacy as a calcium channel blocker has also been demonstrated. ...
Gastrodin, a bioactive compound derived from the rhizome of the orchid Gastrodia elata, exhibits a diverse range of biological activities. With documented neuroprotective, anti‐inflammatory, antioxidant, anti‐apoptotic, and anti‐tumor effects, gastrodin stands out as a multifaceted therapeutic agent. Notably, it has demonstrated efficacy in protecting against neuronal damage and enhancing cognitive function in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Additionally, gastrodin showcases immunomodulatory effects by mitigating inflammation and suppressing the expression of inflammatory cytokines. Its cytotoxic activity involves the inhibition of angiogenesis, suppression of tumor growth, and induction of apoptosis. This comprehensive review seeks to elucidate the myriad potential effects of Gastrodin, delving into the intricate molecular mechanisms underpinning its pharmacological properties. The findings underscore the therapeutic potential of gastrodin in addressing various conditions linked to neuroinflammation and cancer.
... Mechanisms of gastrodin treatment of hypertension. The improvement of gastrodin on the balance between endothelin and NO levels in the plasma are beneficial for elderly refractory hypertensive patients [54]. Meta-analyses have shown that gastrodin, when combined with conventional treatment, lowers blood pressure, improves systolic and diastolic blood pressure, enhances endothelial function, and improves clinical symptoms in hypertensive patients. ...
... Gastrodin has been used to treat neurodegenerative diseases in clinical practice, such as epilepsy, migraine and convulsions [12][13][14], the underlying mechanisms are related to apoptosis, oxidative stress and neurotransmitter release. In addition, Gastrodin has been shown to lower blood pressure and alleviate cardiac hypertrophy [15,16]. In the context of cardiac hypertrophy, Gastrodin was reported to target insulin-like growth factor type 2 gene (IGF2) and its receptor IGF2R [15]. ...
Background
Gastrodin is an effective polyphenol extracted from Chinese natural herbal Gastrodiae elata Blume, which exhibits antioxidant and anti-inflammatory effects. It has been reported to benefit neurodegenerative diseases, but the effect of Gastrodin on atherosclerosis and the underlying mechanisms remain elusive. The aim of this study is to investigate the function and mechanism of Gastrodin in atherosclerosis.
Methods
Atherosclerosis mouse model was established by fed low density lipoprotein receptor-deficient (Ldlr−/−) mice with a high fat diet (HFD, 20% fat and 0.5 cholesterol) for 8 weeks and Gastrodin was administered daily via oral gavage. Plasma lipid levels were measured using commercial kits. En face and aortic sinus lipid accumulation were analyzed with Oil Red O staining. In vitro cell models using foam cell formation model and classical atherosclerosis inflammation model, macrophages were incubated with oxygenized low-density lipoproteins (ox-LDL) or lipopolysaccharide (LPS) in the presence of different concentration of Gastrodin or vehicle solution. Foam cell formation and cellular lipid content were evaluated by Oil Red O staining and intracellular lipids extraction analysis. Gene expression and proteins related to cholesterol influx and efflux were examined by quantitative reverse transcription PCR (RT-qPCR) and western blotting analysis. Furthermore, the effect of Gastrodin on LPS induced macrophage inflammatory responses and NF-κB pathway were evaluated by RT-qPCR and western blotting analysis.
Results
Gastrodin administration reduced the body weight, plasma lipid levels in Ldlr−/− mice after fed a high fat diet. Oil Red O staining showed Gastrodin-treated mice displayed less atherosclerosis lesion area. Furthermore, Gastrodin treatment significantly ameliorated ox-LDL-induced macrophage-derived foam cells formation through suppressing genes expression related to cholesterol efflux including scavenger receptor class B and ATP-binding cassette transporter A1. Moreover, Gastrodin markedly suppressed pro-inflammatory cytokines secretion and LPS induced inflammatory response in macrophage through downregulating NF-κB pathway.
Conclusions
Our study demonstrated that Gastrodin attenuates atherosclerosis by suppressing foam cells formation and LPS-induced inflammatory response and represents a novel therapeutic target for the treatment of atherosclerosis.
... Moreover, a previous clinical study has confirmed that gastrodin exerts a significant antihypertensive effect. Gastrodin injection is also widely used in the clinical treatment of patients with hypertension in China (Zhang et al., 2008). ...
Background: Gastrodin has been widely used clinically in China as an antihypertensive drug. However, its effect on hypertensive renal injury is yet to be elucidated. The current study aimed to investigate the effects of gastrodin on hypertensive renal injury and its underlying mechanisms by network pharmacology analysis and validation in vivo and in vitro.
Methods: A total of 10 spontaneously hypertensive rats (SHRs) were randomly categorized into the following two groups: SHR and SHR + Gastrodin groups. Wistar Kyoto (WKY) rats were used as the control group (n = 5). The SHR + Gastrodin group was intragastrically administered gastrodin (3.5 mg/kg/day), and the rats in both WKY and SHR groups were intragastrically administered an equal amount of double-distilled water for 10 weeks. Hematoxylin-eosin, Masson’s trichrome, and Sirius red staining were used to detect the pathological changes and collagen content in the renal tissues. Network pharmacology analysis was performed to explore its potential targets and related pathways. In vitro, the CCK-8 assay was used to determine the cell viability. Immunohistochemistry and western-blotting analyses were employed to assess the protein expression associated with renal fibrosis and transforming growth factor-β1 (TGF-β1) pathway-related proteins in the renal tissues or in TGF-β1-stimulated rat kidney fibroblast cell lines (NRK-49F).
