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Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.
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ObjectiveTo explore the effect of intervention based on theory of planned behavior on muscle attenuation and balance of the elderly with sarcopenia. MethodsFrom September, 2022 to February, 2023, 124 elderly people with sarcopenia were conveniently sampled from Lishuiwan Community and Shuxiangyuan Community in Shijiazhuang City, Hebei Province. According to the coin toss, 62 elderly people from Shuxiangyuan Community were designated as control group, and 62 elderly people from Lishuiwan Community were as intervention group. The intervention group implemented the intervention based on the theory of planned behavior, including behavior attitude, behavior, subjective norms, perceived behavior control and behavior awareness; the control group maintained their original lifestyle, for twelve weeks. Before and after intervention, the grip strength, time of Five-Times-Sit-to-Stand Test, relative appendicular skeletal muscle index (RASM), 6-minute walking speed and the score of Berg Balance Scale (BBS) were compared. ResultsAfter intervention, the grip strength, RASM, 6-minute walking speed, and the score of BBS significantly increased, and the time of Five-Times-Sit-to-Stand Test shortened in the intervention group (|Z| > 6.257, |t| > 28.643, P < 0.001), and they were better in the intervention group than in the control group (|Z| > 2.288, |t| > 3.177, P < 0.05). ConclusionThe intervention based on theory of planned behavior can effectively relieve the muscle attenuation of the elderly with sarcopenia, and improve their balance ability.
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Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.
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To summarize the status quo of clinical evidence on oral Chinese patent medicine in the treatment of hyperlipidemia through scoping review and thereby provide a reference for clinical application and decision-making in health care. Proprietary Chinese medicines for the treatment of hyperlipidemia (dyslipidemia) were retrieved from relevant catalogs and then screened based on their instructions. Articles on the selected Chinese patent medicines were searched from Chinese and english electronic databases and screened according to the inclusion criteria, followed by data extraction and analysis. The results were described with text and graphs. ①A total of 32 Chinese patent medicines and 1 010 related articles were screened out. ②All the included Chinese patent medicines were made from Chinese medicinal materials, of which 5 were Chinese medicinal extracts,and the remaining 27 were pure Chinese medicinal preparations (the compositions of 1 prescription is confidential). ③As indicated in the instructions, all the 32 Chinese patent medicines can be used to treat hyperlipidemia with the main syndrome of combined phlegm and blood stasis, and the main effect of them is activating blood and resolving stasis. ④Among the 32 medicines, Xuezhikang tablets (Capsules) and Gypenosides Tablets have the lowest price. ⑤For the 328 key clinical studies, 248 were randomized controlled trials and 80 non-randomized controlled trials. ⑥As for the sample size, randomized controlled trials generally included 28-579 cases, and non-randomized controlled trials 24-152 cases. Clinical studies with more than 200 cases accounted for 9.3% (12/129). ⑦The most common method was the comparison of the intervention effect of Chinese patent medicine and western medicine (36.5%) and Atorvastatin Calcium Tablets was the preferred western medicine control. The observation duration was generally 56 days (8 weeks). ⑧In clinical practice, the absolute value of blood lipid decrease and (total) effective rate were often used to evaluate the efficacy, and the effective rate was generally determined based on Clinical Guidelines for New Chinese Medicines. The overall quality of clinical studies on oral Chinese patent medicines is uneven and there is a lack of high-quality clinical evidence. Moreover,there are the risks of unreasonable use and uneasy use of Chinese patent medicine.It is recommended that researchers on proprietary Chinese medicine should further broaden the research ideas,focus on the top-level design of the research plan, and standardize the research process,thereby provide high-quality research evidence for the clinical use of proprietary Chinese medicine. Moreover, more efforts should be made to establish a sound mechanism for information collection and feedback of proprietary Chinese medicine, so as to reduce the risk of uneasy use.We hope that in-depth investigation and discussion should be launched by price, economy, quality evaluation, and other departments headed by the supervision department to make the price of Chinese patent medicine reasonable and fair, thereby promoting the rational use of Chinese patent medicine.
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Three butylphthalide derivatives were isolated from the Rhizome of Ligusticum chuanxiong using a series of isolation and purification approaches including macroporous resin, ODS-A column, Sephadex LH-20 and preparative HPLC. These structures were elucidated based on extensive spectroscopic data (UV, IR, HR-ESI-MS and NMR) and identified as (3Z,3aE)-(6R,7R,2'S)-6-hydroxy-7-(2-carboxyl-2-hydroxyethylthio)-3-(2-hydroxybutylidene)-4,5,6,7-tetrahydro-phthalide (1), (3Z,3aZ)-3-butylidene-6,7-dihydroxy-4,5,6,7-tetrahydro-phthalide 7-O-α-D-glucopyranosyl-(1→2)-β-D-fructo-furanoside (2) and 3-(3-β-D-glucopyranosyloxy-butylidene)-7-hydroxy-phthalide (3).
