Structural identification of the related substances in phloroglucinol injection by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry / 药学学报

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.

Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures / 中国中药杂志

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Cloning and characterization of phloroglucinol biosynthetic gene phlC from an Indian strain of Pseudomonas fluorescens

Phloroglucinol or 2,4-diacetyl phloroglucinol (DAPG) is a polyketide compound produced by gram negative soil bacteria Pseudomonas. It shows broad spectrum antibacterial and antifungal properties against soil-borne plant pathogens. In Pseudomonas spp., genes for biosynthesis of 2,4-DAPG are localized in phlABCD operon. All the four genes in phlABCD operon are indispensable and DAPG synthesis is attenuated even in the absence of one of the genes. In the present study, we identified and cloned phlC gene from an Indian strain of Pseudomonas and analyzed its sequence. The structural details ofthe PHLC protein was generated by three-dimensional homology modelling. Additionally, stereo-chemical properties of PHLC were analyzed by Ramachandran plot analysis and the generated model was validated by PDBsum. Our results demonstrate that the cloned PHLC protein contains structural features typical of a condensing enzyme involved inpolyketide synthesis.

A new phloroglucinol from Dryopteris fragrans and its antibacterial activity in vitro / 中国中药杂志

A new phloroglucinol was isolated from 50% ethanol extract of Dryopteris fragrans by silica gel column chromatography, Sephadex LH-20 gel column chromatography, thin-layer chromatography(TLC), and preparative liquid column chromatography. On the basis of MS, ~1H-NMR, ~(13)C-NMR, and reference materials, compound 1 was identified as 2,5-cyclohexadien-1-one, 2-{[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-isobutyl)phenyl]methyl}-3,5-dihydroxy-4,4-dimethyl-6-(1-oxobutyl)(1), and named disaspidin BB. Compound 1 was evaluated for its antibacterial activity. The experimental results showed that compared with the commonly used topical antibiotics erythromycin or mupirocin, disaspidin BB exhibited significant antibacterial activities against Staphylococcus epidermidis(SEP), S. haemolyticus(SHA), and methicillin-resistant S. aureus(MRSA)(P<0.05). Additionally, disaspidin BB was sensitive to ceftazidime-resistant SEP1-SEP4, SHA5-SHA7, MRSA8, and MRSA9. The MIC values of disaspidin BB against SEP and SHA were 1.67-2.71 μg·mL~(-1) and 10.00-33.33 μg·mL~(-1) respectively. Disaspidin BB has good antibacterial activities and deserves development as a new anti-infective drug for external use.

A new phloroglucinol compound from Dryopteris fragrans / 中国中药杂志

Two phloroglucinol compounds(1-2) were isolated and purified from 95% ethanol extract of Dryopteris fragrans through various column chromatographies on silica gel, Sephadex LH-20, medium pressure column chromatography, and preparative HPLC. Their structures were elucidated as 2',4',6'-trihydroxy-5'-methyl acetate-3'-methyl-1'-butyrophenone(1) and aspidinol B(2) based on their chemical and physicochemical methods and spectroscopic data. Compound 1 is a new phloroglucinol compound named "dryofraginol".

Discovery of Eucalyptin C, derived from the fruits of Eucalyptus globulus Labill., as a novel selective PI3Kγ inhibitor for immunosuppressive treatment / 中国天然药物

The fruits of Eucalyptus globulus Labill. are known to have a plenty of medicinal properties, such as anti-tumor, anti-inflammatory, and immunosuppressive activity. Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E. globulus were immunosuppressive active constituents, especially Eucalyptin C (EuC). Phosphoinositide 3-kinases-γ (PI3Kγ) plays a pivotal role in T cell mediated excessive immune responses. In this study, EuC was first discovered to be a novel selective PI3Kγ inhibitor with an IC

Synthesis of flavaspidic acid AB / 中国药科大学学报

@#Flavaspidic acid AB is a bicyclic phloroglucinol derivative with various biological activities in Dryopteris fragrans (L.) Schott. The structure of flavaspidic acid AB was analyzed by inverse synthesis techniques, and its synthesis was designed under the principle of association. Using phloroglucinol as raw material, the 2-methyl-4-butyrylphloroglucinol was synthesized by Vilsmeier-Haack reaction, reduction and acylation, and the flavaspidic acid fragment was synthesized by acylation, alkylation and deacylation, after which N, N-dimethylmethyleneammonium iodide was activated and the flavaspidic acid AB was obtained. The structures of intermediates and flavaspidic acid AB were confirmed by MS, 1H NMR and 13C NMR, and the yield of the target product reached 14.7%. Results indicate that the designed synthetic route of flavaspidic acid AB is simple and easy.

