Tianma Goutengyin and Its Single Herb in Treatment of Parkinson's Disease： A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a kind of chronic progressive neurodegenerative disease that has a high prevalence rate in recent years， especially in the elderly. PD belongs to the category of "tremor disease" and "tremor" in traditional Chinese medicine， and Tianma Goutengyin is a classic prescription contained in the Synopsis of The New Significance of Patterns and Treatment in Miscellaneous Diseases（《中医内科杂病证治新义》）. This article explored the theory of Tianma Goutengyin in the treatment of PD， and based on network pharmacological research， the article summarized relevant research on Tianma Goutengyin and its single herb in the treatment of PD. Moreover， it discussed the clinical applications and mechanisms of Tianma Goutengyin and its single herb in the treatment of PD. It is found that the mechanisms of Tianma Goutengyin in treating PD may be related to resisting oxidative stress， inhibiting inflammatory response， regulating neurotransmitters， and protecting dopamine （DA） neurons. Besides， the main components of the single herb in Tianma Goutengyin for treating PD are gastrodin， rhynchophylline， geniposide， gardenial alcohol， eucommitol glycoside， motherwort alkaloid， baicalin， pachyman， and achyranthes bidentata sterol. They can improve the related symptoms of PD patients by inhibiting inflammatory response， resisting oxidative stress， affecting calcium ion concentration， restoring mitochondrial function， and and protecting DA neurons. This article summarized the research progress of Tianma Goutengyin and its single herb in treating PD， so as to provide a reference for the prescription and medication of Tianma Goutengyin in the treatment of PD and subsequent research on the mechanisms of Tianma Goutengyin and its single herb in the treatment of PD and give play to the advantages of traditional Chinese medicine in the treatment of PD.

Amino acid metabolism characteristics of Banxia Baizhu Tianma Decoction in realizing drug withdrawal based on transcriptomic analysis / 中国中药杂志

This study aimed to demonstrate the effect of Banxia Baizhu Tianma Decoction(BBTD) on realizing withdrawal of anti-epileptic drugs and explore the relationship between BBTD and the amino acid metabolism by transcriptomic analysis in the rat model of epilepsy induced by lithium chloride-pilocarpine. The rats with epilepsy were divided into a control group(Ctrl), an epilepsy group(Ep), a BBTD & antiepileptic drug integrative group(BADIG), and an antiepileptic drug withdrawal group(ADWG). The Ctrl and Ep were given ultrapure water by gavage for 12 weeks. The BADIG was given BBTD extract and carbamazepine solution by gavage for 12 weeks. The ADWG was given carbamazepine solution and BBTD extract by gavage for the former 6 weeks, and then only given BBTD extract for the latter 6 weeks. The therapeutic effect was evaluated by behavioral observation, electroencephalogram(EEG), and hippocampal neuronal morphological changes. High-throughput sequencing was used to obtain amino acid metabolism-related differen-tial genes in the hippocampus, and the mRNA expression in the hippocampus of each group was verified by real-time quantitative polymerase chain reaction(RT-qPCR). The hub genes were screened out through protein-protein interaction(PPI) network, and Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. Two ceRNA networks, namely circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA, were constructed for ADWG vs BADIG. The experimental results showed that compared with those in Ep, rats in ADWG were significantly improved in the behavioral observation, EEG, and hippocampal neuronal impairment. Thirty-four amino acid metabolism-related differential genes were obtained by transcriptomic analysis, and the sequencing results were confirmed by RT-qPCR. Eight hub genes were obtained through PPI network, involving several biological processes, molecular functions, and signal pathways related to amino acid metabolism. Finally, the circRNA-miRNA-mRNA ternary transcription network of 17 circRNA, 5 miRNA, and 2 mRNA, and a lncRNA-miRNA-mRNA ternary network of 10 lncRNA, 5 miRNA, and 2 mRNA were constructed in ADWG vs BADIG. In conclusion, BBTD can effectively achieve the withdrawal of antiepileptic drugs, which may be related to the transcriptomic regulation of amino acid metabolism.

Mechanism of Banxia Baizhu Tianma decoction to prevent the development of prehypertension and excessive phlegm-dampness syndrome in rats based on metabonomics technology / 药学学报

The alterations of serum biological endogenous chemicals in rats with phlegm dampness accumulation syndrome of prehypertension (PHT) were interfered by Banxia Baizhu Tianma decoction (BBT), and the metabolic regulatory pathway of BBT was clarified using serum metabonomics analysis. To replicate the rat model of prehypertension phlegm dampness syndrome, blood pressure, behavioral markers, and serum biochemical markers of rats were collected. BBT's effectiveness in controlling blood pressure and blood lipids was assessed, and changes in endogenous small molecules in rat serum were determined using UPLC-Q-Orbitrap MS metabolic analysis. The results showed that BBT could regulate 9 metabolites, including arachidonic acid, cholic acid, glycodeoxycholic acid, N-adenosyltyrosine, arginine, lysophosphatidylethanolamine (20:0/0:00), lysophospholipid (P-18:0), lysophospholipid (18:0), lysophospholipid (22:5(7Z,10Z,13Z,16Z,19Z)). MetaboAnalyst was used to analyze the metabolic pathway. There were 7 metabolic pathways closely related to the change of blood pressure in rats, among which arachidonic acid metabolic pathway was the most critical. The metabolism difference foreign body in the model rats tends to return to the normal level, which provides a research basis for the mechanism of BBT from the perspective of metabonomics. This study was approved by the Experimental Animal Welfare Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).

