Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

UPLC-MS/MS determination of active components from Wuzhuyu Decoction in plasma and brain tissues of nitroglycerin-induced migraine rats / 中国中药杂志

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was deve-loped for analysis of rutaecarpine(Ru), evodiamine(Ev), rutaevine(Rv), limonin(Li), ginsendside Rb_1(Rb_1), ginsendside Re(Re) in rat plasma and brain tissues of nitroglycerin-induced migraine rats. Male healthy Sprague-Dawley(SD) rats were orally given multiple dose of optimized(OS) and un-optimized Wuzhuyu Decoction(UNOS), and their blood samples and brainstem were collected at different time points after injection of nitroglycerin(10 mg·kg~(-1)) into the frontal region. The drug concentrations of the 6 analytes in plasma and brainstem were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma were calculated by using Phoenix WinNolin 5.2.1 software. The methodological test showed that all of analytes in both plasma and brainstem homogenate exhibited a good linearity within the concentration range(r>0.994 7). The intra-day and inter-day accuracy, precision, matrix effect, stability of the investigated components meet the requirements for biopharmaceutical analysis. The developed method was successfully applied in pharmacokinetic studies on abovementioned ingredients in rat plasma and brain stem. The plasma pharmacokinetic parameters of active ingredients in two different Wuzhuyu Decoction group were compared, it was found that Rb_1 had higher t_(1/2), T_(max), C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. Meanwhile, Ev had higher t_(1/2) and T_(max) but lower C_(max), AUC_(0-24 h) and AUC_(0-∞), Ru has higher t_(1/2 )but lower C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. The brain tissue distribution of each component were compared between the two groups, the component with higher content in OS, such as Ru at 30 min and 2 h after administration, Ev at 30 min, Rb_1 at 30 min and Rb_1 at 2 h after administration have lower brain tissue distribution than those in UNOS group, while the component with higher content in UNOS, such as Rv at 30 min, 2 h and 12 h after administration had higher brain tissue distribution than those in OS group.

Difference in intestinal absorption of Wuzhuyu decoction between normal and migraine model rats / 中国中药杂志

To compare the intestinal absorption of Wuzhuyu decoction(WZYD) between normal rats and migraine model rats, and investigate the optimized WZYD from aspect of absorption. The rat single pass intestinal perfusion test(SPIP) was adopted for optimized sample and un-optimized sample in normal and migraine model rats induced by nitroglycerin and reserpine. The contents of 8 ingredients were determined by high performance liquid chromatography(HPLC), and 4 absorption parameters for each ingredient were calculated and compared: unit area absorption(Mper area), absorption rate constant(Ka), apparent coefficient(Papp) and relative absorption rate(RA). The results showed that there was a great difference between normal rats and model rats in the intestinal absorption of the same WZYD. As compared with normal rats, the absorption parameters of most ingredients in optimized sample were increased in migraine model rats induced by nitroglycerin; Similar phenomena were also found in migraine model rats induced by reserpine. However, the absorption parameters of most ingredients were decreased in un-optimized sample. Therefore, pathological model rats shall be used for effective ingredient recognition based on the correlation between intestinal absorption spectra and pharmacological effects. As compared with the un-optimized samples, the absorption of effective ingredients was faster, easier and more adequate in the optimized samples, revealing their mechanism on better efficacy from the aspect of absorption.

Study on correlation between color and effective components contents of Glycyrrhiza uralensis / 中国中药杂志

To explore the correlation between color of Glycyrrhiza uralensis and its quality evaluation,the colors of root bark and transverse section were determined by Precision Color Reader and Visual Analyzer,and the contents of six flavonoids and two saponins in G.uralensis were determined by high performance liquid chromatography（HPLC）.The partial least squares regression（PLSR）method was employed to correlate the colors with component contents in G.uralensis. The results showed that there were no significant differences in the colors of root bark but significant or very significant differences（P<0.05,P<0.01）in the colors of transverse section between the wild and cultivated G. uralensis. Compared with those in the cultivated G. uralensis, the contents of liquiritin, isoliquiritin isoliquiritigenin and the contents of ammonium glycyrrhizinate, glycyrrhetinic acid were obviously significant or remarkably significant in the wild G. uralensis.The correlation results showed that there was a significant or very significant correlation between the colors and the effective component contents. This study provides a scientific basis to evaluate the quality of G.uralensis by color and a new reference for the traditional evaluation methods for Chinese drugs.