Chemical constituents from Garcinia multiflora fruits / 中草药

Objective To study the chemical constituents of the fruits of Garcinia multiflora. Methods The constituents were isolated and purified by silica gel column chromatography and semipreparative HPLC, and their structures were elucidated by means of spectroscopic analyses. Results Six compounds were obtained and identified as multiflorone A (1), sargaol (2), δ-tocotrienol (3), luteolin (4), 1,3,6,7-tetrahydroxyxanthone (5), terephthalic acid bis (2-ethyl-hexyl) ester (6). Conclusion Compound 1 is a new homoadamantyl type phloroglucinol, and compounds 2, 3 and 6 are isolated from this plant for the first time.

Determination of 10 phloroglucinol constituents in effective fraction of Dryopteris fragrans with quantitative analysis of multi-components by single marker / 中草药

Objective: To establish quantitative analysis of multi-components with single marker (QAMS) for determination of 10 phloroglucinol contents in effective fraction of Dryopteris fragrans. Methods: The relative correction factors of nine phloroglucinol (aspidin PB, aspidin AB, flavaspidic acid BB, saroaspidin A, flavaspidic acid PB, disflavapidic acid PB, flavaspidic acid AB, compound VI, and aspidinol B) were determined by HPLC method with the aspidinn BB as the internal standard, which were to calculate the content of each. At the same time, external standard method (ESM) was used to determine the contents of 10 components in effective fraction, and the differences between the two methods were compared to verify the feasibility and accuracy of QAMS method. Results: The relative correction factor (RCF) was good. There was no significant difference between the quantitative results with the two methods in the 12 batches of 10 phloroglucinols. Conclusion: The established QAMS method can be used for quantitative analysis of D. fragrans with aspidinn BB as the internal standard in the absence of reference substances, and provided a reference for the multi-index quality evaluation in effective fraction of D. fragrans.

Research progress on phloroglucinol terpenes from Eucalyptus genus and their antitumor mechanism / 中草药

Phloroglucinol terpenes are the mainly naturally active ingredients from Eucalyptus genus. Based on the modern pharmacological studies, phloroglucinol terpenes with unique polyketoditerpenoid skeleton have been confirmed to have the anticancer activity, which could be the important source to find the novel potential anticancer lead compounds. In this article, the structure, antitumor mechanism and activity of these known phloroglucinol terpenes from Eucalyptus genus were reviewed, which can provide the references for the following researches on the novel anticancer drugs of phloroglucinol terpenes.

Potential of phloroglucinol to improve erectile dysfunction associated with streptozotocin-induced diabetes in rats / 中西医结合学报

OBJECTIVE@#Diabetes is a common metabolic disease with several complications in its patients. Often, people living with diabetes develop erectile dysfunction (ED). The primary aim of this work was to investigate the effect of phloroglucinol in diabetes-induced ED in rats.@*METHODS@#Male Wistar rats were given 52 mg/kg of streptozotocin, by intraperitoneal injection, to induce diabetes and ED. Subsequently, animals were grouped into three groups: group 1, diabetic control; group 2, low-dose phloroglucinol (150 mg/kg body weight); and group 3, high-dose phloroglucinol (250 mg/kg body weight). A group of six normal rats served as a normal control. The rats were treated with phloroglucinol for six weeks and then were assessed for treatment effects. Sexual behavior, glycosylated hemoglobin A1c (HbA1c) values, serum testosterone, serum nitric oxide (NO), blood pressure and sperm count were measured after the end of treatment.@*RESULTS@#After a 6-week treatment period, the high dose of phloroglucinol significantly decreased HbA1c values in diabetic rats. Rats treated with phloroglucinol had increased serum testosterone, NO and sperm count. Animals treated with 250 mg/kg phloroglucinol performed similar to normal rats in the sexual behavioral study, suggesting the reversal of complications of ED. Conversely, a decrease in the blood pressure in treated groups was observed.@*CONCLUSION@#The results highlight the protective effect of phloroglucinol in diabetes-induced ED in rats warranting further studies.