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Objective: To observe the relationship between heart rate on atrioventricular node reentrant tachycardia (AVNRT) sustaining and slow path position during procedure of slow path modified ablation using three-dimensional mapping system. Methods: Modified ablation of slow pathway under three-dimensional mapping system was performed in 98 patients with slow-fast (S-F) AVNRT confirmed by invasive electrophysiology examination. The successful target (the site of slow-pathway) and standard His bundle were marked using three-dimensional mapping system, and the distance (Distance A) between the successful target and standard His bundle was measured. The relationship between heart rate in AVNRT and Distance A was analyzed. Results: Distance A was successfully obtained in 96 patients, including 64 tachycardia induced without infusion of isoproterenol, the heart rate was (179.77±29.22)bpm and relevant Distance A was (13.56±5.06)mm, also 32 tachycardia induced with infusion of isoproterenol, the heart rate was (174.91±17.41)bpm and relevant Distance A was (12.43±3.70)mm. No obvious correlation between heart rate and slow path position was found among the above 96 patients (rs=0.048, -0.190; P=0.705, 0.298). Conclusion: There was no obvious correlation between patient's heart rate on AVNRT sustaining and slow path position druing the procedure of slow path modified ablation using three-dimensional mapping system.
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BACKGROUND: Calcium citrate has been used as calcium supplement, anticoagulant, anti-inflammatory agent and bone repair material in biomedical fields. OBJECTIVE: To describe the basic properties of calcium citrate, summarize and discuss the preparation process of calcium citrate and its main applications in biomedical field. METHODS: The research literature related to calcium citrate was searched on the Web of science, CNKI, Medline and other databases by computer. The main key words were “calcium citrate, bone repairing material, citrate and calcium phosphate” in English and “calcium citrate, bone repair materials” in Chinese. The searching time was from February 1920 to February 2020. RESULTS AND CONCLUSION: With the development and exploration of medical materials, it is necessary to change the original process to improve the biological activity of medical calcium citrate. It is an inevitable trend to obtain calcium citrate with various micro-morphology and high biological activity by controllable synthesis method. Calcium citrate is widely used as calcium supplement, anti-inflammatory agent, anticoagulant, bone repair material and other non-medical applications. Its advantages are being gradually explored by researchers. The preparation method plays a decisive role in the application field of calcium citrate. Different internal structure and size will bring different application fields, from the smallest chemical bond connection to the macroscopic morphology or mechanical properties. These factors may be the results of the dedicated exploration of researchers.
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To explore the usability of regional saturation of cerebral oxygenation (rScO2) combined with percentage of α variability (PAV) in predicting brain function prognosis in patients with traumatic brain injury (TBI). Methods A retrospective analysis was conducted. The clinical data of patients with TBI who were monitored rScO2 and bedside quantitative electroencephalogram (qEEG) admitted to intensive care unit (ICU) of Henan Provincial People's Hospital from August 2018 to July 2019 were collected. The rScO2, PAV, and Glasgow coma scale (GCS) score were recorded within 72 hours after the TBI. The primary prognostic indicator was the 3-month Glasgow outcome score (GOS) score. The differences between the two groups of poor prognosis of brain function (GOS score 1-3) and good prognosis (GOS score 4-5) were compared. Binary multivariate Logistic regression analysis was used to analyze the correlation between rScO2, PAV, GCS score and the prognosis of brain function in patients with TBI. In addition, receiver operating characteristic (ROC) curve was plotted to analyze the predicting value of rScO2 and PAV only or combination for prognosis of brain function. Results A total of 42 patients with TBI were enrolled in the study, with rScO2≥0.60 (grade Ⅰ) in 14 patients, 0.50≤rScO2 < 0.60 (grade Ⅱ) in 16 patients,and rScO2 < 0.50 (grade Ⅲ) in 12 patients. PAV 3-4 scores (grade Ⅰ) were detected in 16 patients, 2 scores (grade Ⅱ) in 17 patients, and 1 score (grade Ⅲ) in 9 patients. GCS score 