Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI).@*METHODS@#Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg@*RESULTS@#Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL.@*CONCLUSIONS@#TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

Analysis of molecular mechanism of Bushen Huoxue granules in treating Parkinson's disease based on network pharmacology and molecular docking / 中国药理学通报

Aim To analyze the molecular mechanism of Bushen Huoxue granules in the treatment of Parkinson's disease by using network pharmacology as the main research method combined with molecular docking technology. Methods TCMSP was used to find the active ingredients of Bushen Huoxue granules, and ADME screening was performed. The obtained active ingredients and targets were combined with PD targets to obtain disease-drug co-action targets; STRING 11.0 was used to construct PPI protein interaction network for the obtained disease-drugs. The Metascape platform was used to analyze the enrichment of disease-drug target functions and pathways, and then Cytoscape 3.7. 1 was used to construct a network diagram of Bushen Huoxue granules-PD targets-action pathways; AUTODOCK and PYMOL software were used for molecular docking and visualization operations. Results The core active ingredients of Bushen Huoxue granules in treating PD were quercetin, luteolin, kaempferol, tanshinone, etc.; the main targets were PTGS2, PTGS1, SCN5A, ADRB2 and CHRM1, etc.; the main signaling pathways are PI3K/AKT, Toll, whose function was mainly to regulate cell apoptosis and neuroinflammatory response. Conclusion This study has initially revealed the mechanism of Bushen Huoxue granules in the multi-level and multi-step treatment of PD, laying a foundation for future animal experiments.

Early Intervention of Tongxinluo () on Right Ventricular Function Assessed by Echocardiography in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT).@*METHODS@#A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes.@*RESULTS@#MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices.@*CONCLUSION@#Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.

Preventive effect of Tongxinluo on endothelial survival and vascular integrity, together with inhibition of inflammatory reaction in rats model of intestine ischemia/reperfusion injury

This study was design to investigate preventive function of Tongxinluo [TXL] capsule on micro vascular function and endothelial survival in rats model of intestine ischemia/reperfusion [I/R] injury. We randomly divided fifty male Sprague-Dawley rats into Sham group, I/R group, TXL0.4+I/R group, TXL0.8+I/R group, TXL1.6+I/R group [10 rats each]. Rat intestine I/R injury was carried out using a model of acute superior mesenteric artery occlusion with 30 min ischemia followed by 60 min reperfusion. The distribution of endothelial apoptosis in intestine was determined by CD31+TUNEL immunofluorescent double staining analysis. VE-Cadherin, ANGPTL4, HMGB1 and NF-[kappa]B were determined by immunohistochemical analysis. I/R induced massively endothelial cell apoptosis, accompanied with reduced expression of adherens junction protein VE-Cadherin and up regulation of inflammatory mediator HMGB1 and NF-[kappa]B. TXL pretreatment groups [TXL0.4+I/R, TXL0.8+I/R and TXL1.6+I/R group] significantly attenuated endothelial cell apoptosis with a dose-dependent effect. TXL pretreatment could maintain the expression of VE-Cadherin and promote the expression of ANGPTL4 which help to maintain endothelial integrity. TXL pretreatment also exert great influence in inhibiting HMGB1 expression and NF-[kappa]B expression induced by I/R. It could be concluded from this study that micro vascular dysfunction and endothelial damage play a causal role in rat intestine I/R injury. TXL pretreatment could significantly prevent the I/R induced pathology of endothelial apoptosis, micro vascular integrity disruption and inflammatory reaction

Effectiveness of Bushen Huoxue Granule (补肾活血颗粒) on 5-serotonin and norepinephrine in the brain of Parkinson's disease patients with depressive state / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical curative effect of Chinese medicine Bushen Huoxue Granule(补肾活血颗粒, BHG) on Parkinson's disease (PD) patients with depressive state.</p><p><b>METHODS</b>Sixty-two PD patients with depressive state were randomly assigned to two groups by using a random number table, 31 in each group. Madopar was given to all as the conventional treatment. The fluoxetine hydrochloride dispersible tablet was given to the patients in the control group and BHG was given to those in the treatment group. The therapeutic course for all was 12 weeks. Before and after treatment, Hamilton depression rating scale (HAMD) was applied to judge the curative effect, and the changes of cerebral neurotransmitters levels in the brain of patients were detected by encephalofluctuograph technique.</p><p><b>RESULTS</b>The scores of HAMD in the two groups were decreased markedly after 12-week treatment. It was lower in the treatment group than that in the control group with significant difference (P<0.01). The contents of norepinephrine (NE) and 5-serotonin (5-HT) in the PD patients were obviously lower than normal value. There was no significant difference between the two groups before treatment (P>0.05). The contents of NE and 5-HT were all increased in the two groups after treatment (P<0.05), with significant differences between the two groups (P<0.01).</p><p><b>CONCLUSION</b>BHG could increase the contents of NE and 5-HT in PD patients' brain to improve the depressive state of PD patients.</p>

