最新刊期
卷 29 ， 期 2 ， 2023
- 摘要：ObjectiveTo investigate protective effect of Arctium lappa root aqueous extract （ALR-AE） on hydrochloric acid/ethanol （HCl/EtOH）-induced acute gastric ulcer in rats based on protein kinase B/nuclear transcription factor-κB （Akt/NF-κB） signaling pathway.MethodRats were randomly divided into 5 groups， namely normal group， model group， ranitidine group （35 mg·kg-1）， ALR-AE low dose group （50 mg·kg-1， ALR-AE-L group） and ALR-AE high dose group （100 mg·kg-1， ALR-AE-H group）. Different doses of ALR-AE were orally administered twice daily for three consecutive days before the animals were subjected to HCl/EtOH （60% ethanol in 150 mmol·L-1 HCl） to induce acute gastric ulcer. For the gastric tissue samples， the ulcer surface was recorded by electronic imaging technique， and then the ulcer inhibition rate was calculated using ImageJ 1.8.0， hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining were used to observe the pathological changes and mucoprotein distribution， respectively. The levels of oxidative stress factors of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in rat gastric tissues were determined by colorimetric method， the levels of pro-inflammatory mediators of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β were determined by enzyme linked immunosorbent assay （ELISA）， protein levels of phosphorylation and non-phosphorylation of Akt， NF-κB p65， NF-κB inhibitor protein α （IκBα） and IκB kinase α （IKKα） were evaluated by Western blot.ResultCompared with the normal group， the gastric tissue of the model group was severely damaged， and the area of gastric ulcer were significantly enlarged （P<0.01）， the levels of MDA， TNF-α， IL-6 and IL-1β in gastric tissue were significantly increased （P<0.01）， levels of GSH-Px and SOD were significantly decreased （P<0.01）， and phosphorylation levels of Akt， NF-κB p65， IKKα and IκBα in gastric tissue were significantly increased （P<0.01）. Compared with the model group， ALR-AE significantly attenuated HCl/EtOH-induced gastric tissue damage， significantly increased ulcer inhibition rate （P<0.01）， and dose-dependently reduced the levels of MDA， TNF-α， IL-6 and IL-1β （P<0.05， P<0.01）， and elevated GSH-Px and SOD levels （P<0.01）， ALR-AE-L group could significantly inhibit the phosphorylation levels of Akt （P<0.05）， and ALR-AE-H group could significantly inhibit phosphorylation levels of Akt， NF-κB p65， IKKα and IκBα （P<0.05， P<0.01）.ConclusionALR-AE has a significant protective effect on HCl/EtOH-induced acute gastric ulcers in rats， and its mechanism may be related to the inhibition of inflammatory mediator expression and reduction of oxidative stress levels mediated by Akt/NF-κB signaling pathway.关键词：Arctium lappa root aqueous extract;hydrochloric acid/ethanol;acute gastric ulcer;oxidative stress;Inflammatory mediators;protein kinase B/nuclear transcription factor-κB （Akt/NF-κB）
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发布时间：2022-12-21 - 摘要：ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb.MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C18 column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively.ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）.ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.关键词：Eucommiae Folium;quantitative analysis multi-components by single marker method （QAMS）;aucubin;geniposidic acid;chlorogenic acid;relative correction factor;quality standard
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发布时间：2022-12-21 - 摘要：ObjectiveIn order to explore the utilization value of the seeds dropped in the harvesting， processing， storage and transportation of Prunellae Spica， the character， turgidity and chemical composition of the seeds were analyzed and compared with those of the commercially available varieties， such as chia seeds and basil seeds.MethodCharacter was observed directly. The turgidity was determined according to the method of general rule 2101 of Chinese Pharmacopoeia （part Ⅳ， the 2020 edition）. The contents of six phenolic acids （danshensu， protocatechuic acid， protocatechuic aldehyde， caffeic acid， salviaflaside and rosmarinic acid） were determined by ultra performance liquid chromatography （UPLC）， acetonitrile （A）-0.1% formic acid aqueous solution （B） was used as mobile phase for gradient elution （0-7 min， 2%-8%A； 7-13 min， 8%A； 13-14 min， 8%-17%A； 14-30 min， 17%A）， the detection wavelength was at 280 nm. The liposoluble components were extracted by n-hexane and identified by gas chromatography-mass spectrometry （GC-MS）， and the contents of five fatty acids， namely palmitic acid， oleic acid， stearic acid， linolic acid and α-linolenic acid， were determined on a DB-35MS capillary column （0.25 mm×60.0 m， 0.25 µm）， the injection temperature was 250 ℃， the carrier gas was high-purity helium with a flow rate of 1.0 mL·min-1 and the splitting ratio of 50∶1. The volatile oil was extracted by steam distillation method and its components were identified by GC-MS on a WM-5MS capillary column （0.25 mm×30.0 m， 0.25 µm） with the injection temperature of 250 ℃， the flow rate of 1.0 mL·min-1 and the splitting ratio of 10∶1.ResultPrunellae Spica seeds were slightly smaller than chia seeds and basil seeds， and their color of seed coat was obviously different. Prunellae Spica seeds had strong water absorption and swelling characteristics， and the turgidity was 17.4 mL·g-1， which was lower than that of chia seeds （25.2 mL·g-1） and basil seeds （35.6 mL·g-1）. Prunellae Spica seeds were rich in phenolic and fatty acids， while the content of volatile oil was very low. The main phenolic acids were salviaflaside and rosmarinic acid， with the contents of 0.579% and 0.392%， respectively. The total content of five fatty acids in n-hexane extract was 90.1%， and total content of unsaturated fatty acids was 80.6%， among which content of α-linolenic acid was 50.0%， which was slightly lower than 57.2% of chia seeds and similar to 50.0% of basil seeds.ConclusionPrunellae Spica seeds have good turgidity， rich in phenolic acids and unsaturated fatty acids， and especially with high amount of α-linolenic acid. It is worthy of being developed as functional food to realize comprehensive utilization of the waste resources of Prunellae Spica.关键词：Prunellae Spica seeds;chia seeds;basil seeds;turgidity;phenolic acids;fatty acids;volatile oil
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发布时间：2022-12-21 - 摘要：ObjectiveTo prepare matrine lipid-based cubic liquid crystalline nanoparticle （MAT-LLCN） gels and investigate its in vitro release and transdermal absorption behavior.MethodTaking entrapment efficiency as the index， the optimal formulation of MAT-LLCN was screened by extreme vertex mixture method based on the optimal ratio of glycerol monooleate （GMO） to poloxamer 407 （P407）， and its drug loading was investigated. MAT-LLCN gels was prepared by mixing MAT-LLCN with pre-swelled carbomer 940 as the gel matrix. The structure of MAT-lipid-based cubic liquid crystalline （LLC） was characterized by polarized light microscopy （PLM） and small angle X-ray scattering （SAXS）. The in vitro release and transdermal absorption properties of MAT-LLCN gels and MAT ordinary gels were compared by modified Franz diffusion cell method， skin structure changes caused by them were observed by hematoxylin-eosin （HE） staining.ResultThe optimal formulation of MAT-LLCN gels was 5.5% of GMO-P407 （9∶1）， 1%-6% of MAT， 0.6% of carbomer 940， adding water to sufficient amount. The prepared MAT-LLC was confirmed as body-centered （Im3m） LLC. The in vitro release behavior of MAT-LLCN gels was in accordance with the Weibull equation （R2=0.954 0）， and the release mechanism was the Fick diffusion. In vitro transdermal test showed that all the parameters of MAT-LLCN gels were higher than those of MAT ordinary gels （P<0.05）， including cumulative release rate， steady-state release rate and the amount of drug retention in skin. HE staining results showed that MAT-LLCN gels could loose the cellular arrangement of skin stratum corneum， and maintain the stability of the cell structure of the dermis.ConclusionThe prepared MAT-LLCN gels can accelerate the transdermal drug transport and form drug storage in the dermis by rapidly opening the skin stratum corneum barrier， suggesting that LLC has good application prospects in the field of transdermal drug delivery.关键词：matrine;cubic liquid crystalline nanoparticles;gels;extreme vertex mixture design;in vitro release;in vitro transdermal;retention