9-14 (grade Ⅰ) were observed in 13 patients,4-8 (grade Ⅱ) in 23 patients, and 3 (grade Ⅲ) in 6 patients; 18 patients had poor prognosis and 24 had good one. The rScO2, PAV and GCS scores of the poor-prognosis group were significantly higher than those in the good-prognosis group [rScO2 with grade Ⅲ: 55.6% (10/18) vs. 8.3% (2/24), PAV with grade Ⅲ: 38.9% (7/18) vs. 8.4% (2/24), GCS score with grade Ⅲ: 27.7% (5/18) vs. 4.1% (1/24)] with significant differences (all P < 0.05). There was no significant difference in other general data including gender, age, total length of hospital stay or acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score between the two groups. Binary multivariate Logistic regression analysis showed that rScO2 and PAV were independent risk factors for prognosis of brain in patients with TBI [rScO2: odds ratio (OR) = 4.656, 95% confidence interval (95%CI) was 1.071-20.233, P = 0.040; PAV: OR = 3.525, 95%CI was 1.044-11.906, P = 0.042]. ROC curve analysis showed that both of rScO2 and PAV had predictive value for the prognosis of brain function in patients with TBI (AUC was 0.796 and 0.780, respectively, both P < 0.01), and rScO2 combined with PAV had higher predictive value with the AUC of 0.851 (P < 0.01) than rScO2 or PAV alone, the sensitivity was 94.4% and the specificity was 62.5%. Conclusions rScO2 and PAV were associated with early brain function prognosis in patients with TBI. The combination of two monitoring indicators can reliably assess the prognosis of brain function in patients with TBI.
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Objective@#To explore the usability of regional saturation of cerebral oxygenation (rScO2) combined with percentage of α variability (PAV) in predicting brain function prognosis in patients with traumatic brain injury (TBI).@*Methods@#A retrospective analysis was conducted. The clinical data of patients with TBI who were monitored rScO2 and bedside quantitative electroencephalogram (qEEG) admitted to intensive care unit (ICU) of Henan Provincial People's Hospital from August 2018 to July 2019 were collected. The rScO2, PAV, and Glasgow coma scale (GCS) score were recorded within 72 hours after the TBI. The primary prognostic indicator was the 3-month Glasgow outcome score (GOS) score. The differences between the two groups of poor prognosis of brain function (GOS score 1-3) and good prognosis (GOS score 4-5) were compared. Binary multivariate Logistic regression analysis was used to analyze the correlation between rScO2, PAV, GCS score and the prognosis of brain function in patients with TBI. In addition, receiver operating characteristic (ROC) curve was plotted to analyze the predicting value of rScO2 and PAV only or combination for prognosis of brain function.@*Results@#A total of 42 patients with TBI were enrolled in the study, with rScO2≥0.60 (grade Ⅰ) in 14 patients, 0.50≤rScO2 < 0.60 (grade Ⅱ) in 16 patients, and rScO2 < 0.50 (grade Ⅲ) in 12 patients. PAV 3-4 scores (grade Ⅰ) were detected in 16 patients, 2 scores (grade Ⅱ) in 17 patients, and 1 score (grade Ⅲ) in 9 patients. GCS score 9-14 (grade Ⅰ) were observed in 13 patients, 4-8 (grade Ⅱ) in 23 patients, and 3 (grade Ⅲ) in 6 patients; 18 patients had poor prognosis and 24 had good one. The rScO2, PAV and GCS scores of the poor-prognosis group were significantly higher than those in the good-prognosis group [rScO2 with grade Ⅲ: 55.6% (10/18) vs. 8.3% (2/24), PAV with grade Ⅲ: 38.9% (7/18) vs. 8.4% (2/24), GCS score with grade Ⅲ: 27.7% (5/18) vs. 4.1% (1/24)] with significant differences (all P < 0.05). There was no significant difference in other general data including gender, age, total length of hospital stay or acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score between the two groups. Binary multivariate Logistic regression analysis showed that rScO2 and PAV were independent risk factors for prognosis of brain in patients with TBI [rScO2: odds ratio (OR) = 4.656, 95% confidence interval (95%CI) was 1.071-20.233, P = 0.040; PAV: OR = 3.525, 95%CI was 1.044-11.906, P = 0.042]. ROC curve analysis showed that both of rScO2 and PAV had predictive value for the prognosis of brain function in patients with TBI (AUC was 0.796 and 0.780, respectively, both P < 0.01), and rScO2 combined with PAV had higher predictive value with the AUC of 0.851 (P < 0.01) than rScO2 or PAV alone, the sensitivity was 94.4% and the specificity was 62.5%.@*Conclusions@#rScO2 and PAV were associated with early brain function prognosis in patients with TBI. The combination of two monitoring indicators can reliably assess the prognosis of brain function in patients with TBI.