Differences in the origin of philosophy between Chinese medicine and Western medicine: Exploration of the holistic advantages of Chinese medicine / 中国结合医学杂志

To explore advantages of Chinese medicine (CM) by analyzing differences in the origin of philosophy for human health between CM and Western medicine (WM). Methodologically, a distinctive feature of CM is its systems theory, which is also the difference between CM and WM. Since the birth of CM, it has taken the human body as a whole from the key concepts of "qi, blood, yin-yang, viscera (Zang-Fu), and meridian and channel", rather than a single cell or a particular organ. WM evolves from the Western philosophic way of thinking and merely uses natural sciences as the foundation. The development of WM is based on human structures, or anatomy, and therefore, research of WM is also based on the way of thinking of decomposing the whole human body into several independent parts, which is the impetus of promoting the development of WM. The core of CM includes the holistic view and the dialectical view. Chinese herbal medicines contain various components and treat a disease from multiple targets and links. Therefore, Chinese herbal medicines treat a diseased state by regulating and mobilizing the whole body rather than just regulating a single factor, since the diseased state is not only a problem in a local part of the body but a local reflection of imbalance of the whole body.

The treatment of non-small cell lung cancer by interstitial I-125 seeds implantation combined with chemotherapy and Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of brachytherapy with computed tomography-guided percutaneous radioactive I-125 seeds interstitial implantation (ISI) synchronized chemotherapy and Chinese medicine (CM) for the treatment of advanced stage of non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Ninety patients diagnosed with NSCLC by biopsy were randomly assigned to three groups: the synchronized therapy group (A), the chemotherapy plus CM-treated group (B), and the chemotherapy-treated group (C); a 2-month course of treatment was administered to them all. The effectiveness of treatment was evaluated based on tumor size, tumor markers (carcinoembryonic, squamous cell carcinoma-associated antigen, and cytokeratin 19 fragment), clinical symptoms, and quality of life (QOL) in patients.</p><p><b>RESULTS</b>The total effective rates of Groups A to C were 83.33%, 46.67%, and 43.33%, respectively. The tumor markers were reduced obviously in Group A, showing signifificant difference compared with those in the other two groups. Additionally, QOL was elevated and cancer-related symptoms were alleviated more signifificant in Group A than those in Group C (all P<0.05).</p><p><b>CONCLUSION</b>The synchronized therapy of I-125 implantation with chemotherapy and CM was a safe therapeutic method and can be regarded as a new mode for treatment of advanced-stage NSCLC.</p>

Effect of bushen huoxue granule on dopamine neurotransmitter and dopamine transporter in the brain of patients with Parkinson's disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Bushen Huoxue Granule (BHG) on dopamine (DA) neurotransmitter and dopamine transporter (DAT) in the brain of patients with Parkinson's disease (PD) as an adjunctive therapy.</p><p><b>METHODS</b>Ninety-four PD patients were randomly assigned to two groups, 47 in each group. Madopar was given to all as the basic treatment group. The placebo was given to those in the control group while BHG was given to those in the treatment. The therapeutic course for all was three months. Before and after treatment DA levels in the brain of patients were detected by encephalofluctuograph (EFG) technique. Changes of DAT in the striatum of patients in the treatment group were detected by positron emission tomography (PET) and region of interest (ROI) analysis.</p><p><b>RESULTS</b>(1) Before treatment the DA level was lower in the two groups than the normal value, showing significant difference (P < 0.01), but with no significant difference between the two groups (P > 0.05). After treatment the DA level obviously increased in the two groups, showing significant difference from that before treatment (P < 0.01). No significant difference existed in the DA level in the two groups when compared with the normal value (P > 0.05), but with significant difference between the two groups (P < 0.05). Better results were obtained in the treatment group than in the control group. (2) The DAT radioactive accumulation inside the striatum increased obviously in the treatment group after treatment. ROI analysis showed the total ratio of striatum/cerebellum before and after treatment was 1.86 +/- 0.32 and 2.61 +/- 0.53 respectively, showing statistical difference (P < 0.05).</p><p><b>CONCLUSION</b>BHG could improve the DA level of PD patients, and increasing DAT contents in the striatum, thus playing a role in effectively treating PD.</p>

Effect of Bushen Huoxue Decoction on dopamine D2 receptor in the brain of rats with Parkinson's disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the mechanism underlying the therapeutic effect of Bushen Huoxue Decoction (BHD), a traditional Chinese medicinal preparation, on dopamine D2 receptor (DRD2) in the brain of rat models of Parkinson's disease (PD).</p><p><b>METHODS</b>A total of 120 SD rats were randomized into normal control group, saline model group and BHD-treated group. In the latter two groups, PD rat models were established by direct injection of 6-OHDA to destruct the substantia nigra compact part (SNC) with corresponding treatments. The behavioral changes of the rats were observed. Radioimmunoassay was employed to determine the changes in the equilibrium dissociation constant (Kd) and maximal binding capacity (B(max)) of DRD2, and immunohistochemistry was used to observe the number of the DRD2-positive cells in the brain of the rats.</p><p><b>RESULTS</b>BHD can markedly improve the behavioral abnormalities of PD model rats. Compared with those in the saline model group, the B(max) of DRD2 in the damaged hemisphere increased while the Kd of BHD decreased significantly after BHD treatment (P<0.01). The number of DRD2-positive cells in BHD-treated group was significantly higher than that in the model group (80.9∓13.59 vs 11.15∓6.78, P<0.01), but showed no significant difference from that in the normal control group (P>0.05).</p><p><b>CONCLUSION</b>BHD can improve the behavioral abnormalities and increase the cerebral expression and affinity of DRD2 in PD rat models.</p>

