ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Modulatory Effects of Co-Fermented Pu-erh Tea with Aqueous Corn Silk Extract on Gut Microbes and Fecal Metabolites in Mice Fed High-Fat Diet.

Pu-erh tea is recognized for its weight loss effects, but its potential association with gut microbiota and metabolites remains unclear. This research explored the alterations in gut flora and metabolite composition upon treatment with a co-fermented Pu-erh tea with an aqueous corn silk extract (CPC) in obese mice by employing integrated 16S ribosomal RNA gene sequencing and untargeted metabolomics processes. For 8 weeks, mice were fed control, high-fat, and high-fat diets which included a 46 mg/mL CPC extract. The CPC extract the alleviated high-fat diet (HFD), it stimulated systemic chronic inflammation, and it reduced the body weight, daily energy consumption, and adipose tissue weight of the mice. It also modified the gut microbiota composition and modulated the Lactobacillus, Bifidobacterium, Allobaculum, Turicibacter, and Rikenella genera. Fecal metabolomics analysis revealed that the CPC extract influenced the caffeine, cysteine, methionine, tryptophan, biotin metabolism pathways, primary bile acid, and steroid biosynthesis. This research revealed that the CPC extract could inhibit HFD-stimulated abnormal weight gain and adipose tissue accumulation in mice, and modulate mice gut microbiota composition and multiple metabolic pathways.

Study on material basis and anti-hypertensive metabolomics of different extraction methods of the Uncaria rhynchophylla Scrophularia Formula.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.

The In Vitro Effect of Psoralen on Glioma Based on Network Pharmacology and Potential Target Research.

Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored. In this study, we investigated the in vitro inhibition effect and potential targets of psoralen on glioma through network pharmacology and in vitro glioma treatment experiments. First, we used network pharmacology to preliminarily predict the 21 core genes of psoralen in the treatment of glioma, including PIK3CA, PIK3CB, PIK3CG, and JAK2. The CCK-8 method was used to detect the effect of psoralen on the proliferation of glioma U87 and U251 cells, and the results showed that psoralen could significantly inhibit the proliferation of U87 and U251 cells. The flow cytometry was used to detect the apoptosis and cell cycle changes, and it was found that psoralen could significantly promote the early apoptosis of U87 and U251 cells and had a significant cycle arrest effect on the two cells. The cell scratch test showed that psoralen could significantly inhibit the migration of U87 and U251 cells. The relative expression levels of PIK3CA, PIK3CB, PIK3CG, and JAK2 were analyzed by Real-time Quantitative polymerase chain reaction (QT-PCR), and the results showed that psoralen could inhibit the gene expression of PIK3CA, PIK3CB, PIK3CG, and JAK2. Later, Western blotting (WB) experiments showed that psoralen could inhibit the protein expressions of PI3K and JAK2. This study has preliminarily explored and verified the antiglioma effect of psoralen in the form of inhibiting cell proliferation and migration, promoting cell apoptosis and organizing cell cycle in vitro. And may play a role by inhibiting the expression of PIK3CA, PIK3CB, PIK3CG, JAK2 gene and PI3K, JAK2 protein, psoralen has become a potential antiglioma drug.

Aqueous extracts of tree peony petals: renin and angiotensin I-converting enzyme inhibitory activities in different colours and flowering stages.

