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Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.
Subject(s)
Animals , Alkaloids , Arthropods , Chilopoda , QuinolinesABSTRACT
Objective:In this paper,the network pharmacology method was used to explore the material basis and the mechanism of Magnoliae Officinalis Cortex(Houpo) on depressive disorder. Method:Firstly,the main chemical components of Houpo were gathered from CNKI,SciFinder,traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) and other databases.Next,the potential targets of the chemical ingredients in Houpo were searched and selected by BATMAN-TCM database.The targets of depressive disorder were collected from HPO database.Then all the targets were entered into the search tool(String database) for the retrieval of protein-protein interactions so as to confirm antidepressant chemistries and their related targets.Furthermore,the functional enrichment analysis was carried out through the David database.Based on these above results,the networks of "drug targets-disease targets" and "compounds-targets-pathways" of Houpo on depressive disorder were built by Cytoscape v3.5.1 software,respectively.Network topology analysis was used to screen the key targets and the corresponding components.Then molecular docking verification of "component-target proteins" was further conducted. Result:A total of 16 active compounds involving in 74 key targets for depressive disorder were selected and confirmed from 138 chemical components of Houpo.Molecular docking analysis showed that compared with other components,ten volatile components in the 16 active compounds had good binding activities with the top 5 key targets[the top 5 of degree value,including insulin receptor(INS),mitogen-activated protein kinase 1(MAPK1),guanine nucleotide binding protein alpha inhibition 3(GNAI3),phosphatidylinositol 3-kinase receptor 1(PIK3R1) and selective receptor B1(GNB1)] and the 3 direct acting targets of popular drugs for depression[muscarinic acetylcholine receptor M2(CHRM2),5-hydroxytryptamine receptor(HTR)2B and HTR2C].The functional enrichment analysis showed the antidepressant mechanism of Houpo mainly involved neurotrophin signaling pathway,MAPK signaling pathway,calcium signaling pathway and neuroactive ligand-receptor interaction,etc. Conclusion:This study reveals the active ingredients and the mechanism of anti-depression of Houpo based on network pharmacology,a total of 16 key active ingredients related to anti-depression are selected.This paper can provide references for development of antidepressants and the discovery of quality markers of Houpo for anti-depression.
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Objective: To analysis and identify the chemical components in Trichosanthis Fructus by UPLC-LTQ-Orbitrap-MS. Method: Samples of Trichosanthis Fructus were extracted by ultrasonic with 70% methanol after smashing and sifting by 40 mesh sieve. Thermo ScientificTM DionexTM UltiMateTM 3000 Rapid Separation LC system performed UPLC separations with Waters HSS T3-C18(2.1 mm×100 mm,1.8 μm) column. The mobile phase was 0.1% formic acid water(A)-methanol(B) with a gradient elution. The volume flow was 0.3 mL ·min-1. A Thermo ScientificTM LTQ-Orbitrap mass spectrometer equipped with a ESI probe was employed. The samples were respectively scanned in MS1 and MS2 mode of positive and negative ions. According to the chromatographic peak separation,mass signal intensity,and the number of molecular ions in MS1 model,the extraction condition,chromatogram and mass spectrum parameters were optimized. The chemical compounds were identified by the accurate mass measurement of molecular ions and fragment ion and comparation with reference substance. Result: 91 chemical compositions in Trichosanthis Fructus were totally identified,including 14 amino acids,5 monoterpenoids,5 tetracyclic triterpenoids,1 pentacyclic triterpene,14 flavonoids, 17 organic acids,3 polysaccharides,7 nucleotides,7 alkaloids and nitrogen compounds,2 volatile components,1 phytosterol,5 other compositions. Conclusion: The established UPLC-LTQ-Orbitrap-MS method can be used to quickly analyze and identify the main chemical constituents of Trichosanthis Fructus. The chemical information concerning the constituents in Trichosanthis Fructus could be helpful to the quality control and further studies of Trichosanthis Fructus.
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AIM:To explore the effect of sex on the formation of chronic pancreatitis(CP)by comparing the differences in L-arginine-induced CP model between male and female mice.METHODS:Male(n=42)and female(n=42)Kunming mice were randomly divided into 4 groups:female control group, female CP group, male control group and male CP group(n=18 in each control group, n =6 at each time point; n=24 in each CP group, n=8 at each time point).The mice in CP groups were intraperitoneally injected with 20%L-arginine(3 g/kg,twice/d,1 d/week).After modeling for 2 weeks,4 weeks and 6 weeks,the mice were anesthetized and sacrificed.The morphological changes and the degree of fibrosis in the pancreas were observed by HE and Masson staining.The positive expression rate of F4/80 in the pancreatic tissues was observed by the method of immunohistochemistry.The mRNA expression of interleukin-6(IL-6), α-smooth muscle actin(α-SMA)and fibronectin(FN)in the pancreas were detected by real-time PCR.The protein of pancreas was extracted to detect the expression of α-SMA and FN by Western blot.RESULTS:At 2 weeks,4 weeks and 6 weeks after intraperitoneal injection of L-arginine, the pancreatic tissues were obviously injured and exhibited different degrees of fibrosis in female and male CP groups.At the same time,there were significant differences in the degree of pan-creatic injury between male and female mice,and the degree of pancreatic lesion in the male mice was significantly more severe.The positive rate of F4/80 in the pancreas of male CP mice was significantly higher than that in female CP group at the same time point after modeling.At every time point, the mRNA expression of IL-6 in the pancreas was increased in both female and male CP groups,but that in male CP group was higher(P<0.05).The fibrosis indexes,α-SMA and FN, were both highly expressed at mRNA and protein levels after modeling, but compared with the female group, the time of positive expression in male mice was earlier and the expression level was higher(P<0.05).CONCLUSION: The CP model is successfully established by intraperitoneal injection of 20%L-arginine,and a difference in the degree of pathologic alteration in pancreas between male and female mice exists.CP is more effectively induced by L-arginine in male mice,and the degree of fibrosis is more pronounced.The reason may be related to the sensitivity of male mice to L-arginine,causing more serious inflammatory response.Therefore,male mice are more suitable for establishing CP animal model.
