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Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium(EF)and possess excellent therapeutic effects on various diseases.Encouragingly,in 2022,icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma(HCC)by National Medical Products Administration(NMPA)of China.Moreover,recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects.Nonetheless,both production effi-ciency and clinical applications of epimedium flavonoids have been restrained because of their low content,poor bioavailability,and unfavorable in vivo delivery efficiency.Recently,various strategies,including enzyme engineering and nanotechnology,have been developed to increase productivity and activity,improve delivery efficiency,and enhance therapeutic effects of epimedium flavonoids.In this review,the structure-activity relationship of epimedium flavonoids is described.Then,enzymatic en-gineering strategies for increasing the productivity of highly active baohuoside I and icaritin are dis-cussed.The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized.Finally,the challenges and an outlook on clinical translation of epi-medium flavonoids are proposed.
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OBJECTIVE:To provide reference for quality evaluation of Ejiao. METHODS:The contents of 17 amino acids in 18 batches of Ejiao from 18 manufacturers were analyzed by automatic amino acid analyzer;the content data was processed by prin-cipal component analysis (PCA) and hierarchical clustering analysis (HCA),in order to understand the relationship among these amino acids and categorize the Ejiao products. RESULTS:Except for a batch of Ejiao,the other 17 batches contained 17 various amino acids,including 7 necessary amino acids(Thr,Val,Met,Ile,Leu,Phe and Lys)for human being,especially the contents of Gly and Pro were higher. The total content of amino acids was arranged from 66.1% to 82.0%,showing great difference. Four main components were extracted by PCA,the cumulative contribution of which was 89.578%,and accordingly it may be consid-ered that Pro,Ala,Glu,Asp,Leu,Ile and Thr were characteristic amino acids of Ejiao products. In hierarchical clustering analy-sis,3 tree figures of commercial Ejiao product were achieved and Euclidean distance was varied among 0-25. CONCLUSIONS:There is great difference in total control of amino acid in commercial Ejiao product;Ejiao products from various manufacturers dif-fer in their amino acid contents. Ejiao is rich in collagen,and therefore,using amino acid determination would be helpful to moni-tor its quality.
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OBJECTIVE:To establish the method for the content determination of L-Hyp and collagen in gelatinous medicinal material,and to compare the contents of two components in reference medicinal material and commercially available medicinal material.METHODS:Pre-column derivatization was adopted for pretreatment.The content of L-Hyp was determined by HPLC.The determination was performed on Kromasil C18 column with mobile phase consisted of acetonitrile-0.1 mol/L sodium acetate buffer (pH 6.5,7 ∶ 93,V/V)-acetonitrile-water (4 ∶ 1,V/V) (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 254 urn,and column temperature was set at 43 ℃.The sample size was 20 μL.The content of collagen was calculated by using convert coefficient.RESULTS:The linear range of L-Hyp were 2.5-40 μg/mL(r=0.999 9).LOQ was 0.20 μg/mL,and LOD was 0.05 t g/mL.RSDs of precision,stability and reproducibility tests were all lower than 4.0％.The recoveries were 96.03％-102.07％ (RSD =2.20％,n =9).There was difference in the contents of L-Hyp and collagen among 28 batches of commercially available medicinal material.The contents of two components in 13 batches of commercially available Colla Corii Asini were relative close to reference medicinal material;5 batches of Colla Carapacis et Plastri Testudinis and 7 batches of Cervi Comus Colla were much higher than those of reference medicinal material.CONCLUSIONS:The method is accurate,reliable and suitable for the content determination of L-Hyp and collagen in gelatinous medicinal material.
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OBJECTIVE:To establish the method for the content determination of L-Hyp and collagen in gelatinous medicinal material,and to compare the contents of two components in reference medicinal material and commercially available medicinal material.METHODS:Pre-column derivatization was adopted for pretreatment.The content of L-Hyp was determined by HPLC.The determination was performed on Kromasil C18 column with mobile phase consisted of acetonitrile-0.1 mol/L sodium acetate buffer (pH 6.5,7 ∶ 93,V/V)-acetonitrile-water (4 ∶ 1,V/V) (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 254 urn,and column temperature was set at 43 ℃.The sample size was 20 μL.The content of collagen was calculated by using convert coefficient.RESULTS:The linear range of L-Hyp were 2.5-40 μg/mL(r=0.999 9).LOQ was 0.20 μg/mL,and LOD was 0.05 t g/mL.RSDs of precision,stability and reproducibility tests were all lower than 4.0％.The recoveries were 96.03％-102.07％ (RSD =2.20％,n =9).There was difference in the contents of L-Hyp and collagen among 28 batches of commercially available medicinal material.The contents of two components in 13 batches of commercially available Colla Corii Asini were relative close to reference medicinal material;5 batches of Colla Carapacis et Plastri Testudinis and 7 batches of Cervi Comus Colla were much higher than those of reference medicinal material.CONCLUSIONS:The method is accurate,reliable and suitable for the content determination of L-Hyp and collagen in gelatinous medicinal material.
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Objective To investigate regional ventricular long-axis velocity and adjacent intraventricular flow velocity using dual-pulse wave(PW) Doppler echocardiography synchronously,and to analyze the coupling relationship between regional ventricular long-axis strain and adjacent intraventricular pressure gradients in normal cases using dual-PW Doppler echocardiography.Methods Eighty-six normal subjects aged 19～66 years [mean age (37.49 ± 11.97)years] underwent routine echocardiography and dualPW Doppler echocardiographic exam.Total 18 segments were sampled using dual-PW Doppler (PW/TDI mode) images at basal,mid and apical levels on three standard apical views,and electrocardiogram was recorded simultaneously.Peak early diastolic velocity (emax),peak late diastolic velocity (amax),peak early mitral diastolic inflow velocity (Emax),regional peak early diastolic velocity (Em),regional peak late diastolic velocity (Am) and regional peak early diastolic inflow velocity (E) were measured simultaneously in the same one cardiac cycle.Myocardial variations of left ventricular segments were observed.Em,Am and E of different levels from different ventricular wall were analyzed.The co-relationship between regional ventricular long-axis strain and adjacent intraventricular pressure gradients were calculated and analyzed.Results ①Regional myocardial velocity and regional peak early diastolic inflow velocity in normal subjects declined from basal to apical segments gradually at the same ventricular wall (P ＜ 0.01).② Emax was correlated with emax(r =0.418,P ＜0.001),and E was correlated with Em (posterior septum,r =0.610,P ＜0.001 ；anterior wall,r =0.499,P ＜0.001).③There was a medium correlation between normal longaxis strain in segments and adjacent intraventricular pressure gradients (the global,r =0.412,P ＜0.001 ；posterior septum,r =0.319,P ＜0.005).Conclusions The acquirement of E and Em by dual-PW Doppler showed downtrend of segmental wall movement and regional blood flow from basal segment to apex.Emax is correlated with e E is correlated with Em,and long-axis strain at segments is correlated with adjacent intraventricular pressure gradients partly.Dual-PW Doppler might provide a potential method for the more precise evaluation of left ventricular fluid-solid coupling during diastole.