Diverse prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with anti-inflammatory and antiviral activities.

Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.

Protection of Oxygen Glucose Deprivation-Induced Human Brain Vascular Pericyte Injury: Beneficial Effects of Bellidifolin in Cellular Pyroptosis.

Pericytes play critical roles in the maintenance of brain vascular homeostasis. However, very little is currently known about how pericytes regulate ischemic stroke-induced brain injury. Inflammation is a key event in the pathobiology of stroke, in which the nod-like receptor protein-3 (NLRP3) inflammasome is involved in, triggering sterile inflammatory responses and pyroptosis. In the current study, an immortalized cell line derived from human brain vascular pericytes (HBVPs) was constructed, and it showed that HBVPs challenged with oxygen glucose deprivation (OGD) displays pronounced cellular excretion of LDH, IL-1ß, IL-18 and increased PI positive staining. Mechanistically, upon OGD treatment, NLRP3 forms an inflammasome with its adaptor protein apoptosis-associated speck-like protein, containing a caspase recruitment domain (ASC) and caspase-1, manifested as much more co-stainings of NLRP3, ASC and Caspase-1 in HBVPs, accompanied by the increased protein levels of NLRP3, ASC, caspase-1 as well as the pyroptosis-associated protein gasdermin D (GSDMD). Intriguingly, GSDMD-N shuttled to the mitochondrial membrane triggered by OGD exposure, which promoted massive mitochondria-derived ROS generation. Importantly, the invention value of the specific targets was evaluated by treatment with bellidifolin, a kind of ketone compound derived from Swertia chirayita in traditional Tibetan medicine. It showed that bellidifolin exerts beneficial effects and attenuates the formation of NLRP3/ASC/Caspase-1 complex, thereby impeding GSDMD-N shuttling and resultant ROS generation, protecting against OGD-induced HBVPs pyroptosis. Overall, these findings unravel the potential mechanisms of pericyte injury induced by OGD and indicate that bellidifolin may exert its beneficial effects on pyroptosis, thus providing new therapeutic insights into stroke.

[Stable angina pectoris of coronary heart disease treated with different acupuncture and moxibustion therapies: a network Meta-analysis].

To compare the clinical efficacy among different acupuncture and moxibustion therapies on stable angina pectoris (SAP) of coronary heart disease by means of network Meta-analysis. The articles of randomized controlled trial (RCT) for SAP of coronary heart disease treated with acupuncture and moxibustion therapies were searched from PubMed, Web of Science, Cochrane Library, CNKI, Wanfang database and VIP database from May 1, 2002 to May 1, 2022. The quality of them was assessed with the risk of bias assessment tool of Cochrane 5.3, and the network Meta-analysis was undertaken with Stata 13.1 software. A total of 29 articles were included with the acupuncture and moxibustion therapies involved, e.g. acupuncture, acupoint application and moxibustion. In comparison with the simple routine western medication, the effective rate was better on SAP treated with the combined treatments, in which, acupoint application, moxibustion, acupuncture and intradermal needling were combined with routine western medication (P<0.05). Of those combined treatments, the combination of the acupoint application with routine western medication had high probability, suggesting the optimal regimen (area under the curve [SUCRA]=0.711, P<0.05). The effective rate of acupuncture combined with routine western medication for ECG improvement was better than that of routine western medication (P<0.05), and such combined treatment was high in probability, underlying its optimal treatment (SUCRA=0.800, P<0.05). Combined with routine western medication, acupuncture, acupoint application, moxibustion and intradermal needling all improve the clinical efficacy on SAP of coronary heart disease. But, with different outcomes considered, the optimal treatments may be different. It needs more multi-central and large-sample randomized controlled trials to validate these results.

Ethanolic extract of root from Arctium lappa L ameliorates obesity and hepatic steatosis in rats by regulating the AMPK/ACC/CPT-1 pathway.