Clinical application of Phloroglucinol combined with Dexamethasone in ureteroscopy lithotripsy / 中国内镜杂志

Objective To evaluate the clinical effect of Phloroglucinol combined with Dexamethasone in ureteroscopy lithotripsy. Methods Patients with severe urinary infection, urinary tract tuberculosis, congenital urinary tract malformation were excluded. The clinical data of 124 patients with ureteral calculus was retrospectively analyzed, Group control with 29 patients who underwent conventional ureteroscopy lithotripsy, 32 patients were given Phloroglucinol (80 mg) as Group phloroglucinol, 29 patients were given Dexamethasone (10 mg) as Group Dexamethasone, 34 patients were given combination drugs of Phloroglucinol (80 mg) plus Dexamethasone (10 mg) as Group combination therapy, intravenously 15 min prior to surgery, respectively. The surgical complication, side-effects, operation time, duration of postoperative hematuria, and expulsion rate were recorded. Results All surgeries were accomplished successfully, and none severe side-effects were observed among these cases. In comparison of operation time and duration of postoperative hematuria, there were no significant difference between group Dexamethasone and group control, and both group Phloroglucinol and group combination therapy were better than that of group control (P < 0.05), furthermore, group combination therapy was better than group phloroglucinol (P < 0.05). In comparison of the expulsion rate, there were no significant difference between group control and group Phloroglucinol or group Dexamethasone (P > 0.05), however, group combination therapy is better than that of group control (P = 0.017). Conclusion Combined treatment with Phloroglucinol and Dexamethasone in ureteroscopy lithotripsy would shorten the operation time and duration of postoperative hematuria significantly, and improve the expulsion rate eventually.

Efficacy of using combination of phloroglucinol and dyclonine hydrochloride mucilage in preventing cath-eter-related bladder discomfort during recovery from anesthesia in the patients undergoing general anes-thesia / 临床麻醉学杂志

Objective To evaluate the efficacy of phloroglucinol combined with dyclonine hydrochloride mucilage in preventing catheter-related bladder discomfort (CRBD)during recovery from anesthesia in patients under general anesthesia.Methods A total of 120 male patients scheduled for laparoscopic cholecystectomy under general anesthesia,aged 18-60 years,weighing 46-80 kg, ASA physical status I or II,were randomly divided into 3 groups (n=40 in each group):group of combination of phloroglucinol and dyclonine hydrochloride mucilage (group P),sufentanil group (group S)and control group (group C).After induction of general anesthesia,the patients in group P were tracheally incubated and then inj ected with 5 ml dyclonine hydrochloride mucilage per urethra.In the meantime,for patients of groups S and C,equal volume of normal saline was inj ected and paraffin oil was used to lubricate for urethral catheterization.The catheter was clamped and then reopened 30 min later.At 15 min before the end of surgery,80 mg Phloroglucinol,0.10 μg/kg sufentanil and an equal volume of normal saline were injected intravenously in group P,group S and group C,respec-tively.The catheter was removed when the patients were fully awake.The awakening time and extu-bation time were recorded.In addition,Riker sedation-agiation scale (SAS)score was documented at 5 min (T1),15 min (T2),30 min (T3),1 h (T4)and 2 h (T5)after extubation.The occurrence and severity of CRBD within 2 h after surgery,as well as occurrence of nausea and vomiting and respira- tory depression were recorded.Results Compared with group C,the SAS score at T1-T4and inci-dence and severity CRBD were decreased,whereas the emergence time and extubation time were pro-longed in group S.The SAS score at T1-T5,incidence and severity of CRBD were decreased (P<0.05),and no significant change was found in emergence time and extubation time in group P.Com-pared with group S,the SAS score at T1-T4was increased,whereas the SAS score at T5,incidence and severity of CRBD were decreased,and the emergence time and extubation time were shortened in group P (P<0.05).There was no significant difference in the incidence of nausea and vomiting,re-spiratory depression and extubation time among the three groups. Conclusion Dyclonine hydrochloride mucilage injected per urethra combined with phloroglucinolol injected intravenously at 1 5 min before the end of surgery can reduce the incidence and severity of CRBD during the recovery from anesthesia in the patients under general anesthesia.

