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Shenxian Shengmai Oral Liquid for treatment of slow arrhythmia: a randomized controlled trial
Li Jing, Zhao Chen, Chen Jing, Xing Yan-Wei, Qian Ke, Liu Zhi, Zhai Jing-Bo, Shi Yang
TMR Modern Herbal Medicine    2018, 1 (2): 51-56.   https://doi.org/10.12032/TMRmhm2017A12
Abstract HTML PDF (352KB)  

Background:Slow arrhythmia, a common clinical condition, has a higher incidence in the elderly population. Shenxian Shengmai Oral Liquid has been shown to improve the symptoms of patients with slow arrhythmia in many clinical studies and systematic reviews. Sixty participants with slow arrhythmia will be randomized to treatment group (Shenxian Shengmai Oral Liquid) and control group (Shenxian Shengmai Oral Liquid Placebo) in a 2:1 ratio. This clinical trial is a pilot study to compare the effects of Shenxian Shengmai Oral Liquid and the control groups; to analyze the effect of Shenxian Shengmai Oral Liquid for slow arrhythmia.

Highlights

1.This is the clinical trial plan of oral liquid of Chinese medicine for the treatment of slow arrhythmia.2.This study is a pilot study. Sixty patients with slow arrhythmia were randomly divided into observation group (40 cases) and control group (20 cases) to explore the safety and effectiveness of Shenxian Shengmai Oral Liquid.3.The study will be a randomized, double-blind, placebo-controlled clinical trial.

Metabolites identification and quantification of antcin H in mice tumors after oral administration of the anticancer mushroom Antrodia camphorata
Li Zi-Wei, Ji Shuai, Li Bin, Wang Shuang, Tzeng Yew-Min, Qiao Xue, Ye Min
TMR Modern Herbal Medicine    2018, 1 (2): 40-50.   https://doi.org/10.12032/TMRmhm2017A15
Abstract HTML PDF (1080KB)  

Objective:Antrodia camphorata (AC), a precious medicinal mushroom in Taiwan, is popularly used for adjuvant cancer therapy. This paper aims to clarify the metabolites which are present in tumor tissues after oral administration of AC in Sarcoma-180 tumor-bearing mice, as well as their contents in tumors. Methods:Tumors of Sarcoma-180 tumor-bearing mice were obtained at 1 h and 4 h after oral administration of AC extract, and the metabolites in the tumor homogenate samples were characterized using UHPLC-orbitrap/MS analysis. Then, a fully validated LC-MS/MS method was developed for quantitative analysis of the most abundant compounds in tumor tissues, namely (25R/S)-antcin H. Results:A total of 33 compounds were characterized in tumor homogenate samples including 28 prototypes of triterpenoids and 5 metabolites. Among them, (25R)-antcin H and (25S)-antcin H had the highest contents of 2.03 and 0.66 μg/g tumor tissues for the 1 h group, and 2.04 and 0.59 μg/g tumor tissues for the 4 h group, respectively. It was obvious that (25R)-antcin H had higher tumor affinity than (25S)-antcin H, since the content of (25R)-antcin H was lower than that of (25S)-antcin H in AC extract (P < 0.01). Conclusion:Triterpenoids can enter tumor tissues after oral administration of AC. Particularly, (25R)-antcin H showed higher exposure to tumor than (25S)-antcin H. These compounds could contribute to the anticancer activities of AC.

Highlights

Metabolites of Antrodia camphorata in mice tumor tissues were profiled by UHPLC-orbitrap/MS analysis for the first time after oral administration, and a total of 33 compounds were characterized. The most abundant compounds in tumor tissues, namely (25R)-antcin H and (25S)-antcin H, were quantified by a fully validated LC-MS/MS method. The results indicated that (25R)-antcin H had higher tumor affinity than (25S)-antcin H.

