Research on the mechanisms of ethanol extract of Scutellaria baicalensis Georgi in improving CFA-induced inflammatory pain rats based on 1H NMR metabolomics / 药学学报

The purpose of this study was to investigate the effects of ethanol extract of Scutellaria baicalensis Georgi (SGE) on endogenous metabolites in toes of rats with inflammatory pain induced by complete Freund's adjuvant (CFA) based on 1H NMR metabolomics, which would provide foundation for revealing the effects and mechanisms of SGE in improving inflammatory pain. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2022062). The rats model of inflammatory pain was induced by subcutaneous injection of CFA (0.1 mL), and the effect of low, medium and high doses of SGE (1.5, 3, 6 g·kg-1) on inflammatory pain were explored. The effects of SGE on relieving inflammatory pain was evaluated by mechanical nociceptive thresholds (MNTs) test. Western blot was used to detect the effects of SGE on protein expression of cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB) and phospho-NF-κB (p-NF-κB). 1H NMR metabolomics was used to analyze the regulatory effects of SGE on endogenous metabolites in the toes of rats with inflammatory pain. The results showed that SGE (6 g·kg-1) could significantly relieve CFA-induced inflammatory pain, and also notably inhibit the protein expression of COX-2, NF-κB and p-NF-κB. SGE could markedly reverse the changes of 8 differential metabolites, such as glycine, glutamine, succinate, phosphorylcholine, etc. The metabolites were involved in eight metabolic pathways, such as glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glutathione metabolism, glycerophospholipid metabolism. These results suggest that SGE may relieve inflammatory pain by regulating NF-κB signaling pathway and metabolic abnormality.

Study on the differences in chemical composition of Scutellaria baicalensis leaves from different origins in Shanxi Province based on plant metabolomics and targeted quantitative analysis / 药学学报

By integrating plant metabonomics and target quantitative analysis methods, this study systematically analyzed the differences of chemical constituents in Scutellaria baicalensis leaves from different producing areas in Shanxi, so as to provide theoretical basis for rational and effective utilization of Scutellaria baicalensis leaves. Based on the idea of plant metabonomics, the liquid quality of 53 batches of Scutellaria baicalensis leaves from 8 different producing areas in Shanxi was analyzed by UPLC-QTOF-MS, and the collected data were imported into SIMCA 14.1 software for multivariate statistical analysis to screen the different chemical constituents among different habitats in Shanxi. Meanwhile, a method for simultaneous determination of 7 flavonoids and 3 organic acids in Scutellaria baicalensis leaves was optimized and established to quantitatively analyze the differences of chemical components in Scutellaria baicalensis leaves from different producing areas in Shanxi. The results of plant metabonomics showed that there were differences in the chemical composition of Scutellaria baicalensis leaves in northern Shanxi (Datong, Xinzhou), Jinzhong (Yangquan, Luliang) and southern Shanxi (Changzhi, Yuncheng, Jincheng, Linfen): there were 14 significant differences in chemical composition between northern Shanxi and Jinzhong; there were 18 significant differences in chemical constituents between southern Shanxi and central Shanxi. There were 15 significant differences in chemical constituents between northern Shanxi and southern Shanxi. Among them, scutellarin and isocarthamidin-7-O-glucuronide were the common differences among the three regions, and the content of scutellarin was the highest in southern Shanxi and the lowest in northern Shanxi. The content of isocarthamidin-7-O-glucuronide was the highest in Jinzhong area and the lowest in northern Shanxi area. Quantitative analysis further confirmed that the average contents of apigenin, naringenin and citric acid were the highest in northern Shanxi, scutellarin, caffeic acid, apigenin-7-O-glucuronide, malic acid and wogonoside were the highest in southern Shanxi, and wogonoside and baicalin were the highest in central Shanxi. This study is of great significance to the quality control of Scutellaria baicalensis leaf resources, and provides theoretical basis for rational and effective utilization of Scutellaria baicalensis leaf resources.