Tree peony (Paeonia suffruticosa Andr.) is an ornamental and medicinal plant from China. Previous studies have detected novel blood pressure-regulating substances in this species, which potentiate its value of utilization. To explore these substances, the aqueous extracts of 7 different colours of tree peony petals were assessed for inhibitory activity on renin and angiotensin-converting enzyme (ACE). The results showed that the activity of dark-coloured samples was significantly stronger than that of light-coloured ones. Furthermore, the inhibitory activity of the red tree peony petals 'Hong TaiYang' on renin and ACE indicated a downward trend from bud compaction to the full opening stage. The antioxidant activities of the aqueous extracts, on one side, and the correlations between phenolics and flavonoids functionalities and total contents, on the other, were also evaluated. In this regard, the extracts of different samples had ABTS free radical scavenging capacities of 17.28-210.41 mg TE per g DW, DPPH radical scavenging capacities of 35.45-150.78 mg TE per g DW, iron ion reduction capacities of 16.66-150.77 mg TE per g DW, and total phenolic content of 23.94-150.78 mg GAE per g DW. Correlation analysis revealed that the renin and ACE inhibitory activities, the DPPH and ABTS free radical scavenging capacities, and the iron reduction ability of different sample extracts were positively correlated with total phenolic contents (p < 0.01). Finally, the aqueous phenolic compounds in the sample extracts tended to show strong renin and ACE inhibitory activities and therefore exhibit a potential auxiliary blood pressure control prospect.

TCM Regulates PI3K/Akt Signal Pathway to Intervene Atherosclerotic Cardiovascular Disease.

Vascular endothelial injury is the initial stage of atherosclerosis (AS). Stimulating and activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway can regulate the expression of vascular endothelial cytokines, thus affecting the occurrence and development of AS. In addition, the PI3K/Akt signaling pathway can regulate the polarization and survival of macrophages and the expression of inflammatory factors and platelet function, thus influencing the progression of AS. In recent years, traditional Chinese medicine (TCM) has been widely recognized for its advantages of fewer side effects, multiple pathways, and multiple targets. Also, the research of TCM regulation of AS via the PI3K/Akt signaling pathway has achieved certain results. This study aimed to analyze the characteristics of the PI3K/Akt signaling pathway and its role in the pathogenesis of AS, as well as the role of Chinese medicine in regulating the PI3K/Akt signaling pathway. The findings are expected to provide a theoretical basis for the clinical treatment and pathological mechanism research of AS.

Toward the Development of Personalized Syndrome Discriminant Systems: A Discriminant System for Hypertension with Liver Yang Hyperactivity Syndrome.

Traditional Chinese medicine has shown promising results in treating the symptoms of hypertension, a major global health concern not yet fully managed by modern medicine. It is, therefore, of high priority to clarify the altered pathophysiology of hypertension in individuals with liver Yang hyperactivity syndrome (HLYH) in response to effective treatments to better understand this disorder. The primary aim of this study was to construct a personalized syndrome discriminant system based on data capable of informing management strategies prior to the initiation of antihypertensive therapy or the implementation of screening strategies in at-risk HLYH. Based on the successful replication of HLYH rat models, we extracted the core discriminant factors of the disorder through the integration of physical signs, biochemical indicators, and metabolic markers. Macro and micro information was correlated to construct a syndrome discriminant system. At the macroscopic level, HLYH rat models characterized by elevated blood pressure were found to be associated with significant changes in water intake, pain threshold, retention time on a rotating platform, and body surface temperature. A total of 27 potential biomarkers and 14 metabolic pathways appeared to reflect the primary metabolic characteristics. Through the integration of these data, we successfully constructed a combined macro-micro personalized syndrome discriminant system, which provides a foundation for research regarding the risk loci of HLYH. Our findings also broaden our understanding of the biological pathways involved in HLYH.

[Non-targeted metabolomics study and biomarker screening of prehypertensive liver-fire hyperactivity syndrome based on UPLC-Q-Exactive MS technology].