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发布时间：2022-12-21 - 摘要：ObjectiveTo investigate the mechanism of protective effect of ethanol extracts of Hemsleya chinensis （HC-EE） on hydrochloric acid/ethanol （HCl/EtOH）-induced acute gastric ulcer in rats.MethodLipopolysaccharide （LPS）-induced RAW264.7 cells were used to evaluate inhibitory effect of HC-EE on the production of inflammatory mediators in vitro. A rat acute gastric ulcer model induced by HCl/EtOH （60% ethanol in 150 mmol·L-1 HCl） was used to evaluate protective effect of HC-EE on acute gastric ulcer. Rats were divided into five groups， including normal group， model group， HC-EE low dose （HC-EE 30， 30 mg·kg-1） group， HC-EE high dose （HC-EE 60， 60 mg·kg-1） group and ranitidine （35 mg·kg-1） group. For model and drug-treated groups， vehicle solvent or drugs were orally administered twice daily for 7 consecutive days before the rats were subjected to HCl/EtOH to induce acute gastric ulcer. After being anesthetized， ulcer surface of each rat was obtained and recorded using electronic imaging technology， and the ulcer inhibition rate was calculated by ImageJ 1.8.0. Hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining were used to observe the pathological histological changes in rats. Content of nitric oxide （NO） in cell culture medium was measured by the Griess method. The levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-6， vascular cell adhesion molecule-1 （VCAM-1） and prostaglandin E2 （PGE2） in rat serum （or cell culture medium） were determined by enzyme linked immunosorbent assay （ELISA）. The protein expressions of phosphorylation （p）-p38 mitogen activated protein kinase （MAPK）/p38 MAPK and p-nuclear transcription factor-κB （NF-κB） p65/NF-κB p65 in rat gastric tissue were detected by Western blot.ResultIn vitro assay showed HC-EE could significantly down-regulate the expressions of NO， TNF-α， IL-1β， IL-6 and VCAM-1 in LPS-induced cells （P<0.05， P<0.01）. In vivo experimental results showed that， compared with the normal group， gastric tissue of the model group was severely damaged， and the area of gastric ulcer was significantly enlarged， levels of TNF-α， IL-6 were significantly increased （P<0.01）， and the level of PGE2 was significantly decreased （P<0.01）， the phosphorylation levels of of p38 MAPK， NF-κB p65 in gastric tissue were significantly increased （P<0.01）. Compared with the model group， HC-EE dose-dependently improved HCl/EtOH-induced gastric tissue injury and inflammatory cell infiltration， and it could increase ulcer inhibition rate， significantly decreased the release of TNF-α and IL-6 （P<0.01）， HC-EE 60 group could increase the content of PGE2 （P<0.05）， and significantly inhibit the phosphorylation levels of p38 MAPK and NF-κB p65 （P<0.05， P<0.01）.ConclusionHC-EE can exert protective effect on HCl/EtOH-induced acute gastric ulcer in rats， and its mechanism may be related to the inhibition of expression of inflammatory mediators mediated by p38 MAPK/NF-κB signaling pathway.关键词：ethanol extract of Hemsleya chinensis;acute gastric ulcer;Inflammatory mediators;p38 mitogen activated protein kinase;nuclear transcription factor-κB;interleukin;staining
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发布时间：2022-12-21
Research topics on the comprehensive utilization of Chinese medicines and their non-medicinal parts
- 摘要：ObjectiveTo investigate the mechanism of Chaihu Shugansan in the treatment of functional dyspepsia in rats based on mitophagy and PTEN-induced kinase 1 （Pink1）/E3 ubiquitin ligase （Parkin）. signaling pathway.MethodAccording to the principle of random grouping， 40 SD rats were assigned into a normal group， a model group， a Chaihu Shugansan group， and a positive drug （domperidone） group， with 10 rats in each group. The rats in other groups except the normal group received tail-clamping stimulation to replicate the model of functional dyspepsia. After each time of stimulation， the rats in the normal， model， Chaihu Shugansan， and positive drug groups were administrated with normal saline， normal saline， Chaihu Shugansan （4.8 g·kg-1）， and an aqueous solution of domperidone （4.5 mg·kg-1）， respectively. After 28 days of modeling， the gastric emptying rate and the small intestine propulsion rate of the rats in each group were measured and the tissue samples were collected. Hematoxylin-eosin （HE） staining was employed for observation of damage in gastric antrum