Results: Gastrodin treatment attenuates renal injury and pathological alterations in SHRs, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilation. Gastrodin also reduced the accumulation of collagen in the renal tissues of SHRs, which were confirmed by downregulation of α-SMA, collagen I, collagen III protein expression. Network pharmacology analysis identified TGFB1 and SMAD2 as two of lead candidate targets of gastrodin on against hypertensive renal injury. Consistently, gastrodin treatment downregulated the increase of the protein expression of TGF-β1, and ratios of both p-Smad2/Smad2 and p-Samd3/Smad3 in renal tissues of SHRs. In vitro, gastrodin (25–100 μM) treatment significantly reversed the upregulation of α-SMA, fibronectin, collagen I, as well as p-Smad2 and p-Smad3 protein expressions without affecting the cell viability of TGF-β1 stimulated NRK-49F cells.
Conclusion: Gastrodin treatment significantly attenuates hypertensive renal injury and renal fibrosis and suppresses TGF-β1/Smad2/3 signaling in vivo and in vitro.
... The phenolic glycoside gastrodin (GAS) is a monomeric component derived from Gastrodia elata Blume and has a variety of properties. It has long been used in treating cerebrovascular and cardiovascular diseases (161). Previous studies have demonstrated that GAS could reduce oxidative stress, lower inflammatory levels, and elevate hypoxia tolerance (162). ...
Percutaneous coronary intervention (PCI) is one of the most effective reperfusion strategies for acute myocardial infarction (AMI) despite myocardial ischemia/reperfusion (I/R) injury, causing one of the causes of most cardiomyocyte injuries and deaths. The pathological processes of myocardial I/R injury include apoptosis, autophagy, and irreversible cell death caused by calcium overload, oxidative stress, and inflammation. Eventually, myocardial I/R injury causes a spike of further cardiomyocyte injury that contributes to final infarct size (IS) and bound with hospitalization of heart failure as well as all-cause mortality within the following 12 months. Therefore, the addition of adjuvant intervention to improve myocardial salvage and cardiac function calls for further investigation. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in Chinese herbal medicine. Great effort has been put into phytochemicals because they are often in line with the expectations to improve myocardial I/R injury without compromising the clinical efficacy or to even produce synergy. We summarized the previous efforts, briefly outlined the mechanism of myocardial I/R injury, and focused on exploring the cardioprotective effects and potential mechanisms of all phytochemical types that have been investigated under myocardial I/R injury. Phytochemicals deserve to be utilized as promising therapeutic candidates for further development and research on combating myocardial I/R injury. Nevertheless, more studies are needed to provide a better understanding of the mechanism of myocardial I/R injury treatment using phytochemicals and possible side effects associated with this approach.
... 15,16 In addition, many studies have demonstrated that gastrodin has antioxidant activity. 17,18 Thus, it is expected that gastrodin would weaken oxidative damage associated with aging and protect against neurodegeneration. However, the effects of gastrodin on aging have not been deeply investigated. ...
Gastrodin is the main bioactive ingredient of a famous Chinese herb Rhizoma Gastrodiae. Many studies have reported that gastrodin has antioxidative and neuroprotective effects, although its effect on longevity and the mechanism of neuroprotection have not been well studied. Here, we use Drosophila melanogaster as a model to investigate the longevity and neuroprotective effects of gastrodin. Gastrodin significantly extended the lifespan, increased the climbing ability, enhanced the resistance to oxidative stress, increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT), and promoted the expression of anti-oxidative genes in old flies. The food intake, reproduction and starvation resistance were not affected in flies treated with gastrodin. Moreover, gastrodin delayed the onset of Parkinson-like phenotypes in Pink1B9 mutant flies, including the prolongation of the lifespan, rescue of the climbing ability, rescue of the progressive loss of a cluster of dopaminergic neurons in the protocerebral posterial lateral 1 region, and increase of the dopamine content in the brain. Gastrodin did not ameliorate the tau-induced neurobehavioral deficits in the fly AD model of taupathy. Together, these results indicate that gastrodin could prolong the lifespan by regulating the antioxidant ability, and protect against neurodegeneration in the Pink1B9 model of PD. This suggests that gastrodin can be considered as an ideal therapeutic candidate for drug development towards anti-aging.
... Furthermore, GAS exhibits low toxicity, significant pharmacological effects, and therapeutic potential for the prevention and treatment of certain diseases, especially neurological disorders (Zhan et al. 2016). For example, GAS has been shown to have anti-epileptic , anti-depressant, anti-anxiety (Peng et al. 2013), and anti-aging effects (Wang et al. 2007) and can further improve memory (Hsieh et al. 1997), lower blood pressure (Zhang et al. 2008), and prevent osteonecrosis (Zheng et al. 2014). Its mechanisms include the regulation of neurotransmitters, mitochondrial cascade and neurotrophic factors, inhibition of microglia activation, anti-oxidation, and anti-inflammation (Liu et al. 2018b). ...
