[Flavorand taste change rules of Sophora Flavescentis Radix processed using ancient classical method:an exploration based on intelligent sensory analysis].

This study was designed to investigate the flavor and taste change rules of Sophora Flavescentis Radix processed using the ancient classical method documented in Master Lei's Discourse on Medicinal Processing(Lei Gong Pao Zhi Lun). The Sophora Flavescentis Radix pieces and the corresponding test samples in each processing stage were first prepared based on the processing method for Sophora Flavescentis Radix recorded in Master Lei's Discourse on Medicinal Processing(Lei Gong Pao Zhi Lun). Then the flavors and tastes of Sophora Flavescentis Radix test samples undergoing the soaking in rice-washed water, washing with clean water, and steaming for different time were compared with the electronic nose and tongue. The results showed that in the preparation of Sophora Flavescentis Radix with the ancient method, such processes as soaking in rice-washed water and washing with clean water had no significant influences on the flavor, which, however, was weakened by steaming. In terms of the taste, soaking with rice-washed water enhanced the bitter taste of Sophora Flavescentis Radix, which remained unchanged after being washed with the clean water. The steaming would also diminish the bitter taste, making it taste similar to the original Sophora Flavescentis Radix medicinal materials. During the steaming for six to eight hours, the flavor did not vary significantly over time, while the bitter taste was first weakened and then intensified. The bitter taste of Sophora Flavescentis Radix steamed for six hours was similar to that steamed for eight hours. In addition, the differences in flavor and taste between Sophora Flavescentis Radix pieces processed by the ancient method in Master Lei's Discourse on Medicinal Processing(Lei Gong Pao Zhi Lun)and those by the modern method in the 2020 edition of Chinese Pharmacopoeia were analyzed. The findings demonstrated that the flavor of Sophora Flavescentis Radix pieces prepared by the ancient method was weaker than that by the modern method, whereas the bitter taste showed the opposite trend. The exploration on the flavor and taste change rules of Sophora Flavescentis Radix in its preparation by the ancient classical method and the differences in flavor and taste between Sophora Flavescentis Radix decoction pieces prepared by ancient and modern methods will lay a foundation for further elucidation of the scientific connotation of the ancient processing method and the medication principles of Sophora Flavescentis Radix in both ancient and modern times.

Amelioration of muscular spasm-induced pain of Guangtongxiao recipe in a non-everted gut sac in vitro model.

BACKGROUND: The modern study of the traditional Chinese medicine (TCM) compound recipes is a complex issue because of the large number of components in the recipes that would produce several metabolites after entering the body. The TCM compound recipes are known to have the advantage of synergistic treatment by multiple targets due to diverse components. Therefore, a research method that can reflect the overall effect of compounds with multi-components is essential. The pharmacological studies of the classic TCM compound recipes mainly use the sero-pharmacological method. It is a semi-in vivo study method, and the drug to be tested in the in vitro experiment is the drug-containing serum from the model animals (the drug to be tested is a mixed drug system containing the prototype drugs in animal bodies that have pharmacodynamic effects and the metabolites). Herein, a safe and effective external TCM recipe was used to develop another semi-in vivo experimental method to reflect the overall effects of TCM. AIM: To observe the effects of in-vitro intestinal absorption liquid of aqueous extracts of the TCM compound recipe-Guangtongxiao foam aerosol (Guangtongxiao)-on the tension of isolated rectal rings of mouse and investigate the underlying mechanisms of antispasmodic and amelioration of muscular spasm-induced pain. METHODS: Intestinal absorption liquid of the Guangtongxiao aqueous extract at the five time points (30, 45, 75, 105, and 120 min) was prepared using a non-everted gut sac method. The isolated rectal rings of mice were prepared by pre-contraction using potassium chloride (KCl) or acetylcholine chloride (ACh) to make steady contraction. The intestinal absorption liquid were added cumulatively to the sink with the constricted rectal rings. The effects of the five groups of the intestinal absorption liquid with different drug concentration were observed on the tension of the isolated rectal rings. Then the ex vivo perfusion of the mouse rectal ring was performed as same as Guangtongxiao intestinal absorption liquid experiments, and the effects of two major components of Guangtongxiao, paeoniflorin (Pae) and tetrahydropalmatine (THP), on the rectal ring pre-treated with high concentration of KCl and ACh to induce contraction were studied. RESULTS: The relaxation rate of the five groups of the intestinal canals increased significantly with 3200 µL cumulative sample volume as compared to the blank group (P < 0.01). It suggested that the relaxation activity of the intestinal absorption liquid enhanced significantly with the prolongation of the interaction between isolated rectal rings and intestinal absorption liquid in a time-dependent manner. Also, significant differences were detected while comparing between the 120-min intestinal absorption liquid group and the blank group with respect to various cumulative sampling volumes (P < 0.01). In addition, the intestinal relaxation rate elevated gradually with the increase in sampling volume, indicating that the concentrations of active substances in the intestinal absorption liquid prepared by the non-everted gut sac model increased and the intestinal relaxation activity was enhanced with the prolongation of the absorption time in a dose-dependent manner. And Pae and THP in a concentration-dependent manner caused relaxation of the rectal ring, which is pretreated with high K+(KCl) and ACh to induce contraction. The EC50 of Pae and THP was 8.67 × 10-5 M (6.68 × 10-5-1.13 × 10-4) and 1.41 × 10-4 M (1.24 × 10-4-1.61 × 10-4) in the contraction model induced by KCl, and was 6.15 × 10-5 M (4.47 × 10-5-8.45 × 10-5), and 1.31 × 10-4 M(1.22 × 10-4-1.42 × 10-4) in the model induced by ACh, respectively. CONCLUSION: The intestinal absorption liquid of Guangtongxiao exerted a remarkable relaxation activity for the rectal rings, and relaxation of the smooth muscle tension might be one of the antispasmodic mechanisms of Guangtongxiao compound recipe. Also, adopting a semi-in-vivo experimental method to study the efficacy of topical external TCM recipe medicine is optimal.

