Structure-aware deep model for MHC-II peptide binding affinity prediction.

The prediction of major histocompatibility complex (MHC)-peptide binding affinity is an important branch in immune bioinformatics, especially helpful in accelerating the design of disease vaccines and immunity therapy. Although deep learning-based solutions have yielded promising results on MHC-II molecules in recent years, these methods ignored structure knowledge from each peptide when employing the deep neural network models. Each peptide sequence has its specific combination order, so it is worth considering adding the structural information of the peptide sequence to the deep model training. In this work, we use positional encoding to represent the structural information of peptide sequences and validly combine the positional encoding with existing models by different strategies. Experiments on three datasets show that the introduction of position-coding information can further improve the performance built upon the existing model. The idea of introducing positional encoding to this field can provide important reference significance for the optimization of the deep network structure in the future.

Heart Protection by Herb Formula BanXia BaiZhu TianMa Decoction in Spontaneously Hypertensive Rats.

Modern research has shown that BanXia BaiZhu TianMa decoction (BBT) has the potential effect of lowering BP in vitro and in vivo. However, its therapeutic mechanism has not been clearly defined. The present study was designed to evaluate the protective effect of BBT on the heart by examining heart functioning and anti-inflammatory characteristics and to obtain scientific evidence for its further medical applications. BBT was extracted by decocting the herb extraction and analysed by HPLC. The left ventricular mass index (LVMI) was measured, and a histological examination of samples of the heart was performed. Inflammatory status was investigated by measuring tissue levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and molecules of the nuclear factor κB (NF-κB) pathway. The BBT treatment significantly reversed the course of hypertension-derived heart damage. Meanwhile, the herb formula markedly reduced levels of IL-1, IL-6, TNF-α, and iNOS. In addition, the traditional compound suppressed the activity of the NF-κB pathway. The present study provides evidence of heart protection by BBT in SHRs. The action mechanisms may be partially attributable to the anti-inflammatory characteristic of the formula. Understanding the pharmacological action of BBT will benefit its impending use.

Metabolomic signatures and microbial community profiling of depressive rat model induced by adrenocorticotrophic hormone.

BACKGROUND: Adrenocorticotrophic hormone (ACTH)-treatment rat model has been utilized as a widely accepted model of treatment-resistant depression. Metabolomic signatures represent the pathophysiological phenotype of diseases. Recent studies in gut microbiota and metabolomics analysis revealed the dramatic role of microbiome in psychoneurological system diseases, but still, the mechanisms underlying gut microbiome-host interaction remain unclear. METHODS: Male Wistar rats were s.c. injection of ACTH fragment 1-24 for 14 days to induce treatment-resistant depression. Depression-related behavioral tests, analysis of serum monoamine neurotransmitters and hypothalamic-pituitary-adrenal (HPA) axis-related hormones were determined for assessment of ACTH-induced depression rat model. A gas chromatography-time-of-flight mass spectrometer based urinary metabolomic signatures integrated 16S rRNA sequence analysis based gut microbial profiling was performed, as well as Spearman's correlation coefficient analysis was used to manifest the covariation between the differential urinary metabolites and gut microbiota of genus level. RESULTS: Chronic injection of ACTH-induced depression-like phenotype (increased immobility time in forced swimming test and tail suspension test) was accompanied by peripheral serotonin down-regulation and HPA axis overactivation (ACTH and corticosterone up-regulation). Urinary metabolomics analysis indicated that pyruvic acid, L-threonine, mannitol, D-gluconic acid, 4-hydroxybenzoic acid, D-arabitol, myo-inositol and ascorbic acid levels were reduced in ACTH-treated rats' urine, while hippurate level was elevated. In addition, microbial community profiling revealed bacterial enrichment (e.g. Ruminococcus, Klebsiella) and reduction (e.g. Akkermansia, Lactobacillus) in the ACTH-induced depression rat model. Correlation analysis showed that Akkermansia and Lactobacillus were closely relevant to metabolites myo-inositol and hippurate, which were included in host inositol phosphate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. CONCLUSIONS: Depression rat model induced by ACTH is associated with disturbance of pyruvate metabolism, ascorbate and aldarate metabolism, inositol phosphate metabolism, glycine, serine and threonine metabolism, and glycolysis or gluconeogenesis, as well as changes in microbial community structure. Gut microbiota may participate in the mediation of systemic metabolomic changes in ACTH-induced depression model. Therefore, integrated metabolomic signatures and gut microbial community profiling would provide a basis for further studies on the pathogenesis of depression.