Effects of arteannuin B, arteannuic acid and scopoletin on pharmacokinetics of artemisinin in mice

Objective To explore the effects of arteannuin B, arteannuic acid and scopoletin on the pharmacokinetics of artemisinin in mice. Methods Artemisinin and a combination of artemisinin, arteannuin B, arteannuic acid and scopoletin were administered together to mice via oral administration. Blood samples were collected at different time intervals and pretreated by liquid–liquid extraction. The contents of four compounds in mouse plasma were determined by a validated HPLC-MS/MS method. Results Compared to single artemisinin group, the C

Effects of arteannuin B, arteannuic acid and scopoletin on pharmacokinetics of artemisinin in mice

OBJECTIVE@#To explore the effects of arteannuin B, arteannuic acid and scopoletin on the pharmacokinetics of artemisinin in mice.@*METHODS@#Artemisinin and a combination of artemisinin, arteannuin B, arteannuic acid and scopoletin were administered together to mice via oral administration. Blood samples were collected at different time intervals and pretreated by liquid-liquid extraction. The contents of four compounds in mouse plasma were determined by a validated HPLC-MS/MS method.@*RESULTS@#Compared to single artemisinin group, the Cmax values from the combination group rose from 947 ng/mL to 1254 ng/mL. AUC(0-t) (2371 h ng/mL) was significantly higher than that from single artemisinin group (747 h ng/mL). The peak time lag and the CL values reduced at a proportion of 66%.@*CONCLUTIONS@#Arteannuin B, arteannuic acid and scopoletin can markedly affect the pharmacokinetics of artemisinin.

Study on intestinal absorption of ingredients from different compatibilities of Shaoyao Gancao decoction / 中国中药杂志

To study the compatible mechanisms and compatible proportion of Shaoyao Gancao decoction, the intestinal absorption of main ingredients in Shaoyao Gancao decoction SG11 (Baishao-Zhigancao 1: 1) , SG31 (Baishao-Zhigancao 3: 1), Baishao water decoction S and Zhigancao (G) were investigated and compared using in vitro everted intestinal sac model and in situ single pass intestinal perfusion (SPIP) model. The concentration of paeoniflorin (PF), liquiritin (LQ) and mono-ammonium glycyrrhizinate (GL) in test samples and samples of intestinal sac and intestinal perfusion was determined by HPLC. The intestinal absorptive amount and absorption parameters were calculated. Results showed that in the everted intestinal sac model, three ingredients could be absorbed by duodenum, jejunum and ileum, and the absorption in the jejunum was best for all 3 ingredients. The absorption rate of three ingredients in SG11 was significantly higher than that in single decoction (P < 0.05), but had no significant difference compared with SG31. In SPIP model, the absorption rate constant K(a), the apparent absorption coefficient P(app) and the absorption rate of three ingredients in SG11 were significantly higher than those in single decoction. Parameters of PF and GL in SG11 were significantly higher than those in SG31, but had no differences of LQ. It proved that the compatibility of Baishao and Zhigancao could improve the intestinal absorption of PF, LQ and GL. The absorption of each ingredient in SG11 was better than that in SG31.

Triterpenoids from Stauntonia obovatifoliola Hayata subsp. intermedia stems / 中国中药杂志

In the current study, a total of nineteen triterpenoids (1-19) from 60% EtOH extracts of Stauntonia obovatifoliola Hayata subsp. intermedia stems were separated and purified by solvent extraction and chromatographic methods including silica gel, ODS as well as preparative HPLC. According to the results of chemical reactions and spectral data, compounds were identified as: lupeol (1), betulinonic acid (2), betulinic acid (3), 3-epi-betulinic acid (4), quinatic acid (5), 24-O-acetyl quinatic acid (6), 3-O-α- L-arabinopyranosyl-30-nor-hederagenin-28-O-α-L-rhamnopyranosyl-(1 --> 4) -β-D-glucopyranosyl-(1 --> 6) -β-D-glucopyranosyl ester (7), Stauntoside A (8), kalopanax saponin A (9), kalopanax saponin J (10), Kizuta saponin K10 (11), 3-O-α-L-rhamnopyranosyl (1--> 2) -α-L-arabinopyranosyl-hederagenin-28-O-β-D-xylopyranosyl-(1 --> 6) -β-D-glucopyranosyl ester (12), kalopanax saponin B (13), 3-O-α-L-rhamnopyranosyl-(1 --> 2) -α-L-arabinopyranosyl-hederagenin-28-O-β-D-glucopyranosyl-(1 --> 6) -β-D-glucopyranosyl ester (14), sieboldianoside A (15), septemoside A (16), kalopanax saponin K (17), septemloside I (18), and 3-O-α-L-arabinopyranosyl (1 --> 2)-β-D-glucuronopyranosyl- hederagenin (19). Among them, compounds 4, 6, 10, 12, 14, and 16-19 were isolated from the Stauntonia genus for the first time, and compound 6 was a new natural product.