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals the Anti-Ischemic Stroke Mechanism of Nuciferine in MCAO Rats.

Nuciferine is an aporphine alkaloid monomer that is extracted from the leaves of the lotus species Nymphaea caerulea and Nelumbo nucifera Gaertn. Nuciferine was reported to treat cerebrovascular diseases. However, the potential mechanism of the neuroprotective effects of nuciferine at the metabolomics level is still not unclear. The present research used neurological score, infarct volume, cerebral water content, and ultraperformance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based serum metabolomics to elucidate the anti-ischemic stroke effect and mechanisms of nuciferine. The results showed that nuciferine significantly improved neurological deficit scores and ameliorated cerebral edema and infarction. Multivariate data analysis methods were used to examine the differences in serum endogenous metabolism between groups, and the biomarkers of nuciferine on ischemic stroke were identified. Approximately 19 metabolites and 7 metabolic pathways associated with nuciferine on treatment of stroke were found, which indicated that nuciferine exerted a positive therapeutic action on cerebral ischemic by regulating metabolism. These results provided some data support for the study of anti-stroke effect of nuciferine from the perspective of metabolomics.

Detection of Vasodilators From Herbal Components by a Transcriptome-Based Functional Gene Module Reference Approach.

Vasodilatation is one of the key therapeutic strategies for the treatment of various cardiovascular diseases with high blood pressure. Therefore, development of drugs assisting blood vessel dilation is promising. It has been proven that many drugs display definite vasorelaxant effects. However, there are very few studies that systemically explore the effective vasodilators. In this work, we build a transcriptome-based functional gene module reference approach for systematic pursuit of agents with vasorelaxant effects. We firstly curate two functional gene modules that are specifically involved in positive and negative regulation of vascular diameter based on the known gene functional interaction knowledge. Secondly, a collection of gene expression profiles following herbal component treatment are collected from a public gene expression database. Then, the correlation of the gene modules is evaluated in each herbal component-induced gene expression profile by gene set enrichment analysis. The vasorelaxant effects of the candidate compounds can be predicted and ordered by the values of a defined index. Finally, the top 10 candidate compounds are experimentally tested for their vasorelaxant effects on vessel contraction induced by Phe in aortic rings. This strategy integrating different types of technologies is expected to help to create new opportunities for the development of novel vasodilators.

Treatment Mechanism of Gardeniae Fructus and Its Carbonized Product Against Ethanol-Induced Gastric Lesions in Rats.

