Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium:Integration of herbal medicine,enzyme engineering,and nanotechnology / 药物分析学报

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.

Protective effect and mechanism of Ecliptae Herba on cigarette smoke extract-induced cytotoxicity of NHBE cells / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effect and mechanism of Ecliptae Herba extract on cigarette smoke extract-induced cytotoxicity.</p><p><b>METHOD</b>The effect of Ecliptae Herba extract on CSE-induced NHBE cell proliferation was detected by MTT assay. GSH content was determined by DTNB colorimetry. GST activity was measured by CDNB colorimetric assay. NQO1 activity was detected by NADPH and DCIP. The protein expression was determined by Western blot assay.</p><p><b>RESULT</b>Ecliptae Herba extract reduced CSE's inhibitory effect on NHBE cells, recover the decrease in intracellular GSH caused by CSE and reduce the CSE-induced activity of GST and NQO1 and NQO1 protein expression.</p><p><b>CONCLUSION</b>Ecliptae Herba extract can reduce CSE-induced injury on NHBE cells, which may be related to phase II detoxification enzymes.</p>

Construction of multiple drug release system based on components of traditional Chinese medicine / 中国中药杂志

With the development of the modernization drive of traditional Chinese medicine (TCM) preparations, new-type TCM dosage forms research have become a hot spot in the field. Because of complexity of TCM components as well as uncertainty of material base, there is still not a scientific system for modern TCM dosage forms so far. Modern TCM preparations inevitably take the nature of the multi-component and the general function characteristics of multi-link and multi-target into account. The author suggests building a multiple drug release system for TCM using diverse preparation techniques and drug release methods at levels on the basis the nature and function characteristics of TCM components. This essay expounds elaborates the ideas to build the multiple traditional Chinese medicine release system, theoretical basis, preparation techniques and assessment system, current problems and solutions, in order to build a multiple TCM release system with a view of enhancing the bioavailability of TCM components and provide a new form for TCM preparations.

New idea of traditional Chinese medicine quality control based on "composition structure" theory / 中国中药杂志

On the road of the modern Chinese medicine developing internationally, there is a key issues that setting up a reasonable, accurate and be quantified quality evaluation system which is comply with the basic theory of Chinese medicine. Based on the overall understanding of the role of traditional Chinese medicine components, author suggested that the idea of "structural components" theory should be embedded into the system and thought the Chinese medicine play a multi-target, multi-channel pharmacodynamic effects founded on the specific microcosmic structural relationship between the components and the components within the group. At present, the way of Chinese pharmacopoeia checking the quality of Chinese medicine is mainly depends on controlling the single or multiple targets of ingredients. In fact, this way is out of the overall effectiveness of the Chinese medicine, so we can not thoroughly controlling the quality of Chinese medicine from the essence of the Chinese medicine. Secondly, it's only macro-structural quantity that the Chinese pharmacopoeia just controlling the less effective ingredients, this is not enough to reflect the internal microstructure of the integrity and systematic. In other words, this cannot reflect the structural components of the Chinese medicine (the essence of traditional Chinese medicine). In view of above mentioned reasons, the author propose the new idea on the quality control in the medicine that quantify the ratio structural relationship in component and the ingredients of the components, set the optimal controlling proportion between the components and ingredients. At the same time, author thought we should conduct the depth study in the micro-quantified the multi-component and multi-ingredient, in the process of studying the material basis of Chinese medicine. Therefore, it could establish a more rational basis for the Chinese medicine quality controlling system.

Study on solid dispersion of binary vector of tanshinone II A / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare the solid dispersion of tanshinone II A (TS II A) by the combined application of nano-silica and poloxamer 188 (F68), in order to observe its dissolution and stability.</p><p><b>METHOD</b>Tanshinone II A solid dispersion was prepared by the solvent method with nano-silica and poloxamer 188 as binary vectors. Its physical characteristics, in vitro dissolution and stability were further assessed.</p><p><b>RESULT</b>The tanshinone II solid dispersion was prepared with the weight ratio of nano-silica and poloxamer 188 of 1: 3. The differential scanning calorimetry (DSC) demonstrated that Tanshinone II A existed in vectors as amorphous state. The in vitro dissolution of tanshinone II A solid dispersion is up to 90% at 60 min. Accelerating experiment showed that content and in vitro dissolution of tanshinone II A solid dispersion did not change after storage over 3 months.</p><p><b>CONCLUSION</b>Solid dispersion of binary vector of tanshinone II A can obviously improve the dissolution and stability of tanshinone II in practice.</p>

