Integrative Medicine

Danshensu Ameliorates Cardiac Ischaemia Reperfusion Injury through Activating Sirt1/FoxO1/Rab7 Signal Pathway Abstract Objective: To explore the specific molecular mechanisms of Danshensu (DSS) in the treatment of ischemia reperfusion injury (IRI). Methods: IRI model was established with isolated rat hearts by performing global ischaemia for 30 min, and then followed by 60 min reperfusion. Also, H9C2 cells were subjected to 4-h hypoxia followed by 3-h reoxygenation. Then 10 μmol/L DSS were added in the reperfusion/reoxygenation step to intervene IRI. Cardiac function, structural change and apoptosis were respectively tested by Langendorff System, hematoxylin and eosin (HE) and terminal-deoxynucleotidyl transferase mediated nick endabeling (TUNEL) stainings. Then lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide gasififi cation enzyme (SOD) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay (ELISA). Sirt1/FoxO1/Rab7 Signal Pathway was monitored at both protein and mRNA levels. Results: The results showed that IRI not only greatly attenuated cardiac function (LVDP and ±dp/dtmax, P<0.01, P<0.05) and increased the level of the marker enzymes (cardiac troponin T, LDH, P<0.01) from the coronary effluents, but also markedly induced changes in the structure of cardiomyocytes and contributed to apoptosis, which were mediated by boosted endogenous ROS. However, after treatment with DSS all above indexes were improved, which was related to activating Sirt1/FoxO1/Rab7 signal pathway accompanied with the enhancement of antioxidant defense system, such as superoxide gasififi cation enzyme and glutathione peroxidase. Conclusion: DSS is able to protect hearts from IRI, which may be attributable to inhibiting excessive ROS through Sirt1/FoxO1/Rab7 signaling.

Effects and Mechanism of Action of Artemisinin on Mitochondria of Plasmodium berghei Abstract Objective To study the antimalarial effects and mechanisms of artemisinin (Qinghaosu in Chinese, QHS) on mitochondria in mice infected with Plasmodium berghei. Methods A total of 108 C57 mice infected with Plasmodium berghei were randomly divided into 3 groups by weight: the control group, 200 and 400 mg/kg QHS groups. The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time, 0.5, 1, 2, and 4 h. Normal saline was intragastrically (i.g.) administered to the control group. The other two groups received different doses of QHS by i.g. administration. Animals were treated once with QHS for different detection time as follows: 0.5, 1, 2, and 4 h. The mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane permeability and other indexes were detected. Results After administration of 200 and 400 mg/kg QHS, adenosine triphosphate (ATP) levels in Plasmodium and its mitochondria were reduced (P<0.05), the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased (P<0.05), and the activity of superoxide dismutase (SOD) was also increased (P<0.05). At the same time, the membrane potential of the mitochondria was reduced and the degree to which the membrane permeability transition pore was opened was irreversibly increased (P<0.05). Conclusions Mitochondria in Plasmodium were the targets of QHS, which can adversely affect mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane opening, and ultimately exert an antimalarial effect.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System Abstract Objective To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (通心络胶囊, 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-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. 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.

Oral Chinese Herbal Medicine for Depressive Disorder in Patients after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis Abstract Objective: To evaluate the effectiveness and safety of oral Chinese herbal medicines (CHMs) on post-percutaneous coronary intervention (PCI) patients with depressive disorder in coronary heart disease (CHD). Methods:A literature search was conducted through databases including PubMed, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Chinese Biomedical Literature Database (SinoMed), Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and Wanfang Database up to August 2018. Randomized controlled trials (RCTs) comparing CHMs with placebo or no additional treatments on the basis of standard conventional pharmacological therapies were included. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 software was used to synthesize the results. Results: A total of 16 RCTs enrolling 1,443 participants were included in this systematic review. When compared with antidepressants alone, CHMs showed similar benefits with less side effects [risk ratio=0.54, 95% confidence interval (CI) 0.43 to 0.69, 582 patients]; meanwhile, the combination therapy may have more advantages than antidepressants alone [mean difference (MD)=–1.03, 95%CI–1.81 to–0.25, 267 patients). When identified with placebo, CHMs seem to have more advantages in relieving depressive symptoms (MD=–19.00, 95%CI–20.02 to–17.98, 189 patients). However, when compared with basic treatment of post- PCI, CHMs showed different results in two trials. In terms of post-PCI related clinical symptoms, CHMs seem to have more advantages in relieving chest pain and other general clinical symptoms. However, the heterogeneity in this review was generally high, it may be caused by different interventions used in each trial and the low quality of the trials. Conclusions: In total, CHMs showed potentially beneficial effects on depressive symptoms and post-PCI related clinical symptoms. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.