Clinical evaluation of Xiaoyao Jieyu prescription in the treatment of persistent postural-perceptual dizziness
Yang Shang-Yi, Shang Hong-Cai
TMR Modern Herbal Medicine    2018, 1 (2): 57-66.   https://doi.org/10.12032/TMRmhm2017B16
Abstract HTML PDF (513KB)  

Objective:The objective of this study is to evaluate the clinical efficacy of Xiaoyao Jieyu prescription (XJP) in the treatment of persistent postural-perceptual dizziness (PPPD). Methods:A total of 33 PPPD patients were randomly divided into test group and control group. Two groups of patients were given psychological treatment. The test group was given XJP and the control group was given escitalopram. The course of treatment was 12 weeks. Before and after 4 weeks and 8 weeks and 12 weeks, the dizziness handicap inventory (DHI), Hamilton anxiety scale (HAMA) and Hamilton Depression scale (HAMD) were used to evaluate the treatment effect. Results:The total scores of HAMA, HAMD, DHI and the respective factor scores of DHI significantly decreased in both groups after 4 weeks of treatment compared with those before the treatment (P < 0.01). The DHI scores and the score of function, physiology at 8-week, 12-week, as well as the HAMA and HAMD scores at 4-week, 8-week, 12-week in the test group were significantly lower than those in the control group (P < 0.05). The incidence of adverse reactions in the test group was significantly lower than the control group (P < 0.05). Conclusion:XJP can improve the clinical symptoms of patients with PPPD. It can both improve the physical and functional symptoms of PPPD and reduce anxiety and depression. In the course of treatment, the adverse reaction of the prescription is less and mild. It has the advantages of high efficiency, safety, low price and easy access to materials.

Highlights

Persistent postural-perceptual dizziness is a new disease name. It was proposed by Stabb and Ruckenstein on the basis of chronic subjective dizziness and phobic postural vertigo in 2014. At present, the main treatment methods of PPPD is psychotherapy, vestibular balanced rehabilitation and drug therapy, but each method has its limitations. Xiaoyao Jieyu prescription was adjusted on the basis of the ancient formula “Xiaoyao San”. It can improve the clinical symptoms of patients with PPPD, which has the advantages of high efficiency, safety, low price and easy access to materials.

Antioxidative and antiapoptotic effects of (+)-clausenamide on acetaminophen-induced nephrotoxicity in mice
Yu Hong-Min, Wang Min, Yu Zong-Chao, Li Yi-Fang, Huang Chun-Xin, Han Fang-Xuan, Liu Fan-Na, He Rong-Rong
TMR Modern Herbal Medicine    2018, 1 (3): 127-135.   https://doi.org/10.12032/TMRmhm2017A20
Abstract HTML PDF (727KB)  

Objective: (+)-Clausenamide ((+)-CLA), the active ingredient of wampee, was isolated from the leaves of Clausena lansium (Lour.) Skeels. This study aimed to evaluate the protective potential of (+)-CLA against acetaminophen (APAP)-induced nephrotoxicity in mice. Methods: Mice were divided into control, APAP, high-dose (+)-CLA, and low-dose (+)-CLA groups. Then, mice were preadministered (+)-CLA (50 and 100 mg/kg) for 5 consecutive days. After the last treatment, the animals received a single intraperitoneal injection of APAP (600 mg/kg). Renal histopathology was evaluated by staining with hematoxylin and eosin. The levels of malondialdehyde (MDA) and glutathione (GSH) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined using corresponding kits. Western blotting was used to analyze the expression of apoptosis-related proteins in renal tissue. Results: Administration of APAP increased serum creatinine and blood urea nitrogen levels in comparison with the control group. An increase in renal MDA level, depletion of GSH, and reductions in CAT and SOD activities in renal tissue indicated that APAP-induced kidney injury was mediated by oxidative stress. The expressions of Bax and caspase-3, cleavage of caspase-3, and cytoplasm cytochrome c levels were up-regulated in renal tissue, whereas Bcl-2 expression and mitochondrial cytochrome c levels were down-regulated in the APAP group, which revealed that APAP-induced kidney injury significantly increased cell apoptosis in renal tubules. The histopathology of kidney tissue supported these biochemical mechanisms. (+)-CLA can reverse changes in most of the abovementioned parameters and nearly restore the normal structure of the kidney. Conclusion: Oxidative stress and apoptosis are considered to be the mechanisms underlying APAP-induced nephrotoxicity. (+)-CLA could be a promising antidote for APAP-induced acute renal damage owing to its antioxidative and antiapoptotic effects.