Gardeniae Fructus (GF) and carbonized GF (GFC) have been shown to exert a gastrointestinal protective effect and are frequently used in clinical practice for the treatment of hemorrhage and brown stool. In this study, we employed a combination of pharmacological methods and metabolomics in a rat model of ethanol-induced acute stomach ulcer to investigate the gastroprotective effect of GF and GFC water extracts and the potential mechanism involved in this process. The levels of nitric oxide (NO) and interleukin 6 (IL-6) in the plasma of rats were determined. The results showed that both GF and GFC reduced the ethanol-induced gastric lesions and expression of NO and IL-6 in these rats. Of note, 16 and 11 feature metabolites were filtered and identified in the GF and GFC groups, respectively. Both GF and GFC act by restoring the biosynthesis of valine, leucine, and isoleucine, and the metabolism of glycerophospholipids. Moreover, histological evaluation revealed that heat processing of GF to create GFC enhanced the gastric mucosa protective effect. Furthermore, heat processing converted the main pathway from alanine, aspartate, and glutamate metabolism, associated with GF, to histidine metabolism, associated with GFC. GF and GFC ameliorated gastric mucosa lesions in rats via reductions in NO production and inflammatory cytokine secretion, and the induction of prostaglandin E2.

Pharmacokinetic comparisons of major bioactive components after oral administration of raw and steamed rhubarb by UPLC-MS/MS.

A study was performed to compare the pharmacokinetics of major bioactive analytes in rhubarb plants to explore the pharmacological differences between raw pieces (RP) and steamed pieces (SP) of rhubarb. A rapid and efficient ultra-performance liquid chromatographic coupled with mass/mass spectrometry (UPLC-MS/MS) method was established to determine the concentrations of six analytes in rat plasma after oral administration of RP and SP. It was found that the AUC (area under the plasma concentration-time curve), Tmax (time to reach maximum plasma concentration) and Cmax (maximum plasma concentration) values were obviously increased in RP for rhein-8-O-ß-d-glucophyranoside, rhein and aloe-emodin. On the contrary, emodin, physcion and chrysophanol had higher bioavailability in SP. The significant differences indicated that steamed by wine may alter pharmacokinetic behaviors of analytes, providing theoretical basis of differences in pharmacological activity between SP and RP.

Global metabolite profiling and diagnostic ion filtering strategy by LC-QTOF MS for rapid identification of raw and processed pieces of Rheum palmatum L.

Due to its variety of functions, rhubarb has been used for thousands of years in many countries. It is commonly used after processing. Processing usually affect the chemical profile and the contents of active compounds in herbals, leading to changes of their bioactivities. Here, an approach of metabolite profiling and diagnostic ion filtering strategy with liquid chromatography-quadrupole/time-of-flight mass spectrometry was established for rapid identification of raw and processed pieces of Rheum palmatum L. (RPL). The comprehensive and unbiased information of 30 batches of RPL covering raw and two general processing methods were given by metabolomic profiles. Using molecular feature extraction algorithm, non-targeted compounds were analyzed in minutes. In total, 73 characteristic markers were extracted and identified by diagnostic ion filtering. They have been further analyzed by partial least squares-support vector machine-based pattern recognition. The comprehensive and rapid method for raw and processed pieces of RPL classification shows good sensitivity, specificity and prediction performance.

Rapid identification of the quality decoction pieces by partial least squares -based pattern recognition: grade classification of the decoction pieces of Saposhnikovia divaricata.

Herbal medicines are commonly used in many countries after they undergo processing. Quality decoction pieces are a guarantee of the efficacy and safety of the herbal medical products. Here, a strategy based on chemical analysis combined with chemometric techniques was proposed for the classification and prediction of the different grades of the decoction pieces. Considering the necessity for a shared and simple method for the grade classification for the public, in this paper, the characterization of the chemical constituents was determined by utilizing high-performance liquid chromatography (HPLC)/diode array detection. HPLC was first established for the characterization of the chemical constituents of the different grade decoction pieces. Furthermore, a simultaneous quantification of several of the marker compounds in these decoction pieces was obtained. Finally, a partial least squares-based pattern recognition method was utilized to obtain a predictive model for the grade classification of the decoction pieces. Saposhnikovia divaricata (Turcz.) Schischk was used as a case study. The partial least squares -based pattern recognition for the grade classification of the decoction pieces of S. divaricata demonstrated good sensitivity, specificity and prediction performance, which may efficiently validate the identification results of appearance assessment. The proposed strategy is expected to provide a new insight for the grade classification and quality control of the decoction pieces. Copyright © 2016 John Wiley & Sons, Ltd.