To investigate the effects of gastrodin (GAS) on methamphetamine (MA)-induced conditioned place preference (CPP) in rats and explore its potential mechanisms. MA (10 mg/kg) was initially injected intraperitoneally (i.p.) in rats, after which they were administered either MA or saline alternately from day 4 to 13 (D4–13) for 10 days, followed by treatment with GAS (10 or 20 mg/kg, i.p.) on D15–21 for 7 days. The rats underwent CPP testing after MA and GAS treatment. In vitro, SH-SY5Y cells were exposed to MA (2.0 mM) for 24 h, followed by treatment with GAS (2.0 or 4.0 mM) for 24 h. The expression levels of PKA, P-PKA, CREB, and P-CREB proteins in the prefrontal cortex, nucleus accumbens, and ventral tegmental area of MA-induced CPP rats and in SH-SY5Y cells were detected by Western blot analysis. The MA-induced CPP rat model was successfully established. The administration of MA stimulated a significant alteration in behavior, as measured by the CPP protocol. After treatment with GAS, the amount of time rats spent in the MA-paired chamber was significantly reduced. Results also showed that MA increased the expression levels of PKA, P-PKA, CREB, and p-CREB proteins in the prefrontal cortex, nucleus accumbens, and ventral tegmental area of CPP rats and in SH-SY5Y cells (p < 0.05). GAS attenuated the effect of MA-induced CPP in rats and decreased the expression levels of proteins in vivo and in vitro. Our study suggests that GAS can attenuate the effects of MA-induced CPP in rats by regulating the PKA/CREB signaling pathway.
... Therefore, on the basis of these data, compound 4 was elucidated to be kaempferol-3-O-β-D-glucopyranoside. [30]. Therefore, on the basis of these data, compound 5 was elucidated to be kaempferol-3,7-di-O-β-D-glucopyranoside. ...
Crude extracts of Sedum formosanum N.E.Br. obtained from n-butanol partition (BP) and isopropanol salting-out pretreatment (ISP) were analyzed using antioxidation assays. The results indicated that the extract from ISP contained more potent antioxidants and thus exhibited more antioxidant activity in all the assays. The superoxide radical-scavenging activity and inhibition of nitric oxide radicals achieved after ISP were 3.65 and 2.18 times higher than those achieved through BP, respectively. Eight bioactive natural products were isolated and identified according to an analysis of antioxidation activity in different fractions of the ISP crude extract, namely three cyanophoric glycosides 1-3, three flavonoids 4-6 and two phenolic compounds (7 and a new compound 8). Among them, compounds 5 and 6 exhibit the highest antioxidation capability, and the ISP is suitable for obtaining compounds 5 and 6 using HPLC chromatograms. Therefore, ISP is an excellent extraction technology that can be used to extract antioxidant compounds in the nutraceutical and pharmaceutical industries.
... En plus d'une administration orale, la gastrodine a déjà été utilisée par voie intraveineuse et intramusculaire dans des essais cliniques en Chine (Ojemann et al., 2006;Zhang et al., 2008). Bien que la gastrodine soit l'un des composés actifs principaux tenu pour responsable des effets cliniques de la GeB, différentes études ont suggéré que les effets pharmacologiques ne puissent pas être expliqués par le seul fait de la gastrodine (Junhua et al., 1989). ...
In the western world, cerebral vascular accidents (CVA) represent one of the major causes of handicap and mortality. Nevertheless, therapeutic approaches are helpless at the hands of this public health problem. They are made of prevention or suppression of risk factors, such tobacco addiction, high blood pressure or hypercholesterolemia. The CVA can be haemorrhagic, but for 80% of the cases, its vascular origin is obstructive. In this case, the acute treatment benefits of thrombolytic agents, whose administration is time dependent. Neuroprotective agents protect the brain from deleterious consequences of cerebral ischemia reperfusion at the time of CVA (irreversible injury and handicap). Nowadays the efficiency of these agents is disappointing.
Therefore, research for novel therapeutic targets is obvious in this area. A preliminary proteomic study has taken an interest in proteins whose concentration was modified during cerebral ischemia reperfusion (CIR). This study gave rise to protein disulfide isomerase (PDI), a result in agreement with data from literature (Tanaka, S., Uehara, T., Nomura, Y., 2000, J. Biol. Chem. 275, 10388-10393).
PDI is a chaperone protein, with an oxidoreductase activity, mainly localised in the endoplasmic reticulum. It assists the protein folding by the formation or isomerisation of disulfure bridges.
PDI modulatory agents are 4-hydroxybenzylic alcohol (4-HBA) and bacitracin, PDI inductor and inhibitor respectively. To determine the potential salutary or deleterious effect of PDI in IRC, the cerebral impact of these modulatory agents was studied in a murine model of CIR, based on transient middle cerebral artery occlusion. In this experimental model, 4-HBA significantly reduces cerebral infarct size in cortex and striatum areas (22 and 55% respectively). PDI involvement in this cerebral protection is corroborated by the elimination of 4-HBA neuroprotective effect by bacitracin. In addition, 4-HBA does not show anto oedematous properties in this CIR model. PDI induction by 4-HBA was shown on healthful mice brain, by western blot experiment. 4-HBA position isomers (2-hydroxybenzylic alcohol and 3-hydroxybenzylic alcohol) and aliphatic analogues (1,4-butanediol and 1,5 pentanediol) were not able to reduce cerebral injury size and to induce cerebral PDI in the experimental CIR model, in opposition to 4-HBA.
The neutroprotective potential of 4-HBA was studied in another model, the audiogenic seizure test on magnesium deficient mice, known for its response to anticonvulsivant agents but also to antioxidant compounds (Vamecq, J., Maurois, P., Bac, P., Bailly, F., Bernier, J.L., Stables, J.P., Husson, I.,Gressens, P., 2003, Eur. J. Neurosci. 18, 1110-1120). The 4-HBA dose which protects 50% of animals to audiogenic seizure was 25mg/kg, against 35mg/kg for 6-hydroxyflavanone (6-HFN), a reference flavone active in this test. As these results suggested a similar antioxydant potential for these two compounds, their protective effects were compared in the CIR model on mice. This study confirmed the neuroprotection given by 4-HBA, but revealed the inability of 6-HFN to induce a significant protection. Conversely to 4-HBA, 6-HFN did not induce cerebral PDI in mice, consolidating the hypothesis that 4-HBA protection at the hands of CIR is more due to its ability to induce PDI than to other properties such as its antioxidant potential. Finally, 4-HBA, at doses up to 200 mg/kg, turned out devoid of toxicity in the rotarod test.