Burdock (Arctium lappa L) root is eaten as a vegetable in many countries and used as an ethnomedicine because of its various pharmacological effects. The objective of this study was to investigate the underlying mechanisms of ethanolic extract of root from Arctium lappa L root (ALE) to lose weight and regulate lipid metabolism. The results showed that ALE can regulate lipid metabolism level and inhibit the weight gain of rats induced by the high-sugar and high-fat diet. The contents of triglyceride and cholesterol in the liver of obese rats significantly reduced, and hepatic steatosis was ameliorated. In addition, this study identified that ALE enhanced hepatic fatty acid ß-oxidation and ameliorated hepatic steatosis by activating AMPK/ACC/CPT-1 pathway. These results indicated that ALE has a potential preventive and therapeutic effect on metabolic-associated fatty liver disease and obesity. PRACTICAL APPLICATIONS: Obesity is already a global health problem. Obesity causes accumulation of triglycerides, which leads to hepatic steatosis. Long-term steatosis causes liver damage and metabolic fatty liver disease. Plant-derived functional foods or herbal medicines have better effects on weight loss and liver protection, which are more conducive to long-term use with less toxic side effects. As a medicinal and edible plant material, Arctium lappa L root has the effect in losing weight. Our study showed that ethanolic extract of Arctium lappa L root effectively regulates lipid metabolism and inhibits hepatic steatosis. Arctium lappa L root may be used as a therapeutic drug and functional food raw material for obesity and fatty liver disease.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Antidiarrheal effect of the ethanol extract from Scutellaria barbata and its effect on the contraction of jejunum smooth muscles.

Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.

A Novel Biocompatible Herbal Extract-Loaded Hydrogel for Acne Treatment and Repair.

A novel herbal extract-loaded gel containing several biofunctional extracts, including green tea, Zingiber officinale Rosc, Phyllanthus emblica, and salicylic acid, was developed for acne vulgaris. These natural raw materials were blended with suitable dosages of gelatin and carboxymethyl cellulose (CMC) to produce a biocompatible herbal gel. The physical chemistry properties of the hydrogel were determined by Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), rheometry, and scanning electron microscopy (SEM), and the hydrogel showed good mechanical and morphological characteristics. The herbal extract-loaded hydrogel mimicked extracellular matrix properties and showed good antioxidant and anti-inflammatory properties and various advantages, serving as a potential wound dressing material because of its high moisture retention ability, wound exudate absorption behavior, and biocompatibility. It exhibited moderate-high antioxidative and anti-inflammatory qualities that were important for dermis wound closure. The clinical trial results showed that most patients experienced moderate to high healing rates, and four of twenty-four individuals (16.67%) had recovery area ratios greater than 80%. This herbal extract-loaded hydrogel has effective ingredients and excellent mechanical properties as a bioactive dressing agent for acne treatment.

Specialised metabolites as chemotaxonomic markers of Coptosapelta diffusa, supporting its delimitation as sisterhood phylogenetic relationships with Rubioideae.

From the aerial extracts of Coptosapelta diffusa (Champ. ex Benth.) Steenis, twenty-one compounds were isolated and identified by means of column chromatography and NMR and MS techniques, respectively. Amongst, ten ones were determined to be undescribed compounds including six seco-iridoid glucosides (1-6), 2-(hydroxymethyl)-1,2,3,4-tetrahydroanthracene-9,10-dione (7) and three guaiane-type sesquiterpenes (15-17). Compounds 7, 8 and 9 exhibited inhibitory activities against Staphylococcus aureus ATCC25923 with MIC of 8, 4 and 8 µg/mL. The use of 1-6 (iridoids), 7-14 (anthraquinones) and 15-17 (sesquiterpenes) as chemotaxonomic markers for this species was evidenced. Structurally, 7-14 are similar to those anthraquinones isolated from other species of the family Rubiaceae, confirming their close phylogenetic relationship. Whereas, these iridoids and sesquiterpenes with unique structures provided chemotaxonomic evidence to support the genus Coptosapelta (the tribe Coptosapelteae) as a sister of the subfamily Rubioideae. These results contrast with the general producing tendency of indole alkaloids by the species of the subfamily Cinchonoideae, and merit chemotaxonomic significance for the delimitation of Coptosapelta.

[Variation analysis of genomic methylation induced by high temperature stress in Pinellia ternata].