Highlights

(+)-Clausenamide ((+)-CLA), an acid amide isolated from the leaves of Clausena lansium (Lour.) Skeels, significantly decreases creatinine and blood urea nitrogen levels and increases the antioxidative abilities. The underlying mechanisms of (+)-CLA were involved in improving the antioxidative and antiapoptotic effects. This study provides a basis to clinical application of (+)-CLA.

Pharmacological effects of Paeoniflorin and Albiflorin on IL-3, GM-CSF, IL-6 and TNF-α in the rats of syndrome of stagnation of liver qi and blood deficiency
Wang Cheng-long, Qin Yu-wang, Pan Shi-xia, Zhang Jian-jun, Teng Hong-li
TMR Modern Herbal Medicine    2018, 1 (3): 155-163.   https://doi.org/10.12032/TMRmhm2017A22
Abstract HTML PDF (530KB)  

Objective: To observe the effect of paeoniflorin (PF), albiflorin (AF) on the hemogram, visceral index and hematopoiesis cytokine in the rats of syndrome of stagnation of liver qi and blood deficiency, and to discuss the material base and mechanism of effect of nourishing blood and smoothing the liver of Baishao (Radix Paeoniae Alba). Methods: Male SD rats were randomly divided into groups according to the sucrose preference test and body weight (n = 12). Except the normal control, the other groups were treated with the chronic stress stimulation combined with radiation respectively to establish the model of syndrome of stagnation of liver qi and blood deficiency. The body weight, visceral index and the quantity of Leucocyte, Red Blood Cells, Hemoglobin in peripheral hemogram were monitored, then plasma and serum were separated. Radioimmunoassay was used to analyze the levels of Lnterleukin-3, Granulocyte-macrophage Colony-stimulating Factor, Lnterleukin-6 and Tumor Necrosis Factor-α in plasma. Results: Compared with that of model group, 30 mg?kg-1 PF and 30 mg?kg-1 AF of the weight, spleen index, quantity of Leucocyte were increased significantly (P < 0.05, P < 0.01). The results of Radioimmunoassay showed that the levels of Interleukin-3 increased (P < 0.05, P < 0.05) and the levels of Tumor Necrosis Factor-α decreased in both 30 mg?kg-1 PF and 30 mg?kg-1 AF groups (P < 0.05, P < 0.05). Conclusion: The effect of PF and AF on the regulation of bone marrow hematopoietic system and immune system play a role in the blood of rats with syndrome of stagnation of liver qi and blood deficiency, which suggests that both of them are the main active ingredients of nourishing blood and smoothing the liver of Baishao.

Highlights

Baishao (Radix Paeoniae Alba), a well-known Chinese herbal, has been widely used in Chinese Medicine for thousands of years. And Paeoniflorin (PF), albiflorin (AF) are the main active ingredients of Baishao. PE and AF can significantly increase the body weight, spleen index, WBC count and IL-3 level in models of Syndrome of Stagnation of Liver Qi and Blood Deficiency. Experimental results show that the effect of PF and AF on the regulation of bone marrow hematopoietic system and immune system play a role in the blood of rats with syndrome of stagnation of liver qi and blood deficiency, which suggests that both of them are the main active ingredients of nourishing blood and smoothing the liver of Baishao.