Comparative Studies of Two Major Sets of Tibetan Medical Paintings: A Historical Perspective Abstract Tibetan medicine, one of the time-honored medical systems in the world, has increasingly been receiving attention the world over. Tibetan medical paintings (TMP, tib. Sman thang) has become one of the focal points in the studies of this medical system. To date, there are many atlases and publications on TMP, which are principally based on the two major sets of TMP series existing today in the world, the Lhasa set and the Buryat set. It has been found that the Buryat set is based on the Lhasa set, which was brought in late 19th to the first half of the 20th century from Tibet to Buryatia, Russia. A careful investigation on the basic structure of the two sets reveals that there are many differences between the two sets of paintings, including the total number of the paintings involved, of which some are missing in one set, the details of the captions of some of the paintings, the existence of the 80th painting and its supervisor, and the overall order of the entire set, etc. The details of the differences are elaborated and discussed, and the prospective of developing the research to arrive at a standard and perfect TMP set in the future is also analyzed and anticipated.

Effect of Shexiang Baoxin Pill (麝香保心丸) in Alleviating Early Hypertensive Renal Injury in Rats Abstract Objective To investigate the effect of Shexiang Baoxin Pill (麝香保心丸, SBP) on early hypertensive renal injury in rats and to explore the possible mechanism. Methods Twelve-week-old spontaneous hypertensive rats (SHRs) with high-salt diet (dietary containing 8% NaCl) were randomized into the SBP group [40 mg/(kg·d)], losartan potassium group [20 mg/(kg·d)] and saline group by stratified random sampling method, 12 in each group. Blood pressure and urea albumin creatinine ratio were measured. After 10 weeks, the expression levels of serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1 β, IL-6, tumor necrosis factor α (TNF-α), and transforming growth factor β (TGF-β) in serum were assessed. Kidney pathology periodate-schiff staining was performed. Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining. Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), monocyte chemokine peptide (MCP-1), inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). Results SBP did not affect the mortality of SHR (P<0.05). SBP significantly reduced the level of elevated blood pressure of SHRs, but the effect was less significantly than that of losartan potassium. SBP decreased urine protein (P<0.01) and the expression levels of IL-1 β, IL-6, TNF-α, and TGF-β in serum. The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells, glomerular ischemic lesions, inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis. Both SBP and losartan potassium had alleviated renal pathological change, and significantly reduced the infiltration of macrophage (P<0.05, P<0.01). SBP and losartan potassium decreased the expressions of TLR4, NF-κB, MCP-1, iNOS, and Arg-1. Conclusion SBP significantly modified the early hypertensive renal injury by reducing inflammation, and the effect was similar to losartan potassium.

Changes of Intestinal Microecology in Patients with Primary Sjogren's Syndrome after Therapy of Yangyin Yiqi Huoxue Recipe (养阴益气活血方) Abstract Objective To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (养阴益气活血方, YYHD). Methods Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. Results The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P<0.05). After the treatment with YYHD, patients' ESSDAI score and levels of IgG and ESR have decreased significantly (P<0.05). At the phylum level, the proportions of Actinobacteria, Firmicutes, Fusobacteria and Proteobacteria have reduced sharply, while the proportions of Bacteroidetes, Teneriquetes and Candidate-division-TM7 have increased significantly by treatment (all P<0.05). At the classification level, such treatment has caused a significant decrease in the proportions of Bacteroidaceae, Ruminococcaceae, Veillonellaceae, and Enterobacteriacea (all P<0.05), but a significant increase in the proportion of Lachnospiraceae (P<0.05). At the genus level, the treatment has significantly decreased the proportions of Bifidobacterium, Bacteroides, Escherichia-Shigella, Faecalibacterium and Prevotella (all P<0.05), but significantly increased the proportion of Clostridia (P<0.05), close to the levels of healthy subjects (P>0.05). Conclusions There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.

Anticancer Effects of Constituents of Herbs Targeting Osteosarcoma Abstract Osteosarcoma is a rare primary malignancy of bone that is prone to early metastasis. Resection surgery and chemotherapeutic regimens are current standard treatments for osteosarcoma. However, the long-term survival rate of patients with osteosarcoma is low due to a high risk of metastasis. Hence, a new approach is urgently needed to improve the treatment of osteosarcoma. Compared with chemotherapy, natural active constituents isolated from herbs exhibit less adverse effects and better anti-tumor effects. This study aimed to summarize the anticancer effects of constituents of herbs on the progression and metastasis of osteosarcoma cells. It showed that many constituents of herbs inhibited osteosarcoma by targeting proliferation, matrix metalloproteinases, integrin and cadherin, and angiogenesis. The findings might be beneficial for the development of new drugs and treatment strategies.

Is Acupressure Useful for Alleviating Hyperventilation Syndrome?

Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits Abstract Objectives To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. Methods BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. Results The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). Conclusions The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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2841026182

6948891480

alsfakia@gmail.com