In this study, patients with prehypertensive liver-fire hyperactivity syndrome(LFHS) were selected as the research objects. The plasma samples of healthy volunteers and patients with prehypertensive LFHS were analyzed by non-targeted metabolomics based on UPLC-Q-Exactive MS. The differential biomarkers and metabolic pathways were screened out by multivariate statistics and metabolic pathway analysis, which revealed the characteristics of metabolic patterns of the syndrome. Thirty-three potential biomarkers such as androsterone and lysophosphatidylcholine and 16 related metabolic pathways such as steroid hormone metabolism and lipid metabolism were identified, and a partial least squares-discriminant analysis(PLS-DA) model of traditional Chinese medicine(TCM) syndromes was preliminarily constructed: Y =-0.070X_(13)-0.006X_8+ 0.040X_5-0.152X_1+0.131X_(10)+0.036X_(11)+0.043X_(23)+0.076X_(16)+0.132X_(20)+0.081X_(19)-0.101X_(31)+0.082X_(15)-0.038X_9+0.079X_(24). The predictive value of the model was 88.1%, and the explanatory power was 88.4%. In this study, the characteristic metabolic pattern of the prehypertensive LFHS was distinguished and revealed by metabolomics. The constructed PLS-DA model is expected to provide an objective basis for the identification of TCM syndromes in prehypertension, and inspiration for exploring the biological basis of TCM syndromes at small-molecular and overall levels.

Ongoing Supplementation of Probiotics to Cesarean-Born Neonates during the First Month of Life may Impact the Gut Microbial.

OBJECTIVE: The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates. STUDY DESIGN: Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n = 3), CD (cesarean-born neonates, n = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3-V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology. RESULTS: The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the ß-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins. CONCLUSION: This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota. KEY POINTS: · Cesarean-born neonates. · Probiotic supplementation impact gut flora. · Bifidobacterium and Lactobacillus.

Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats.

Essential hypertension is a major risk factor for cardiovascular disease that can lead eventually to structural and functional alterations in the brain. Accumulating evidence has suggested that the increased activities in renin-angiotensin system and sympathetic nerve participated in the pathogenesis of hypertension that is related to the imbalance between neurotransmitters. The potential role in essential hypertension arising from alterations of neurotransmitters in the central nervous system remains understudied. Isorhynchophylline is a major oxindole alkaloid extracted from Uncaria rhynchophylla, which has been widely used for treating hypertension and neurodegenerative diseases. Whether isorhynchophylline acts on neurotransmitters to lower blood pressure has been hypothesized but rarely demonstrated unequivocally. Here, we studied the metabolic neurotransmitter profiles in the hypothalamus using a targeted metabolomic approach in spontaneously hypertensive rats after isorhynchophylline intervention. Our study demonstrated that isorhynchophylline exhibited a strong anti-hypertensive effect in spontaneously hypertensive rats by improving the neurotransmitter imbalance in the hypothalamus and inhibiting the overactivation of the renin-angiotensin system and sympathetic nerve system. Overall, this study played an essential role in enhancing our understanding of the mechanism of isorhynchophylline in essential hypertension and in providing theoretical evidence for future research and clinical application.

Ginsenoside Rg1-Notoginsenoside R1-Protocatechuic Aldehyde Reduces Atherosclerosis and Attenuates Low-Shear Stress-Induced Vascular Endothelial Cell Dysfunction.

Background: The Fufang Danshen formula is a clinically important anti-atherosclerotic preparation in traditional Chinese medicine. However, its anti-atherosclerotic effect is not well recognized, and the mechanisms of its combined active ingredients, namely Ginsenoside Rg1-Notoginsenoside R1-Protocatechuic aldehyde (RRP), remain unclear. The purpose of this study was to investigate the anti-atherosclerotic effects and potential mechanism of RRP in ApoE-/- mice and in low-shear stress-injured vascular endothelial cells. Methods: ApoE-/- mice were randomly divided into three groups: model group, rosuvastatin group, and RRP group, with C57BL/6J mice as the control group. Oil-red O, hematoxylin and eosin, Masson, and Movat staining were utilized for the observation of aortic plaque. Changes in the blood lipid indexes were observed with an automatic biochemistry analyzer. ET-1, eNOS, TXA2, and PGI2 levels were analyzed by enzyme-linked immunosorbent assay. In vitro, a fluid shear stress system was used to induce cell injury. Piezo1 expression in HUVECs was silenced using siRNA. Changes in morphology, proliferation, migration, and tube formation activity of cells were observed after RRP treatment. Quantitative Real-Time PCR and western blot analysis were employed to monitor mRNA and protein expression. Results: RRP treatment reduced the atherosclerotic area and lipid levels and improved endothelial function in ApoE-/- mice. RRP significantly repaired cell morphology, reduced excessive cell proliferation, and ameliorated migration and tube formation activity. In addition, RRP affected the FAK-PI3K/Akt signaling pathway. Importantly, Piezo1 silencing abolished the protective effects of RRP. Conclusion: RRP has anti-atherosclerotic effects and antagonizes endothelial cell damage via modulating the FAK-PI3K/Akt signaling pathway. Piezo1 is a possible target of RRP in the treatment of atherosclerosis. Thus, RRP has promising therapeutic potential and broad application prospect for atherosclerosis.