Tianma Gouteng Yin protects rotenone-induced PC12 cell damage by inhibiting ferroptosis-lipid metabolism / 中国临床药理学与治疗学

AIM: To investigate the effects and protective mechanism of Tianma Gouteng (TGY) against rotenone (Rot) damage in PC12 cells. METHODS: PC12 cells were treated with Rot to establish nerve injury model and cell survival rate was determined by MTT colorimetry to determine the optimal modeling concentration of Rot and effective intervention concentration of TGY. Lipid reactive oxygen species (ROS) were detected by flow cytometry and fluorescence intensity was observed by inverted fluorescence microscope. The biochemical methods were used to detect, superoxide dismutase (SOD), glutathione (GSH) levels and activity and the contents of malondialdehyde (MDA). Transmission electron microscopy observed morphological change of mitochondria and protein expression of glutathione peroxidase 4 (GPX4), long chain lipoyl-coa synthase 4 (ACSL4) and lysophospholipid cholinyltransferase 3 (LPCAT3) were detected by western blot. RESULTS: The survival rate of cells treated with 0.6 μmol/L Rot for 24 h was close to 50%(56.7%±9.9%). Pretreatment with TGY for 12 h could inhibit the damage of Rot. At the same time, the leakage rate of lactate dehydrogenase (LDH) was reduced in a dose-dependent manner. Lipid ROS content increased after the treatment of Rot, whereas pretreatment with TGY effectively reduced lipid ROS content, decreased MDA level and increased SOD activity and GSH level in damaged cells in cells damaged by Rot. Transmission electron microscopy showed that the mitochondria of PC12 cells were shrunk after the damage of 0.6 μmol/L Rot and the mitochondrial morphology of PC12 cells was improved to some extent after preprotection of TGY compared with normal group. Western blot results showed that TGY pretreatment could increase the expression of GPX4 and reduce the expression of ACSL4 and LPCAT3 after damage of Rot to a certain extent. CONCLUSION: TGY can improve nerve damage by up-regulating the expression of GPX4 protein, down-regulating the expression of ACSL4 and LPCAT3 protein to inhibit the oxidation of unsaturated fatty acids, reduce the level of lipid peroxidation and ROS content.

Clinical study on Tianma Gouteng Decoction combined with amlodipine besylate tablets in the treatment of hypertension of liver-yang hyperactivity with left ventricular hypertrophy / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of Tianma Gouteng Decoction combined with amlodipine besylate tabletsin treating patients with hypertension of liver-yang hyperactivity complicated with left ventricular hypertrophy (LVH).Methods:A total of 80 patients with hypertension of liver-yang hyperactivity complicated with LVH, who met the inclusion criteria and were treated in the hospital between June 2019 and January 2021, were divided into two groups, with 40 in each group according to the random number table method. The control group was treated with amlodipine besylate tablets orally, and the observation group was treated with granules of Tianma Gouteng Decoction on the basis of the control group. Both groups were treated for 2 months. Before and after treatment, the TCM syndromes were scored and the office blood pressure was measured with sphygmomanometer, and color Doppler ultrasonic diagnostic apparatus was adopted to detect the interventricular septum thickness (IVST), left ventricular posterior wall thickness (PWT), left ventricular end diastolic diameter (LVDd) and left ventricular mass index (LVMI), and the levels of homocysteine (Hcy) and Cystatin C (Cys-C) were determined by ELISA and the level of uric acid (UA) was determined by fully automatic biochemical analyzer. The clinical efficacy was evaluated.Results:The total effective rate was 95.0% (38/40) in the observation group and that of the control group was 77.5% (31/40) ( χ2=5.17, P=0.023). After treatment, the scores of dizziness, headache, insomnia and dreaminess and vexation and forgetfulness and total score of the observation group were significantly lower than those in the control group ( t=10.06, 14.47, 15.47, 8.74, 14.50, all Ps<0.001), and the systolic blood pressure and diastolic blood pressure were significantly lower than those in the control group ( t=6.30, 8.79, P<0.001). The IVST [(9.36±1.32) mm vs. (11.23±1.07) mm, t=6.96], PWT [(8.89±1.14)mm vs. (10.03±1.02)mm, t=4.71], LVDd[(40.36±4.29) mm vs. (47.62±4.19) mm, t=7.66] and LVMI [(112.39±22.29) g/m 2vs. (148.26± 21.39) g/m 2, t=7.34] were significantly lower compared to the control group ( P<0.01). The levels of Hcy[(12.87±3.11) μmol/L vs. (19.85±3.67) μmol/L, t=9.18], UA [(276.29±19.56) μmol/L vs. (338.52±17.07) μmol/L, t=16.65] and Cys-C [(0.86±0.15) mg/L vs. (1.10±0.17) mg/L, t=6.70] were significantly lower than those in the control group ( P<0.01). Conclusion:The Tianma Gouteng Decoction can improve the clinical symptoms, control the blood pressure, relieve the left ventricular hypertrophy and improve the renal function of patients with hypertension of liver-yang hyperactivity complicated with LVH.