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics / 药学学报

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Qualitative studies on raw materials for Hepaclin-4 prescription / Монголын эм зүй, эм судлал

Background@#In 2021, 5981 of cancer new cases was registered in Mongolian population. Among those cases, liver cancer was commonly registered with a prevalence of 32.7%. Studies on anticancer agents with no-adverse effects and good-preventive efficacy against cancer have been attracted more attention from the researchers in the field of pharmaceutical sciences. Scutellaria baicalensis Georgi, Saussurrea amara.L, Chiazospermum erectum Berh, and Carthamus tinctorius.L are well recognized as effective agent against liver diseases. Using these raw materials, researchers have been invented a traditional prescription and named as Hepaclin-4. In this study, we aimed to investigate the qualitative study of raw materials and some biologically active sub- stances in the compounds.@*Purpose@#To study the qualitative study of raw materials for Hepaclin-4 prescription@*Materials and methods@#Some qualitative properties of raw materials for Hepaclin-4 prescription, including appearance, minerals, some organic compounds, total ash, water-soluble substances and fungi, were investigated according to Mongolian pharmacopeia and total flavonoid was detected by thin layer chromatography.@*Results@#No changes were observed on the appearance of raw materials, and minerals and organic compounds weren’t detected in the prescription. No contamination with fungi and insects were identified. The moist in the raw materials were 5.9 to 8.1%, total ash was 4.7 to 13.3% and the water-soluble substances were detected 33.8 to 42.9%. Number of aerobic bacteria, fungi and E.coli, Salmonella species were detected in normal range, indicating that the prescription was matched with the requirement of pharmacopeia. According to the thin layer chromatography study of the raw materials, a yellow spot on the chromatogram were identified and same as quercetin (Rf=0.9-0.98) and rutin ((Rf=0.18-0.23)) as standard compounds, which indicated that the spot which indicated that the spot was flavonoids in the prescription.@*Conclusions@#These results showed that the appearance, moist, minerals, organic compound, water-soluble substances, ash and biologically active substances of the raw materials for Hepaclin-4 prescription was corresponded with the requirements of pharmacopeia, and flavonoid was detected in raw materials of Hepaclin-4.

Scutellaria Baicalensis Polysaccharides Alleviates the Inflammation of DSS-induced UC Model Mice by Regulating JAK2/STAT3 Pathway and IL-23/IL-17 Inflammatory Axis / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect and mechanism of Scutellaria Baicalensis polysaccharides on intestinal immunity in mice with ulcerative colitis （UC）. MethodsC57BL/6 mice were randomly assigned to blank group， model group， mesalazine group and Scutellaria Baicalensis polysaccharides low-dose， medium-dose and high-dose groups （n=10 mice/group）. The daily status of mice was observed and the disease activity index （DAI） score was recorded. The expression of cytokines including IL-6， IL-17 and IL-23 in serum was detected by ELISA. After the mice were sacrificed， HE was used to observe the intestinal mucosal damage in mice， and the colonic tissue damage index （TDI） score was recorded. Western blot and immunohistochemistry were used to detect the expression levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription （STAT3）， p-JAK2 and p-STAT3 proteins. ResultsCompared with the blank group， the DAI score of the model group was significantly increased， the contents of IL-6， IL-17 and IL-23 in serum were significantly increased， the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in colon tissue was significantly increased， and the expression levels of p-JAK2 and p-STAT3 were significantly increased. Compared with the model group， the DAI score of mice in each administration group was significantly decreased. The contents of IL-6， IL-17 and IL-23 in serum were decreased， the TDI score was decreased， the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in colon tissue was decreased， and the expression of p-JAK2 and p-STAT3 was decreased. ConclusionScutellaria Baicalensis polysaccharides may improve the inflammatory effect of UC mice through JAK2/STAT3 pathway and IL-23/IL-17 inflammatory axis.

Effectiveness of Scutellaria baicalensis Georgi root in pregnancy-related diseases: A review / 中西医结合学报

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.

Optimization of preparation technology and in vitro release of baicalin-glycyrrhizic acid solid nanocrystals / 中国药房

