[Clinical study on treatment of carotid atherosclerosis with extraction of polygoni cuspidati rhizoma et radix and crataegi fructus: a randomized controlled trial].

OBJECTIVE: To observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis. METHOD: Sixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1. RESULT: After 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05). CONCLUSION: Detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.

Red yeast rice prevents atherosclerosis through regulating inflammatory signaling pathways.

OBJECTIVE: To observe the effects of red yeast rice (RYR) on blood lipid levels, aortic atherosclerosis (AS), and plaque stability in apolipoprotein E gene knockout (ApoE-/-) mice. METHODS: Twenty-four ApoE-/- mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups (n = 8 in each group): model group (ApoE-/- group), RYR group (ApoE-/- + RYR group), and simvastatin group (ApoE-/- + simvastatin group). Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured with enzyme-linked immunosorbent assay. The level of high sensitivity C-reaction protein (Hs-CRP) was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9 (MMP-9) and nuclear factor κB (NF-κB) in aorta were tested by immunohistochemistry. RESULTS: Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein (a), and apolipoprotein B100 in ApoE-/- mice (P<0.01). Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α (P<0.01). RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta. CONCLUSIONS: RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflflammatory signaling pathways.

[Effect of maixinkang capsule on Ca2+ and mitochondrial membrane potential in liver cells of ApoE(-/-) mice].

OBJECTIVE: To observe the effect of Maixinkang Capsule (MXK) on Ca2t concentration and mitochondrial membrane potential in liver cells of ApoE(-/-) mice. METHODS: Liver cells from ApoE(-/-) mice were separated using collagenase digestive method. After the primary cells were cultured for 8 days in vitro, the concentration of 10% MXK contained rat's serum was added into the culture fluid. The Ca2+ concentration and mitochondrial membrane potential in liver cells after 48-hr culture were measured by confocal laser scanning microscopy with Flou-3 and Jc-1 as probes. RESULTS: MXK could decrease Ca2+ concentration in liver cells, which was significantly different to that in the control group (P < 0.01). Meanwhile, MXK could significantly improve mitochondrial membrane potential in liver cells (P < 0.01). There was no obvious dose-effect relationship shown in both effects of MXK. CONCLUSION: MXK can decrease Ca2+ concentration and improve the mitochondrial membrane potential in liver cells of ApoE(-/-) mice so as to regulate the lipids and prevent the occurrence and development of hyperlipemia and atherosclerosis.

[Clinical and experimental study on jiangzhi tiaoya granule in treating essential hypertension and protecting function of vascular endothelium].

OBJECTIVE: To observe the therapeutic effect of Jiangzhi Tiaoya Granule (JZTYG) in treating essential hypertension and its protection on function of vascular endothelial cells (VEC). METHODS: Fifty-nine patients of essential hypertension divided into two groups were treated with JZTYG (the treated group) and Jinjia Yixintong (the control group) respectively. The changes of symptoms, signs, blood pressure, heart rate were observed and the levels of endothelin (ET), calcitonin gene related peptide (CGRP) content were determined by radioimmunoassay (RIA). RESULTS: The total effective rates of JZTYG in lowering blood pressure and improving symptoms were both 90.0%, markedly effective rate in lowering blood pressure and improving symptoms was 36.7% and 60.0% respectively. The symptom improved in the treated group was better than that in the control group (P < 0.05). It also could reduce the plasma ET level (P < 0.05) and ET/CGRP ratio (P < 0.01), and increase the CGRP level (P < 0.05). CONCLUSION: JZTYG has a promising clinical therapeutic effect in treating essential hypertension and is able to protect the VEC function.

[Effect of xinmaitong on wild-type p53 gene expression in rabbits with carotid endothelial injury].

OBJECTIVE: To explore the mechanism of prevention and treatment of post-PTCA restenosis with Xinmaitong (XMT). METHODS: Rabbit carotid endothelial injury model was established using Fishman air drying method. Effect of XMT on model rabbits wild-type p53 gene expression was observed by tissue in situ hybridization. RESULTS: p53 gene expression appeared on the 3 days after operation, enhanced on the 7 days, reached the peak on the 14th day, weakened on the 21th, and still showed on the 28th day. The strongest expression was shown in rabbits treated by XMT, second in those treated by Warfarin, and the weakest in the operated control group. CONCLUSION: XMT could promote the high expression of wild-type p53 gene expression in rabbit with carotid endothelial injury, which is possibly one of the important mechanism of XMT in preventing and treating arterial restenosis.