Systematic evaluation and trial sequential analysis of Tianma Gouteng Granules combined with anti-hypertensive drugs in treatment of essential hypertension / 中国中药杂志

To systematically evaluate the efficacy and safety of Tianma Gouteng Granules combined with conventional anti-hypertensive drugs in the treatment of essential hypertension. The clinical randomized controlled trials(RCTs) on the treatment of essential hypertension with Tianma Gouteng Granules combined with conventional anti-hypertensive drugs were searched in PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, SinoMed since the establishment of the databases to April 2020 based on inclusion and exclusion criteria, and Meta-analysis was conducted by using RevMan 5.3 software. A total of 15 RCTs were included, involving a total of 1 508 patients. Meta-analysis results showed that Tianma Gouteng Granules combined with conventional Western medicine were supe-rior to the control group in reducing systolic blood pressure(MD=-10.24, 95%CI[-13.54,-6.95], P<0.000 01), diastolic blood pressure(MD=-5.33, 95%CI[-7.21,-3.45], P<0.000 01), improving the clinical efficacy of patients(RR=1.22, 95%CI[1.15, 1.28], P<0.000 01) and curative effect of traditional Chinese medicine syndrome(RR=1.26, 95%CI[1.02, 1.57], P=0.04), increasing nitric oxide content(MD=9.59, 95%CI[7.23, 11.96], P<0.000 01), reducing endothelin-1(MD=-10.74, 95%CI[-15.74,-5.75], P<0.000 1), tumor necrosis factor(MD=-0.28, 95%CI[-0.36,-0.19], P<0.000 01), and interleukin-6(MD=-39.71, 95%CI[-43.40,-36.03], P<0.000 01). There was no statistically significant difference between the test group and the control group in the incidence of adverse reactions. No liver and kidney dysfunction occurred. The results of the subgroup analysis showed that the effect of Tianma Gouteng Granules combined with ARB drugs was more obvious in reducing the systolic and diastolic pressure. Trial sequential analysis showed that the studies accumulatively included for clinical efficacy crossed the traditional threshold and the TSA threshold, further affirming its clinical efficacy. The clinical application of Tianma Gouteng Granules combined with conventional Western medicine in the treatment of primary hypertension and accompanying symptoms has clear efficacy and certain safety, so it is recommended for clinical application.

Textual Research of Origin and Clinical Application of Banxia Baizhu Tianma Tang / 中国实验方剂学杂志

After a comprehensive analysis and research of ancient books and literatures， we discovered that six Banxia Baizhu Tianma Tang prescriptions have the same name. It was originally created by LI Gao. The idea of composition has a certain inheritance relationship with ZHANG Yuan-su′s Tianma Banxia Tang and Huatan Yuhu Wan， which are recorded in Prescription of Peaceful Benevolent Dispensary. In later generations， four doctors developed five prescriptions of the same name. CHENG Guo-peng of the Qing dynasty reformed the prescription based on the theory of phlegm and dampness. He reduced tonic components based on LI's ideas to strengthen the expectorant function， and then transformed the prescription into two of the same name， one for headache and the other for vertigo. The latter was recorded in the textbook of Chinese Herbal Medicine and The Catalogue of Classic Prescriptions （batch 1）， which has the greatest impact on the contemporary prescriptions. Its composition is Pinelliae Rhizoma Praeparatum Cum Zingbere et Alumine （5.595 g）， Atractylodis Macrocephalae Rhizoma （11.19 g）， Gastrodiae Rhizoma， Poria， Citri Exocarpium Rubrum （each 3.73 g）， Glycyrrhizae Radix et Rhizoma （2 g）， 2 pieces of fresh Zingberis Rhizoma Recens （about 2 g） and 2 Jujubae Fructus. The botanical origin of these herbs is clear， and the dosage of herbs is safe in accordance with the Pharmacopoeia of the People's Republic of China.P. The total amount of each dose is about 37.975 g， while the daily dosage is not far different from that of invention. Since its invention， it has been mainly used in the treatment of phlegm headache and vertigo caused by wind phlegm disturbance. In modern clinical practice， it is widely used in treating various diseases with vertigo and headache as the main symptoms， mainly including hypertension， acute ischemic stroke， vertebrobasilar insufficiency， cervical spondylosis， primary headache， Meniere's disease and benign paroxysmal positional vertigo. When the syndrome differentiation is consistent with relevant syndrome type with phlegm as the main pathological factor in traditional Chinese medicine， we can modify the prescription as appropriate.