Neuroprotective Effect of Bu-Shen-Huo-Xue Extract against High Glucose-induced Apoptosis in PC12 Cells
Zhao Shao-Yang, Dong Xin, Tu Peng-Fei, Zeng Ke-Wu, Wang Xue-Mei
TMR Modern Herbal Medicine    2018, 1 (3): 143-154.   https://doi.org/10.12032/TMRmhm2017A21
Abstract HTML PDF (1116KB)  

Objective: To investigate the neuroprotective effect of Bu-Shen-Huo-Xue (BSHX) extract, a polyherbal formula, against High Glucose (HG)-induced neurotoxicity in PC12 cells. Methods: Cell viability assay, Lactate Dehydrogenase (LDH) assay, Reactive Oxygen Species (ROS) detection, Hoechst 33258, Acridine Orange (AO)/Ethidium Bromide (EB) double stain and Mitochondrial Membrane Potential (MMP) assay were performed. In addition, Bax, Bcl-2, caspase-3, cleaved caspase-3, PARP, cleaved PARP, cytochrome c and Mitogen-Activated Protein Kinases (MAPKs) were detected by western blot. Results: BSHX extract increased cell viability and decreased LDH leakage in a concentration-dependent manner in HG-induced PC12 cells. Moreover, BSHX extract decreased the level of intracellular ROS, increased mitochondrial membrane potential, regulated the expressions of Bax and Bcl-2, and inhibited the release of cytochrome c from mitochondria. Furthermore, BSHX extract attenuated the activation of caspase-3 and PARP, and inhibited the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 MAPKs. Conclusion: BSHX extract exhibited significant neuroprotective effect on HG-induced apoptosis in PC12 cells. This effect may be associated with the suppression of ROS generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways.

Highlights

High glucose (HG)-induced neurotoxicity is implicated in the pathology of diabetic encephalopathy (DE). In our study, Bu-Shen-Huo-Xue extract (BSHX), a polyherbal formula, exhibits neuroprotective activity on HG-induced PC12 cells and the possible mechanisms may be associated with the suppression of reactive oxygen species (ROS) generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways. This study provids a promising agent for the treatment of DE in clinical applications.

Effect of splitting combination of different components of Zhilong Huoxue Tongyu Capsule on vascular remodeling in hypertension
Liao Hui-ling, Ma Qian, Fu Ling
TMR Modern Herbal Medicine    2018, 1 (3): 164-170.   https://doi.org/10.12032/TMRmhm2017A24
Abstract HTML PDF (605KB)  

Objective: To observe the effects of the components of Zhilong Huoxue Tongyu Capsule (ZLHXTY) on the expression of NF-κB-P65 and ICAM-1 in blood vessels of rats, and to explore the effect and mechanism of ZLHXTY and its ingredients on vascular remodeling in hypertension. Methods: A rat model of renal hypertension was established by narrowing the left renal artery in the operation group. The corresponding drugs were given once a day respectively. The Normal group, Sham-operation group and Model group were administered with the same volume of normal saline. After 4 weeks of gavage, the thoracic aorta of rat was taken, followed by fixation, embedding, sectioning and HE staining, and NF-κB -p65 was detected by immunohistochemistry. Results: 1. The effect of drugs on the expression of NF-κB in thoracic aorta of hypertensive rats (immunohistochemistry): A small amount of NF-κB protein was expressed in the Normal group and the Sham-operate group. The NF-κB expression in the Model group was significantly increased, and the electron microscope image showed that the brown-yellow granule was distributed in the vascular smooth muscle of the membrane. After treatment, the expression of NF-κB in the Captopril group and the Whole prescription group was significantly reduced compared with the Model group, while the protein expression in other groups was decreased compared with the Model group. The protein expression of captopril group was decreased compared with that of the Whole prescription group. Compared with Promoting blood circulation for removing blood stasis group, the expression of NF-κB in Benefiting qi group was significantly decreased and was similar to that in Warming meridian group. Conclusion: The vascular remodeling mechanism of ZLHXTY on renal hypertension rats may be related to its effects on lowering blood pressure, antioxidant stress and anti-inflammation. After the compatibility of formula produced a significant synergistic effect, and its compatibility after embodies multiple targets for treatment of advantages of traditional Chinese medicine.

