Strategy and challenge of innovative drug research and development from clinically effective ingredients of traditional Chinese medicine / 中国中药杂志

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.

Quality analysis of Rosae Radix et Rhizoma / 中国中药杂志

Rosae Radix et Rhizoma is a herbal medicine in a variety of famous Chinese patent medicines, while the quality standard for this medicine remains to be developed due to the insufficient research on the quality of Rosae Radix et Rhizoma from different sources. Therefore, this study comprehensively analyzed the components in Rosae Radix et Rhizoma of different sources from the aspects of extract, component category content, identification based on thin-lay chromatography, active component content determination, and fingerprint, so as to improve the quality control. The results showed that the content of chemical components varied in the samples of different sources, while there was little difference in the chemical composition among the samples. The content of components in the roots of Rosa laevigata was higher than that in the other two species, and the content of components in the roots was higher than that in the stems. The fingerprints of triterpenoids and non-triterpenoids were established, and the content of five main triterpenoids including multiflorin, rosamultin, myrianthic acid, rosolic acid, and tormentic acid in Rosae Radix et Rhizoma was determined. The results were consistent with those of major component categories. In conclusion, the quality of Rosae Radix et Rhizoma is associated with the plant species, producing area, and medicinal parts. The method established in this study lays a foundation for improving the quality standard of Rosae Radix et Rhizoma and provides data support for the rational use of the stem.

Quality evaluation and multi-spectral identification of origin herbs of Lonicerae Japonicae Flos based on grey correlation-TOPSIS method / 中国中药杂志

The grey correlation-TOPSIS method was used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos, and the Fourier transform near-infrared(NIR) and mid-infrared(MIR) spectroscopy was applied to establish the identification model of origin herbs of Lonicerae Japonicae Flos by combining chemometrics and spectral fusion strategies. The content of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, secoxyloganin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C in six origin herbs of Lonicerae Japonicae Flos was determined by high-performance liquid chromatography(HPLC), and their quality was evaluated by the grey correlation-TOPSIS method. The Fourier transform NIR and MIR spectra of six origin herbs of Lonicerae Japonicae Flos(Lonicera japonica, L. macranthoides, L. hypoglauca, L. fulvotomentosa, L. confuse, and L. similis) were collected. At the same time, principal component analysis(PCA), support vector machine(SVM), and spectral data fusion technology were combined to determine the optimal identification method for the origin herbs of Lonicerae Japonicae Flos. There were differences in the quality of the origin herbs of Lonicerae Japonicae Flos. Specifically, there were significant differences between L. japonica and the other five origin herbs(P<0.01). The quality of L. similis was significantly different from that of L. fulvotomentosa, L. macranthoides, and L. hypoglauca(P=0.008, 0.027, 0.01), and there were also significant differences in the quality of L. hypoglauca and L. confuse(P=0.001). The PCA and SVM 2D models based on a single spectrum could not be used for the effective identification of the origin herbs of Lonicerae Japonicae Flos. The data fusion combined with the SVM model further improved the identification accuracy, and the identification accuracy of the mid-level data fusion reached 100%. Therefore, the grey correlation-TOPSIS method can be used to evaluate the quality of the origin herbs of Lonicerae Japonicae Flos. Based on the infrared spectral data fusion strategy and SVM chemometric model, it can accurately identify the origin herbs of Lonicerae Japonicae Flos, which can provide a new method for the origin identification of medicinal materials of Lonicerae Japonicae Flos.

Component identification and analysis in vivo of Sanhan Huashi formula / 中国中药杂志

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers / 中国中药杂志

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, β-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction / 中国中药杂志

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Structure-activity relationship of Lycium barbarum polysaccharides / 中国中药杂志

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification / 中国天然药物

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.

Research progress on vesicles from Chinese medicinal herbs / 浙江大学学报·医学版

Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.

Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing / 中国中药杂志

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Qualitative and quantitative study of constituents in Lysionoti Herba based on UHPLC-Q-Exactive Orbitrap HRMS and HPLC-UV / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HRMS) was employed to systematically analyze the chemical constituents in Lysionoti Herba, and high perfor-mance liquid chromatography-ultraviolet(HPLC-UV) to determine the content of main compounds. A Synergi~(TM) Hydro-RP 100 Å colu-mn(2 mm×100 mm, 2.5 μm) was used for gradient elution with acetonitrile-0.1% aqueous formic acid as the mobile phase at a flow rate of 0.2 mL·min~(-1) and a column temperature of 40 ℃. MS and MS/MS were conducted with electrospray ionization(ESI) in both positive and negative modes. The chemical components in Lysionoti Herba were identified by comparison with the retention time and mass spectra of reference compounds and the relevant mass spectral data reported in MS databases and relevant literature. Furthermore, the content of five constituents(neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin) in different Lysiono-ti Herba samples was simultaneously determined by HPLC-UV at the wavelength of 330 nm. A total of 84 compounds were identified in Lysionoti Herba, including 27 flavonoids, 20 phenylethanoid glycosides, 5 amino acids, 18 organic acids, 1 alkaloid, 6 nucleosides, and 7 others. The content of neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin showed good linear relationship(r>0.999) with the peak area within certain concentration ranges, which were 3.22-102.90, 12.84-410.82, 31.63-1 012.01, 25.00-800.11, and 4.08-130.51 μg·mL~(-1), respectively. The instrument precision, method repeatability, and solution stability all met requirement, and the average recovery rate was 97.31%-100.2%, with RSD ranging from 0.95% to 2.4%. The content of the five components varied among different Lysionoti Herba samples collected from different regions of Guizhou, and the average content of forsythoside B was the highest. The established qualitative method can rapidly and efficiently identify the chemical components of Lysionoti Herba, and the developed HPLC-UV method can simultaneously determine the content of five components in a simple, ra-pid, and accurate manner, providing a scientific basis for the quality evaluation of Lysionoti Herba.

A new dihydrochalcone from Humulus scandens / 中国中药杂志

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Progress in Mechanism of Astragalus membranaceus and Its Chemical Constituents on Multiple Sclerosis / 中国结合医学杂志

The primary chemical components of Astragalus membranaceus include polysaccharides, saponins, flavonoids, and amino acids. Recent studies have shown that Astragalus membranaceus has multiple functions, including improving immune function and exerting antioxidative, anti-radiation, anti-tumor, antibacterial, antiviral, and hormone-like effects. Astragalus membranaceus and its extracts are widely used in clinical practice because they have obvious therapeutic effects against various autoimmune diseases and relatively less adverse reaction. Multiple sclerosis (MS) is an autoimmune disease of central nervous system (CNS), which mainly caused by immune disorder that leads to inflammatory demyelination, inflammatory cell infiltration, and axonal degeneration in the CNS. In this review, the authors analyzed the clinical manifestations of MS and experimental autoimmune encephalomyelitis (EAE) and focused on the efficacy of Astragalus membranaceus and its chemical components in the treatment of MS/EAE.

Identification of chemical components and network pharmacology of Huanglian Decoction based on UPLC-Q-TOF-MS/MS technology / 中国中药杂志

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.

Main components from cultivated and wild Nardostachyos Radix et Rhizoma by LC-MS and GC-MS / 中国中药杂志

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.

Quality evaluation of Galli Gigerii Endothelium Corneum based on HPLC fingerprints and content determination of nucleosides / 中国中药杂志

Galli Gigerii Endothelium Corneum(GGEC), the dried gizzard membrane of Gallus gallus domesticus is a Chinese medicinal material commonly used for digestion. However, due to the particularity of texture and composition, its active ingre-dients have not been clarified so far, and there is also a lack of quality evaluation indicators. In this study, UPLC-Q-TOF-MS was used to analyze the chemical components from the water extract of GGEC, and ten nucleosides were identified for the first time. HPLC fingerprints of the water extracts of GGEC were established and the content of seven nucleosides was determined. The fingerprint similarities of 40 batches of GGEC samples ranged from 0.765 to 0.959, indicating that there were great differences among the GGEC products processed with different methods. In addition, SPSS 22.0 and SIMCA 14.1 were used for hierarchical cluster analysis(HCA) and principal component analysis(PCA) on the 19 common peaks of the HPLC fingerprints of GGEC, and the 40 batches of samples were divided into three categories: raw GGEC, fried GGEC and vinegar-processed GGEC. Eight differential components in GGEC were marked by orthogonal partial least squares discrimination analysis(OPLS-DA), two of which were adenine and thymine. The results of content determination showed that the total content of the seven nucleosides in raw GGEC, fried GGEC and vinegar-processed GGEC were 182.5-416.8, 205.3-368.7, and 194.2-283.0 μg·g~(-1), respectively. There were significant differences in the content of hypoxanthine, thymine and thymidine among the GGEC products processed with different methods(P<0.05), which were graded in the order of fried GGEC>vinegar-processed GGEC>raw GGEC. This suggested that the content of hypoxanthine, thymine and thymidine tended to increase during the frying process, and the variation range might be related to the degree of heat exposure. The established methods in this study were simple and reproducible, and could be used for qualitative and quantitative analysis of GGEC and its processed pro-ducts. This study also provided reference for the establishment of quality standards of GGEC with chemical components as control index.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology / 中国中药杂志