Traditional Chinese medicine insights of newly-diagnosed and young hypertension and clinical practice of Tianma Gouteng Decoction for hypertension treatment / 中国中药杂志

Hypertension is a global major public health problem. Early intervention and timely blocking are necessary for newly-diagnosed hypertensive and young hypertensive patients. Tianma Gouteng Decoction recorded in Zabing Zhengzhi Xinyi written by HU Guangci has the major functions in treating excess syndrome and wind-Yang disturbance syndrome with effects in calming liver-wind, clearing heat and activating blood, and nourishing liver and kidney. As we known, Tianma Gouteng Decoction is a classical formula for treating hypertension. However, due to the limitation of historical conditions, some problems impede Tianma Gouteng Decoction from being handed down successfully, such as uncertain diagnosis, uncertain antihypertensive efficacy and treatment-course. In this case, we ask whether Tianma Gouteng Decoction can be used as antihypertensive therapy and the exactly decrease of systolic and diastolic blood pressure, and wonder the half-life of Tianma Gouteng Decoction and the relationship with Western medicine. Therefore, defined prescription and syndrome, efficacy, treatment-course are important in clinical practice. According to the findings, ① previously, we thought that hypertension was a liver-Yang hyperactivity and liver-wind stirring syndrome, and the liver-based therapy theory was effective. However, based on our study, long-term treatment with Western medicine could block disease progression, control the increased blood pressure and change the pathogenesis and syndrome of traditional Chinese medicine. Therefore, the frequency of liver-Yang hyperactivity syndrome "fire syndrome" decreased sharply, and the main syndrome was fluid-retention syndrome and deficiency syndrome. The etiology and pathogenesis of hypertension was prone to deficiency syndrome accompanied with excess syndrome. Therefore, it was necessary to intervene hypertension in "liver-wind" and "liver-Yang" excess syndrome stage, and the early intervention and treatment are important. ② The newly-diagnosed hypertensive and young hypertensive patients usually had no Western medicine intervention. Thus, the etiology and pathogenesis of hypertension were free from Western medicine, which maintained the initial stage of hypertension in line with the liver-Yang hyperactivity syndrome. ③ The pathological mechanisms of newly-diagnosed and young hypertension were mainly increase in sympathetic activity, active renin-angiotensin-aldosterone system, change in morphology of vascular smooth muscle cells and endothelial cell dysfunction. ④ According to the syndrome of Tianma Gouteng Decoction, in modern medicine, Tianma Gouteng Decoction was widely used to treat the early-stage hypertension and the early-intervention of hypertension without Western medicine, particularly newly-diagnosed, young hypertension, Ⅲ hypertension, hypertensive crisis and hypertensive emergency. Tianma Gouteng Decoction can treat such symptoms as headache, dizziness, fullness of head, slurring of speech; facial flushing, conjunctival congestion and blurred vision; dysphoria, anxiety, palpitation, insomnia, mental disorder and hot flushes; dry-mouth with bitter taste and sweeting; myasthenia of limbs and lassitude in loin and legs; brown urine with burning sensation during urination; a solid or liquid stool consistency; red tongue, slippery and rapid pulse, wiry and rapid pulse over to Cunkou. ⑤ After treatment with Tianma Gouteng Decoction for three to six months, the blood pressure was decreased, and the symptoms were improved with reduction or even discontinuance of Western medicine. ⑥ According to recent studies, Caul is Polygoni Multiflori of Tianma Gouteng Decoction induced certain hepatotoxicity and increased the risk of long-term treatment. However, with the regular monitoring of biomedical index, long-term treatment with Caulis Polygoni Multiflori(3-10 g·d~(-1) for 3 to 6 months) didn't show hepatic dysfunction. ⑦ The pharmacological activity of Tianma Gouteng Decoction coincided with the pathology and disease mechanism of newly-diagnosed and young hypertension. Therefore, Tianma Gouteng Decoction was the specific recipe for newly-diagnosed and young hypertension. Therefore, further studies of efficacy, safety and molecular mechanism of Tianma Gouteng Decoction may make a medical breakthrough for hypertension treatment.

