Triterpenoids are one of the most active constituents in Ligustri Lucidi Fructus, but only oleanolic acid has been mostly studied. In recent years, a growing number of studies have shown that other triterpenes from Ligustri Lucidi Fructus also have various biological activities, so it is necessary to build up a detailed profile of the triterpenoids in Ligustri Lucidi Fructus. The chromatographic separation was performed on a C_(18) column(4.6 mm×250 mm, 5 μm) with mobile phase of methanol-acetonitrile-0.2% formic acid for gradient elution. The detection wavelength was set at 210 nm, with a flow rate of 0.5 mL·min~(-1), and the column temperature of 25 ℃. The HPLC fingerprint of triterpenoids in Ligustri Lucidi Fructus was built by testing 21 batches of samples from different sources. The structures of the total 15 common chromatographic peaks were elucidated with UHPLC-ESI-Orbitrap-MS/MS technique and six of them were identified as tormentic acid, pomolic acid, maslinic acid, botulin, oleanolic acid and ursolic acid by comparison to the reference substances. Under the same chromatographic condition, four main triterpenes(podocarboxylic acid, hawthorn acid, oleanolic acid and ursolic acid) were quantified and the results of system adaptability and methodology investigation all met the requirements of content determination. Meanwhile, with oleanolic acid(A) as the internal reference substance, quantitative analysis of multi-components by single marker(QAMS) method was used to analyze the above four components. The relative correction factor of oleanolic acid(B), hawthorn acid(C) and ursolic acid(D) to oleanolic acid was f_(B/A)=1.12, f_(C/A)=1.02 and f_(D/A)=0.88, respectively, and the relative retention values of these three to oleanolic acid was RRV_(B/A)=0.46, RRV_(C/A)=0.70 and RRV_(D/A)=1.03, respectively. The contents determined by two methods were similar. In conclusion, the method built in this paper is proved to be simple, reliable and specific for the simultaneous qualitative and quantitative analysis of the triterpenoids in Ligustri Lucidi Fructus, which can lay foundation for further assays of the triterpenoids in Ligustri Lucidi Fructus and the relative products.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Fruit ; Ligustrum ; Tandem Mass Spectrometry ; Triterpenes

A quantitative analysis method for ten principal components (phenylethanol, iridoids and triterpenes) of raw Ligustri Lucidi Fructus and its wine-steamed product was developed using liquid chromatography tandem triple quadrupole mass spectrometry (LC-QQQ-MS) to study their pharmacokinetic behavior in vivo. The results of methodological investigation were in accord with the criteria of biological analysis. After a single administration to rats of the water extracts of Ligustri Lucidi Fructus and its wine-steamed product, the plasma concentration of each component at different time points was measured and the pharmacokinetic parameters were determined. The AUC_{0-24 h} and C_max of the phenylethanol components (salidroside, tyrosol, hydroxytyrosol) were the greatest, suggesting that these components are the main pharmacological substances of Ligustri Lucidi Fructus. In addition, the t_max values of the eight major components were even lower with administration of the wine-steamed product, suggesting that these components are rapidly absorbed. However, the t_max values of specnuezhenide and oleanolic acid were greater with administration of the wine-steamed product, indicating that these two components were more slowly absorbed. A secondary peak phenomenon of tyrosol and hydroxytyrosol were observed in two sample groups, whereas the secondary peak phenomenon of salidroside occurred only with the wine-steamed product. This result suggests that the effect of wine-steamed product could persist for a long period. Meanwhile, the relative bioavailability of specnuezhenide and oleanolic acid was greater than 100% with administration of the wine-steamed product, consistent with the Traditional Chinese Medicine theory of the wine-steamed product being more effective than the raw material. The results reveal the different pharmacokinetic parameters and relative bioavailability of each component of Ligustri Lucidi Fructus and its wine-steamed product, and also demonstrate the variation and correlation of various components in vivo and in vitro, providing an experimental basis for the selection of quality control indexes, mechanisms of processing and the metabolic rule in vivo of Ligustri Lucidi Fructus. These experiments were approved by the Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medicine Science.