In conclusion, 4-HBA represents a neuroprotective agent active in several evaluation models. Its efficiency at the hands of injury induced by CIR seems bound to its capacity to induce cerebral PDI. This protein is therefore a promising pharmacological target for the development of active compounds in the CVA.
Myocardial infarction (MI) is a prevalent disease with high mortality rates worldwide. The course of MI is intricate and variable, necessitating personalized treatment strategies based on different mechanisms. However, variety of postoperative complications and rejections, such as heart failure, arrhythmias, cardiac rupture, and left ventricular thrombus, contribute to a poor prognosis. Despite the inclusion of antiplatelet agents and statins in the conventional treatment regimen, their clinical applicability is constrained by potential adverse effects and limited efficacy. Additionally, the mechanisms leading to MI are complex and diverse. Therefore, the development of novel compounds for MI treatment. The use of traditional Chinese medicine (TCM) in the prevention and treatment of cardiovascular diseases, including MI, is grounded in its profound historical background, comprehensive theoretical system, and accumulated knowledge. An increasing number of contemporary evidence‐based medical studies have demonstrated that TCM plays a significant role in alleviating symptoms and improving the quality of life for MI patients. Chinese herbal formulations and active ingredients can intervene in the pathological process of MI through key factors such as inflammation, oxidative stress, apoptosis, ferroptosis, pyroptosis, myocardial fibrosis, angiogenesis, and autophagy. This article critically reviews existing herbal formulations from an evidence‐based medicine perspective, evaluating their research status and potential clinical applications. Additionally, it explores recent advancements in the use of herbal medicines and their components for the prevention and treatment of MI, offering detailed insights into their mechanisms of action.
The effects and underlying mechanisms of gastrodin treatment on hypertensive vascular dysfunction and proliferation of vascular smooth muscle cells (VSMCs) were determined in vitro and in vivo. Using a pharmacological target network interaction analysis, 151 common targets and a PPI network were identified containing the top 10 hub genes. Kyoto encyclopedia of genes and genomes (KEGG) analysis identified the PI3K/AKT pathway as a significantly enriched pathway. Both spontaneous hypertensive rats (SHRs) and Wistar Kyoto rats were used to assess the therapeutic effects of gastrodin on hypertension. Gastrodin treatment of the SHRs resulted in a marked attenuation of elevated blood pressure, pulse wave velocity, and pathological changes in the abdominal aorta. Moreover, gastrodin treatment significantly inhibited cell growth and downregulated the expression of PCNA as well as the p-PI3K/PI3K and p-AKT/AKT levels in angiotensin II-stimulated VSMCs. Taken together, gastrodin treatment attenuates blood pressure elevation, vascular dysfunction, and proliferation of VSMCs and inhibits the activation of the PI3K/AKT pathway.
Ethnopharmacological relevance:
Gastrodia elata Bl. (GE) is one of the rare Chinese medicinal materials with a long history of medicine and cooking. It consists of a variety of chemical components, including aromatic compounds, organic acids and esters, steroids, saccharides and their glycosides, etc., which has medicinal and edible value, and is widely used in various diseases, such as infantile convulsions, epilepsy, tetanus, headache, dizziness, limb numbness, rheumatism and arthralgia. It is also commonly used in health care products and cosmetics. Thus, its chemical composition and pharmacological activity have attracted more and more attention from the scientific community.
Aim:
In this review, the processing methods, phytochemistry and pharmacological activities of GE were comprehensively and systematically summarized, which provides a valuable reference for researchers the rational of GE.
Materials and methods:
A comprehensive search of published literature and classic books from 1958 to 2023 was conducted using online bibliographic databases PubMed, Google Scholar, ACS, Science Direct Database, CNKI and others to identify original research related to GE, its processing methods, active ingredients and pharmacological activities.
Results:
GE is traditionally used to treat infantile convulsion, epilepsy, tetanus, headache, dizziness, limb numbness, rheumatism and arthralgia. To date, more than 435 chemical constituents were identified from GE including 276 chemical constituents, 72 volatile components and 87 synthetic compounds, which are the primary bioactive compounds. In addition, there are other biological components, such as organic acids and esters, steroids and adenosines. These extracts have nervous system and cardiovascular and cerebrovascular system activities such as sedative-hypnotic, anticonvulsant, antiepileptic, neuron protection and regeneration, analgesia, antidepressant, antihypertensive, antidiabetic, antiplatelet aggregation, anti-inflammatory, etc. CONCLUSION: This review summarizes the processing methods, chemical composition, pharmacological activities, and molecular mechanism of GE over the last 66 years, which provides a valuable reference for researchers to understand its research status and applications.
Ethnopharmacological relevance:
Qingda granule (QDG) exhibits significant therapeutic effects on high blood pressure, vascular dysfunction, and elevated proliferation of vascular smooth muscle cells by inhibiting multiple pathways. However, the effects and underlying mechanisms of QDG treatment on hypertensive vascular remodeling are unclear.
Aim of the study:
The aim of this study was to determine the role of QDG treatment in hypertensive vascular remodeling in vivo and in vitro.