Study on pharmacological ingredients of wuzhuyu tang treating migraine by correlating absorption ingredients in everted intestinal sac and pharmacodynamics / 中国中药杂志

Wuzhuyu Tang is a classical formula for treating migraine, but its' pharmacological ingredients is unclear yet. Present study employed the everted intestinal sac model to collect the absorption samples of 10 kinds of Wuzhuyu decoction, and then analyzed the contents of 9 ingredients in Wuzhuyu Tang and absorption samples quantitatively or semi-quantitatively by HPLC-DAD method. Reserpine was used to establish the mice model of migraine, and then the contents and activities of 5-hydroxytryptamine, noradrenaline, dopamine, nitric oxide and nitricoxide synthase in brain tissues and serums were determined respectively after oral administration of Wuzhuyu Tang. Using the partial least squares regression method to correlate the total absorption quantity of 9 ingredients and pharmacodynamics. The result shows that limocitrin-3-O-beta-D-glucoside, ginsenoside Rg1 and Rb1, rutaevine, limonin, evodiamine and rutaecarpine are the main ingredients influenced the effects in absorption samples in everted intestinal sacs, especially ginsenoside Rg1, rutaevine, evodiamine and rutaecarpine among them have obvious improving effects to most pharmacodynamics index, might be the pharmacological ingredients influenced the therapeutical effects of Wuzhuyu Tang treating migraine.

A new beta-naphthalenecarboxylic acid biglycoside from Chirita longgangensis var. hongyao / 药学学报

To investigate the chemical constituents in the stems of Chirita longgangensis var. hongyao, methanol extract of the stems was subjected to column chromatography with various chromatographic techniques. One new beta-naphthalenecarboxylic acid biglycoside, 1, 4-dihydroxy-2-naphthalenecarboxylic acid methyl ester-4-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (1) was isolated, along with two known compounds: isotaxiresinol 4-O-methyl ether (2) and (R)-7-hydroxy-alpha-dunnione (3). Compound 2 was first obtained from Chirita genus and compound 3 was isolated from this plant for the first time. All structures were elucidated on the basis of spectral and chemical evidence, and the NMR spectroscopic data of compound 2 was published for the first time.

Opinions on research patterns for pharmacodynamic chemical substances in compound prescription of Chinese medicinal materials / 中国中药杂志

The research patterns for the pharmacodynamic chemical substances in compound prescriptions of Chinese medicinal materials in recent years were summarized, and the deficiencies of the commonly used patterns were commented on. A research pattern for the pharmacodynamic chemical substances in compound prescriptions of Chinese medicinal materials was raised, which is suitable for the characteristics of the Chinese medicine. The trend of the research work was predicted, which would provide some thinking for the pharmacodynamic chemical substances in compound prescription of Chinese medicinal materials.

Determination of zizybeoside II of Ziziphus jujuba by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a quantitative method for determination of zizybeoside II in Ziziphus jujuba.</p><p><b>METHOD</b>The samples were separated at 30 degrees C on a Zorbax SB-C18 column eluted with methanol-water (20 : 80) as the mobile phase. Flow rate was set at 1.0 mL x min(-1) and the detection wavelength was set at 210 nm.</p><p><b>RESULT</b>The calibration curve was linear within the range from 0.046 to 0.582 microg (r = 0.999 9) and the average recovery was 97.2%. 12 batches of the crude drugs purchased from different areas were determined and the contents of zizybeoside II in Fructus Jujubae were fluctuated from 0.013% to 0.041%.</p><p><b>CONCLUSION</b>The method is simple, repeatable and could be used for the quality control of Z. jujuba.</p>