[Development and innovation of traditional Chinese medicine processing discipline and Chinese herbal pieces industry].

To elucidate the key issues in the development and innovation of traditional Chinese medicine processing discipline and Chinese herbal pieces industry Chinese herbal pieces industry. According to the author's accumulated experience over years and demand of the development of the Chinese herbal pieces industry, the key issues in the development and innovation on the Chinese herbal pieces industry were summarized. According to the author, the traditional Chinese medicine processing discipline shall focus on a application basis research. The development of this discipline should be closely related to the development of Chinese herbal pieces. The traditional Chinese medicine processing discipline can be improved and its results can be transformed only if this discipline were correlated with the Chinese herbal pieces industry, matched with the development of the Chinese herbal pieces industry, and solved the problems in the development on the Chinese herbal pieces industry. The development of traditional Chinese medicine processing discipline and the Chinese herbal pieces industry also requires scientific researchers to make constant innovations, realize the specialty of the researches, and innovate based on inheritance.

Isolation and purification of six iridoid glycosides from gardenia jasminoides fruit by medium-pressure liquid chromatography combined with macroporous resin chromatography.

Gardeniae fructus is one of the most frequently used herbs in traditional Chinese medicine. In the present study, a process for the enrichment of six iridoid glycosides from Gardeniae fructus was developed using medium-pressure liquid chromatography combined with macroporous resin and reversed-phase chromatography. The purities of different fractions from Gardeniae fructus were assessed using quantitative high-performance liquid chromatography. After fractionation using HPD-100 column chromatography, a 30% ethanol fraction was selected based on high-performance liquid chromatography and liquid chromatography with mass spectrometry qualitative analysis to separate and purify. Based on the orientation analysis results, six compounds-deacetyl asperulosidic acid methyl ester, gardenoside, ixoroside, scandoside methyl ester, genipin-1-O-ß-d-gentiobioside, and geniposide-were successfully isolated and purified in three to four combined steps from Gardeniae fructus. The purities of these compounds were found by high-performance liquid chromatography analysis to be 97.9, 98.1, 95.5, 96.3, 97.1, and 98.7%, respectively. Moreover, their structures were elucidated by NMR spectroscopy and liquid chromatography with tandem mass spectrometry. The separation process was highly efficient, rapid, and accurate, making it a potential approach for the large-scale production of iridoids in the laboratory and providing several marker compounds for quality control. This procedure may be meaningful for the purification of other natural products used in traditional Chinese medicine.

Synergism and rules of the new combination drug Yiqijiedu formulae (YQJD) on ischemic stroke based on amino acids (AAs) metabolism.

The use of combination drugs is considered to be a promising strategy to control complex diseases such as ischemic stroke. The detection of metabolites has been used as a versatile tool to reveal the potential mechanism of diverse diseases. In this study, the levels of 12 endogenous AAs were simultaneously determined quantitatively in the MCAO rat brain using RRLC-QQQ method. Seven AAs were chosen as the potential biomarkers, and using PLS-DA analysis, the effects of the new combination drug YQJD, which is composed of ginsenosides, berberine, and jasminoidin, on those 7 AAs were evaluated. Four AAs, glutamic acid, homocysteine, methionine, and tryptophan, which changed significantly in the YQJD-treated groups compared to the vehicle groups (P < 0.05), were identified and designated as the AAs to use to further explore the synergism of YQJD. The result of a PCA showed that the combination of these three drugs exhibits the strongest synergistic effect compared to other combination groups and that ginsenosides might play a pivotal role, especially when combined with jasminoidin. We successfully explored the synergetic mechanism of multi-component and provided a new method for evaluating the integrated effects of combination drugs in the treatment of complex diseases.

[Content comparison of main chemical compositions in Gardenia jasminoids roasted with ginger juice].