Materials and methods:
An ACQUITY UPLC I-Class system coupled with a Xevo XS quadrupole time of flight mass spectrometer was used to characterize the chemical components of QDG. Twenty-five spontaneously hypertensive rats (SHR) were randomly divided into five groups, including SHR (equal volume of double distilled water, ddH2O), SHR + QDG-L (0.45 g/kg/day), SHR + QDG-M (0.9 g/kg/day), SHR + QDG-H (1.8 g/kg/day), and SHR + Valsartan (7.2 mg/kg/day) groups. QDG, Valsartan, and ddH2O were administered intragastrically once a day for 10 weeks. For the control group, ddH2O was intragastrically administered to five Wistar Kyoto rats (WKY group). Vascular function, pathological changes, and collagen deposition in the abdominal aorta were evaluated using animal ultrasound, hematoxylin and eosin and Masson staining, and immunohistochemistry. Isobaric tags for relative and absolute quantification (iTRAQ) was performed to identify differentially expressed proteins (DEPs) in the abdominal aorta, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Cell Counting Kit-8 assays, phalloidin staining, transwell assays, and western-blotting were performed to explore the underlying mechanisms in primary isolated adventitial fibroblasts (AFs) stimulated with transforming growth factor-β 1 (TGF-β1) with or without QDG treatment.
Results:
Twelve compounds were identified from the total ion chromatogram fingerprint of QDG. In the SHR group, QDG treatment significantly attenuated the increased pulse wave velocity, aortic wall thickening, and abdominal aorta pathological changes and decreased Collagen I, Collagen III, and Fibronectin expression. The iTRAQ analysis identified 306 DEPs between SHR and WKY and 147 DEPs between QDG and SHR. GO and KEGG pathway analyses of the DEPs identified multiple pathways and functional processes involving vascular remodeling, including the TGF-β receptor signaling pathway. QDG treatment significantly attenuated the increased cell migration, actin cytoskeleton remodeling, and Collagen I, Collagen III, and Fibronectin expression in AFs stimulated with TGF-β1. QDG treatment significantly decreased TGF-β1 protein expression in abdominal aortic tissues in the SHR group and p-Smad2 and p-Smad3 protein expression in TGF-β1-stimulated AFs.
Conclusions:
QDG treatment attenuated hypertension-induced vascular remodeling of the abdominal aorta and phenotypic transformation of adventitial fibroblasts, at least partly by suppressing TGF-β1/Smad2/3 signaling.
Gatrodin is an active compound with cardio-protective potentials. In the current study, the mechanism underlying the effects of gastrodin was explored. Myocardial infarction was induced and handled with gastrodin. The role of miR-30a-5p and its downstream effector, ATG5, in the cardio-protective effects of gastrodin was verified. Gastrodin induced the dys-expresseion of 72 miRs in oxygen/glucose deprivation (OGD) cardiomyocytes and miR-30a-5p was selected as the potential therapeutic target. Gastrodin increased viability and suppressed autophagy in OGD cardiomyocytes, which was associated with the induction of miR-30a-5p and deactivation of ATG5. In rat models, gastrodin attenuated structure deterioration and dysfunction in heart, and suppressed autophagy. At molecular level, miR-30a-5p was induced and ATG5 were down-regulated. After the suppression of miR-30a-5p or the overexpression of ATG5, the cardio-protective effects of gastrodin were compromised. Gastrodin induced the expression of miR-30a-5p, which contributed to the attenuation of autophagy in infarcted heart tissues.
Background:
Despite research on the molecular bases of Alzheimer's disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers.
Methods:
We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials.
Results:
Our results demonstrated the increased bioactivity of three plants' metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau.
Conclusions:
This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.
Septic shock leads to myocardial dysfunction and induces inflammation. Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes are involved in inflammation, and gastrodin can inhibit the activity of inflammasomes. Our study aimed to explore the effect of gastrodin against septic shock–induced injury through inhibiting NLRP3. Before establishing septic shock mice model, the mice were injected with gastrodin of various concentrations. The cardiac function of mice was detected by a PowerLab, and the histopathological changes of mouse myocardial tissues were detected by hematoxylin-eosin staining. Apoptosis of cardiomyocytes from mice was detected by TUNEL assay, and IL-1β concentration was detected by enzyme-linked immunosorbent assay. After culture in vitro and treatment with gastrodin, lipopolysaccharide (LPS), and NLRP3 vector, the cell viability and apoptosis of cardiomyocytes were detected by cell counting kit-8 and flow cytometry respectively. Besides, the expressions of NLRP3, Caspase-1, IL-1β, Bax, and Bcl-2 in mouse myocardial tissue or cultured cardiomyocytes were detected by Western blot. Gastrodin improved survival and promoted the recovery of cardiac function in septic shock mice, as it reversed the abnormality of left ventricular function indices in septic shock mice. Besides, gastrodin decreased IL-1β concentration and apoptosis in myocardial tissues of septic shock mice and decreased apoptosis and increased cell viability in LPS-induced cardiomyocytes. In addition, gastrodin downregulated NLRP3, Caspase-1, IL-1β, and Bax expressions and upregulated Bcl-2 expression in myocardial tissues of septic shock mice and LPS-induced cardiomyocytes. NLRP3 overexpression reversed the effect of gastrodin on LPS-induced cardiomyocytes. Gastrodin promoted cardiac function recovery and protected cardiomyocytes against septic shock–induced injury by regulating NLRP3.