Pinellia ternata belongs to the Araceae family and is a medicinal herb. The tuber is the medicinal organ with antitussive, antiemetic and anti-tumor activities. It is easy to encounter high temperature environment during the growth periods, leading to decrease of tuber production. At present, the mechanism of response to high temperature stress in P. ternata is still unknown. DNA methylation plays a vital role in plant protection against adversity stress as a way of epigenetic regulation. In this study, P. ternata was used as material for treatment of high temperature stress at 0 h, 6 h and 80 h, and methylation sensitive amplification polymorphism(MSAP) analysis was conducted on the changes of DNA methylation in its genome. The results showed that 20 pairs of MSAP primers were selected from 100 MSAP primers with multiple clear and uniform bands, and 353, 355 and 342 loci were amplified from materials of P. ternata treated in the high temperature stress 0 h, 6 h and 80 h, respectively. Cytosine methylation levels of CCGG context in the above materials were characterized as 60.91%, 44.79% and 44.74%, respectively. And the full methylation ratios were 16.71%, 22.25% and 29.24, respectively. It demonstrated that high temperature stress significantly induced the down-regulation of DNA methylation level and up-regulation of the full methylation rate in P. ternata genome. This study provides a preliminary theoretical reference for analyzing the mechanism of P. ternata responding to high temperature stress from the epigenetic perspective.

In silico identification of EP400 and TIA1 as critical transcription factors involved in human hepatocellular carcinoma relapse.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality worldwide. Transcription factors (TFs) are crucial proteins that regulate gene expression during cancer progression; however, the roles of TFs in HCC relapse remain unclear. To identify the TFs that drive HCC relapse, the present study constructed co-expression network and identified the Tan module the most relevant to HCC relapse. Numerous hub TFs (highly connected) were subsequently obtained from the Tan module according to the intra-module connectivity and the protein-protein interaction network connectivity. Next, E1A-binding protein p400 (EP400) and TIA1 cytotoxic granule associated RNA binding protein (TIA1) were identified as hub TFs differentially connected between the relapsed and non-relapsed subnetworks. In addition, zinc finger protein 143 (ZNF143) and Yin Yang 1 (YY1) were also identified by using the plugin iRegulon in Cytoscape as master upstream regulatory elements, which could potentially regulate expression of the genes and TFs of the Tan module, respectively. The Kaplan-Meier (KM) curves obtained from KMplot and Gene Expression Profiling Interactive Analysis tools confirmed that the high expression of EP400 and TIA1 were significantly associated with shorter relapse-free survival and disease-free survival of patients with HCC. Furthermore, the KM curves from the UALCAN database demonstrated that high EP400 expression significantly reduced the overall survival of patients with HCC. EP400 and TIA1 may therefore serve as potential prognostic and therapeutic biomarkers.

Naturally occurring nanotube with surface modification as biocompatible, target-specific nanocarrier for cancer phototherapy.

Phototherapy has drawn increasing attention including the use of nanocarriers with high drug loading capacity and delivery efficacy for target-specific therapy. We have made use of naturally-occurring halloysite nanotubes (HNTs) to build a biomimetic nanocarrier platform for target-specific delivery of phototherapeutic agents. The HNTs were decorated with poly(sodium-p-styrenesulfonate) (PSS) to enhance the biocompatibility, and were further functionalized by lumen loading the type-II photosensitizer indocyanine green (ICG). The HNT-PSS-ICG nanocarrier, without further tethering targeting groups, was shown to associate with the membrane of giant unilamellar vesicles (GUVs) via Pickering effects. Application of HNT-PSS-ICG nanocarrier to human breast cancer cells gave rise to a cell mortality as high as 95%. The HNT-PSS-ICG nanocarrier was further coated with MDA-MB-436 cell membranes to endow it with targeting therapy performance against breast cancer, which was confirmed by in vivo experiments using breast cancer tumors in mice. The membrane-coated and biocompatible nanocarrier preferentially concentrated in the tumor tissue, and efficiently decreased the tumor volume by a combination of photodynamic and photothermal effects upon near-infrared light exposure. Our results demonstrate that the HNT-based nanocarrier by virtue of facial preparation and high loading capacity can be a promising candidate for membrane-targeting nanocarriers.