IL-24 Induces Apoptosis via Upregulation of RNA-Activated Protein Kinase and Enhances Temozolomide-Induced Apoptosis in Glioma Cells.

Human interleukin-24 (IL-24) has been found recently to play a tumor-suppressor role in a variety of tumors, including gliomas. However, the exact mechanism of glioma tumor suppression by IL-24 remains unclear. We collected by surgery 30 gliomas at different grades and evaluated IL-24 and double-stranded RNA-activated protein kinase (PKR) expression using fluorescence quantitative real-time PCR and immunohistochemical techniques. Two human glioma cell lines, U87 and U251, were transfected with Ad5F35-IL24 via recombinant adenovirus-mediated gene transfer and apoptosis, as well as PKR and eIF-2α expression analyzed. The results showed that IL-24 and PKR expression decreased with increasing tumor grade. Compared with cells of the control groups, Ad5F35-IL24-infected U87 and U251 cells exhibited a significantly increased apoptosis and elevated PKR, eIF-2α, p-PKR, and p-eIF-2α levels, while the expression of Bcl-2 was decreased. Finally, IL-24 also sensitized apoptosis of glioma cells to temozolomide (TMZ). This study indicates that IL-24 upregulates expression and activation of PKR, further increasing expression and activation of eIF-2α, and decreasing Bcl-2 to promote apoptosis. IL-24 also increases chemosensitivity of glioma cells to TMZ.

The progress of the research on cardio-vascular effects and acting mechanism of polydatin.

Rhizoma Polygoni Cuspidati, a Chinese herbal drug, has actions of dispelling dampness, alleviating jaundice, clearing heat, subsiding toxin, activating blood, and removing stasis. Polydatin (PD), one of its chief active ingredients, has been proved by modern pharmacological studies to possess extensive cardiovascular pharmacological activity, showing marked effects on protecting cardio-myocyte, dilating blood vessel, antagonizing platelet aggregation, thrombosis, and atherosclerosis. The progress of the research on cardiovascular pharmacological actions and the acting mechanism of PD was reviewed in this paper.

Mechanism of thalidomide to enhance cytotoxicity of temozolomide in U251-MG glioma cells in vitro.

BACKGROUND: Glioma is the most common primary brain tumor with poor prognosis. Temozolomide has been used with thalidomide to treat gliomas. We investigated the synergistic mechanism of these two drugs in vitro. METHODS: Human malignant glioma cells U251-MG were cultured and assigned to four groups with different treatments for 3 days: temozolomide group (100 micromol/L), thalidomide group (100 microg/L), temozolomide (100 micromol/L) plus thalidomide group (100 microg/L) and control group. MTT assay was applied to evaluate the cell viability. Cell cycle was analyzed by flow cytometry. The ultra-structural features of autophagosomes were observed with electron microscope. Acridine orange and monodansylcadaverine were adopted to label autophagosomes and flow cytometry was applied for quantification of autophagosomes. The expression of autophagy-associated protein was detected by Western blotting. RESULTS: Proliferation of tumor cell was obviously suppressed by temozolomide with thalidomide treatment than by either drug used alone (P = 0.000 for each day). The combination treatment induced cell cycle arrest at G0/G1 phase. Typical autophagic ultra-structural character was found after the combined treatment. Thalidomide promoted the autophagy induced by temozolomide. The autophagy-associated proteins-microtubule associated protein 1 light chain 3 (MAP1LC3) and Beclin1 were more significantly up-regulated by the combined treatment than temozolomide used alone (MAP1LC3, P = 0.000; Beclin1, P = 0.004). The expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN), which promoted autophagy by suppressing PI3K/Akt/mTOR signaling pathway, was elevated by thalidomide (thalidomide group: P = 0.000; combined group: P = 0.002). CONCLUSIONS: Thalidomide enhances the cytotoxicity of temozolomide by promoting the autophagy induced by temozolomide. Contributing to the up-regulation of PTEN by thalidomide, the expression of autophagy associated protein-MAP1LC3 and Beclin1 was enhanced, which leads to a reinforced autophagy in the combined treatment of temozolomide and thalidomide in vitro.