In this study, we investigated the protective effects of gastrodin (Gas) against homocysteine‐induced human umbilical vein endothelial cell (HUVEC) injury and the role of the phosphoinositide 3‐kinase (PI3K)/threonine kinase 1 (Akt)/endothelial nitric oxide synthase (eNOS) and NF‐E2‐related factor 2 (Nrf2)/antioxidant response element (ARE) pathways. We stimulated cells with homocysteine (1 mmol/L, 24 hours) and tested the effects of gastrodin (200‐800 μg/mL) on cell viability and the production of malondialdehyde (MDA), lactate dehydrogenase (LDH) and reactive oxygen species (ROS). Then, Nrf2 distribution in the cytoplasm and nucleus as well as the expression of enzymes downstream of Nrf2 was determined. Furthermore, we analysed the expression of bax, bcl‐2 and cleaved caspase3, and assessed the involvement of the PI3K/Akt/eNOS pathway by Western blots. Finally, we tested the vasoactive effect of gastrodin in thoracic aortic rings. The results showed that gastrodin decreased MDA, LDH and ROS production and increased cell viability, NO production and relaxation of thoracic aortic rings. Moreover, the protective effects of Gas on NO production and relaxation of thoracic aortic rings were blocked by L‐NAME but enhanced by Cav‐1 knockdown, and MK‐2206 treatment abolished the effect of Gas on the ROS. In addition, treatment with gastrodin increased Nrf2 nuclear translocation, thus enhancing the expression of downstream enzymes. Finally, gastrodin increased the expression of PI3K, p‐Akt, and eNOS and decreased Cav‐1 protein expression. In conclusion, our study suggested that gastrodin may protect HUVECs from homocysteine‐induced injury, and the PI3K/Akt/eNOS and Nrf2/ARE pathways may be responsible for the efficacy of gastrodin.
Stories on the legendary origin of Tiama or tubers of the parasitic orchid, Gastrodia elata, are used to open the chapter to highlight the observation that efficacy in traditional herbal medicine is almost invariably ‘proven’ by anecdotes. Chinese scientists determined to prove that the herb is truly effective in managing ‘diseases of wind’ (strokes and other diseases of the nervous system) have isolated over a hundred compounds from Tianma. In vitro and animal experiments which suggest that crude Tianma extracts and several pure compounds both exhibit neuroprotective properties are discussed and explained. Hopefully this will translate into clinically proven items for the management of neurological disorders of old age. Cultivated Tianma accounts for approximately 80% of the tremendous market demand exceeding 100 tons.
Brain damage, including blood-brain barrier (BBB) dysfunction, neurological behavior deficit, cerebral infarction and inflammation, is commonly caused by ischemic-reperfusion (I/R) injury. Prevention of the above biological process defects is considered beneficial for patient recovery after I/R injury. This study was aimed to assess the neuroprotective effect of Gastrodin (GAS), an herbal agent, in experimentally induced cerebral ischemia. Sprague-Dawley adult rats were randomly divided into six groups: Sham-operated control group (Sham), middle cerebral artery occlusion (MCAO) group, GAS (50, 100, and 200 mg/kg) pretreatment + MCAO groups (GAS) and Nimodipine (NIM) + MCAO, namely, the NIM group. Additionally, an OGD/R model using BV-2 microglia was established in vitro to simulate I/R injury. We showed here that the neurological scores of rats in the GAS groups were significantly improved compared with the MCAO group. Moreover, the area of cerebral infarction in the GAS pretreatment groups and the NIM group was significantly reduced. Furthermore, Evans blue leakage volume was significantly reduced with GAS pretreatment notably at dose 100 mg/kg. Expression of matrix metalloproteinase 2 (MMP2) and MMP9 in GAS groups was markedly decreased when compared with MCAO group. In BV-2 microglia exposed to OGD/R given GAS pretreatment, MMP2 and MMP9 positive cells were reduced in numbers. The present results have shown that GAS pretreatment significantly compensated for neurological behavior defects in rats with I/R-induced injury, reduced brain infarction size, reversed BBB impairment, and attenuated inflammation. It is suggested that pretreatment with GAS before surgery is beneficial during recovery from I/R injury.
Gastrodin is extracted from Gastrodia elata, which is widely used for the treatment of vertigo, headache, neuralgia, neurasthenia syndrome, and brain traumatic syndrome. Studies showed that gastrodin has many pharmacological effects, including hypnosis, sedation, and anticonvulsive. At present, to reduce the frequency of administration, the fluctuations of blood drug concentration, as well as side effects, some new dosage forms have been developed in recent years, such as Gastrodia dispersible tablets, Gastrodia sustained-release tablet, sustained-release pellets and osmotic pump tablets, etc. Although gastrodin has been applied clinically, a lot of studies still need to be done to confirm the efficacy and safety of gastrodin, and the other compositions of Gastrodia elata are subjected to further investigation.
Rhizoma Gastrodiae (also known as Tian ma), the dried rhizome of Gastrodia elata Blume, is a famous Chinese herb that has been traditionally used for the treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive constituent of Rhizoma Gastrodiae. Since identified in 1978, gastrodin has been extensively investigated on its pharmacological properties. In this article, we reviewed the central nervous system (CNS) effects of gastrodin in preclinical models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment as well as the underlying mechanisms involved and, where possible, clinical data that support the pharmacological activities. The sources and pharmacokinetics of gastrodin were also reviewed here. As a result, gastrodin possesses a broad range of beneficial effects on the above-mentioned CNS diseases, and the mechanisms of actions include modulating neurotransmitters, antioxidative, anti-inflammatory, suppressing microglial activation, regulating mitochondrial cascades, up-regulating neurotrophins, etc. However, more detailed clinical trials are still in need for positioning it in the treatment of neurological disorders.