Highlights

By observing the effect of each component of Zhilong Huoxue Tongyu Capsule (ZLHXTY) on the expression of blood vessel NF-κB -P65 and ICAM-1 in rats, to explore the effect of ZLHXTY and its ingredients on vascular remodeling in hypertension and its mechanism. The experimental results indicate that different components of ZLHXTY exert therapeutic effects on vascular remodeling in hypertensive rats from different aspects. Huangqi (Radix Astragali seu Hedysari) plays an important role in lowering blood pressure. The combination of Guizhi (Ramulus Cinnamomi) and Daxueteng (Caulis Sargentodoxae) has a significant effect on the expression of NF- induced B protein. Shuizhi (Hirudo) and compatibility of Dilong (Lumbricus) can lower blood pressure, the NF-κB protein expression. The synergistic effects of the combination of various components are significant, which reflects the therapeutic advantages of multiple targets of traditional Chinese medicine.

Analysis of pharmacological action and clinical application of DaXueTeng based on its anti-inflammatory action
Zhang Li-hui, Lin Miao-miao, Chen Ying, Wu Xue-song, Cai Li-jing, Li Mei-shan, Zhang Guo-wei
TMR Modern Herbal Medicine    2018, 1 (4): 233-240.   https://doi.org/10.12032/TMRmhm2017B29
Abstract HTML PDF (404KB)  

As one of the representative drugs for clearing heat-toxicity, Chinese medicine DaXueTeng (Caulis Sargentodoxae) contains various chemical substances such as tannins, glycosides, cyclic polyphenols, triterpenoids, lignins, flavonoids, terpenoids and organic acids. It has a wide range of pharmacological effects. Meanwhile, it is valued by the doctor. Modern research suggests that DaXueTeng has antibacterial, antiviral, anti-inflammatory, anti-tumor, and immunosuppressive effects. It has been experimentally and clinically proven that the active constituents of DaXueTeng have a good therapeutic effect on inflammatory diseases. It is widely used in the treatment of pelvic inflammatory disease, annexitis, prostatitis, appendicitis, periappendiceal abscess, inflammatory intestinal obstruction, UC, endometriosis, inflammatory secondary infertility, gouty arthritis, pharyngitis, and stomatitis. Here we review the anti-inflammatory pharmacological effects and clinical applications of.

Highlights

DaXueTeng (Caulis Sargentodoxae) belongs to Angiospermae, Dicotyledons, Lardizabalaceae, Sargentodoxa, deciduous woody liana. Caulis Sargentodoxae was first recorded in the “BenCaoTuJing”, saying that it can attack blood and cure blood clots. This dissertation first overview relevant literatures of DaXueTeng recent years. We review the anti-inflammatory effects and clinical application of the current active components of DaXueTeng, which provides a good application prospect in clinic.

Effect of TongFengNing Decoction on Uric Acid Levels and Xanthine Oxidase Activity in Hyperuricemia Rats
Wang Jian-hui, Guo Jie-mei, Li Bao-lin, Teng Fang-zhou, Zhu Ya-ju, Lin Jian-ping, Xiao Yan, Mao Xiao, Huang Lu-lu, Su You-xin
TMR Modern Herbal Medicine    2018, 1 (4): 189-197.   https://doi.org/10.12032/TMRmhm2017A35
Abstract HTML PDF (1926KB)  