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Effects of different extraction methods on chemical compositions and biological activities of polysaccharides from Lycium barbarum / 中国中药杂志

In this study, five polysaccharides from Lycium barbarum(LBPs)(LBP-1-LBP-5) were selectively extracted by different extraction methods, and the chemical composition, structural characteristics, and biological activities of LBPs were explored. The results of chemical composition analysis showed that alkaloids were not detected in the five LBPs. The total polysaccharide content was(81.95%±1.6%)-(92.96%±0.76%), the uronic acid content was(8.26%±0.46%)-(24.81%±0.46%), and the protein content was(0.06%±0.03%)-(1.35%±0.13%). The monosaccharide compositions of the five LBPs were basically same, mainly including glucose, xylose, and galactose. However, there was significant difference in the content ratio of different monosaccharide. The results of infrared spectra analysis indicated that the five LBPs had typical infrared spectral characteristics of polysaccharides. The results of nuclear magnetic resonance characteristic spectrum analysis revealed that the five LBPs had two configurations of α and β. Meanwhile, there were triple helix structures in LBP-2, LBP-3, and LBP-4, which enhanced the activities of polysaccharides. The results of activities screening suggested that the biological activities of the five LBPs were significantly different. LBP-3 showed the highest lipid oxidation clearance rate, and its antioxidant activity was equivalent to that of the positive control group. The inhibitory rate of LBP-4 on α-amylase and its activation rate of alcohol dehydrogenase were better than those of other fractions, and the inhibitory rate of LBP-4 on α-amylase was slightly higher than that of the positive control group when the mass concentration was 10 g·L~(-1). LBP-2 showed stronger inhibitory activity against α-glucosidase and hyaluronidase. This study provides references for the precise development and utilization of LBPs.

Anti-depression targets and mechanism study of Kaixin San / 中国中药杂志

This study identified the anti-depression targets of Kaixin San(KXS) in the brain tissue with "target fishing" strategy, and explored the target-associated pharmacological signaling pathways to reveal the anti-depression molecular mechanism of KXS. The Balb/c mouse model of depression was established by chronic unpredictable mild stress(CUMS) and the anti-depression effect of KXS was evaluated by forced swimming test and sucrose preference test. KXS active components were bonded to the benzophenone-modified magnetic nanoparticles by photocrosslinking reaction for capturing target proteins from cortex, thalamus and hippocampus of depressive mice. The target proteins were identified by liquid chromatography-mass spectrometry/mass spectrometry(LC-MS/MS). The enrichment analysis on signaling pathways was performed by Cytoscape. The potential biological functions of targets were verified by immunohistochemistry and Western blot assay. The results showed that KXS significantly improved the behavioral indexes. There were 64, 91, and 44 potential targets of KXS identified in cortex, thalamus, and hippocampus, respectively, according to the target identification experiment. The functions of these targets were mainly associated with vasopressin-regulated water reabsorption, salmonella infection, thyroid hormone synthesis, and other signaling pathways. Besides, the results of immunohistochemistry and Western blot showed that KXS up-regulated the expressions of argipressine(AVP) in the cortex, heat shock protein 60(HSP60), cytochrome C oxidase 4(COX4), and thyrotropin-releasing hormone(TRH) in the thalamus, and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and nuclear factor kappa B(NF-κB) p65 in the thalamus. Therefore, KXS may exert anti-depression effect through regulating vasopressin signaling pathway in the cortex and inflammation, energy metabolism, and thyroid hormone signaling pathways in the thalamus, and the effect of KXS on hippocampus is not significant.