Multi-channel analysis and comparison on absorption difference between paeoniflorin and Paeonia lactiflora extracts / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the difference of the absorption difference between paeoniflorin monomer and Paeonia lactiflora extracts in rat intestinal canals by multi-channels.</p><p><b>METHOD</b>The rat intestinal perfusion model was established. The intestinal perfusate, bile and plasma samples were collected, in combination of the intestinal enzymes incubation test and the partition coefficient determination, to conduct a multi-channel analysis and comparison on absorption difference between paeoniflorin and P. lactiflora extracts.</p><p><b>RESULT</b>In the same concentration, permeability coefficient P(eff)* of paeoniflorin in the different intestinal segments of P. lactiflora extract higher than the monomer of paeoniflorin, especially in the jejunum and ileum intestinal segments (P < 0. 05). However, both paeoniflorin monomer and P. lactiflora extracts showed less P(eff)* in four intestinal segments, with the former ranging between 0. 209-0.290 and the latter 0.252-0.333. No paeoniflorin and its metabolin was determined in bile samples, plasma samples and intestinal enzymes incubation samples of paeoniflorin monomer and P. lactiflora extracts.</p><p><b>CONCLUSION</b>Compared with the paeoniflorin monomer, P. lactiflora extract showed significantly increase in P(eff)*, which indicated that other ingredients in the extract can improve the absorption of paeoniflorin. However, due to the poor absorption of paeoniflorin, this effect fails to increase the concentration of paeoniflorin in bile and plasma within short period of time.</p>

Ideas and methods of fresh herb basic research based on constituent structure theory / 中国中药杂志

Application of fresh herbs is a kind of special forms of traditional Chinese medicine. In China, there is a long and rich experience in clinical application of fresh herbs. Many studies showed that the efficacy of fresh herbs was better than that of dried herbs, but the further study about the difference of their chemical composition, effective components and the overall material basis were few. In this paper, the ideas and methods to study on material basis of the fresh herbs by comparing the difference of the fresh and dry herbs in medicine chemical composition and pharmacological activity of effective components with modern advanced separation, analysis and screening technology under the "Constituent structure theory" were proposed. It was an effectual method for studying on the reasonable development of Chinese medicine and fresh herbs resources.

Chromatographic fingerprint of Dipsacus asper and analysis by HPLC-MS / 中国中药杂志

A high performance liquid chromatography (HPLC) method was developed for fingerprint of Dipsacus asper. Analysis were carried out on a Zorbax C-18 column by gradient elution using 0.1% phosphoric acid and acetonitrile as the mobile phases. The column was maintained at 25 degrees C, the flow rate was 1 mL x min(-1), and the detection wavelength was set at 205 nm. Asperosaponin VI was selected as reference compound, Seventeen common peaks were selected, and the fingerprint with good precision, stability and repeatability was successfully used to evaluate quality of 24 batches of crude extracts of D. asper. Chemical characteristics of D. asper was analyzed by DAD detection and HPLC-MS techniques with an ESI source. The quasi-molecular ions of compounds in both negative and positive modes were observed for molecule mass information of 33 compounds, and the potential structures of 10 characteristic components were identified by study on the mass spectra of compounds and comparing with reference data and some of standards. The results indicate the HPLC fingerprint of D. asper will show more characters through identification of component structures using an HPLC-ESI-MS method, and will control the quality of D. asper more effectively and reasonable.

Optimization of extraction procedure of tongmai granules by orthogonal design with pharmacodynamic index / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize the extraction technology for anti-myocardial ischemia active component group in tongmai granules.</p><p><b>METHOD</b>The extracting conditions were optimized by using orthogonal experiment and pharmacodynamic index. Employing puerarin, ferulic acid, tanshinone IIA, and salvianolic acid B as indexes, the effects of ethanol concentration, solvent volume, extraction times and extraction time on the extracting process were investigated.</p><p><b>RESULT</b>The optimum extraction process was adding 8 times amount of 70% alcohol, refluxing and extracting for 3 times, 1.5 h each time.</p><p><b>CONCLUSION</b>This extraction process shows good stability and is available for extracting anti-myocardial ischemia component group in tongmnai granules.</p>