Objective: To observe the effect of TongFengNing Decoction (TD) on uric acid levels, xanthine oxidase (XOD) activity, and XOD mRNA expression of hyperuricemia (HUA) model rats. Methods: 90 rats were randomly divided into 6 groups (n=15), and the HUA model in all groups except the blank group was established by administering hypoxanthine (HX) by gavage and injecting potassium oxonate (OAPS) intraperitoneally. Rats in all TD groups and allopurinol group were administered multiple doses of TD and a single dose of allopurinol by gavage twice daily for 21 days, while the blank group and the model group were administered normal saline. On the 7th, 14th, and 21st days of drug intervention, serum uric acid (SUA), urine uric acid (UUA), intestinal uric acid (IUA), as well as XOD activity and mRNA expression in the liver and small intestine were measured in randomly selected 5 rats of each group. Results: On the 14th and 21st days of intervention, all TD dose groups and the allopurinol group showed decreased SUA and IUA levels, increased UUA levels, as well as decreased XOD activity and mRNA expression in the liver and small intestine, compared with the model group (P < 0.05). The low- and high-dose TD group and the allopurinol group showed increased SUA and IUA levels, as well as XOD activity and mRNA expression in the liver and small intestine, and decreased UUA levels, compared with the moderate-dose TD group (P<0.05). Upon extending the drug intervention time of each TD dose group, SUA and IUA levels, XOD activity, and XOD mRNA expression in the liver and small intestine decreased and UUA levels increased (P < 0.05). Conclusion: TD reduces SUA levels in HUA model rats, which promotes uric acid excretion and inhibits XOD activity and XOD mRNA expression to reduce uric acid production. The reduction in uric acid level by the intermediate dose of TD was better than that by allopurinol and the low and high doses of TD.

Highlights

The effect of TongFengNing Decoction (TD) on xanthine oxidase (XOD) activity and mRNA expression in the liver and small intestine of a hyperuricemia (HUA) rat model was explored as the possible mechanism of action for reducing serum uric acid (SUA). The experimental results show that TD reduces SUA levels in HUA model rats by promoting uric acid excretion and inhibiting XOD activity and mRNA expression. These results demonstrate the probable mechanism by which TD lowers uric acid, highlight its clinical application, and reflect the therapeutic advantage of using traditional Chinese medicine.

Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine
Liu Xiao-Mei, Lv Hong, Wang Xiao-Ming, Guo Ya-Qing, Li Ting-Ting, Pan Gui-Xiang
TMR Modern Herbal Medicine    2018, 1 (4): 209-219.   https://doi.org/10.12032/TMRmhm2017B32
Abstract HTML PDF (523KB)  

We summarized the discovery of liquid chromatography mass spectrometry (LC-MS) based glutathione (GSH) capture of reactive metabolites in traditional Chinese medicine (TCM), which provides scientific basis for further research and clinical application of Chinese medicine toxicity discovery. This dissertation overviews relevant literatures of GSH capture of reactive metabolites in recent years. And then we review the principles and methods of LC-MS based GSH capture of reactive metabolites, as well as the research progress in the discovery of toxicity of TCM including pyrrolizidine alkaloids, furans and quinoid species. The review shows that the representative compounds of TCM includes adonifoline, lasiocarpine, diosbulbin B and safrol are well dctected by LC-MS based GSH capture technique. And the main analytic systems of LC-MS are triple quadrupole and Q-Trap mass spectrometer. Constant neutral loss scan (CNLS), precursor ion scan (PIS) and multiple reaction monitor (MRM) are main detection methods to monitor the characteristic GSH conjugate fragmentations. The approach of LC-MS based GSH-trapped metabolites has a good application prospect in the discovery of toxic components of TCM.

Highlights

Metabolic bioactivation of certain drugs can generate reactive metabolites (RM) that are capable of covalently modifying cellular biomolecules and are implicated in drug induced toxicity. These electrophilic metabolites, also known as intermediates, cannot easily be detected due to the chemical instability and shorter half-life. As a natural nucleophilic agent, glutathione (GSH) can capture these electrophilic RM, forming GSH covalent conjugates. GSH conjugates screening by liquid chromatography-mass spectrometry (LC-MS) can be applied for rapid characterization and detection of potential toxicity of traditional Chinese medicine (TCM). In this paper, we briefly introduced the principle of RM trapped by GSH, as well as mentioned some qualitative and quantitative methods by LC-MS for GSH conjugates screening over recent years. Moreover, the application of this technology in the discovery of toxicity of TCM, especially those containing pyrrolizidine alkaloids, furans and quinoid species, were also reviewed. In short, the approach of LC-MS based GSH-trapped RM can be employed for rapid and sensitive detection of potential toxic RM in TCM, with a good prospect in application.

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