Chronic paradoxical sleep deprivation-induced depression-like behavior, energy metabolism and microbial changes in rats.

AIMS: Given the lasting impact of chronic paradoxical sleep deprivation (PSD) on behavior and organism metabolic alternations, along with the role of the microbiome in neurobehavioral development and metabolism, we sought to examine the relationship between the microbiota and chronic PSD-induced behavioral and metabolic changes. MATERIALS AND METHODS: Psychological status of 7-day PSD (7d-PSD) male rats was tested by behavioral method, serum inflammatory cytokines and hypothalamic-pituitary-adrenal (HPA) axis-related hormones. In addition, GC-MS based urine metabolomics and 16S rRNA gene sequencing approaches were applied to estimate the influences of chronic PSD on host metabolism and gut-microbiota. Furtherly, microbial functional prediction and Spearman's correlation analysis were implemented to manifest the relations between the differential urinary metabolites and gut microbiota. KEY FINDINGS: 7d-PSD rats displayed depression-like behavior, metabolic and microbial changes. By integrating differential gut bacteria with indicators of depression and differential metabolites, we found that the alterations of Akkermansia, Oscillospira, Ruminococcus, Parabacteroides, Aggregatibacter and Phascolarctobacterium were closely related to abnormalities of depression symptoms and inflammatory cytokines. These bacteria also had close connections with host energy metabolism concerning arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism, pyruvate metabolism, which overlapped with the results of 16S rRNA gene function annotation. SIGNIFICANCE: These data suggest that a specific situation of circadian disturbance, chronic PSD-induced alterations in gut microbiota and related host changes in metabolism may be the pathogenesis of depression.

Characterization of polysaccharide from Scutellaria barbata and its antagonistic effect on the migration and invasion of HT-29 colorectal cancer cells induced by TGF-ß1.

In this study, we purified a water-soluble polysaccharide, SBPW3, from the whole plant of Scutellaria barbata D. Don through ethanol precipitation, deproteinization, lyophilization, dialysis and separation using a DEAE cellulose column and a Superdex 200 gel filtration chromatography column. SBPW3 is a homogeneous polysaccharide with a molecular weight of 10.2 kDa and is composed of rhamnose (2.51%), arabinose (25.68%), xylose (10.94%), mannose (12.56%), glucose (20.59%) and galactose (27.72%). FT-IR spectrum analysis of the polysaccharide showed that SBPW3 contained a pyranose ring. The effects of SBPW3 on TGF-ß1-induced epithelial-mesenchymal transition (EMT) were tested in colon cancer cells. These results suggested that SBPW3 significantly suppressed TGF-ß1-induced migration and invasion. Additionally, SBPW3 reduced EMT by increasing the expression of epithelial markers and by decreasing the expression of mesenchymal markers by blocking the Smad2/3 signalling pathway in colon cancer cells. Furthermore, to explore the anti-metastatic effect of SBPW3, we established a mouse model of colon cancer metastasis and found that SBPW3 significantly inhibited the metastatic dissemination of the primary tumour to the liver. These findings provide us with a potential chemotherapeutic strategy for the treatment of human colorectal cancer.

20(S)-protopanaxadiol induces apoptosis in human umbilical vein endothelial cells by activating the PERK-eIF2alpha-ATF4 signaling pathway.

20(S)-protopanaxadiol (PPD)-type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer cells, which suggests that they have anti-cancer activity. Anti-angiogenesis is a promising therapeutic approach for controlling angiogenesis-related diseases such as malignant tumors, age-related macular degeneration, and atherosclerosis. Studies showed that 20(S)-PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)-PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)-PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)-PPD induces apoptosis in HUVECs for the first time. We found that caspase-9 and its downstream caspase, caspase-3, were cleaved into their active forms after 20(S)-PPD treatment. Treatment with 20(S)-PPD decreased the level of Bcl-2 expression but did not change the level of Bax expression. 20(S)-PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R-like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP-homologous protein (CHOP) expression increased after treatment with 20(S)-PPD. Furthermore, siRNA-mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)-PPD-induced apoptosis. Collectively, our findings show that 20(S)-PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK-eIF2α signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)-PPD could be used to treat angiogenesis-related diseases.

Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation.

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.

Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.

REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

Differential contribution of endothelium-derived relaxing factors to vascular reactivity in conduit and resistance arteries from normotensive and hypertensive rats.

The endothelium contributes to the maintenance of vasodilator tone by releasing nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). In hypertension, endothelium-dependent relaxation is attenuated (a phenomenon referred to as endothelial dysfunction) and contributes to the increased peripheral resistance. However, which vasodilator among NO, PGI2, and EDHF is impaired in hypertension remains largely unknown. The present study was designed to study the exact contribution of NO, PGI2, and EDHF to vascular reactivity in conduit and resistance artery, under physiological and pathological conditions. The aorta and the second-order mesenteric artery from spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were used to measure the vasorelaxation with myograph technology, in the presence or absence of different inhibitors. The results showed that the endothelium-dependent vasodilatation in the conduit artery was mediated mainly by NO, whereas the resistant artery by NO, PGI2, and EDHF together. In hypertension, both NO-mediated relaxation in the conduit artery and NO-, PGI2-, and EDHF-mediated dilation in the resistant artery were markedly impaired. Furthermore, the endothelium-dependent and the endothelium-independent vasorelaxation in conduit artery was attenuated more pronouncedly than that in the resistant artery from hypertensive rats, suggesting that the conduit artery is more vulnerable to hypertensive condition. In conclusion, vasodilators including NO, PGI2, and EDHF contribute distinctively to endothelium-dependent relaxation in conduit and resistance artery under physiological and pathological conditions.

[Effect of tianma gouteng decoction on the endothelial function and the renal protein expression in spontaneously hypertensive rats].

OJECTIVE: To observe the effect of tianma gouteng decoction (TGD) on the endothelial function and the renal protein expression of spontaneously hypertensive rats, and to analyze its possible mechanism. METHODS: Totally 18 6-week-old SHR were randomly divided into 3 groups according to randomized block design, the SHR control group, the TGD group, and the captopril group, 6 in each group. Meanwhile, Wistar Kyoto (WKY) rats of the same age were recruited as a WKY control group. Rats in the TGD group were administered with TGD at the daily dose of 10. 260 g/kg. Rats in the captopril group were administered with captopril at the daily dose of 3. 375 g/kg. 2 mL/100 g distilled water was administered to rats in the SHR control group and the WKY control group. All medication was performed by gastrogavage once per day till rats were 24 weeks old. Changes of blood pressure were measured once per two weeks. The relaxation of the thoracic aorta and the superior mesenteric artery was determined by vascular ring in vitro to reflect the endothelial function. The total renal protein was separated by two-dimensional electrophoresis (2-DE). The significantly deviated protein was verified by Western blot. RESULTS: (1) Compared with the SHR control group, blood pressure was significantly lowered in rats (10 - 24 weeks old) of the captopril group (P <0.01, P <0.05). The hypotensive effect of TGD was obvious at the beginning of hypertension (10 -12 weeks) (P <0. 01). But along with the progression of hypertension, its hypotensive effect was not obvious (P>0. 05). (2) Compared with the SHR control group, the relaxation of the superior mesenteric artery was obviously improved in the TGD group (P <0. 05); the relaxation of the thoracic aorta and the superior mesenteric artery was obviously superior in the WKY control group (P <0. 01, P <0. 05). But there was no statistical difference in each relaxation index between the captopril group and the SHR control group (P >0. 05).(3) RESULTS: of 2-DE found 16 significantly differential renal protein, mainly involved nitric oxide (NO) system, oxidative stress, and cytoskeleton-related proteins. Results of Western blot showed that TGD could significantly improve expressions of Cu-Zn superoxide dismutase (SOD), N(G, N(G)-dimethylarginine dimethylaminohydrolase 2 (DDAH2), and pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1) (P <0. 05). CONCLUSION: GTD could protect the endothelial function of the superior mesenteric artery in SHR, and its intervention mechanism of hypertension induced early renal injury might be relevant to regulating the NO system and antioxidative stress.