OBJECTIVE To optimize the preparation technology of baicalin （BCN）-glycyrrhizic acid （GA） solid nanocrystals （BCN-GA-SN）， to characterize them and investigate their in vitro release characteristics. METHODS According to the compatibility ratio of classic couplet medicinals “Scutellaria baicalensis-Glycyrrhiza uralensis”， the compatibility ratio of BCN and GA was determined as 6∶1 （m/m）； BCN-GA nanosuspension was prepared by precipitation method combined with high-pressure homogenization method. The preparation technology of BCN-GA nanosuspension was optimized by using mean particle size and polydispersity index （PDI） as indexes and with types and dosage of stabilizers， stirring speed and time， high-pressure homogenization pressure and frequency as factors. The freeze-dried consolidation process of BCN-GA nanosuspension was optimized to prepare BCN-GA-SN using average particle size， PDI and redispersibility index （RDI） as indicators， with the type and dosage of freeze-dried protective agents as factors； then， the physicochemical properties and in vitro release of BCN-GA-SN were investigated. RESULTS The optimal preparation technology of BCN-GA-SN was as follows： BCN-GA nanosuspension was prepared by using 15% sodium dodecyl sulfate as a stabilizer， stirring at 1 000 r/min for 15 minutes， and homogenizing at 100 MPa for 20 times； then， BCN-GA nanosuspension was freeze-dried and solidified with 5% mannitol （corresponding to the dosage of BCN）. The average particle size of prepared BCN-GA-SN was （442.2±5.7） nm with PDI of 0.225±0.015 and RDI of 1.055± 0.013. The prepared BCN-GA-SN presented as the irregularly spherical shape with more uniform size； the drug-loading amount of BCN in the nanocrystal was （62.5±0.7）%， and that of GA was （9.4±0.2）%； the in vitro release results showed that the cumulative dissolution of BCN-GA-SN was higher than that of the physical mixture of BCN and GA. CONCLUSIONS BCN-GA-SN is prepared successfully in this study with uniform particle size and even distribution， which can effectively improve the dissolution of BCN.

Establishment of fingerprints ，anti-inflammatory activities and spectrum-effect relationship study of pith-nodecayed and pith-decayed Scutellaria baicalensis / 中国药房

OBJECTIVE To es tablish the fingerprints of pith-nodecayed and pith-decayed Scutellaria baicalensis ，and to investigate the difference of their anti-inflammatory activities. METHODS HPLC method was adopted to establish the fingerprints of 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis . SIMCA 14.1 software was adopted to screen the markers of weight difference between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis ，using variable importance in projection （VIP）＞1 as standard. Using the inhibitory rates of NO ，IL-6 and IL- 1β in supernatant of lipopo- lysaccharide（LPS）-induced monocyte macrophages （RAW264.7 cells）as indexes ，the anti-inflammatory activities of pith-decayed and pith-nodecayed S. baicalensis were evaluated and median effective concentration （EC50）of NO were calculated. The gray correlation method was used for spectrum-effect relationship analysis ；SPSS 26.0 software was used for cluster analysis using the inhibitory rates of NO ，IL-6 and IL- 1β in cells at the concentration of 50 μg/mL. RESULTS There were 15 common peaks in 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis ，and the similarity of them was greater than 0.990. There were total of 8 peaks with VIP 1.0，they were peak 14，12，15，6，10，13，11 and 4. At jcqinge@163.com the concentration of 50 μg/mL，the inhibitory rates of pith- decayed S. baicalensis extract to NO ，IL-6，IL-1 β and the average EC 50 were 62.14％-71.13％，3.32％ -18.38％ and 93.12％-95.47％ and 25.35 μg/mL，respectively；those of pith-nodecayed S. baicalensis extract were 39.52％-50.19％， 6.21％-22.55％，94.10％-96.44％ and 58.63 μg/mL，respectively. Average NO inhibition rate of pith-decayed S. baicalensis extract was significantly higher than that of pith- nodecayed S. baicalensis extract；average EC 50 and average IL- 6 inhibitory rate of pith-decayed S. baicalensis extract were significantly lower than those of pith-nodecayed S. baicalensis extract（P＜0.05）. There was no statistical significance in average inhibitory rate of IL- 1β（P＞0.05）. The correlation degrees of peaks 2-3，5-8 and 10-11 with inhibitory rate of NO were all greater than 0.8. The correlation degrees of peaks 2，5，8-9 with inhibitory rate of IL- 1β were all greater than 0.9. The correlation degrees of 15 common peaks with inhibitory rate of IL- 6 were all less than 0.8. Ten batches of samples could be grouped into two categories ，K1-K5 were clustered into one category and T 12-T16 were clustered into one category. CONCLUSIONS At the concentration of 50 µg/mL，the inhibitory effect of pith-decayed S. baicalensis extract to NO is stronger than that of pith-nodecayed S. baicalensis extract，while the inhibitory effect on IL- 6 is weaker than that of pith-nodecayed S. baicalensis extract；they have similar inhibitory effect on IL- 1β. The corresponding components of peak 6，10-11 are preliminarily identified as main chemical components of the difference in anti-inflammatory activity between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis .

Identification and quality evaluation of germplasm resources of commercial Scutellaria baicalensis based on DNA barcode and HPLC / 中国中药杂志

Scutellaria baicalensis is a commonly used Chinese medicinal herb. In this study, we identified the germplasm resources of commercial S. baicalensis samples based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences according to the available chloroplast genome sequencing results, and measured the content of baicalin by HPLC. Through the above means we determined the best DNA barcode that can be used to detect the germplasm resources and evaluate the quality of commercial S. baicalensis samples. A total of 104 samples were collected from 24 provinces, from which DNA was extracted for PCR amplification. The amplification efficiencies of trnH-psbA, petA-psbJ, and ycf4-cemA sequences were 100%, 59.62%, and 25.96%, respectively. The results of sequence analysis showed that 5, 4, and 2 haplotypes were identified based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences, respectively. However, the sequences of haplotypes in commercial samples were different from that of the wild type, and the joint analysis of three fragments of S. baicalensis only identified 6 haplotypes. Furthermore, the phylogenetic analysis and genetic distance analysis indicated that trnH-psbA could be used to identify S. baicalensis from adulterants. The above analysis showed that trnH-psbA was the best fragment for identifying the germplasm resources of commercial S. baicalensis samples. We then analyzed the haplotypes(THap1-THap5) of commercial S. baicalensis samples based on trnH-psbA and found that THap2 was the main circulating haplotype of the commercial samples, accounting for 86.55% of the total samples, which indicated the scarce germplasm resources of commercial S. baicalensis samples. The content of baicalin in all the collected commercial S. baicalensis samples exceeded the standard in Chinese Pharmacopoeia and had significant differences(maximum of 12.21%) among samples, suggesting that the quality of commercial S. baicalensis samples varied considerably. However, there was no significant difference in baicalin content between different provinces or between different haplotypes. This study facilitates the establishment of the standard identification system for S. baicalensis, and can guide the commercial circulation and reasonable medication of S. baicalensis.

Discovery and functional characterization of flavone O-glycosyltransferases in Scutellaria baicalensis / 药学学报

Huang-Qin is a traditional Chinese medicine with antiviral, antioxidant, and anti-inflammatory activities. Its major bioactive compounds are diverse flavone O-glucuronides and glucosides. Although three flavonoid O-glycosyltransferases have been identified from S. baicalensis, this information is not sufficient to elucidate the structural diversity of flavonoid glycosides. In this study, nine glycosyltransferase candidate genes were discovered from S. baicalensis by BLAST analysis and their functions were characterized after heterologous expression. Three new flavone O-glycosyltransferases were able to catalyze the formation of major compounds in S. baicalensis, including baicalin and wogonoside. These enzymes could also utilize exogenous flavones as sugar acceptors. This work further elucidates biosynthetic pathways for Scutellaria flavonoid O-glycosides.

Biological Essence of Component Complexity in Herbal Medicine： Based on Changed Metabolism of Scutellaria baicalensis Under Drought Stress / 中国实验方剂学杂志

Objective:To investigate the biological essence of the content variation of differential primary and secondary metabolites in fresh<italic> </italic>roots of <italic>Scutellaria baicalensis </italic>under drought stress. Method:The changes of metabolites were analyzed by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass/mass （UHPLC-ESI-Q-TOF-MS/MS）. Result:A total of 11 differential compounds were identified from the roots of <italic>S. baicalensis</italic> （VIP≥2）. Under drought stress， citric acid content increased and shikimic acid content decreased， indicating that the drought stress weakened the primary metabolism but strengthened secondary metabolism. Drought stress raised the content and regulated the proportion of various secondary metabolites by modulating the biosynthesis and biotransformation of them. To be specific， the content of free flavonoids with many phenolic hydroxyl groups and high biological activity and pharmacological activity， such as baicalin， wogonoside， baicalein， wogonin， chrysin， eriodictyol， 5，2'，6'-trihydroxy-7，8-dimethoxyflavone， 5，8-dihydroxy-6，7-dimethoxyflavone， and 3，5，7，2'，6'-pentahydroxyflavanone， was significantly increased. The massive compounds， like an intricate buffer， maintain metabolism stable as quickly and accurately as possible through biosynthesis and biotransformation， thus responding to the changing environment， which reveals how the quality of genuine regional drugs is influenced and why compounds in herbal medicine are complex. Conclusion:Secondary metabolites with low content but high activity are important influencing factors of medicinal material quality and metabolites with high content and high activity are evaluation indicators of genuine regional drug quality.