Gastrodin, one of the major components extracted from the Chinese herb Gastrodia elata Bl., has been widely used as an anticonvulsant, sedative, analgesic and hypotensive. In our study, we aimed to investigate the effects and possible mechanisms of gastrodin on vascular KATP channels. Tension experiments were used on rat mesenteric artery rings without an endothelium. Patch clamp experiments were executed to investigate the influences of gastrodin on the membrane current in mesenteric artery smooth muscle cells. Gastrodin induced vasorelaxation in a concentration dependent manner when rat mesenteric artery rings were pre-contracted with Phenylephrine. The vasorelaxation effect was partially diminished by pre-treating with a KATP channel inhibitor, or a PKA inhibitor. With whole-cell patch-clamp recording techniques, we found that gastrodin is a activator of KATP in rat mesenteric artery smooth muscle cells, and this effect was eliminate by pre-treating with H89or PKI, PKA inhibitor. In addition, when rat vascular smooth muscle cells were treated with 100 μM gastrodin for 24 h, maximum KATP current density increased by 28.1%. The results indicate that gastrodin exerts vasorelaxation effect through activation of PKA and subsequent opening of smooth muscle KATP channels.
Gastrodia elata (Tianma) is the most important species of orchid used in traditional medicine. It is the principal herb used for the prevention and treatment of strokes and for neurological disorders which include Parkinsonism and dementia. Gastrodia elata is present in many patent Chinese herbal remedies. More than 50 compounds have been isolated from this orchid. Their neuro-protective and other effects, and those of crude Gastrodia elata extracts are extensively discussed in this chapter. Chinese scientists have also discovered a way to cultivate the orchid. Other orchid genera described in this chapter are Galeola, Gastrochilus, Geodorum, Goodyera, Grammatophyllum and Gymadenia. Examples are provided on how these orchids are used in Traditional Chinese Medicine and other traditions.
Objective: To investigate the effect of gastrodin against oxidative stress induced by high glucose in human umbilical vein endothelial cells (HUVEC). Methods: Primary HUVEC were isolated and cultured, then the oxidative injury model of HUVEC was established by high glucose, and the cells were treated with different concentration of gastrodin. The cell viability of HUVEC, nitric oxide (NO) content, superoxide dismutase (SOD) and catalase (CAT) activities, total anti-oxidative capacity (T-AOC), malondialdehyde (MDA) content, and intracellular reactive oxygen species (ROS) level were determined. Furthermore, the expression of NF-κB mRNA in HUVEC was also detected by real-time fluorescent quantitative PCR. Results: Compared with the control group, the oxidative stress was strengthened obviously in cells treated with high glucose. However, gastrodin could increase the activity of SOD and CAT and enhance T-AOC in HUVEC. Meanwhile, the amounts of MDA and ROS were decreased, and the level of NF-κB mRNA was also reduced markedly. Conclusion: These results indicate that gastrodin could inhibit the oxidative stress in HUVEC by enhancing the activity of anti-oxidative enzyme, and decreasing the amounts of lipid peroxidation products and ROS. The mechanism may be involved in NF-κB pathway.
Highly practical, four-step synthesis of gastrodin was developed using penta- O-acetyl-β-D-glucopyranose and p-cresol as glycosyl donor and glycosyl acceptor, respectively, in 58.1% overall yield. As the initial step, the penta-O-acetyl-β-D-glucopyranose was treated with p-cresol in the presence of BF3 •Et2O as catalyst to generate 4-methylphenyl 2,3,4,6-tetra-O-acetyl-β-D- -glucopyranoside in 76.3% yield. Further, this product was subjected to radical bromination with N-bromosuccinimide (NBS) to provide 4-(bromomethyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside in 91% yield. Subsequently, reaction of 4-(bromomethyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside with a solution of acetone and saturated aqueous sodium bicarbonate led to 4-(hydroxymethyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside in 93% yield. Finally, global deprotection of 4-(hydroxymethyl)phenyl 2,3,4,6-tetra-O- -acetyl-β- D-glucopyranoside under Zemplen conditions furnished gastrodin in 90% yield. Compared to the previously reported methods, this protocol has the advantages of operational simplicity, chromatography-free separation, high overall yield, inexpensive and common reagents as well as less waste pollutants, rendering it an alternative suitable for industrial production.
Gastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH.
All 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups.
The incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower.
Gastrodin could prevent steroid-induced ONFH by anti-apoptosis.
Objective:
There are more than 300 million patients with hypertension in China, and at least 1 in 5 is using or has ever used Chinese Medicine (CM) treatment.
Scope:
This article reviews the efficacy and safety of CM as monotherapy and in combination with western medicine (WM) to explore its potential role in the clinical management of hypertension.
Methods:
Relevant articles were identified through PubMed, Chinese National Knowledge Infrastructure (CNKI) Database, VIP Chinese Journal Database, Wanfang Database, and China Biological Medicine Database (CBM-disc) search (up to 31 March, 2013).
Findings:
A total of 27 RCTs and 7 systematic reviews (including meta-analyses) were identified. These articles suggested that although as monotherapy, CM has limited effect for hypertension, while combined with WM, it does have a favorable effect of antihypertension. The combination therapy could not only improve the quality of life and the symptoms of hypertensive patients, such as dizziness and headache, but also stabilize blood pressure variability (BP). Moreover, the combined treatment of CM and WM may further reduce BP to the target levels for patients failed with hypertension control. Besides, the combination therapy also has more favorable effects than any WM monotherapy in protecting target organs as well as avoiding adverse reactions.
Conclusion:
When combined with WM, CM as a complementary treatment approach has certain effects for the control of hypertension and protection of target organs. However, more well-designed studies should be conducted to make a solid conclusion.