Optimization of extraction technology of Banxia Baizhu Tianma Decoction by chemometrics combined with information entropy weighting / 中草药

Objective: The extraction process optimization method of chemometrics combined with information entropy weight was established and applied to the water extraction process optimization of Banxia Baizhu Tianma Decoction (BBTD), in order to fully ensure the effectiveness and quality consistency of classical prescription. Methods: Taking BBTD as the model drug, the fingerprint was established by HPLC method. The common peak area was analyzed by principal component analysis (PCA), the total factor score of PCA, the similarity of fingerprint and the yield of dry paste were used as evaluation indexes. L9(34) orthogonal design was used to investigate the effects of adding water, soaking time and boiling time on the extraction effect, and the Objective: weight of each index was determined by information entropy weighting method. The technological parameters of water extraction were optimized. Results: Twenty-six common peaks and seven compounds were identified by the similarity evaluation system of chromatographic fingerprints of traditional Chinese medicine. According to the results of comprehensive score, the optimum extraction process of the preparation was determined to be 12 times the amount of water, decoction twice, 1 hour each time. The average comprehensive score of the three batches of verification was 0.418 0 with RSD of 3.32%. Conclusion: The optimized process has high extraction rate, good stability and repeatability, and is suitable for the industrial production of BBTD.

Identification of quality markers (Q-marker) of Banxia Baizhu Tianma Decoction based on component difference analysis and multivariate statistical method / 中草药

Objective: To identify the quality markers (Q-marker) for Baizhu Tianma Decoction from different batches based on multivariate statistical analysis. Methods: The fingerprint data of 18 batches of Banxia Baizhu Tianma Decoction were processed by the Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine (2012A Edition). SPSS 20.0 was used for cluster analysis and principal component analysis (PCA). According to PCA results, cluster analysis was carried out to screen out the markers that might affect the quality difference of Banxia Baizhu Tianma Decoction and determine its content in the samples. Results: A total of 12 chromatographic peaks were selected as common peaks of fingerprint, and the similarity of 18 batches of samples was greater than 0.900, which indicated that each batch had good consistency. Eighteen batches of samples were clustered into three groups by cluster analysis. Five marker peaks were screened out from PCA results. Two of them were identified as gastrodin and naringin. The five marker peaks were further clustered and the results were basically the same as before. There was a certain correlation between the comprehensive score of principal components and the determination results of gastrodin and naringin in 18 batches of samples. Conclusion: Through multivariate statistical analysis, the Q-markers that may affect the difference of Banxia Baizhu Tianma Decoction were better identified, which can lay the foundation for the comprehensive quality control of Banxia Baizhu Tianma Decoction and its compound preparations, and provide reference for the further study of the correlation between the different components and pharmacodynamics of Banxia Baizhu Tianma Decoction.

Molecular Mechanism of Banxia Baizhu Tianma Tang in Treating Hypertension Based on Integrated Pharmacological Platform / 中国实验方剂学杂志

Objective:To explore the molecular mechanism of Banxia Baizhu Tianma Tang in treating hypertension. Method:Based on an internet-based computation platform for integrated pharmacology of traditional Chinese medicine(TCM),TCM prescription database,TCM database,TCM component database and disease/symptoms target database,information on the chemical compositions contained in TCM was retrieved,an interaction network between potential targets and disease targets of Banxia Baizhu Tianma Tang was built,then core target was enriched and calculated,gene function and pathway analysis was carried out,the multi-dimensional relationship network of "Chinese herbs-ingredients-critical targets-key pathways" of Banxia Baizhu Tianma Tang was further constructed. Result:A total of 90 active ingredients in Banxia Baizhu Tianma Tang were obtained,including alkaloids,nucleosides,flavonoids,saponins,organic acids and other ingredients;they involved 287 core targets,including 13 direct targets,such as adenylate cyclase,G protein coupled with β1 receptor,glucose kinase,etc;they also involved nervous system,endocrine system,circulatory system,estrogen signaling pathway,chemokine signaling pathway and other related biological processes and signaling pathways. Conclusion:Banxia Baizhu Tianma Tang can regulate neurotransmitter concentration and activity abnormalities,improve the protective effect of vascular endothelial cells by improving insulin resistance,regulating the production of inflammatory factors,and inhibiting inflammatory reactions,thereby exerting pharmacological effects on the treatment of hypertension.This study can provide a scientific basis for comprehensive interpretation of mechanism of Banxia Baizhu Tianma Tang.

Effects of Banxia Baizhu Tianma Decoction on Expression of miRNA-146a-5p in Hippocampus of Epileptic Rats and Bioinformatic Analysis / 中国中医药信息杂志