Ecologically suitable areas for growing Scutellaria baicalensis worldwide: an analysis based on GMPGIS / 中国中药杂志

This paper explored the ecologically suitable areas for growing Scutellaria baicalensis using Geographic Information System for Global Medicinal Plants(GMPGIS), to figure out the resource distribution of S. baicalensis worldwide and provide a scientific basis for its scientific introduction. A total of 349 S. baicalensis sampling sites were selected all over the world for GMPGIS-based analy-sis of the ecologically suitable areas with six ecological factors including annual average temperature, average temperature during the coldest season, average temperature during the warmest season, average annual precipitation, average annual relative humidity, and annual average illumination and soil type as the ecological indexes. The results demonstrated that the ecologically suitable areas for growing S. baicalensis were mostly located in the Northern hemisphere, and the suitable areas in the United States, China, and Russia accounted for 19.25%, 18.66%, and 13.15% of the total area worldwide, respectively. In China, the Inner Mongolia, Heilongjiang province, and Yunnan province occupied the largest proportions of the total area, namely 14.28%, 8.72%, and 6.18%, respectively. As revealed by ecological factors of each sampling site, S. baicalensis was resistant to low temperature but not to high temperature. The adaptive range of average annual precipitation is narrower than that of average annual air humidity. The suitable soils were mainly inceptisol, alfisol, and fluvisol. High temperature and rainy climate or excessively high soil bulk density was not conducive to the growth of S. baicalensis. The adoption of GMPGIS enabled to obtain areas with the greatest ecological similarity for S. baicalensis, which were reliable data supporting the exploration of resource distribution and reasonable introduction of S. baicalensis.

Cloning and temporal-spatial expression analysis of dfr gene from Scutellaria baicalensis with different colors / 生物工程学报

Dihydroflavanol-4-reductase (Dfr) is a key enzyme that regulates the synthesis of anthocyanin and proanthocyanidin in the flavonoid biosynthesis pathway. To investigate the difference of dfr gene in Scutellaria baicalensis Georgi with different colors in the same ecological environment, three complete full-length sequences of dfr gene were cloned from the cDNA of S. baicalensis with white, purple-red and purple colors using homologous cloning and RACE techniques. The three genes were named Sbdfr1, Sbdfr2 and Sbdfr3, respectively, and their corresponding structures were analyzed. The results showed that all three Dfr proteins have highly conserved NADPH binding sites and substrate-specific binding sites. Phylogenetic analysis showed that they are closely related to that of the known S. viscidula (ACV49882.1). Analysis of key structural domains and 3D models revealed differences in the catalytically active regions on the surface of all three Dfr proteins, and their unique structural characteristics may provide favorable conditions for studying the substrate specificity of different Dfr proteins. qRT-PCR analysis shows that dfr was expressed at different level in all tissues except the roots of S. baicalensis in full-bloom. During floral development, the expression level of dfr in white and purple-flowered Scutellaria showed an overall upward trend. In purple-red-flowered Scutellaria, the expression first slowly increased, followed by a decrease, and then rapidly increased to the maximum. This research provides a theoretical basis for further exploring the mechanism and function of Dfr substrate selectivity, and are of great scientific value for elucidating the molecular mechanism of floral color variation in S. baicalensis.

Exploration of the Mechanism about Couplet Medicine of Bupleurum falcatum-Scutellaria baicalensis Intervening in Podocyte Lesion Based on Network Pharmacology / 中国药房