Effect of Bushenhuoxue Yin on cerebral levels of nitric oxide, tumor necrosis factor-α and interferon-γ in a mouse model of Parkinson disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of Bushenhuoxue Yin (BSHXY), a compound traditional Chinese herbal medicine, on nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) levels in the brain of a mouse model of Parkinson disease (PD).</p><p><b>METHODS</b>Forty-five C57BL/6 mice were randomized into MPTP-induced PD model group, BSHXY treatment group and normal control group. The contents of NO and the two cytokines in the brain tissue of the mice were determined by spectroscopy and enzyme-linked immunosorbent assay, respectively.</p><p><b>RESULTS</b>The concentration of NO in the brain tissue of the PD model group was 5.93 ∓ 0.79 µmol/g.protein, significantly higher than that in BSHXY group (P<0.01) and normal control group (P<0.01). The levels of TNF-α and IFN-γ in the PD model group were 0.36 ∓ 0.11 ng/L and 0.83 ∓ 0.25 ng/L, respectively, also higher than those in the other two groups (P<0.01 or 0.001). But BSHXY group and the normal control group showed no significant differences in the levels of NO, TNF-α and IFN-γ (P>0.05).</p><p><b>CONCLUSION</b>The therapeutic effect of BSHXY on PD is partially attributed to decreased content of NO, TNF-α and IFN-γ in the brain.</p>

Effect of scalp point penetration needling on sleep quality and sleep structure of insomnia patients / 中国针灸

<p><b>OBJECTIVE</b>To observe the improving effect of scalp point penetration needling on sleep quality and sleep structure for insomnia patients.</p><p><b>METHODS</b>Sixty-six cases of insomnia were randomly divided into a scalp point penetration needling group (observation group, 32 cases) and a routine acupuncture group (control group, 34 cases). The observation group was treated with Houshencong (EX-HN 1) penetrating to Qianshencong (EX-HN 1) and Xinhui (GV 22) penetrating to Shenting (GV 24) etc.; Baihui (GV 20), Anmian (EX- HN 22) and Neiguan (PC 6) etc. were selected in control group. The Pittsburgh Sleep Quality Index (PSQI) and micro-sensitive mattress sleep monitoring system were used to observe the sleep quality and sleep structure of the patients before and after treatment, respectively.</p><p><b>RESULTS</b>The completely improved rate of the sleep quality of 65. 6%(21/32)in observation group was superior to that of 35.3 (12/34) in control group (P < 0.05). There were significant differences between two groups in latency of falling asleep, total time of sleep, time of deep sleep stage and more than 5 min awakening times of sleep structure after treatment (all P < 0. 01), the observation group was superior to control group.</p><p><b>CONCLUSION</b>The scalp point penetration needling has more significant effects for improving the sleep quality and sleep structure of insomnia patients than the routine needling.</p>

Clinical study on treatment of severe acute respiratory syndrome with integrative Chinese and Western medicine approach / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics of severe acute respiratory syndrome (SARS) and observe the therapeutic effect with integrative Chinese and western medicine (ICWM) approach in treating patients with SARS.</p><p><b>METHODS</b>Forty-eight patients selected from the authors' hospital, whose diagnosis confirmed as SARS were analysed to sum-up the diagnostic type and basic feature of patients and the chief clinical characteristics. All the patients were randomly divided into the trial group and the control group, 24 in each. The control group was treated with the western medical therapeutic program and the trial group was treated with ICWM therapeutic program. The differences between the two groups were compared in terms of development of illness, time of using corticosteroid and absorption time of pulmonary inflammatory lesion, etc.</p><p><b>RESULTS</b>Most patients were youth and adult aged between 18 to 40 years old, the initial symptom was mainly the high fever, accompanied with general soreness, chest stuffiness and cough, etc. The hospitalization time, body temperature fluctuation sustaining time and time of using corticosteroid in the trial group were shorter than those in the control group, showing significant difference (P < 0.05). ICWM treatment showed a better effect in defervescence and inflammatory lesion absorption time, but with no statistical significance.</p><p><b>CONCLUSION</b>Patients of SARS are mainly youth and adults in the prime of life, fever always appears as the initiation of illness and some accompanying symptoms would appear. As compared with the western treatment, ICWM treatment could evidently shorten the course of illness, prevent the rebounding of fever and reduce the time of using corticosteroid.</p>