Objective To lay the foundation for studying the possible pathogenesis of epilepsy and the anti-epileptic mechanism of Banxia Baizhu Tianma Decoction through the bioinformatic analysis of target gene prediction and signal pathway of miRNA-146a-5p in hippocampus of epileptic rats. Methods Lithium-pilocarpine was used to induce seizures in rat models. The experiment rats were randomly divided into normal control group, model group, Banxia Baizhu Tianma Decoction group, with 20 rats in each group. The method of miRNA expression profiling was used to observe the miRNA differential expression of hippocampus neuron cell of rats. The expression level of miRNA-146a-5p was detected by real-time quantitative PCR. MiRDB was used for target gene prediction of miRNA-146a-5p, and miRTarBase and DAVID were used for enrichment analysis on the GO function and KEGG signaling pathway. Results The attack times and grades of the rats in Banxia Baizhu Tianma Decoction group were significantly lower than those in the model group from behavioral observation. MiRNA microarray analysis showed that the expression level of miRNA-146a-5p in model group was 2.107 times normal control group (P＜0.05), and the expression level decreased to 1.377 times after treatment with Banxia Baizhu Tianma Decoction (P＜0.05). The results of RT-PCR was consistent with that of miRNA microarray, with statistical significance (P＜0.05). MiRNA-146a-5p target gene prediction results had 140 target genes by GO, and there were 14 annotation information of biological process (P＜0.05), 9 annotation information of cellular component (P＜0.05), 11 annotation information of molecular function (P＜0.05). Enrichment analysis of KEGG biological pathway showed that 140 target genes of miRNA-146a-5p were enriched in EB virus infection signal pathway and thyroid hormone signaling pathway (P＜0.05). Conclusion miRNA-146a-5p is closely related to the inflammatory reaction after epilepsy, and Banxia Baizhu Tianma Decoction can control epilepsy possibly by controlling the inflammatory reaction after epilepsy.

Study of the neuroprotective effects and mechanisms of Tianma Gouteng Decoction on retinal ganglion cells in rat optic nerve crush model / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the mechanism of Tianma Gouteng Decoction on the protein molecular level in the optic nerve crush model rats.METHODS:Totally 36 participants 36 male Wistar rats were divided randomly into six groups(6 in every group):normal control group,negative control group,Tianma Gouteng Decoction treatment groups (con-centrations were 0.6g/mL,1.2g/mL,2.4g/mL respictively) and ginkgo biloba tablets positive control group (concentrations was 1.2mg/mL).Nothing was done in the normal control group.The optic nerve of right eye in the other groups was done with the optic nerve crush model.Normal control group and negative control group was treated only with water.The average grey scale values of the N-methyl-D-aspartic acid receptor 2B (NMDA2B) receptor protein,beta-amyloid protein (Aβ) in the average grey scale values were detected.RESULTS:The average grey scale value of Tianma Gouteng Decoction in low,medium and high dose groups about NMDA2B receptor protein was significantly less than that of the negative control group (all P＜0.001),and there was no significant difference with the positive control group (P=0.092,0.411,0.676),the difference between normal control group and negative control group was significant (P＜0.001).The high dose group of betaamyloid's average grey scale value reduced significantly than the negative control group (P=0.030,0.001).The low dose group than the negative control group was not obviously (P=0.614).The high dose group was not significantly different from the positive control group (P=0.927),the difference between normal control group and negative control group was significant (P＜0.001).CONCLUSION:Tianma Gouteng Decoction can go through the decrease of the NMDA2B receptor protein expression and the control of beta-amyloid deposition to reduce the retinal ganglion cell injury and apoptosis.

Study on extraction and clathration process of volatile oil in Tianma-Shouwu tablet / 国际中医中药杂志

Objective To optimize the extraction and β-cyclodextrin clathration process of volatile oil in Tianma-Shouwu tablet.Methods The extraction of volatile oil was optimized through the orthogonal design L9(34) with the volatile oil extraction amount as assessment index. The saturated aqueous solution preparation of clathrate form was used. The volume of β-cyclodextrin and volatile oil, clathration temperature, clathration time was investigated by central composite design-response surface methodology, with the score of volatile oil inclusion ratio and utilization ratio as the index. The results were fitted by second-order polynomial equation, and then the best clathration process was determined. Results The optimization extraction process of volatile oil in Tianma-Shouwu tablet was as follows:to add 8 times water,immerse 30 minutes,steam distill 6 hours;and the best clathration process was as follows: the ratio of β-cyclodextrin and volatile oil was 9.50:1, clathration temperature 43 ℃, and clathration time 4.2 hours. Conclusions The optimized extraction and clathration process were reasonable, stabled and repeatable.

Decomposition and Reformulation of Banxia Baizhu Tianma Decoction: A Vasodilatory Approach / 中草药·英文版