OBJECTIVE：To predict the pot ential target and mechanism of Xintong Changluo Method carrier-Compund Shensu Ⅱ couplet medicine of Bupleurum falcatum-Scutellaria baicalensis intervening in podocyte lesion ，and to provide reference for the development of sequential clinical and basic research of Xintong Changluo Method in the prevention and treatment of podocyte lesion. METHODS ：Based on TCMSP database ，chemical components and target protein of B. falcatum and S. baicalensis were retrieved，and Cytoscape 3.2.1 software was used to draw a “TCM-component-target”network. The targets related to podocyte lesion were searched from OMIM database ，DrugBank database and Digsee online text ，and the intersection genes of above targets and“B. falcatum -S. baicalensis ”target were obtained by Venny 2.1.0 online mapping tool. The protein-protein interaction （PPI） network was constructed by STRING database ，and the core targets were obtained by topology analysis of the network by using CytoNCA plug-in Cytospace 3.2.1 software. With the help of DAVID database ，the fu nction of Gene Ontology （GO）was annotated and KEGG pathway was enriched ；and the enrichment results were visualized through OmicShare Tools online mapping platform. RESULTS ：Based on retrieval results of TCMSP database，44 active components were obtained ，involving 13 com of B. falcatum and 32 of S. baicalensis ； stigmasterol is common component of B. falcatum and S. baicalensis Quercetin，kaempferol and wogonin were the compounds withmain potential targets. T he target proteins wi th high node degree were prostaglandin endoperoxide synthase 2（PTGS2），PTGS1， nuclear receptor coactivator 2 and heat shock protein 90α，which were associated with 37，30，25 and 25 active components respectively. Twenty genes were obtained from the interaction between “B. falcatum -S. baicalensis ”and podocyte lesion related targets，including PTGS2，VEGFA，MMP9，TNF and IL6. PPI network diagram of the above intersection genes contained 20 nodes and 110 lines，with MMP9，VEGFA，IL6 and other genes at the core. The results of GO analysis showed that a total of 154 biological information items were obtained （P＜0.05），including 139 biological process items ，8 cell composition items and 7 molecular function items. Among them ，biological processes mainly involved in the positive regulation of NO biosynthesis process ， inflammatory response ，immune response. Cell composition mainly involved in extracellular space ，extracellular region ，external side of plasma membrane ，etc.，and molecular function mainly involved in protein binding ，cytokine activity ，growth factor activity，etc. At the same time ，47 KEGG pathways were obtained （P＜0.05），mainly including cytokine-cytokine receptor interaction，rheumatoid arthritis ，malaria，cancer signaling pathways. CONCLUSIONS ：The active components of Compund Shensu Ⅱ couplet medicine of “B. falcatum -S. baicalensis ”may act on MMP9，VEGFA，IL6，TNF and other targets through cytokine-cytokine receptor interaction ，rheumatoid arthritis ，malaria，cancer signal pathway ，so as to play its intervention effect on podocyte lesion.

Anti-aging effect of Scutellaria baicalensis Georgi leaves based on 1H NMR serum and liver metabolomics / 药学学报

@#In this study a <italic>D</italic>-galactose-induced aging rat model combined with ¹H NMR of serum and liver metabolomics were used to explore the anti-aging effect and the potential metabolic regulatory mechanism of <italic>Scutellaria baicalensis</italic> Georgi leaves. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of Shanxi University. The results of physical characteristics, an open field test and serum biochemical indexes indicated that <italic>Scutellaria baicalensis</italic> Georgi leaves had an anti-aging effect that could ameliorate the characteristics of aging rats such as acquired hair loss and slow response, improve the spontaneous activity of aging rats, and decrease lipid peroxidation and glycosylation damage induced by <italic>D</italic>-galactose. Serum and liver metabolomics further revealed that <italic>Scutellaria baicalensis</italic> Georgi leaves could decrease serum and liver metabolism disturbances in aging rats, mainly through different metabolites and metabolic pathways. Specifically, 12 differential metabolites including glutamine and glutamate, 11 metabolic pathways including <italic>D</italic>-glutamine and <italic>D</italic>-glutamate metabolism and alanine, aspartate and glutamate metabolism in serum were significantly altered after the treatment. Simultaneously, five differential metabolites such as <italic>α</italic>-glucose and <italic>β</italic>-glucose, two metabolic pathways that are glycolysis or gluconeogenesis, and starch and sucrose metabolism in the liver were markedly altered.

The anti-aging effects of different parts of Scutellaria baicalensis Georgi based on 1H NMR urine metabolomics / 药学学报

The effects of alcohol extracts from roots, stems, leaves, and flowers of Scutellaria Baicalensis Georgi (SBG) on endogenous metabolism in D-gal-induced aging-model rats were investigated by 1H NMR metabolomics. Results showed that 32 endogenous metabolites were identified in the urine. Combined with the VIP value and t-test, 14 different metabolites were found by multivariate statistical analysis of the spectrum. Compared with the control group, the content of α-ketoglutaric acid, hippuric acid and 3-hydroxybutyrate in the urine of rats in the model group was significantly decreased (P<0.05) and the content of trimethylamine oxide, glycine, alanine, lactic acid, dimethylglycine, acetate, pyruvate, taurine, allantoin, betaine, N-acetylated glycoprotein was significantly increased (P<0.05). The metabolites were mainly derived from taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; pyruvate metabolism; glycolysis/gluconeogenesis; glyoxylic acid and dicarboxylic acid metabolism; and the tricarboxylic acid cycle. The content of differential metabolites in urine samples was altered by the alcohol extracts from the different parts of SBG. Leaves extracts of SBG had the greatest effect on urine metabolites, and mainly affected taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; and pyruvate metabolism. This study provides a reliable experimental basis for the future development of SBG. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036).