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This study was undertaken to explore the myocardioprotective effects of the combination of ischemic preconditioning (IP) with hypothermia and St.II Thomas crystalloid cardioplegic solution (CCS) on immature hearts in the rabbit. Isolated immature rabbit hearts were perfused with Krebs-Henseleit bicarbonate buffer on Langendorff apparatus. In experiment 1, 24 hearts were divided into 4 groups (n=6 in each group): Con, IP1, IP2 and IP3 group. Hearts of the four groups underwent 0, 1, 2 or 3 cycles of IP respectively. Then all the hearts were subjected to a sustained ischemia period of 2 h at 20 degrees C and a postischemic reperfusion period of 30 min at 37 degrees C. In experiment 2, 48 hearts were divided into 6 groups (n=8 in each group): SCon1, SIP1, SCon2, SIP2, SCon3 and SIP3 group, according to hypothermia and the duration of sustained ischemia (30 min at 32 degrees C; 90 min at 25 degrees C, 2 h at 20 degrees C). The SIP1, SIP2 and SIP3 groups were preconditioned twice before the sustained hypothermic ischemia, while the SCon1, SCon2 and SCon3 groups were not preconditioned. CCS was applied during sustained ischemia, all the hearts were reperfused for 30 min at 37 degrees C. Heart rate (HR), left ventricular developed pressure (LVDP) and peak rate of increase or decrease of left ventricular pressure (+/-dp/dt(max)) were recorded. Tissue concentration of adenosine triphosphate (ATP), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. At the end of reperfusion, values of product of LVDP and HR, +/-dp/dt(max) in IP2 group were 96%+/-21%, 101%+/-19% and 84% +/-15% of the baseline values respectively, which were significantly higher than those of Con group and IP3 group (P<0.01, P<0.05); also, the ATP content of IP2 group was higher than that of the Con group (P<0.01). When CCS was applied during sustained period of hypothermic ischemia at 32 degrees C or 25 degrees C, recovery rates of RPP (rate product, =LVDPxHR) and +dp/dt(max) in SIP1 group were 87% +/-14% or 99% +/-26% of the baseline values respectively (P<0.05, vs SCon1 group), the values in SIP2 group changed to 87% +/-16% or 102% +/-20% respectively (P<0.05, vs SCon2 group). Contents of ATP in SIP1 and SIP2 groups were significantly higher than those of SCon1 or SCon2 groups respectively (P<0.05), but MDA content of the two groups were significantly lower than those of SCon1 or SCon2 groups (P<0.05) respectively. The study indicates that IP attenuates hypothermic ischemia/reperfusion injury to immature rabbit hearts under 20 degrees C ischemia, two cycles of IP showing better myocardioprotective effects than 1 or 3 cycles of IP. When IP was combined with CCS which were applied during hypothermic ischemia period, the beneficial effects of IP were weakened as the temperature during the hypothermic period was elevated.
Subject(s)
Animals , Female , Male , Rabbits , Animals, Newborn , Cardioplegic Solutions , Pharmacology , Hypothermia, Induced , In Vitro Techniques , Ischemic Preconditioning, Myocardial , Methods , Isotonic Solutions , Pharmacology , Myocardial Reperfusion InjuryABSTRACT
<p><b>AIM</b>To study effects of ischemic preconditioning on the hypothermic ischemia/reperfusion injury of immature rabbit hearts.</p><p><b>METHODS</b>The isolated immature rabbit (3-4 weeks) hearts were perfused on Langendorff apparatus. After 30 min perfusing with 37 degrees C K-H perfusate, the hearts in part one were yielded 0, 1, 2 or 3 times of IP respectively before 120 min ischemia at 20 degrees C hypothermia, and the hearts in part two were yielded 0 or 2 times of IP before being arrested by infusion of St. Thomas II crystalloid cardioplegic solution, then the arrested hearts were yielded ischemia for 30, 90 or 120 min at 32 degrees C, 25 degrees C and 2 degrees C hypothermia respectively. Then all the hearts were reperfused for 30 min at 37 degrees C normothermia. Heart rate (HR), left ventricular developed pressure (LVDP), +/- dp/dt(max) were recorded at baseline, preischemic and 1, 3, 5, 10, 20, 30 min after reperfusion. Also contents of ATP and MDA and activity of SOD and Ca(2+) -ATPase of myocardium were measured.</p><p><b>RESULTS</b>At the end of reperfusion, the recovery rate of left ventricular function in IP2 group were significantly higher than that of control group and IP3 group (P < 0.01, P < 0.05), also the IP2 group showed a higher content of ATP and activity of Ca(2+) -ATPase than control group and IP3 group (P < 0.01, P < 0.05). When the ischemic hearts were at different hypothermia accompanied with CCS, the recovery rate of left ventricular function and contents of ATP in SIP1 and SIP2 group were significantly higher than that of SCon 1 group and SCon 2 group respectively (P < 0.01, P < 0.05), the contents of MDA in the two IP groups were lower than that of the two control groups.</p><p><b>CONCLUSION</b>IP can attenuate the hypothermic ischemia/reperfusion injury of immature rabbit hearts, the cardioprotective effects are dependent on the mode of IP and the possible mechanisms may involve the following aspects: decrease the consumption of ATP, inhibit lipid peroxidation and maintain the activity of Ca(2+) -ATPase of cardiac myocyte.</p>