Coffee and tea consumption and the risk for subarachnoid hemorrhage: A meta-analysis.

OBJECTIVES: Reports on the association between coffee or tea consumption and subarachnoid hemorrhage (SAH) risk are inconsistent. The aim of this study was to determine if an association exists between consumption of coffee or tea and the risk for SAH. METHODS: A random-effects model was used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity among studies was assessed using the statistics Cochran's Q and I2. Seven studies on coffee consumption and five on tea consumption were included in the meta-analysis. RESULTS: The pooled RRs of SAH for the highest versus the lowest categories of coffee and tea consumption were 1.31 (95% CI, 0.84-2.05) and 0.83 (95% CI, 0.65-1.08), respectively. There was evidence of heterogeneity among studies of coffee consumption (Pheterogeneity = 0.002, I2 = 71.7%) but not among studies of tea consumption (Pheterogeneity = 0.34, I2 = 11.3%). Omitting one study that substantially contributed to the heterogeneity among studies of coffee consumption yielded a pooled RR of 1.51 (95% CI, 1.10-2.06). Dose-response analysis showed that the summary RRs of SAH for an increase of one cup of coffee and tea consumption per day were 1.00 (95% CI, 0.96-1.04) and 0.97 (95% CI, 0.85-1.11), respectively. There was no evidence of publication bias. CONCLUSION: Our meta-analysis of current evidence does not support an association between the consumption of coffee or tea and SAH risk. Further studies with prospective designs that control for important confounders and provide sufficient data for dose-response analysis are warranted.

Traditional Chinese medicine Qiliqiangxin attenuates phenylephrine-induced cardiac hypertrophy via upregulating PPARγ and PGC-1α.

BACKGROUND: Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown. METHODS: The effects of QLQX were investigated based on PE induced cardiac hypertrophy mouse models. Echocardiography and hematoxylin-eosin (HE) staining were used to determine cardiac function and cross-sectional area, respectively. Quantitative real time PCR (qRT-PCR) was used to determine ANP and BNP expressions. Based on primary neonatal rat ventricular cardiomyocytes (NRVMs) treated with PE, the cell size and expressions of ANP and BNP were determined by immunofluorescent staining and qRT-PCR, respectively. In addition, western blot was used to determine PPARγ and PGC-1α expressions. RESULTS: In present study, we confirmed that QLQX could significantly attenuate cardiac hypertrophy in mice treated with PE. Then we showed that PPARγ and PGC-1α were downregulated in PE-induced cardiac hypertrophy, and QLQX could block the decrease of PPARγ and PGC-1α both in vitro and in vivo. Importantly, we found that PPARγ inhibitors or PGC-1α siRNAs eliminated the protective effects of QLQX on PE-induced cardiac hypertrophy. CONCLUSIONS: Our study suggested that QLQX prevents from PE-induced cardiac hypertrophy by activating PPARγ and its coactivator PGC-1α.

Vx3-Functionalized Alumina Nanoparticles Assisted Enrichment of Ubiquitinated Proteins from Cancer Cells for Enhanced Cancer Immunotherapy.

A simple and effective strategy was developed to enrich ubiquitinated proteins (UPs) from cancer cell lysate using the α-Al2O3 nanoparticles covalently linked with ubiquitin binding protein (Vx3) (denoted as α-Al2O3-Vx3) via a chemical linker. The functionalized α-Al2O3-Vx3 showed long-term stability and high efficiency for the enrichment of UPs from cancer cell lysates. Flow cytometry analysis results indicated dendritic cells (DCs) could more effectively phagocytize the covalently linked α-Al2O3-Vx3-UPs than the physical mixture of α-Al2O3 and Vx3-UPs (α-Al2O3/Vx3-UPs). Laser confocal microscopy images revealed that α-Al2O3-Vx3-UPs localized within the autophagosome of DCs, which then cross-presented α-Al2O3-Vx3-UPs to CD8+ T cells in an autophagosome-related cross-presentation pathway. Furthermore, α-Al2O3-Vx3-UPs enhanced more potent antitumor immune response and antitumor efficacy than α-Al2O3/cell lysate or α-Al2O3/Vx3-UPs. This work highlights the potential of using the Vx3 covalently linked α-Al2O3 as a simple and effective platform to enrich UPs from cancer cells for the development of highly efficient therapeutic cancer vaccines.

Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose adefovir dipivoxil.

OBJECTIVE: To investigate the predictors of hypophosphatemic osteomalacia induced by adefovir dipivoxil (ADV) and to monitor for early detection. PATIENTS AND METHODS: Hospitalized patients who were diagnosed with ADV-related hypo-phosphatemic osteomalacia were recruited and retrospectively analyzed in our hospital from January 2012 to December 2016. A telephone interview was conducted at 1, 3, 6, 9, 12, and 24 months after cessation of ADV. RESULTS: In the 8 patients enrolled in the study, the hypophosphatemic osteomalacia symptoms developed at an average of 5.14 (4-7) years since ADV treatment (10 mg/d). The average alkaline phosphatase (ALP) level was 279.50 (137-548) U/L, which was significantly higher than the normal level (45-125 U/L). The serum phosphorus level was an average of 0.59 (0.43-0.69) mmol/L, which was lower than the normal range (2.06-2.60 mmol/L). Serum calcium levels of the enrolled patients remained within normal limits. Reduced estimated glomerular filtration rate (eGFR <29 mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly progressive systemic bone and joint pain, frequent fractures, trouble in walking, height reduction (4-6 cm), and so on. After cessation of ADV, symptoms like bone pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months after the withdrawal of ADV. However, in 4 patients, renal function failed to return to normal in 24 months. CONCLUSION: More attention should be paid to the duration of ADV treatment. The level of serum phosphorus and ALP, as well as renal function, should be monitored for early detection of potential adverse drug reactions.

Metabolic benefits of rivaroxaban in non-valvular atrial fibrillation patients after radiofrequency catheter ablation.

BACKGROUND AND OBJECTIVE: Rivaroxaban is a new oral anticoagulant for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), which has less drug-food interaction than warfarin. We conducted this prospective randomized study to evaluate the metabolic benefits as well as the safety and efficacy with rivaroxaban versus warfarin in patients with NVAF following radiofrequency catheter ablation (RFCA). METHODS: From April to July 2014, 60 patients with NVAF undergoing RFCA were prospectively enrolled in our study. Following RFCA, all patients were randomly assigned to receive rivaroxaban (Group R, n=30) or warfarin (Group W, n=30). Metabolic indices including serum total protein, albumin, globulin, and high-density lipoprotein (HDL) as well as bleeding, stroke, and systemic thromboembolism events were evaluated and compared during follow-up after 15, 30, 60, and 90 d of RFCA procedure. RESULTS: Serum total protein, albumin, globulin, and HDL levels were all significantly elevated at each follow-up stage in Group R when compared to the baseline (P<0.05 respectively). In Group W, the metabolic indices decreased at first and then had an increasing trend. There were no deaths or thromboembolic complications in each group. The prevalence of total bleeding complications was similar between Group R and Group W (11/30, 36.7% vs. 10/30, 33.3%, P=0.79). CONCLUSIONS: Patients with NVAF receiving rivaroxaban after RFCA procedures appear to benefit from a metabolic perspective compared with warfarin, providing practical clinical reference for the choice of the anticoagulant. Rivaroxaban seems to be as safe and effective in preventing thromboembolic events as warfarin for these patients.

[Triterpenoids from roots of Rosa laevigata].