Prediction and analysis of quality markers between crude and wine-processed Scutellaria baicalensis based on "components-targets-metabolism" network analysis / 中草药

Objective: To explore the potential Q-markers between crude Scutellaria baicalensis (CSR) and wine-processed S. baicalensis (WSR) based on "components-targets-metabolism" network analysis. Methods: According to the differential components between CSR and WSR, the network relationship of "components-target-metabolomics" was constructed combining network pharmacology and metabolomics. The correlation analysis was then conducted between flavonoids glycosides, and aglycones in S. baicalensis, between differential components and endogenous metabolites to predict the potential quality markers. Results: In this study, combining the results of network pharmacology and metabolomics, baicalin and oroxylin A-7-O-glucuronide were regarded as the quality markers of CSR; Baicalein and wogonin were considered as the quality markers of WSR. Conclusion: It is crucial wine-processed mechanism of S. baicalensis that glutinous rice wine can promote the dissolution and absorption of aglycones. Overall, identification of the differences between Chinese herbal decoction pieces and it processed product, combining analysis of network pharmacology and metabolomics, which provides a demonstration for the investigation of quality markers of Chinese herbal pieces.

Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics / 药学学报

The property of medicine is the "identity card" of traditional Chinese medicine (TCM), and the key to crack the theory of property of TCM. Based on molecular thermodynamics, the effects of interaction between TCM and organs in vitro were studied from the perspective of micro-energy release and absorption in order to construct a new idea of characterizing meridian theory. Scutellaria baicalensis, for example, application of isothermal titration calorimetry (ITC) were used to determine the energy changes during the interaction of Scutellaria baicalensis and its main active ingredient baicalin with brain, heart, lung, spleen and kidney in vitro, comparison including the association constant (Ka) and disassociation constant (Kd), combined with thermodynamic parameters, such as stoichiometry ratio (n), enthalpy change (ΔH), entropy change (ΔS), Gibbs free energy (ΔG), it is found that the interaction intensity between Scutellaria baicalensis and lung is significantly stronger than that of other organs, which is consistent with the theory of the return of Scutellaria baicalensis in ancient books. In addition, baicalin, the main active ingredient, showed the same action pattern as Scutellaria baicalensis. The thermodynamic parameters analysis showed that the action was a weak bond-induced spontaneous chemical binding reaction driven by both entropy and enthalpy. The results of specific curl measurement further proved the interaction between baicalin and lung, and were consistent with the results of ITC titration, indicating that ITC could be used to characterize the meridian tropism of TCM. Therefore, based on ITC, it is scientific and feasible to characterize the meridian of TCM by the energy change of the interaction between the decoction of TCM and its active components and the in vitro tissues respectively. This experiment provides a new idea for the discussion of meridian of TCM.

Effects of SSTF on lipid metabolism and oxidative stress in rats with hypertriglyceridemia / 医学研究生学报