Simultaneously determination of atropine sulphate, diphenhydramine hydrochloride, capsaicin and dihydrocapsaicin in pain-relieving plaster for arthritis by RP-HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish RP-HPLC method for determination of atropine sulphate, diphenhydramine hydrochloride, capsaicin and dihydrocapsaicin in pain-relieving plaster for arthritis.</p><p><b>METHOD</b>The sample were separated on an Alltima C18 Column (4.6 mm x 250 mm, 5 microm) with the moblie phase of CH3 CN-0.1% H3 PO4. Flow rate was 1 mL x min(-1). The detective wavelength was set at 210 and 280 nm. Column temperature was 30 degrees C.</p><p><b>RESULT</b>The calibration curve for atropine sulphate, diphenhydramine hydrochloride, capsaicin and dihydrocapsaicin revealed linearity in the range of 2.01-50.25, 15.08-377.00, 5.02-125.50, 5.03-125.75 mg x L(-1), respectively. The recoveries of atropine sulphate, diphenhydramine hydrochloride, capsaicin and dihydrocapsaicin were 99.00% with RSD of 0.95%, 99.89% with RSD of 1.2%, 100.1% with RSD of 1.5% and 99.51%, with RSD of 1.4%, respectively.</p><p><b>CONCLUSION</b>The method is simple, rapid and accurate, which is suitable for the quality control of pain-relieving plaster for arthritis.</p>

Market investigation report on Epimedium material drugs and decoction pieces / 中国中药杂志

According to the survey on 7 medicinal material markets, 15 factories of Chinese materia medica slices, 27 medicine shops and 110 samples collected, this report anglyzed and summarized, the sources, provenances, characters of crude drugs, characters of decocting slices and merchandise circulation of Epimedium material drugs and decoction pieces.

Correlation of powder properties and formability of traditional Chinese medicine pellets / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the correlation of powder properties and formability of traditional Chinese medicine pellets prepared by extrusion/spheronization.</p><p><b>METHOD</b>The present effort was designed to evaluate the effects of the characters of powder on pellets formation by extrusion-spheronization, taking Danggui Buxue decoction extracts as a model drug and microcrystalline cellulose (MCC) as an ideal balling material for extrusion-spheronization.</p><p><b>RESULT</b>The diameter of powder had correlation with the plane critical angle of pellets in a certain scope and the sticky coefficient of wet mass affected roundness of pellets.</p><p><b>CONCLUSION</b>Properties of powder have influence on formability of traditional Chinese medicine pellets.</p>

Study on preparation of CIT microemulsion and its absorption in intestine / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare CIT microemulsion and to investigate its properities and the absorption character in rat intestine in situ.</p><p><b>METHOD</b>The optimum formulation of the blank microemulsion was selected by pseudo tertiary phase diagrams and the CIT microemulsion was prepared based on the blank microemulsion. The appearance, particle diameter distribution and Zeta potential were investigated by electron microscopy and grainsize analyzer. The entrapment efficiency was determined by sephadex column chromatography. An in situ single pass intestine perfusion method was used to investigate the intestinal absorption of CIT microemulsion. HPLC method for determination of CIT in the intestinal flux was established.</p><p><b>RESULT</b>The formulation was OP-glycerol-water-ethylis oleas (3:3:4:2). CIT microemulsion in electron microscopy was consisted of small spherical drop. The mean diameter was 61.7 nm, Zeta potential was -46.3 mV. The Entrapment efficiency was (92.1 +/- 1.74)% (n=3). Both CIT and CIT microemulsion had been absorbed in general intestinal tract,and the absorption of CIT microemulsion was significantly high compared with CIT in duodenum, colon, jejunum and ileum (P < 0.01).</p><p><b>CONCLUSION</b>The preparation technology of CIT microemulsion was feasible,and the microemulsion system might improve the absorption of CIT in the intestinal tract.</p>

Intestinal absorption properties of flavones and extract of fructus aurantii immaturus in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the intestinal absorption of naringin, hesperidin, neohesperidin and the extract of Fructus Aurantii Immaturus in rats.</p><p><b>METHOD</b>The rat intestinal perfusion and enzymes incubation models were used, together with the determination of the n-octanol/water partition coefficient of the components (P).</p><p><b>RESULT</b>In perfusion model, the P(eff) of all components were low, and the P(eff) of naringin, hesperidin and neohesperidin were 0.140-0.252, 0.156-0.268 and 0.154-0.285, respectively. In four different regions of intestine of rat and with different concentration, the P(eff) of the components both had no significant difference, whereas the P(eff) of the extract were higher than the P(eff) of the single component. The metabolite of components was not detected in intestine. The P of naringin, hesperidin and neohesperidin were 0.36, 0.40 and 0.48, respectively, and the pH of buffer solution had no influence to its distribution coefficient.</p><p><b>CONCLUSION</b>Poor permeation contributed to the poor intestinal absorption of naringin, hesperidin and neohesperidin. The absorption of components in extract were increased, and the results suggest that the extract may enhance the intestinal absorption of the components.</p>