Objective To decompose and reformulate Banxia Baizhu Tianma Decoction (BBT) in order to optimize its ratio for vasodilatory effect. The fingerprints of these six component herbs were also studied via Tri-step FTIR analysis. Methods The herbal components of BBT were extracted separately with different solvents, such as 95% ethanol, 50% ethanol, and distilled water. The vasodilatory effect of the extracts was studied using the in vitro pre-contracted aortic ring model. Among these extracts, the water extracts of Pinellia ternata [PT(W)] and Citri reticulatae [CR(W)], 50% ethanol extracts of Gastrodia elata [GE(50)] and Glycyrrhiza uralensis [GU(50)], and 95% ethanol extracts of Atractylodes macrocephala [AM(E)], and Poria cocos [PC(E)] were selected for the orthogonal stimulus-response compatibility group study due to their high effectiveness in vasodilation. Results The best combination ratio (G2) was GE(50), GU(50), AM(E), PC(E), CR(W), and PT(W) at EC0, EC5, EC5, EC5, EC5, and EC5, with EC50 of (0.06 ± 0.01) mg/mL. Comparison between the vasodilatory effects of extracts derived from G2 and BBT were also studied. From the results, the 50% ethanol extract following G2 ratio was found to be most potent extract with the highest vasodilatory effect compared with other extracts derived from G2 or BBT, with EC50 of (0.05 ± 0.005) mg/mL. Conclusion The optimum ratio and appropriate extraction method for the new BBT formulae are obtained. G2 is determined as the best formulae with the highest potency in producing the vasodilatory effect on isolated rat aortic rings. The results obtained suggest that 50% ethanol is found to be the best solvent to extract the vasoactive compounds of G2 in order to exhibit the highest efficacy of vasodilatory effect.

Pharmacodynamic study on Tianma Lingzhi Granules / 中草药

Objective: To study the pharmacodynamics of Tianma Lingzhi Granules (TLG). Methods: Mouth breathing experiment and hypoxia tolerance experiment under atmospheric pressure with mice, experiment of dizziness of guinea pigs caused by chloroform, and stimulus ischemic vertigo of model rats caused by rotating in water maze experiment was used to investigate the anti-vertigo effect of TLG; The experiment of autonomic activities of mice and hypnosis experiment of mice with pentobarbital sodium was used to investigate the sedative hypnotic effect of TLG; The experiments of torsion body and hot plate of mice was used to investigate the analgesic effect of TLG; The experiments of swimming and regulating immune experiment was used to investigate the anti-fatigue and immune regulation effect of TLG. Results: TLG could promote the supplying of oxygen in the brain, significantly reduce the times of autonomic activities of mice, increase the number of sleeping mice at the subthreshold dose of sodium pentobarbital, shorten the sleep latency of mice with hreshold dose of sodium pentobarbital and prolong the sleep time, significantly increase mice body torsion reaction latency by the acetic acid and reduce the body torsion times, and increase the spleen thymus index, clearance coefficient and phagocytic index of mice. Conclusion: TLG has the effect of treating dizziness, forgetfulness, waist and knee fatigue weakness and so on.

Development of Tianma HPLC fingerprint and discriminant analysis / 中国中药杂志

Tianma(the tuber of Gastrodia eleta) is a widely used and pricy Chinese herb. Its counterfeits are often found in herbal markets, which are the plant materials with similar macroscopic characteristics of Tianma. Moreover, the prices of Winter Tianma(cultivated Tianma) and Spring Tianma(mostly wild Tianma) have significant difference. However, it is difficult to identify the true or false, good or bad quality of Tianma samples. Thus, a total of 48 Tianma samples with different characteristics(including Winter Tianma, Spring Tianma, slice, powder, etc.) and 9 plant species 10 samples of Tianma counterfeits were collected and analyzed by HPLC-DAD-MS techniques. After optimizing the procedure of sample preparation, chromatographic and mass-spectral conditions, the HPLC chromatograms of all those samples were collected and compared. The similarities and Fisher discriminant analysis were further conducted between the HPLC chromatograms of Tianma and counterfeit, Winter Tianma and Spring Tianma. The results showed the HPLC chromatograms of 48 Tianma samples were similar at the correlation coefficient more than 0.848(n=48). Their mean chromatogram was simulated and used as Tianma HPLC fingerprint. There were 11 common peaks on the HPLC chromatograms of Tianma, in which 6 main peaks were chosen as characteristic peaks and identified as gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, parishin E, respectively by comparison of the retention time, UV and MS data with those of standard chemical compounds. All the six chemical compounds are bioactive in Tianma. However, the HPLC chromatograms of the 10 counterfeit samples were significantly different from Tianma fingerprint. The correlation coefficients between HPLC fingerprints of Tianma with the HPLC chromatograms of counterfeits were less than 0.042 and the characteristic peaks were not observed on the HPLC chromatograms of these counterfeit samples. It indicated the true or false Tianma can be identified by either the similarity or characteristic peaks on HPLC fingerprint. Comparing the Winter Tianma with Spring Tianma showed that the HPLC chromatograms of 15 winter Tianma samples and 11 spring Tianma samples were similar at the mean correlation coefficient of 0.908. But the intensity of the characteristic peaks were different between the two groups of Tianma samples, i.e. the intensity of gastrodin, paishin A and C in winter Tianma was lower than those in spring Tianma. The Winter Tianma and Spring Tianma could be discriminated by either the Fisher unstandardized discrimination function or Linear discriminant function, based on the peak areas of 11 common peaks on HPLC chromatograms as variate.