Study on the Intervention Effects of Pinggan Prescription () on Spontaneously Hypertensive Rats Based on Metabonomic and Pharmacodynamic Methods.

OBJECTIVE: To investigate the effects of Pinggan Prescription (, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic. METHODS: A total of 32 male spontaneously hypertensive rats (SHRs) were randomly divided into two groups by using the random number table method: a treatment group (n=18) and a model group (n=14). The Wistar rats (n=14) were used as the normal group. Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg (PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate (cAMP) and angiotensin II (Ang II) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry (GC-MS). RESULTS: Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP (P<0.01). The pharmacodynamic results illustrated that the content of Ang II increased with the raised blood pressure and the cAMP expressed the converse trend. After curing with PGP, the content of Ang II decreased, the difference between model group and treatment group was significant (P<0.01), and the cAMP expressed the converse trend. Five potential biomarkers were identified, including arachidonic acid, hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown significantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were significantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with the reduced blood pressure. CONCLUSIONS: PGP intervention for hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.

Serum Metabolomics Study Based on LC-MS and Antihypertensive Effect of Uncaria on Spontaneously Hypertensive Rats.

Our previous studies have shown that Uncaria has an important role in lowering blood pressure, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, a combination method of HPLC-TOF/MS-based metabolomics and multivariate statistical analyses was employed to explore the mechanism and evaluate the antihypertensive effect of Uncaria. Serum samples were analyzed and identified by HPLC-TOF/MS, while the acquired data was further processed by partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to discover the perturbed metabolites. A clear cluster among the different groups was obtained, and 7 significantly changed potential biomarkers were screened out. These biomarkers were mainly associated with lipid metabolism (dihydroceramide, ceramide, PC, LysoPC, and TXA2) and vitamin and amino acids metabolism (nicotinamide riboside, 5-HTP). The result indicated that Uncaria could decrease the blood pressure effectively, partially by regulating the above biomarkers and metabolic pathways. Analyzing and verifying the specific biomarkers, further understanding of the therapeutic mechanism and antihypertensive effect of Uncaria was acquired. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine (TCM) in treating hypertension.

Metabolic characteristics of Rhizoma Coptidis intervention in spontaneously hypertensive rats: Insights gained from metabolomics analysis of serum.

The present study aimed to investigate the intervention mechanisms of Rhizoma Coptidis using spontaneously hypertensive rats. A serum metabolomics analysis was performed with high performance liquid chromatography­quadrupole/time of flight mass spectrometer in positive mode. The obtained data were further analyzed by principal component and partial least­squares discriminant analysis to reveal differentiating metabolites. The pattern of metabolites in the serum after Rhizoma Coptidis exhibited distinct alterations. A total of 10 potential biomarkers were significantly altered in the serum and may be associated with the underlying mechanism. Alterations were primarily associated with phospholipid metabolism, fatty acid metabolism, amino acid metabolism and arachidonic acid metabolism. In addition, biochemical alterations in potential biomarkers were associated with inflammation, nitric oxide production, platelet aggregation and endothelial function. By analyzing and verifying the specific biomarkers, metabolomics may be helpful to further understand the underlying therapeutic mechanism of Rhizoma Coptidis. Metabolomics is a powerful tool used to investigate the therapeutic effects of herbal medicine with multiple targets.