Chemical constituents of Hypericum perforatum / 中国中药杂志

A chemical investigation on the aerial parts of Hypericum perforatum resulted in the isolation of a new phloroglucinol derivatives (1), and seven known compounds (2-8). The structures of the compounds were elucidated by means of spectroscopic methods (MS, IR, 1D NMR, and 2D NMR) as 3-methyl-4,6-di (3- methyl-2-butenyl)-3-(4-methyl-3-pentenyl)-2-(2-ethyl-1-oxobutyl)-cyclohexanone (1)，hyperforin (2)，(2R,3R,4S,6)-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxo-propyl)-3-(4-methyl-3-pentenyl)-cyclohexanone (3)，hyperscabrin B (4)，hyperscabrin C (5)，furohyperforin isomer 1 (6)，furoadhyperforin (7)，and furohyperforin (8). Compound 1 was a new compound, and compounds 3-5 were obtained from H. perforatum for the first time.

Isolation and antifungal activities of a pair of isomers of phloroglucinol derivatives from Dryopteris fragrans / 中草药

Objective: To study the chemical constituents and antifungal activitiy of phloroglucinol derivatives from Dryopteris fragrans. Methods: The phloroglucinol derivatives were isolated by silica gel column chromatography, Sephadex LH-20 column chromatography, and pre-HPLC. The chemical structures were elucidated on the basis of physicochemical and spectral properties. The antifungal activities against Trichophyton rubrum and Microsporum gypseum were tested by CLSI M38-A2 broth microdilution methods. Results: Two phloroglucinol derivatives were isolated and identified as disflavaspidic acid PB (1) and flavaspidic acid PB (2). The minimum inhibitory concentration (MIC) of compounds 1 and 2 were 13.33 and 1.875 μg/mL against T. rubrum respectively, 10 and 1.325 μg/mL against M. gypseum. Conclusion: Compound 1 is a new compound named disflavaspidic acid PB. Compound 2 is isolated from D. fragrans for the first time. Compounds 1 and 2 are a pair of isomers with promising antifungal activity.

Research progress on chemical constituents of Hypericum attenuatum and their pharmacological activities / 中草药

Hypericum attenuatum is a Guttiferae Hypericum Linn. plant, which is a folk commonly used drug.H. attenuatum has great medical development value of detoxicating, diminishing inflammation, stopping bleeding, promoting tissue regeneration, regulating menstruation, activating blood, and so on. It was used for empyrosis, hyperhidrosis, especially heart disease in Northeast area of China from the folk records. Modern research shows that it has flavonoids, volatile oils, and phloroglucinol derivative; And it has anti-arrhythmia, antimyocardial ischemia, antitumor, antidepression, antibacterial, and other pharmacologic actions. The recent progress in the studies of the constituents and their pharmacological activity of this plant is reviewed in this paper in order to provide reference for clinical application, quality control and drug discovery.

Isolation and antibacterial activities of phloroglucinol derivatives from Dryopteris crassirhizoma / 中草药

Objective To isolate the phloroglucinol derivatives in Dryopteris crassirhizoma and to discuss its antibacterial activity. Methods The phloroglucinol derivatives were isolated and purified by column chromatography on silica gel, Sephadex LH-20, semi preparative liquid phase, and recrystallization. Structures were proved by physicochemical properties and spectral methods (MS, 1H-NMR, 13C-NMR). The antibacterial activities against fungi and bacteria were tested by CLSI M38-A2 and M07-A9. Results 10 derivatives were obtained from ethanol extracts of D. crassirhizoma, and were identified as 1-butyrylphloroglucinol (1), 1-methyl-3-butyrylphloroglucinol (2), 2-acetyl-4-butyrylphloroglucinol (3), 1-methyl-3-acetyl-5-butyrylphloroglucinol (4), flavaspidic acid PB (5), norflavaspidic acid AB (6), flavaspidic acid AA (7), filixic acid ABA (8), flavaspidic acid AB (9), and filixic acid ABP (10). The antibacterial activity of compound 8 against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) was similar to cefoxitin (positive control), and the MIC of compound 8 was 2.5 μg/mL. Conclusion Compounds 1-4, new compounds, are isolated from D. crassirhizoma. Compound 8 has both antibacterial activities against fungi and bacteria.