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In our study of the chemical constituents of the dried mature fruits of Arctium lappa L., ten compounds were isolated by various chromatography methods and preparative HPLC. Their structures were elucidated as (7R,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-4'-oxyneolign-7'-ene-9'-O-β-D-glucopyranoside (1), (7R,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan-9'-O-β-D-glucopyranoside (2), (7R,8R)- 4,7,9,9'-tertahydroxy-3,3'-dimethoxy-8-4'-oxyneolignan (3), (7S,8R)-dihydrodehydrodiconiferylalcohol-4-O-β- D-glucopyranoside (4), (7S,8R,7'R,8'R)-pinoresinol-4,4'-di-O-β-D-glucopyranoside (5), (8S,7'S,8'R)-4,4',9'- trihydroxy-3,3'-dimethoxy-7',9-epoxylignan-7-oxo-4'-O-β-D-glucopyranoside (6), 2-methoxy-4-hydroxyphenol- 1-O-β-D-xylopyranosyl-(1→6)-O-β-D-glucopyranoside (7), 3-methoxy-4-hydroxyphenol-1-O-β-D-xylopyranosyl- (1→6)-O-β-D-glucopyranoside (8), 4-hydroxy-3-methoxybenzylalcohol-4-O-β-D-xylopyranosyl-(1→6)-O-β-D- glucopyranoside (9) and 2-phenethyl β-primeveroside (10) by their spectroscopic data (IR, UV, CD, MS, HR-ESI-MS, and 1D and 2D NMR) and comparison to literature data. Compound 1 is a new 8-O-4'-neolignan. Compounds 2-10 were isolated from the dried mature fruits of Arctium lappa L. for the first time.
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Two flavanone glucosides were isolated from the 80% ethanol extract of Glycyrrhiza uralensis using various chromatographic techniques, including macroporous adsorbent resin, RP-C18, Sephadex LH-20, MCI and preparative HPLC. On the basis of chemical properties and spectra data, these compounds were identified as (2S)-liquiritigenin-4'-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (1), (2R)-liquiritigenin-4'-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside (2), respectively. Compounds 1 and 2 are new compounds, and their aglycones are enantiomers.
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Recently, research on collagen attracts more interests due to its good biological compatibility. The present study attempted to establish a fast and efficient method to purify collagen from soft-shelled turtle and to explore its application in biological materials. The structure and type of collagen fiber in calipash were determined by van Gieson staining and Picrosirius red staining, which could contribute to the isolation of collagen from soft-shelled turtle Calipash (STCC). Collagen fibers were in high content and the main collagen fiber was type I in STCC. The crude STCC solution was purified by dialysis with different cut-off molecular weight. SDS-PAGE demonstrated that the best purification was in applying 100 kDa dialysis bags after 48 h. The water absorbing capacity and holding capacity of STCC were up to 12.06 g/g and 98.21%, respectively. STCC can be degraded by collagenase in vitro entirely after 72 h. The hemolysis, skin sensitization, hemostatic and wound healing of STCC were determined by using SD rat model, and the collagen cross-linked by glutaric dialdehyde was set as a comparison. STCC and STCC cross-linked did not result in destructed red blood cell, inflamed and sensitized skin. Both materials exhibited good hemostatic effect. Thus, STCC improved the wound healing efficiently. This study implies a potential of STCC in the field of biomaterial.