A metabolomic study using HPLC-TOF/MS coupled with ingenuity pathway analysis: Intervention effects of Rhizoma Alismatis on spontaneous hypertensive rats.

Rhizoma Alismatis, an important crude herb component in traditional Chinese medicine, has been commonly used for treating hypertension, but its mechanism has not been clarified in level of metabolic. Therefore, in the present work, metabolomics study coupled with ingenuity pathway analysis (IPA) have been performed to explore the potential mechanism in anti-hypertensive effect of Rhizoma Alismatis. Serum samples from SHRs and WKYs were analyzed with the use of high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) in positive polarity. The obtained data sets were statistically analyzed using univariate and multivariate statistical analyses including the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) for pattern recognition and selection of significant metabolites. 12 potential biomarkers in rat serum were screened out from HMDB, METLIN and KEGG databases. Furthermore, IPA was introduced and Glycerophospholipid metabolism and Purine metabolism were filtered out as potential target pathways. This metabolomic approach coupled with IPA provided a feasible way to understand the therapeutic mechanism of Rhizoma Alismatis on spontaneous hypertensive rats.

Enhanced Protective Effect of the Combination of Uncaria and Semen Raphani on Vascular Endothelium in Spontaneously Hypertensive Rats.

Endothelial dysfunction and low-grade inflammation are closely associated with hypertension and other cardiovascular diseases. The combination of Uncaria (U) and Semen Raphani (R) is common in traditional Chinese medicine for the treatment of hypertension and heart diseases. We aimed to investigate the therapeutic effect of the combination of Uncaria and Semen Raphani on spontaneously hypertensive rats (SHRs), and valsartan was used as a positive control. In the present study, all extracts decreased systolic pressure, diastolic pressure, and mean arterial pressure. U alone showed antihypertensive efficacy and effectively decreased CECs count, while R alone showed efficacy in relieving inflammatory level. The combination of U and R showed enhanced effectiveness at lowering activated CECs and improving endothelial integrity of thoracic aorta and mesenteric artery and normalized the level of plasma biomarkers of endothelial damage. The combination of U and R decreased the mRNA level of VCAM-1, Sel-L, TFPI, and Sel-P, while it elevated mRNA expression of FGF-1 and THBD of the thoracic aorta, which may be, at least in part, involved in the mechanism of protective effect on hypertensive endothelial injury.

Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA)-induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani.

Endothelial dysfunction is closely associated with hypertension. Protection of vascular endothelial cell is the key to prevention and treatment of hypertension. Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid, isolated from traditional Chinese medicine Uncaria rbyncbopbylla and Semen Raphani respectively, exhibit properties of anti-hypertension and protection of blood vessels. In the present study, we observed the protective effect of the combined use of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid to the vascular endothelial cell in N'-nitro-L-arginine-induced hypertensive rats and investigate the preliminary mechanism. Blood pressure was detected by non-invasive rats tail method to observe the anti-hypertension effect of drugs. Scanning electron microscopy was used to observe the integrity or shedding state of vascular endothelial cell. The amount of circulating endothelial cells and CD54 and CD62P expression on circulating endothelial cells were tested to evaluate the endothelium function. In this study, we found that the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility can effectively lower the blood pressure, improve the structural integrity of vascular endothelium, and significantly reduce the number of circulating endothelial cells. Furthermore, the mean fluorescence intensity of CD54 and CD62P expressed showed decrease after the intervention of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility. In conclusion, the combination of effective components of the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid demonstrated good antihypertension effect and vascular endothelium protective effect. The preliminary mechanism of the protective effect may attribute to relieve the overall low-grade inflammation.

Serum metabolomics research of the anti-hypertensive effects of Tengfu Jiangya tablet on spontaneously hypertensive rats.