Objective:To explore the correlation between the level of heart rate deceleration (DC), serum homocysteine(Hcy), the scope and extent of coronary artery lesion in coronary heart disease patients with hypertension.Methods:From January 2019 to October 2019, 103 coronary heart disease patients with hypertension who were diagnosed and hospitalized in cardiovascular department of Binzhou Central Hospital were selected as coronary heart disease(CHD) group, and 52 patients with simple hypertension were selected as control group.The serum Hcy levels of the two groups were measured and analyzed.The DC value and the difference of the two groups were analyzed.The degree of coronary artery lesion was evaluated by the number of coronary artery lesion and Gensini score.The relationship between DC, Hcy and the degree of coronary artery lesion was analyzed.Results:Compared with the control group, the DC value of CHD group was significantly lower [(6.02±1.97)ms vs.(4.97±1.59)ms, t=-3.989, P<0.05], and the serum Hcy level was increased [(11.46±4.38)μmol/L vs.(16.79±6.31)μmol/L, t=4.260, P<0.05]. In the CHD group, the DC values and Gensini scores of the patients with single vessel lesion, double vessel lesions and three vessel lesions were (5.52±1.34)ms, (5.06±1.29)ms, (4.39±1.19)ms, (21.35±17.10)points, (26.93±18.18)points, (49.39±30.14)points, respectively.The DC value of patients with three vessel lesions was lower than that of patients with single vessel lesion( F=7.349, P<0.05), and the Gensini score was higher( F=13.487, P<0.05). There were no statistically significant differences in DC value and Gensini score between patients with three vessel lesions and those with two vessel lesions and those with single vessel lesion( P>0.05). The serum Hcy levels of patients with single, double and three vessel lesions were (14.67±5.97)μmol/L, (15.85±6.29)μmol/L and (16.97±7.13)μmol/L, respectively.The difference among the three groups was statistically significant ( F=12.427, P<0.05). There was a negative correlation between DC and Gensini score( r=-0.310, P<0.05), and a positive correlation between serum Hcy and Gensini score( r=0.369, P<0.05). Conclusion:The DC value and Hcy level in coronary heart disease patients with hypertension are significantly decreased, which are closely related to the degree of coronary artery lesion.

This paper reviewed the literatures of TCM treating diabetes mellitus and pulmonary tuberculosis from two aspects, Chinese patent medicine and TCM decoctions, which showed that TCM therapy can control blood sugar levels, improve clinical symptoms such as cough, expectoration and wheezing, promote pulmonary tuberculosis lesion absorption, cavity closure and sputum vaginal discharge, and improve patients' quality of life.

HPLC specific chromatograms of Poria were established, and the concentrations of 10 triterpenoids(16α-hydroxydehydrotrametenolic acid, poricoic acid B, dehydrotumulosic acid, poricoic acid A, polyporenic acid C, poricoic acid AM, 3-O-acetyl-16α-hydroxydehydrotrametenolic acid, dehydropachymic acid, pachymic acid, and dehydrotrametenolic acid) were simultaneously determined. Chromatographic analysis was conducted on a Welch Ultimate XB C_(18) column(4.6 mm × 250 mm,5 μm). Acetonitrile solution(contain 3% tetrahydrofuran)(A) and 0.1% formic acid aqueous solution(B) were used as the mobile phase with gradient elution at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the injection volume was 20 μL. The experimental data were analyzed by the SPSS 22.0 and GraphPad Prism 7.0. The established triterpenoids fingerprints were specific, and the 10 components were well separated and showed good linearity(r≥0.999 6) within the concentration ranges tested. The mean recoveries were between 98.53%-103.8%(RSD 1.7%-2.7%). The method was specific and repeatable, and could be used for identification and quality evaluation of Poria. The results showed that the contents of 10 triterpenoids were positively correlated with each other. The contents of 10 triterpenoids of samples collected from producing areas were higher than that collected from markets. The total contents of 10 triterpenoids of samples collected from Hubei and Yunnan province were slightly higher than that from Anhui province, but the contents of samples from Anhui province were varied in smaller ranges.
China ; Chromatography, High Pressure Liquid ; Materia Medica ; analysis ; Poria ; chemistry

Objective:To design and synthesize series of rotundic acid derivatives by introducing aromatic ester groups with rotundic acid as the parent nucleus, test their anti-tumor activity in vitro,investigate the structure-activity relationship of rotundic acid derivatives in inhibiting tumor cell proliferation, and obtain the novel rotundic acid derivatives with high anti-tumor activity. Method:Compounds 1-8 were synthesized with rotundic acid as the initial raw material through the 28-etherification,3β and 23di-aromatic esterification eaction. The anti-tumor activities in vitro were evaluated by MTT assay against A375 (human malignant melanoma cells),HeLa (human cervical cancer cells),SPC-A1 (human lung adenocarcinoma cells),and HepG2 (human liver cancer cells). Result:Compounds 2-8 were new compounds. Their structures were identified by melting point (MP),high resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS),¹H nuclear magnetic resonance (¹H-NMR) and ¹³ C nuclear magnetic resonance (¹³ C-NMR). MTT results showed that compounds 3,5 and 8 exhibited significant anti-tumor activity, especially compound 5 was found to have the best inhibition activity on HeLa,A375, HepG2 and SPC-A1 with IC₅₀ values of (5.25±1.08),(5.99±0.88),(3.31±1.89),(5.74±1.78) μmol·L^-1, 1.92,3.22,3.79, 3.72 times of that of rotundic acid,respectively. Conclusion:Compound 5 has significant anti-tumor activity with great significance for further research and development of new anti-tumor medicines.