ObjectiveThe study of the treatment of hypertriglyceridemia with scutellaria baicalensis stem-leaf total flavonoid (SSTF) are rarely reported.The objective of this study is to investigate the effects of SSTF on lipid metabolism and oxidative stress in rats with hypertriglyceridemia.Methods60 SD rats were randomly divided into normal group, model group, fenofibrate group (100 mg·kg-1), SSTF groups with low, medium and high doses (50,100,200 mg·kg-1, respectively). All rats, except those of the normal group, were fed with high-fat diet and given corresponding drug intervention for 6 weeks. Then the body masses at the 2nd, 4th and 6th weeks as well as wet weight of the liver at the end of 6th week were recorded, and liver index was calculated. The serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected. The levels of TG, TC, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver tissue were determined, and liver histopathological changes were observed by hematoxylin-eosin (HE) staining.ResultsIn the model group, compared with the normal group, the body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week were increased, the serum levels of TG, TC and LDL-C got increased with decreased HDL-C level, and the levels of TG[（1.603±0.146）mmol/L], TC[（3.474±0.356）mmol/L] and MDA[（10.288±1.979）nmol/mg] in liver tissue were increased with decreased levels of SOD[（106.840±24.014）U/mg] and GSH-PX[（9.278±2.079）U/mg]. Compared with the model group,the fenofibrate group and all SSTF groups showed decreased body masses at the 2nd, 4th and 6th weeks and liver index at the end of 6th week, decreased serum levels of TG, TC and LDL-C with increased level of HDL-C, and decreased levels of TG, TC and MDA with increased levels of SOD and GSH-PX in liver tissue. The comparsion between the fenofibrate group and the high-dose SSTF group revealed that the body masses at the 4th and 6th weeks and liver index at the end of 6th week were decreased, the serum levels of TG, TC and LDL-C were decreased with increased level of HDL-C, and the levels of TG[（0.718±0.135）mmol/L] and MDA[（5.071±1.305）nmol/mg] in liver tissue got decreased with increased levels of SOD[（172.210±30.214）U/mg] and GSH-PX[（14.623±2.418）U/mg] in the latter group. All the above-mentioned differences were statistically significant (all P<0.05).ConclusionSSTF can regulate lipid metabolism and improve pathological injury of liver in hypertriglyceridemia rats, which may be related with inhibition of lipid peroxidation and reduction of oxidative stress.

Study on Quality-efficiency Evaluation of Scutellaria baicalensis from Different Origins Based on Content Constituent Characteristics of Flavonoids and in vitro Antiviral Activity / 中国药房

OBJECTIVE：To eva luate content constituent characteristics and antiviral activity of main flavonnoids in genuine and non-genuine Scutellaria baicalensis ，and to investigate quality-efficiency relationship and effective substance. METHODS ： Totally 8 batches of S. baicalensis from different origins （S1-S8）were collected to prepare its water extract lyophilized powder. UPLC method was used to determine the contents of baicalin ，wogonoside，baicalein and wogonin ，and calculate their content constituent ratio. According to the content constituent ratio of flavonoids in S. baicalensis from different origins ，the mixture of the above four components was prepared as the corresponding simulated sample of flavonoids （E1-E8）. Using ribavirin as positive control，MTT assay and CPE method were used to investigate half toxic concentration （TD50）of the water extract from 8 batches of S. baicalensis and their corresponding simulated samples to human laryngeal carcinoma cell Hep-2 and their half inhibition concentration（IC50）to respiratory syncytial virus （RSV）；treatment indexes （TI）were calculated. Pearson correlation analysis for the content of baicalin ，wogonoside，baicalein and wogonin with their anti-RSV activity （IC50）was performed by SPSS 17.0 software. RESULTS ：The contents of baicalin and wogonoside in sample S 4（from Hebei Chengde ）were the highest ，and the contents of baicalein and wogonin in sample S 6（from Inner Mongolia- 2）were the highest. The contents of above 4 components were the lowest in sample S 6，S6，S7（from Beijing ），S4. The contents of flavonoid glycosides in sample S 4 were relatively higher， while those of corresponding glycosides were relatively lower ；the content constituent ratio of baicalin ， wogonoside，baicalein and wogonin was 1∶0.224∶0.111∶0.013. The contents of flavonoid glycosides in sample S6 wererelatively lower ，while those of glycosides were relatively 126.com higher；the content constituent ratio of above 4 components was 1∶0.241∶0.713∶0.106. TC 50 of S. bai calensis water extracts from different origins to Hep- 2 cells was all higher than 50 μg/mL， IC50 to RSV was 11.11-51.74 μg/mL；TI was 1.86-5.20. TC 50 of corresponding simulated samples of flavonoids was 23.11-52.23 μg/mL，while IC 50 to RSV was 4.87-14.61 μg/mL；TI was 1.85-4.75. The anti-RSV effects of water extract of S 4 from genuine origins（Hebei Chengde ）and its corresponding simulated sample E 4 were the strongest. Correlation analysis showed that the correlation coefficient between the contents of 4 flavonoids and antiviral activity was less than 0.5，and there was no significant correlation between them. CONCLUSIONS ：When the content constituent ratio of 4 main flavonoids in S. baicalensis was 1∶0.224∶ 0.111 ∶ 0.013，it has a strong inhibition effect on RSV. S. baicalensis from genuine origins has better constituent characteristics of flavonoids，which may be the important material basis for the best antiviral effect of genuine medicinal material.