To study the triterpenoids from the roots of Rosa laevigata. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity, chemical and spectroscopy methods were used to determine their structures. 12 constituents were isolated and identified as(2R, 19R)methyl 2-acetyloxy-19- hydroxyl-3-oxo-urs-12-en-28-carboxylate(1), pomonic acid (2), 18, 19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11, 13(18)-dien-28-oic acid(3), swinhoeic acid (4), myrianthic acid(5), 2α, 3ß, 19α-trihydroxy-24-oxo-urs-12-en-oic acid (6), tormentic acid(7), arjunic acid (8), 1ß-hydroxyeuscaphic acid(9), quadranoside Ⅷ (10), alpinoside(11), rubuside B (12). Compounds 1-4, 6, 9, 11-12 were obtained from this plant for the first time. Compounds 2-4, 6, 11-12 were obtained from the genus Rosa for the first time.

[Pharmacokinetic effect of combined administration on spinosin and ferulic acid in monarch drug Ziziphi Spinosae Semen kernel].

To study the pharmacokinetic effect of different combined administration with monarch drug Ziziphi Spinosae Semen on its main components in rats. Sprague-Dawley (SD) rats were randomly divided into Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi spinosae Semen-Salviae Miltiorrhize Radix et Rhizoma group and Zaoren Ansheng prescription group. After oral administration, HPLC was eluted with the mobile phase of acetonitrle-0.03% phosphate acid water in a gradient mode. The detection wavelength was 280 nm. The pharmacokinetic parameters of spinosin and ferulic acid were calculated by DAS 2. 0 software. Compared with Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi Spinosae Semen-Salviae miltiorrhizae Radix et Rhizoma group showed a lower maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but higher clearance speed (CL/F); whereas the Zaoren Ansheng prescription group showed higher maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but lower clearance speed (CL/F). Compared with Ziziphi Spinosae Semen group, prescription group showed slower metabolism of spinosin and ferulic

[Protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats].

OBJECTIVE: To investigate the protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats under constant pressure and closed conditions. METHOD: The PESI dosage-dependent experiment for hypoxia rats was conducted under constant pressure and closed conditions by intraperitoneally injecting 125, 250, 500 mg x kg(-1) to finalize that the optimum dosage is the high dose of PESI. Afterwards, 90 Wistar rats were randomly divided into the hypoxic model group, the acetazolamide 250 mg x kg(-1) group and the PESI high dose group. Each group was further divided into three subgroups according to different hypoxia times, with 10 rats in each subgroup. Under the same hypoxia and administration conditions, the rats were sacrificed after 0, 3, 6 h respectively. Their brain samples were collected for common pathological observation and immunohistochemical staining of HIF-1alpha. Real-time RT-PCR was used to detect HIF-1alpha, EPO, HO-1 and Caspase-3 gene expressions. And the Western blot assay was adopted to detect HIF-1alpha protein expression. RESULT: The brain tissues of the hypoxia model group were severely damaged with the increase in the hypoxia time. The acetazolamide group and the PESI high does group were damaged in a much lower degree. According to the gene expression and the Western blot assay, high dose of PESI could inhibit HIF-1alpha expression. According to the pure gene expression test, high dose of PESI could increase EPO and HO-1 mRNA expressions, but inhibit Caspase-3 mRNA expression. CONCLUSION: PESI's protective mechanism for brain tissues of hypoxia rats under constant pressure and closed conditions may be related to its effects in inhibiting HIF-1alpha expression, increasing EPO expression and resisting cell apoptosis.

[Effect of ethanol extract from Saussurea involucrata on biochemical indicators of simulated high-altitude hypoxia induced mice].

OBJECTIVE: To estimate the effect of ethanol extract from Saussurea involucrata (EES) on biochemical indicators of simulated high-altitude hypoxia induced mice and its mechanism. METHODS: The oxidative stress indicator( MDA content, SOD activity) and metabolism parameters (LD content, LDH activity, ATP content, Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity) in both brain and heart of the simulated high-altitude hypoxia induced mice were detected. RESULTS: Compared with the model group, the ESS group could significantly increase the activity of SOD and LDH and decrease the content of MDA and LD in both brain and heart, the content of ATP and the activity of Na+ -K -ATPase and Ca2+ -Mg2+ -ATPase were also elevated. CONCLUSION: The results demonstrate that EES can increase the antioxidant ability, decrease the injury of free radical and ease the disfunction of energy metabolism caused by hypoxia.