Comparison of content of clemastanin B of Radix Isatidis in different growing areas / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method for determination of clemastanin B which has anti-viral activity in Radix Isatidis and compare the contents of clemastanin B in the drugs from different origins.</p><p><b>METHOD</b>The samples were separated on an ZORBAX SB-C18 (4.6 mm x 250 mm, 5 microm) column with the mobile phase of acetonitrile-water (11:89). Flow rate was 1.0 mL x min(-1). The detection wavelength was set at 225 nm. Column temperature was 30 degrees C.</p><p><b>RESULT</b>The linear range of clemastanin B was 0.0615-1.8441 microg (r = 0.9995), the average recovery was 97.74%, RSD was 1.4% (n=9). The contents of clemastanin B were in the range of 0.269-0.900 mg x g(-1) in Radix Isatidis from different origins.</p><p><b>CONCLUSION</b>The method for quantitation of clemastanin B in Radix Isatidis was accurate and reliable, which can be used to evaluate the quality of Radix Isatidis.</p>

Conditions for extraction of ergosterol from fruits of Ganoderma lucidum using supercritical fluid extration / 中国中药杂志

<p><b>OBJECTIVE</b>To study the feasibility of supercritical fluid extraction (SFE) for extraction of ergosterols from the fruits of Ganoderma lucidum.</p><p><b>METHOD</b>Optimum extraction conditions were studied by orthogonal tests, the ergosterol were analyzed by RP-HPLC.</p><p><b>RESULT</b>The optimal extraction conditions were pressure as 20 MPa, temperature at 45 degrees C, using ethanol as modifier carrier at the volume of 1 mL x g(-1), and 1.5 hour of extraction time.</p><p><b>CONCLUSION</b>SFE has the superiority of adjustable polarity, and has the ability of extracting ergosterol from fruits of Ganoderma lucidum.</p>

Absorption and metabolism of flavonoids in Herba Epimedii via rat intestinal perfusion model / 中国中药杂志

<p><b>OBJECTIVE</b>To study the absorption and metabolism of five flavonoids of Herba Epimedii (icariin, epimedin A, epi-medin B, epimedin C and baohuoside I) in rat intestine.</p><p><b>METHOD</b>Using the rat intestinal perfusion model, the contents of the five flavonoids in perfusates were measured by HPLC and the permeability coefficients in different intestines were calculated.</p><p><b>RESULT</b>The permeabilities of five flavonoids in duodenum, jejunum, ileum, colon according to the sequence were as: icariin: 6.365, 5.349, 1.004, 0.601, epimedinA: 4.120, 3.397, 0.401, 0.257, epimedin B: 3.645, 3.135, 0.990 7, 0.434, epimedin C: 3.114, 2.882, 0.688, 0.470, baohuoside I: 2.324, 2.398, 1.529, 1.045, respectively. The analysis of the perfusates showed that icariin, epimedin A, epimedin B, epimedin C could be hydrolyzed in intestine. Icariin had two hydrolytic metabolites, whereas epimedin A, B, C only had one hydrolytic metabolite, respectively.</p><p><b>CONCLUSION</b>The results indicated that the absorption of all the five flavonoids was significantly different in different intestinal segments, and the permeability in ileum and colon was significantly lower than that of the duodenum and jejunum. The metabolites of icariin, epimedin A, epimedin B, epimedin C were related with their structures and enzymes in intestine, and the metabolites were more in duodenum, jejunum, whereas were less in ileum and colon.</p>

Research on variation regularity of five main flavonoids contents in Epimedium and processed Epimedium / 中国中药杂志

<p><b>OBJECTIVE</b>To research on the variation regularity of the five main flavonoids contents in Epimedium and processed Epimedium.</p><p><b>METHOD</b>The contents of Epimedin A, Epimedin B, Epimedin C, Icariin and Baohuoside I in Epimedium and processed Epimedium were determined, respectively.</p><p><b>RESULT</b>There were varieties in the contents of Epimedin A, Epimedin B, Epimedin C, Icariin and Baohuoside in Epimedium and processed Epimedium. There were different variety tendencies in different species and different batches.</p><p><b>CONCLUSION</b>The variety tendencies of the contents of five main flavonoids depend on the processing technology and the flavonoids proportion in Epimedium and processed Epimedium.</p>

Progress in research of processing of fructus Evodiae-Rhizoma Coptidis and research thoughts and methods of its processing mechanism / 中国中药杂志

This article ascended the history and successive changes of the processing research of Fructus Evodiae-Rhizoma Coptidis, and its application in classic prescription; made a summary on the research of the processing technology and substances of Fructus Evodiae-Rhizoma Coptidis; discussed the progress in the research of processing of Fructus Evodiae-Rhizoma Coptidis; expounded the overview on mechanism research of the processing of Fructus Evodiae-Rhizoma Coptidis, and proposed new thoughts and methods for the processing of Fructus Evodiae-Rhizoma Coptidis.