Effects of Tianma-Sanqi Decoction on blood pressure variability of hypertensive patients with anxiety / 中华行为医学与脑科学杂志

Objective To observe the efficacy of modified Tianma?Sanqi Decoction on hypertension patients with anxiety. Methods Totally 64 hypertension patients with anxiety patients were randomly divid?ed into control group (32 cases) and treatment group (32 cases).The control group with standard medica?tions for hypertension and treatment group with addition of Tianma?Sanqi Decoction, and both groups were continuously treated for 8 weeks. The changes of 24 hours ambulatory blood pressure and SAS scores were compared.Results ( 1) After treatment in the control group and treatment group of 24 h mean systolic blood pressure (24 hSBP) ((130.13±3.81)mmHg,(123.56±4.37)mmHg) (1 mmHg=0.133 kPa) were lower than before treatment((145.36±7.17) mmHg,(145.16±6.77) mmHg) and the difference was statisti?cally significant( P<0.01).(2) After treatment in the control group and treatment group 24 h systolic pres?sure standard deviation,diurnal systolic pressure standard deviation and nocturnal systolic pressure standard deviation((12.19±3.21) mmHg,(11.16±2.26) mmHg,(10.49±3.76) mmHg and (10.95±2.35) mmHg, (10.08±2.67) mmHg,(10.12±3.78)mmHg) were lower than before treatment ((14.53±3.65) mmHg, (13.81±4.04) mmHg,(12.47±4.23) mmHg and (16.73±7.90)mmHg,(16.06±4.14)mmHg,(13.65± 4.92)mmHg),and the difference was statistically significant( P<0.01 or P<0.05).After treatment in the treatment group, 24 h systolic pressure standard deviation, nocturnal systolic pressure standard deviation ((10.95±2.35) mmHg,(10.08±2.67) mmHg) were lower than control group((12.19±3.21) mmHg, (11.16±2.26) mmHg) and the difference was statistically significant.( P<0.01).(3) After treatment in the treatment group,SAS scores (36.68±3.88) points were lower than before treatment (58.66±3.13) points and the difference was statistically significant(P<0.01).After treatment the SAS score ((36.68±3.88) points) in the treatment group was lower than control group((51.86+2.62) points).Conclusion The hypertension patients with anxiety treated with Tianma?Sanqi Decoction and benazapril can improve blood pressure variability and the symp?toms of anxiety.

Clinical Study on Tianma Gouteng Decoction Combined with Routine Western Therapy in the Treatment of Early Onset Severe Pre-eclampsia / 中国中医药信息杂志

Objective To observe clinical efficacy of Tianma Gouteng Decoction combined with Western medicine for early onset severe pre-eclampsia. Methods Sixty patients were randomly divided into treatment group with 30 cases and control group with 30 cases. Two groups were both given the routine Western therapy, while the treatment group was added with Tianma Gouteng Decoction. Indicators were observed and compared between two groups including blood pressure, 24 h UAE, D-dimer, fibrinogen and their effects on pregnancy. Results Compared with the control group, the blood pressure, 24 h UAE, fibrinogen, D-dimer, hypoproteinemia, and liver and kidney function were reduced obviously in the treatment group (P<0.05);fibrinogen and D-dimer of control group were not changed significantly;gestational weeks of treatment group were extended (15.2 ± 4.8)d, and neonatal asphyxia was 7 cases;gestational weeks of control group were extended (9.3 ± 2.2)d, and neonatal asphyxia was 11 cases. There was no significant difference about cesarean section rate between the two groups. Conclusion Tianma Gouteng Decoction combined with Western medicine for treatment of early onset severe pre-eclampsia have better clinical efficacy.

Effect of Tianma Gouteng Decoction on index of heart function and major cardiovascular events in treatment of H-type hypertension patients with left ventricular hypertrophy / 中国生化药物杂志

Objective To explore the changes of index of heart function and major cardiovascular events (nonfatal myocardial infarction, stroke, and cardiovascular death) to H-type hypertension patients with left ventricular hypertrophy caused by Tianma Gouteng Decoction.Methods 126 H-type hypertension patients with left ventricular hypertrophy from January 2014 to May 2014 in our hospital were divided into observation group and control group,63 cases in each group.Control group was treated with conventional western medicine, observation group was treated with Tianma Gouteng Decoction on the basis of control group.The levels of plasma homocysteine (Hcy), left ventricular ejection fraction (LVEF),the E/A, and the incidence of major cardiovascular events were recorded and compared between the two groups.Results Compared with pre-treatment, the levels of Hcy in the two groups were significantly decreased(P<0.05), and the effect of observation group was better (P<0.05).After the treatment, the E/A and LVEF of the two groups were significantly improved (P<0.05); the E/A ratio and LVEF in observation group were significantly higher than those in control group (P<0.05).The incidence of major cardiovascular events in observation group was significantly lower than that in control group (6.35%VS 19.05%,P<0.05).Conclusion Tianma Gouteng Decoction can significantly reduce the Hcy of patients who get H-type hypertension, improve diastolic and systolic function and lower the occurrence of major cardiovascular events.