Objectives
To explore 1H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats.
Methods
In this research, 1H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats.
Results
24 endogenous metabolites were identified. Body weight, daily diet and the total volume of urine in in each day of each rat were measured synchronously. Modifications in 12 metabolites were observed following gastrodin intervention, indicating gastrodin-induced alterations in carbohydrate and energy metabolism. Interestingly, these metabolic changes were not totally identical in female and male rats. Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male, together with arginine/ornithine, creatine, and glycerol which were on the increase in the female but on the decrease in the male. While the decrease in pyruvate, succinate and glutamate was only shown in the male and the increase in valine, α-ketoglutarate, glycine and glucose was only in the female.
Conclusions
This research shows the sex-specific metabolic response to GAS intervention, weather GAS is a healthy dietary supplement for the male merits further investigation.
A reliable and highly sensitive ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) analytical method was developed for identification and quantification of gastrodin (GAS) and its metabolites in rat plasma. Five metabolites were identified: p-formylphenyl-β-d-glucopyranoside (M1), p-hydroxybenzonic acid (M2), p-hydroxybenzyl alcohol (M3), p-formaldehydephenyl-β-d-glucopyranoside (M4), p-hydroxybenzaldehyde (M5). The molecular structures of metabolites were proposed based on the characters of their precursor ions, product ions and chromatographic retention time. Four of them were reported firstly in rat plasma. This method involved the addition of bergeninum as the internal standard (IS), UFLC separation, and quantification by MS/MS system using negative electrospray ionization in the multiple reaction monitoring (MRM) mode. The lower limit of quantification of gastrodin and five metabolites were all 1ng/mL. The method was linear in the concentration range of 0.001-10μg/mL. The intra- and inter-day precisions (R.S.D %) were within 15.0% for all analytes. No interference was noted due to endogenous substances. All analytes were stable in rat plasma stored at room temperature and 4°C for at least 4h, -20°C combined with three freeze-thaw cycles for at least 1 month. By this method, the influence of multiple-dose and food on the pharmacokinetics behaviors of GAS and its metabolites were studied for the first time. We hope pharmacokinetic data of present study may inspire rational clinical usage of GAS.
ABSTRACT Hypertension is a major risk factor for coronary heart disease (CHD), kidney disease and stroke. Interest in medicinal or nutraceutical plant bioactives to reduce hypertension has increased dramatically. The main biological regulation of mammalian blood pressure is via the renin-angiotensin-aldosterone system (RAAS). The key enzyme is angiotensin converting enzyme (ACE) that converts angiotensin I into the powerful vasoconstrictor, angiotensin II. Angiotensin II binds to its receptors (AT1) on smooth muscle cells of the arteriole vasculature causing vasoconstriction and elevation of blood pressure. This review focuses on the in vitro and in vivo reports of plant-derived extracts that inhibit ACE activity, block angiotensin II receptor binding and demonstrate hypotensive activity in animal or human studies. We describe 74 families of plants that exhibited significant ACE inhibitory activity and 16 plant families with potential AT1 receptor blocking activity, according to in vitro studies. From 43 plant families including some of those with in vitro bioactivity, the extracts from 73 plant species lowered blood pressure in various normotensive or hypertensive models by the oral route. Of these, 19 species from 15 families lowered human BP when administered orally. Some of the active plant extracts, isolated bioactives and BP-lowering mechanisms are discussed.
Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae, respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic (i.g.)/intravenous (i.v.) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101-101μg/mL for Gas and 0.0500-5.98μg/mL for Pur (r(2)>0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486μg/mL, and 0.05, 0.0245μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4±6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g./i.v. administration of Gas and Pur alone or combined with each other (i.g.: 40mg/kg Gas, 400mg/kg Pur; i.v.: 20mg/kg Gas, 20mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C(18) column with a gradient mobile phase of ACN-H(2)O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C(max), T(max), T(1/2), MRT of Gas administrated alone or combined with Pur via i.g. were 21.7μg/mL, 0.250h, 2.81h, 0.830h and 18.4μg/mL, 0.550h, 0.970h, 1.37h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490μg/mL, 1.95h, 1.33h, 2.10h and 2.01μg/mL, 0.570h, 4.00h, 5.10h, respectively. The relative oral bioavailability of Pur in combined administration was 10.7 times as much as that of single administration, whilst 1.52 folds in Gas. These results indicate that co-administration of Gas and Pur is a promising combination to gain higher bioavailability and it is suggested that doctors pay more attention to the dosages of the two when simultaneously using both of them.
The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.
Phenolic glucoside gastrodin (Gas), which is a main component extracted from the Chinese herbs Gastrodia elata Bl, is a well-known natural calcium antagonist with antioxidant and anti-inflammatory functions. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. Previous studies have shown that gastrodin possesses comprehensive pharmacological functions. However, very little is known about whether gastrodin has protective role on cardiac hypertrophy. The aim of this study was to determine whether gastrodin attenuates pressure overload-induced cardiac hypertrophy in mice and to clarify the underlying molecular mechanisms. Our data demonstrated that gastrodin prevented cardiac hypertrophy induced by aortic banding (AB), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters, and gene expression of hypertrophic markers. The inhibitory effect of gastrodin on cardiac hypertrophy is mediated by ERK1/2 signaling and GATA-4 activation. Further studies showed that gastrodin attenuated fibrosis and collagen synthesis through abrogating ERK1/2 signaling pathway. Therefore, these findings indicated that gastrodin, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis through suppression of ERK1/2 signaling.
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