A HPLC/TOF-MS-based metabolomic study was conducted to investigate the holistic therapeutic effects of Tengfu Jiangya Tablet (TJT) on spontaneously hypertensive rats (SHRs). The SHRs were divided into valsartan (VST) group, TJT group and model group, in addition, the Wistar-Kyoto rats (WKY) were taken as normal control. Serum samples were separated and identified by HPLC/TOF-MS, while the obtained data was further processed by partial least-squares discriminant analysis (PLS-DA). A clear cluster among the four groups was observed, and we identified thirteen biomarkers involved involved in sphingolipid metabolism (sphinganine, lysosphingomyelin, ceramide), glycerophospholipid metabolism (phosphatidylcholines, phosphatidylethanolamine, lysophosphatidylcholines), arginine and proline metabolism (l-proline, citrulline), tryptophan metabolism (xanthuiulrenic acid, l-kynurenine, l-tryptophan), arachidonic acid metabolism(leukotriene D4), and linoleic acid metabolism (gamma-linolenic acid). Altered metabolic pathways involved in impaired NO production, inflammation and vascular smooth muscle cells (VSMCs) apoptosis and proliferation, which suggesting the possible pathological state in SHRs. TJT as well as VST altered the metabolic state, suggesting a possible anti-hypertension role by improving NO production, and an extra cardiovascular protection role possibly by amelioration of inflammatory state and vascular remodeling.

Efficacy of Chinese herbal medicine on health-related quality of life (SF-36) in hypertensive patients: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study aims to evaluate published randomized controlled trials (RCTs) of Chinese Herbal Medicine (CHM) improving health-related quality of life (HRQL) in hypertensive patients that employ the Short-Form 36-Item Health questionnaire (SF-36) as an outcome measure. METHODS: Five electronic databases were searched up to October 2013 to identify RCTs of CHM for hypertension. The primary outcome was SF-36. Trial selection, data extraction, methodological quality assessment, and data analyses were conducted according to the Cochrane handbook. RESULTS: Eleven RCTs with total of 1043 participants were identified. The majority of the included trials were assessed to be of poor methodological quality and high clinical heterogeneity. Meta-analysis shows a significant improvement both in physical component summary (PCS) measure and mental component summary (MCS) measure of SF-36, with physical functioning (WMD=8.54[5.34, 11.74], p<0.001), role physical (WMD=13.32[7.03, 19.61], p<0.001), bodily pain (WMD=10.53[6.46, 14.60], p<0.001), general health (WMD=-5.56[2.09, 9.02], p<0.001), vitality (WMD=6.84[4.33, 9.53], p<0.001), social functioning (WMD=7.50[2.63, 12.36], p<0.001), role emotional (WMD=12.06[4.45, 19.68], p<0.001) and mental health (WMD=-5.68[2.90, 8.47], p<0.001). CHM can also decrease systolic blood pressure (WMD=-4.45 [-6.71, -2.19], p<0.001) and relieve symptoms related to hypertension. CONCLUSIONS: CHM appears to have beneficial effects on improvement of HRQL in hypertensive patients. However, the findings should be interpreted with caution due to the poor methodological quality and high clinical heterogeneity of the included trials. Further clinical trials should be carried out to provide more reliable evidence.

[Intervention effects of qingre jiangya capsule on brain hippocampus of spontaneously hypertensive rats based on metabonomic research].

Thirty SHRs were obtained randomly to hypertension, model group, captopril group and Qingre jiangya capsule group. Ten Wistar rats were used as control group. The hippocampus tissue was removed to explore the damage of spontaneously hypertensive rats (SHR) and the protective effect of Qingre jiangya capsule after continuously administered for 14 days. And then the data were processed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The research results revealed captopril group was significantly different from the other three groups. The classification of other three groups is also very clear after captopril group removed. This suggested that Qingre jiangya capsule could improve the overall metabolism compared with captopril. Four metabolites were identified: dimethylglycine, glycerophosphocholine, aldosterone and noradrenaline. Hypertension hippocampus damage may mainly be expressed in tyrosine metabolism, aldosterone-regulated sodium, vascular smooth muscle contraction reabsorption, and Qingre jiangya capsule could reverse the hippocampus tissue damage of SHR.