Cyclosporin A upregulates ETB receptor in vascular smooth muscle via activation of mitogen-activating protein kinases and NF-κB pathways.

Hypertension is one of the most frequent complications of solid organ transplantation, and cyclosporin A (CsA) plays a predominant role in the pathophysiology of post-transplant hypertension. However, the exact molecular mechanisms of CsA-induced hypertension remain obscure. We previously showed that CsA increased the mRNA expression and contractile function of endothelin B (ETB) receptor in vascular smooth muscle cells. The present study was designed to investigate the underlying mechanisms of CsA-induced upregulation of ETB receptor in vasculature. Rat mesenteric arteries were incubated with CsA in an organ culture system, and results showed that CsA enhanced ETB receptor mRNA in the time- and dose-dependent manner, and increased protein expression levels of ETB receptor after treatment with CsA 10(-5)M for 6h. Furthermore, CsA induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), p38, and translocation of nuclear factor-kappaB (NF-κB) p65 in vasculature. Blocking ERK1/2, p38, or NF-κB activation with their specific inhibitors markedly attenuated CsA-induced upregulation of ETB receptor mRNA expression and protein levels, and ETB receptor-mediated contraction. In summary, this study showed that mitogen-activating protein kinases (ERK1/2 and p38) and the downstream transcriptional factor NF-κB pathways were involved in CsA-induced upregulation of ETB receptor in arterial smooth muscle cells.

[Analysis of renal protein expressions of spontaneously hypertensive rat intervention by three different Chinese medicine compounds for hypertension].

OBJECTIVE: To observe the differential protein expression profile of three different Chinese medicine compounds on spontaneous hypertensive rat, which were Banxiabaizhutianma Decoction, Dihuangyinzi Decoction and Tianmagouteng Decoction, and to elaborate their function characters and regulation pathway using the principal component analysis and analyze the basic theory of different treatment of hypertension. METHODS: Give three compounds to 6-week-old SHR (Spontaneous hypertensive rat) as experimental group and captopril to 6-week-old WKY (Wistar-Kyoto rat) as control group by gavage. Monitor the blood pressure of rat tail to 24-week-old and then all rats were decapitated. Extracte the rental protein to finish two-dimensional electrophoresis experiments and get the differential protein spots using PDQuest software. Study the three different compounds' effect of trend on SHR blood pressure using PCAC principal component analysis. RESULTS: The blood pressure of SHR remained rising from 6-week-old to 10-week-old, when Tianmagouteng Decoction had a significant anti-hypertension effect. But as the blood pressure of SHR remained high, Banxiabaizhutianma Decoction and Dihuangyinzi Decoction performed better in lowering blood pressure. At last, renal protein expression profile analysis showed that there were 84 significantly different proteins between SHR and WKY of 24-week-old and the PCA result showed that the principal component extraction was 95.951%, it was sure that Tianmagouteng Decoction and Banxiabaizhutianma Decoction had significantly changed rental protein spots on SHR while Dihuangyinzi Decoction had not. CONCLUSION: In the early stages of rising blood pressure, Tianmagouteng Decoction has significant anti-hypertensive effect. But when the blood pressure remain high, Banxiabaizhutianma Decoction and Dihuangyinzi Decoction are superior to Tanmagouteng Decoction in anti-hypertension. Banxiabaizhutianma Decoction and Tianmagouteng Decoction can significantly improve rental protein spots on SHR while Dihuangyinzi Decoction can not.

A RG-II type polysaccharide purified from Aconitum coreanum alleviates lipopolysaccharide-induced inflammation by inhibiting the NF-κB signal pathway.

Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum coreanum (Lévl.) Rapaics have shown anti-inflammatory activity, which is strongly influenced by their chemical structures and chain conformations. However, the mechanisms of the anti-inflammatory effect by these polysaccharides have yet to be elucidated. A RG-II polysaccharide (KMPS-2E, Mw 84.8 kDa) was isolated from KMPS and its chemical structure was characterized by FT-IR and NMR spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography. The backbone of KMPS-2E consisted of units of [→6) -ß-D-Galp (1→3)-ß-L-Rhap-(1→4)-ß-D-GalpA-(1→3)-ß-D-Galp-(1→] with the side chain →5)-ß-D-Arap (1→3, 5)-ß-D-Arap (1→ attached to the backbone through O-4 of (1→3,4)-L-Rhap. T-ß-D-Galp is attached to the backbone through O-6 of (1→3,6)-ß-D-Galp residues and T-ß-D-Ara is connected to the end group of each chain. The anti-inflammatory effects of KMPS-2E and the underlying mechanisms using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and carrageenan-induced hind paw edema were investigated. KMPS-2E (50, 100 and 200 µg/mL) inhibits iNOS, TLR4, phospho-NF-κB-p65 expression, phosphor-IKK, phosphor-IκB-α expression as well as the degradation of IκB-α and the gene expression of inflammatory cytokines (TNF-α, IL-1ß, iNOS and IL-6) mediated by the NF-κB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced activation of NF-κB as assayed by electrophorectic mobility shift assay (EMSA) in a dose-dependent manner and it reduced NF-κB DNA binding affinity by 62.1% at 200 µg/mL. In rats, KMPS-2E (200 mg/kg) can significantly inhibit carrageenan-induced paw edema as ibuprofen (200 mg/kg) within 3 h after a single oral dose. The results indicate that KMPS-2E is a promising herb-derived drug against acute inflammation.

[The effect of Banxia Baizhu Tianma decoction on renal protein expression in spontaneously hypertensive rats].

OBJECTIVE: To study the effect of Banxia Baizhu decoction on the spontaneously hypertensive rats and its possible mechanism. METHODS: Male SHRs of 6 weeks old were randomly and equally divided into two groups, the control SHR group and the group treated with BXBZTMD, the treated group were treated with BXBZTMD orally for 18 weeks, the control SHR group and normotensive WKY group were fed with the same amount of distilled water. Rats' blood pressure was measured through carotid artery catheterization, and protein of kidney tissues was analyzed by two-dimensional electrophoresis after extraction and purification. Different protein spots expressed significantly which were anlyzed by PDQuest software were then identified by MALDI-TOF/TOF MS. The protein expressions of peroxidase 2 and Cu-Zn superoxide in kidney were determined by Western blot. RESULTS: Compared SHR with WKY, 12 protein spots were changed. BXBZTMD could adjust kidney protein expression such as Cu-Zn superoxide dismutase, peroxidase 2 and may change kidney protein expression such as the alpha-beta-crystallin, which were closely related to oxidative stress. These discoveries of the target proteins suggested that BXBZTMD had curative effect by anti-oxidative stress. CONCLUSION: Oxidative stress plays an important role in the process of hypertensive renal injury. BXBZTMD can play a therapeutic role to oxidative stress. The discovery of the target protein provides a theoretical basis for the mechanism of the therapeutic effect of BXBZTMD.

[Effect of banxia baizhu tianma decoction on the vascular endothelial function of spontaneous hypertensive rats].