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Animals , Rats , Biocompatible Materials , Biotechnology , Collagen , Electrophoresis, Polyacrylamide Gel , Molecular Weight , Rats, Sprague-Dawley , Skin , Turtles , Wound HealingABSTRACT
Based on the theory of traditional Chinese medicine, modern methods for drug investigation such as molecular targets in vitro and effects in vivo were used to study the prescription of Jingdan Yimin(JD), including selection of raw materials, composition, proportion, and effective dose of the compounds for treatment of metabolic syndrome. The IRF mice models, characterized by insulin resistance and hypercholesterolemia, were induced by high fat diet. The insulin sensitivity was estimated with insulin tolerance test(ITT) and glucose tolerance test(GTT); the levels of blood glucose and total cholesterol(TC), and the activities of α-glucosidase, protein tyrosine phosphatase 1B(PTP1B), and fructose phosphate amide transferase(GFAT)were measured with biochemical methods, respectively. The sample H13(h) extracted from Rhodiola crenulata, Y12(y) from Cordyceps militaris, and D(d) from Rheum palmatum were selected according to the inhibition activity on both PTP1B and α-glucosidase in vitro, regulation on hypercholesterolemia in IRF mice, and effects on GFAT activity, respectively; their synergistic effects on the treatment of metabolic syndrome were determined in IRF mice; composition proportion of h∶y∶d was measured in accordance with the results of L8(27) orthogonal experiments targeting on the inhibition of both PTP1B and α-glucosidase; finally, the effective dose was assessed based on the effects on IGT and hypercholesterolemia, respectively, in IRF mice. In conclusion, the prescription JD is composed by R. crenulata, C. militaris, and R. palmatum with the rate of 20∶1∶1, and its effective oral dose is 200 mg•kg⁻¹ for treatment of metabolic syndrome; its main mechanism is to inhibit the targets PTP1B and α-glucosidase. Monarch drug, R. crenulata, can clear away the lung-heat, tonify Qi, resolve stasis and nourish the heart. Adjuvant drug, C. militaris, can tonify the lung Qi and the kidney essence, strengthen waist and knee, accompanied with R. crenulata to enhance the function of invigorating lung and kidney. Assistant drug, rhubarb, can clear heat, detoxify, and remove blood stasis. These three herbs are compatible to show the effects of tonifying Qi, nourishing essence, clearing heat, reducing phlegm and resolving masses for the treatment of metabolic syndrome.
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Objective To evaluate the clinical effect of dorsal interosseous artery island flap to cover soft tissue defects of the hand.Methods Ten cases (8 males and 2 females) treated between 2009 and 2012 were included.The age was from 15 to 74 years.There were 4 patients associated with mechanical injury,3 electric injury,2 chronic ulcer and 1 hot crush injury.Size of the defect ranged from 3.0 cm × 2.5 cm to 12.0 cm × 7.0 cm,and the size of the flap ranged from 4.0 cm× 3.0 cm to 13.0 cm × 8.0 cm.The portable Doppler ultrasound was employed to locate the branches from the forearm dorsal interosseous artery.The dorsal interosseous retrograde artery distally based was used to repair hand softtissue defects.Results All the flaps survived except for some necrosis in one case which healed after dressing change.Eight patients were followed up for 3 months to 1 year and two patients were lost to follow-up.Flap had soft texture and similar color and sensation as the adjacent skin.No apparent hypertrophic scarfing on the donor site was observed.Flap was slighdy swollen in one case.Conclusion Dorsal interosseous artery retrograde island flap is safe and effective to repair hand soft tissue defects.
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OBJECTIVE: To study the chemical constituents of the roots of Rhodiola crenulata. METHODS: The roots of R. crenulata were extracted with 80% ethanol, and the extract was partitioned with ethyl acetate. The chemical components were isolated by various chromatographic methods. Their structures were elucidated by spectral analysis. RESULTS: Eleven compounds were isolated and identified as isolariciresinol-9, 9′-acetonide (1), p-coumaric acid (2), p-coumaric acid-4-O-β-D-glucopyranoside (3), tachio-side (4), dihydroconiferin (5), 2-phenylethyl β-glucopyranoside (6), 2-phenylethyl β-vicianoside (7), 2-phenylethyl-6-0-α -L-arabi-nofuranosyl-β-D-glucopyranoside(8), 2-phenylethyl β-primeveroside (9), benzyl β-D-glucopyranoside (10), and rhodiocyanoside D (11). CONCLUSION: All of the compounds were isolated from Rhodiola crenulata for the first time, and compounds 1, 3, 4, 5, 7, 9 were obtained from the genus of Rhodiola for the first time.
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The microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153 was studied, as well as a microbial model which can be used to mimic metabolism of buflomedil in mammal was established. Experiments were conducted to screen the capabilities of four strains of Cunninghamella species to transform buflomedil, in which C. blakesleana AS 3.153 was selected for a preparative biotransformation. Furthermore, the microbial model was established based on the transformation condition optimization. The parent drug and its metabolites produced by C. blakesleana AS 3.153 were detected by liquid chromatography-mass spectrometry method and three metabolites were identified while two of them were new found metabolites. Two major metabolites, para-O-desmethyl buflomedil and 12-C-oxidated buflomedil, were isolated by semi-preparative HPLC. Based on the comparison between different species, the microbial transformation of buflomedil by C. blakesleana AS 3.153 is more similar to the metabolism of buflomedil in human and Beagle dog than that in rat.