OBJECTIVE： To establish the method for the rapidly non-destructive quality control of Liuwei dihuang capsule. METHODS： AOTF-NIR spectrometry was adopted. Taking 80 batches of Liuwei dihuang capsule produced by a manufacturer in recent three years as samples， HPLC chromatogram was adopted to determine the contents of loganin， morroniside， paeonol， paeoniflorin and ursolic acid； the content of water was determined according to general principles stated in 2015 edition of Chinese Pharmacopeia （part Ⅰ）. Taking 70 batches of samples as correction set， the partial least square method and the cross-validation algorithm were used to establish the NIR quantitative model of 6 indexes in Liuwei dihuang capsules with the Unscrambler quantitative analysis software. Taking residual 10 batches of samples as validation set， external validation was conducted for the model. RESULTS： The correlation coefficients （R2） of internal and external validation of loganin， morroniside， paeonol， paeoniflorin， the content of water quantitative model were all greater than 0.9； the correction of standand deviation （RMSEC） were 0.372 8， 0.025 4， 0.263 3， 0.288 5， 0.186 7 and 0.037 7； the prediction of standard deviation （RMSEP） were 0.462 2， 0.077 5， 0.472 1， 0.634 9， 0.293 4 and 0.206 9； the external verification showed that mean deviations of preclicted value to actual value were 6.04％， 6.05％， 5.87％， 6.97％， 5.62％ and 4.83％， with the mean deviation less than 10％.CONCLUSIONS：The established method can achieve rapidly non-destructive analysis Liuwei dihuang capsule.

OBJECTIVE： To synthesize and identify rotundic acid esters derivatives， and to evaluate in vitro antitumor activity. METHODS： Using rotundic acid as raw material， rotundic acid esters derivatives were synthesized by 28-esterification， 3β and 23-position hydroxyl group combined with acid anhydride. The structure of rotundic acid esters derivatives were identified by HRMS， 1H-NMR， 13C-NMR and physicochemical properties. The in vitro antitumor activities were evaluated by MTT assay against paclitaxel （positive control）， rotundic acid and rotundic acid esters derivatives with human cervical cancer cells HeLa， human malignant melanoma cells A375， human lung adenocarcinoma cells SPC-A1 and human liver cancer cells HepG2 （take IC50 as an indicator）. RESULTS： Totally 6 kinds of rotundic acid esters derivatives were synthesized， i.e. rotundic acid methyl ester（compound 1）， 3， 23-O-di（acetyl） rotundic acid methyl ester（compound 2）， 3， 23-O-di（propionyl） rotundic acid methyl ester（compound 3）， 3， 23-O-di（butyryl） rotundic acid methyl ester（compound 4）， 3， 23-O-di（phthaloyl） rotundic acid methyl ester（compound 5） and 3， 23-O-di（succinyl） rotundic acid methyl ester（compound 6）. Compared with paclitaxel， the antitumor activity of compound 5 and compound 6 to Hela， A375， HepG2 and SPC-A1 was similar to it， and there was no significant difference between them （P＞0.05）； the IC50 of rotuntic acid and other compounds decreased with statistical significance （P＜0.05）. CONCLUSIONS： In the study， 6 kinds of rotundic acid esters derivatives are synthesized and compound 5 and compound 6 have significant antitumor activity in vitro， which can provide reference for further study.

Sinomenine is an alkaloid found in the climbing plant Sinomenium acutum.Structurally,it belongs to the iso-quinoline derivatives,which have various bioactivities.Clinically,it is used in the treatment for rheumatism,rheumatoid arthri-tis and arrhythmia,etc.Nevertheless,due to the need of large dose,photo and thermal instability,quick metabolism in vivo and highly allergic for some patients,scientists have committed to modify its structure to develop the highly effective and low toxic derivatives.In this paper,the recent advances in structural modification of sinomenine are reviewed.

Objective To assess the feasibility and indications of local resection as an alternative to pancreaticoduedenectomy for the treatment of early stage ampullary cancer. Methods In this study,36 patients with an AJCC.stage pTl ampullary carcinoma were operated on between 1989 and 2009.Among those local resection was performed in 11 cases and pancreaticoduodenectomy in 25 cases.The main outcome measures were pre-and intra-operative diagnosis and staing,postoperative morbidity and mortality,recurrence.free and overall survival.Results Amp-llary cancerat early stageWas difficult to be diagnosed and staged before and during operation.It was at a much lower risk to perform local resection than pancreaticoduodenectomy.Postoperative complications were significantly lower in local resefion group than in pancreaticoduodenectomy group(P=0.031);whereas the postoperative hospital stay(P=0.254),perioperative mortality(P=1.000).disease-free survival(P=0:301)and long-term survival(P=0.289) were not statistically different between.the two groups. Conclusions Since accurate diagnosis and staginging of early ampullary cancer was diit3cult to establish perioperatively.local resection should be indicated forpoor risk pafients or those who refuse pancreaticoduedenectomy.