OBJECTIVE: To compare the contents of the main chemical compositions in Gardenia jasminoids before and after being roasted with ginger juice. METHOD: Four diterpenoid pigments constituents (C-1, C-2, C-3, crocetin) were determined simultaneously by UPLC on an Agilent Poroshell 120 EC-C18 column at 35 degrees C with the methanol-0.5% formic acid anhydrous in gradient elution as the mobile phrase. The detection wavelength was set at 440 nm and the flow rate was 0.4 mL x min(-1). Two iridoids constituents (G-1, G-2) were determined simultaneously by HPLC on an Agilent TC-C18(2) column at 35 degrees C with acetonitrile-0.5% formic acid anhydrous (18:82) as the mobile phrase. The detection wavelength was set at 238 nm and the flow rate was 1.0 mL x min(-1). RESULT: After being processed with ginger juice, the contents of the diterpenoid pigments constituents decreased slightly and the contents of the iridoids constituents increased slightly. CONCLUSION: The contents of the main chemical compositions in G. jasminoids roasted with ginger juice increased slightly with some regularity, but there were no significant differences.

[Regularity of changes in main active components of Schisandra chinensis before and after being processed with vinegar].

OBJECTIVE: To investigate the regularity of changes in the main active components of Schisandra chinensis preparations before and after being processed with vinegar. METHOD: High performance liquid chromatography was used to analyze the changes in the content of lignans and organic acids in S. chinensis preparations before and after being processed with vinegar. RESULT: After being processed with vinegar, the content of lignans in S. chinensis preparations significantly reduced, while that of organic acids significantly increased. The ratio between them reduced from 1:16 (raw product) to 1:21 (vinegar products). CONCLUSION: The changes in the main pharmacological effects of S. chinensis are related to not only the changes in the contents of lignan and organic acids, but also the significant changes in the ratio relations between the two components. This is of great significance to the correlation among the principle of S. chinensis processed with vinegar and material basis and the changes in pharmacological effects.

[Analysis of volatile oil in Gardenia jasminoids roasted with ginger juice by GC-MS].

OBJECTIVE: To compare the components and contents of volatile oil in Gardenia jasminoids, Zingiber officinale, G. jasminoids roasted with ginger juice and to provide scientific basis for intrinsic material of G. jasminoids roasted with ginger juice. METHOD: The volatile oil in the three herbal medicines was extracted by steam distillation, the components were analyzed by GC-MS and the contents of the components were calculated by area normalization method. RESULT: The contents of volatile oil in G. jasminoids, Z. officinale, G. jasminoids roasted with ginger juice were 1.0, 2.0, 1.5 microL x g(-1), respectively. A total of 89 components were identified by GC-MS. Although 42, 75 and 77 peaks were separated, only 30, 58 and 67 components were identified accordingly, which accounted 94.1%, 90.52% and 94.38% of the whole volatile oil. CONCLUSION: After being processed with ginger juice, the components and contents of volatile oil in G. jasminoids has been changed obviously.

[Determination of three organic acids in Schisandrae Chinensis Fructus by HPLC].

OBJECTIVE: To establish an HPLC method for determination of three organic acids in Schisandrae Chinensis Fructus. METHOD: The separation was performed on a C18 column with acetonitrile-15 mmol x L(-1) KH2 PO4 (1:99) and methanol-0.5% acetic glacial as the mobile phrase to determine the content of kinic acid, citric acid, and protocatechuic acid. RESULT: Three kinds of organic acid can be detective in different samples, and the average content of the three organic acids were about 18%, among which the citric acid was the highest (18%). CONCLUSION: Since organic acids is an important parts of the material basis in Schisandrae Chinensis Fructus, it is necessary to carry out the pharmacological research associated with the function of Schisandrae Chinensis Fructus. Further, it will provide scientific basis for the drug relevance research between material basis and efficiency, as well as the foundation for the relevance research on the properties and Five Tastes of traditional Chinese medicine.

[Optimization of combination modes of medical materials in extract of Huanglian Jiedu decoction by semi-bionic extraction].

OBJECTIVE: To optimize the combination modes of medical materials in extract of Huanglian Jiedu decoction. METHOD: Divided the medical materials of Huanglian Jiedu decotion into 15 groups and extracted by semi-bionic estraction (SBE), the contents of berberine, baicalin, geniposide, total alkaloid, total flavonoid, total integral calculus area of HPLC and extract of 1 000 were determined, standardized, weighted and evaluated, respectively. RESULT: The maximum evaluated value Y for the extracting technique was AD + BC. CONCLUSION: The optimal combination mode of the perscription is that Rhizoma Coptidis and Fructus Gardeniae, Radix Scutellariae and Cortex Phellodendri Amurensis are decocted together respectively then the two decoctions are merged.