OBJECTIVE: To study the vascular endothelial function recovery and its mechanism of Banxia Baizhu Tianma Decoction (BBTD). METHODS: 54 SH rats were randomly divided into three groups: the blank control group, BBTD group and Captopril treatment group. BBTD (at the daily dose of 4. 320 g crude drug/kg) and Captopril (at the daily dose of 3.375 g/kg) was administered from the 7th week to the 24th week. Another eighteen Wistar-Kyoto rats of the same ages were taken as the control. Medication was discontinued and effects were observed until the 32nd week. The blood pressure was determined by arterial carotis cannula. The concentration of serum NO2(-) and total anti-oxidation were determined by Griess and fluorescence recovery after photobleaching (FRAP). The acetylcholine (Ach)-dependent relaxation of superior mesenteric artery was detected using in vitro vascular ring. The mRNA expressions of IL-1, IL-6 and iNOS were detected by Real-time PCR at the 18th, 24th, and 32nd week. RESULTS: BBTD could significantly lower blood pressure of SHR and the concentration of serum NO2(-) at the 18th and 24th week (P<0.05). The total anti-oxidation of SH rats increased at the 18th week (P<0.01), and ACh-dependent relaxation of superior mesenteric artery increased at the 24th week. The mRNA expressions of IL-1 was markedly suppressed by BBTD at the 18th, 24th, and 32nd week (P<0.05), while IL-6 and iNOS mRNA expression were significantly lowered only at the 32nd week (P< 0.01). Captopril could significantly lower blood pressure of SHR at the 18th and 24th week (P<0.05). It significantly increased the total anti-oxidation of SH rats at the 18th week (P<0.01). However, it could not increase ACh-dependent relaxation of superior mesenteric artery and regulate the concentration of NO2(-) at the 18th, 24th, and 32nd week. The mRNA expression of iNOS was markedly suppressed by Captopril at the 24th and 32nd week, while mRNA expressions of IL-1 and IL-6 were significantly lower only at the 32nd week (P<0.01). CONCLUSIONS: BBTD showed similar effect in decreasing the blood pressure to captopril, but it showed better effect in improving the mesenteric endothelial dysfunction of SHR, which may be associated with its inhibition on NO and IL-1 expression, and improvement of the oxidative stress state.

[Effect of banxia baizhu tianma decoction on the left ventricular hypertrophy of hypertrophied myocardium in spontaneously hypertensive rat].

OBJECTIVE: To investigate the changes in renin angiotensin system (RAS) in hypertrophied myocardium of spontaneous hypertensive rat (SHR), and the effect of Banxia Baizhu Tianma Decoction (BBTD) on the changes in haemodynamic parameters and mRNA of signaling molecules of RAS at different periods. METHODS: Fifty-four male SHRs of 6 weeks old were randomly and equally divided into three groups: the untreated control group, the test group, and the positive control group, and they were treated respectively with distilled water, BBTD and captopril by dissolving in equal volume of water administrated via gavage for 18 weeks. Besides, 18 age matched Wistar-Kyoto (WKY) rats treated with distilled water were allocated in a normal control group. Rats were managed in batches at their age of 18, 24, and 32 weeks old. Rat's hemodynamic parameters were measured through carotid artery catheterization, myocardial pathology was observed, and their mRNA expressions of angiotensin (AGT), angiotensin-converting (ACE) and angiotension-converting 2 (ACE2) were determined by Real-time PCR. RESULTS: Compared with WKY rats, the arterial pressure and left ventricular mass index (LVMI)in SHR were significantly higher at 18, 24 and 32 weeks respectively (P < 0.01); average cycle rate showed in electrocardiogram was higher (P < 0.05), though the blood stream was similar; mRNA expressions of AGT and ACE in heart tissue were markedly higher (P < 0.01), but that of ACE2 at 18 and 24 weeks were lower (P < 0.01). Compared with untreated SHR, arterial pressure at 18 and 24 weeks was lower (P < 0.05); cardiac muscle structure was improved; LVMI at 24 weeks was improved (P < 0.05); the mRNA expressions of AGT and ACE were suppressed but that of ACE2 increased at 18, 24,and 32 weeks significantly in the test group after BBTD treatment (P < 0.05). CONCLUSIONS: Changes in RAS in the hypertrophied myocardium of SHR may be one of the molecular mechanisms for hypertension leading to left ventricular hypertrophy. BBTD can improve the hemodynamic parameters, regulate RAS, so as to lower the arterial pressure.

[Effect of total saponins from rhizomes and flowers of Panax notoginseng on tumor cell induced platelet aggregation].

OBJECTIVE: To investigate the effects of total saponins from rhizomes and flowers of Panax notoginseng on tumor cell induced platelet aggregation (TCIPA). METHODS: MDA-MB-231 breast carcinoma was applied as inductor and the platelet aggregation were investigated by Born's method in vitro and in vivo. RESULTS: Saponins from the flowers of Panax notoginseng inhibited TCIPA at the dose of 120, 240, 480 mg/L respectively in vitro and in vivo. Saponins from rhizomes of Panax notoginseng inhibited TCIPA only at its high dose in vivo. CONCLUSION: The saponins from Panax notoginseng has a dose-dependent inhibition of TCIPA. It may be a new class of antimetastatic agent.