Two new phenolic glycosides isolated from the fruits of Citrus aurantium / 中国天然药物

The present study was designed to investigate the chemical constituents of the fruit of Citrus aurantium L.. The compounds were isolated and purified by various chromatographic techniques, and their structures were elucidated on the basis of physicochemical properties and spectral data. Two new phenolic glycosides (compounds 1 and 2) were obtained and identified as 1-O-3, 5-dihydroxyphenyl-(6-O-4-hydroxybenzoyl)-β-D-glucopyranoside (1) and 1-O-3, 5-dihydroxyphenyl-(6-O-3-methoxy-4-hydroxy benzoyl)-β-D-glucopyranoside (2), respectively.

Advantage of childbirth with ball-assisted free body position / 中国综合临床

Objective To evaluate the clinical effect and safety of intravenous administration of phloroglucinol combined with delivery of ball-assisted free position in parturient women during labor.Methods One hundred and fifty-two primiparous women who were treated by vaginal delivery from June 2015 to August 2016 in Beijing Navy General Hospital were selected as the study subjects.They were given 80 mg of phloroglucinol diluted in saline injection intravenous injection.Observation group were treated with childbirth.Control group treated with traditional supine or lateral body.Results The rate of descending of the observed group was longer than that of the control group((1.09±0.22) cm/h vs.(0.83±0.15) cm/h),the first labor time,the second labor time and the total labor time of the observation group were shorter than the control group((9.57±1.71) h vs.(12.13±2.64) h,(35.75±8.68) min vs.(61.21±10.03) min,(11.34±1.96) h vs.(14.66±2.70) h),the difference between the two groups was statistically significant(t=3.611,4.204,3.307,3.456,P0.05).The percentage of vaginal delivery in the observation group was 89.47%(68/76),significantly higher than that in the control group(73.68%(56/76)),the difference was statistically significant(χ2=4.514,P<0.05).The incidence of vaginal midwifery was 1.32%(1/76) and that of cesarean section was 9.21%(7/76) of observation group,significantly lower than that in control group(5.26%(4/76),21.05% (16/76)),the difference was statistically significant(χ2=5.323,4.376,P<0.05).Observation group 24 h postpartum hemorrhage was (273.12±58.23) ml,significantly less than the control group((385.42±70.13) ml),the difference between the two groups was statistically significant(t=3.744,P<0.05).The observation group had postpartum hemorrhage of 1.32%(1/76),urinary retention of 2.63%(2/76),and the percentage of neonatal asphyxia of 2.63%(2/76),were lower than that of the control group(5.26%(4/76),10.53%(8/76),9.21%(7/76)),the difference between the two groups was statistically significant(χ2=4.103,4.925,4.421,P<0.05).Conclusion The delivery of ball-assisted free-body delivery in active stage of delivery can promote natural childbirth.The medical staff should update the concept of delivery and raise awareness to encourage the use of phloroglucinol combined with free-body delivery.

Application of phloroglucinol injection in embryo transfer in patients with recurrent implantation failure / 中国医师杂志

Objective To investigate the effect of phloroglucinol on pregnancy outcome in patients with recurrent implantation failure (RIF).Methods A total of 146 patients with RIF from March 2014 to March 2016 from the reproductive medical center of the Guangxi Zhuang Autonomous Region people's Hospital was randomly divided into two groups,73 cases were included in study group [16 cases of in vitro fertilization and embryo transfer (IVF-ET) and 57 cases of frozen/thawed embryo transfer (FET)].Patients in study group were given intramuscular injection of phloroglucino140mg,two times a day before the transplantation day to three days after transplantation,73 cases without phloroglucinol injection were included as control group.The biochemical pregnancy rate,clinical pregnancy rate,embryo implantation rate,abortion rate,ectopic pregnancy rate,multiple pregnancy rate and live birth rate were compared between two groups.Results The biochemical pregnancy rate in study group of FET was significantly higher than the control group (57.9％ vs 36.8％,P ＜0.05);the biochemical pregnancy rate in study group of IVF-ET was higher than the control group (50％ vs 37.5％,P ＞ 0.05),but there was no significant difference between the study group and control group;compared to the control group,the study group was increased clinical pregnancy rate,implantation rate,live birth rate,and decreased abortion rate (P ＞ 0.05),but the difference was not statistically significant.Conclusions The application of phloroglucinol in women with RIF may improve the biochemical pregnancy rate,especially in FET cycles.