tissue， and transmission electron microscopy （TEM） for ultrastructural observation of gastric interstitial cells of Cajal （ICCs）. Immunofluorescence co-localization was adopted to observe the expression of cytochrome c oxidase （COX Ⅳ） and Parkin. Western blot was employed to determine the expression levels of microtubule-associated protein 1， light chain 3 （LC3）， and the mitophagy-associated proteins prohibitin2 （PHB2）， Pink1， Parkin， and ubiquitin-specific protease 30 （USP30）.ResultCompared with the normal group， the modeling decreased the gastric emptying rate and the small intestine propulsion rate （P<0.05）. Compared with the model group， Chaihu Shugansan increased the gastric emptying rate and the small intestine propulsion rate （P<0.05）. The results of TEM showed that Chaihu Shugansan reduced the swelling degree of mitochondria in gastric antrum tissue. Compared with the normal group， the modeling increased the fluorescence intensity of Parkin in mitochondria （P<0.01）， while such increase can be alleviated by Chaihu Shugansan （P<0.01）. Western blotting results showed that compared with the normal group， the modeling up-regulated the protein levels of LC3， Pink1， Parkin， and PHB2 （P<0.05， P<0.01） and down-regulated the protein level of USP30 （P<0.01）. Compared with the model group， Chaihu Shugansan down-regulated the protein levels of LC3， Pink1， Parkin， and PHB2 （P<0.05， P<0.01） and up-regulated the protein level of USP30 （P<0.01）.ConclusionChaihu Shugansan may treat functional dyspepsia by blocking the Pink1/Parkin signaling pathway to inhibit excessive mitochondrial autophagy in ICCs.关键词：Chaihu Shugansan;functional dyspepsia;mitophagy;PTEN-induced kinase 1 （Pink1）;E3 ubiquitin ligase （Parkin）
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发布时间：2022-12-21 - 摘要：ObjectiveTo study the effect of Guizhi Shaoyao Zhimutang （GSZMD） on cartilage destruction in mice with collagen-induced arthritis （CIA） and its mechanism.MethodThirty-six DBA/1 mice in SPF grades were randomly divided into 6 groups， namely， the normal group， the model group， the methotrexate （MTX） group， the low-dose GSZMD group， the medium-dose GSZMD group， and the high-dose GSZMD group. Except the normal group， mice in the other 5 groups were used to establish the model of CIA by secondary immunization. The mice were given normal saline， MTX （1.5 mg·kg-1， 2 times a week）， and low， medium， and high-doses GSZMD （6.3， 12.6， 25.2 g·kg-1·d-1） by intragastric administration on the day of the onset of hind limb swelling for 4 weeks. The changes in the degree of foot swelling of mice in each group were observed and recorded. The content of matrix metalloproteinase （MMP）-1， MMP-3， MMP-9， and MMP-13 in serum was determined by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining， and the cartilage destruction was observed by red fast green staining. The protein expression of the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway in ankle joints were detected by Western blot.ResultAs compared with the normal group， the degree of foot swelling， the content of MMP-1， MMP-3， MMP-9， and MMP-13 in serum and the expression levels of phosphorylation （p）-JAK2/JAK2 and p-STAT3/STAT3 in ankle joints of the model group were increased （P<0.01）， and the joint damage was aggravated. As compared with the model group， the degrees of foot swelling of the mice in the MTX group and the low， medium， and high-dose GSZMD group were reduced （P<0.05， P<0.01）， and the content of MMP-1， MMP-3， MMP-9， and MMP-13 in serum was decreased （P<0.05， P<0.01）. The pathological joint damage was alleviated， and the expression levels of p-JAK2/JAK2 and p-STAT3/STAT3 in ankle joints were decreased in the MTX group and GSZMD groups （P<0.05， P<0.01）.ConclusionGSZMD can reduce the degree of joint swelling in mice with CIA， inhibit the expressions of MMP-1， MMP-3， MMP-9， and MMP-13， and alleviate the destruction of articular cartilage. Its mechanism is related to the JAK2/STAT3 signaling pathway.关键词：Guizhi Shaoyao Zhimutang;rheumatoid arthritis;cartilage destruction;collagen-induced arthritis （CIA）;Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway
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发布时间：2022-12-21 - 摘要：ObjectiveTo explore the mechanism of Tibetan medicine Ershiwuwei Guijiuwan against osteoporosis in ovariectomized rats through the classical Wnt/β-catenin signaling pathway.MethodForty-eight 3-month-old SD female rats were randomized into model group （equivalent volume of normal saline）， sham operation group （equivalent volume of normal saline）， estradiol group （0.1 mg·kg-1 estradiol valerate）， and high-， medium-， low-dose Ershiwuwei Guijiuwan groups （800， 400， 200 mg·kg-1， respectively）. For the modeling， some adipose tissue near the ovaries was removed in the sham operation group， and ovaries were excised in other groups. Administration （ig， once a day） started two weeks after the operation and lasted 12 weeks. After sampling， based on hematoxylin and eosin （HE） staining， the morphological changes of the right femur and lumbar spine of the rats were observed. The enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum levels of rat tartrate-resistant acid phosphatase 5b （TRAP5b）， collagen type Ⅰ C-terminal peptide （CTX-Ⅰ）， bone alkaline phosphatase （BALP）， amino-terminal propeptide of type Ⅰ procollagen （PINP）， and bone Gla-protein （BGP）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to examine the mRNA expression of β-catenin and Runt-related transcription factor 2 （Runx2） in femur， and Western blot to detect the protein expression of β-catenin， Runx2， and low-density lipoprotein receptor-related protein-5 （Lrp-5）.ResultCompared with the sham operation group， the model group showed disordered and sparse bone trabecula with fewer connections， decrease in serum levels of BALP， BGP， and PINP （P<0.01）， increase in levels of CTX-Ⅰ and TRAP5b （P<0.01）， reduction in mRNA expression of β-catenin and Runx2 in femoral tissue （P<0.01） and protein expression of Lrp-5， β-catenin， and Runx2 （P<0.01）. Compared with the model group， estradiol and each dose of Ershiwuwei Guijiuwan increased the volume of bone trabecula， made thebone trabecula closely arranged， reduced the loss of the trabecular meshwork， raised the serum levels of BALP and BGP （P<0.01）， and lowered TRAP5b level （P<0.01）. PINP level was significantly increased in the high-dose Ershiwuwei Guijiuwan group and estradiol group （P<0.01） and CTX-Ⅰ level was significantly decreased in the high-dose Erwenwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. The mRNA expression of β-catenin in femoral tissue and protein expression of Lrp-5 and β-catenin in estradiol group and three Ershiwuwei Guijiuwan groups were significantly increased （P<0.05， P<0.01）， and the levels of Runx2 mRNA and protein were significantly increased in the high-dose Ershiwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group.ConclusionTibetan medicine Ershiwuwei Guijiuwan is effective for the osteoporosis in ovariectomized rats， which may be related to the classic Wnt/β-catenin signaling pathway. It affects bone metabolism by up-regulating the expression of osteogenesis-related genes in the signaling pathway.关键词：Tibetan medicine;Ershiwuwei Guijiuwan;osteoporosis;Wnt/β-catenin signaling pathway;phytoestrogens
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发布时间：2022-12-21 - 摘要：ObjectiveTo observe the effect of classic prescription Ermiaosan （EMS） on the differentiation of T helper 17 （Th17） /regulatory T （Treg） cells in collagen-induced arthritis （CIA） DBA/1 mice.MethodDBA/1 mice were randomized into normal group， CIA group， EMS （5.4 g·kg-1） group， and methotrexate （MTX，0.5 mg·kg-1） group according to the body weight. DBA/1 mice in CIA group， EMS group， and MTX group were immunized with equal volume of bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and were immunized with equal volume of bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21st day to induce CIA. On the day of the secondary immunization， intragastric administration started and lasted 28 days （three times/week for MTX group， and once/day for other groups）. The symptoms of CIA mice such as joint redness and swelling were observed from the 22nd day， and the arthritis was scored. After the sampling on the 49th day， synovitis of CIA mice was observed based on hematoxylin-eosin （HE） staining. Double-labeling immunofluorescence （IF） method was used to detect the expression of Th17 cell marker IL-17 and Treg cell marker forkhead transcription factor P3 （FoxP3） in CD4+T cells in CIA mouse joints. The proportion of Th17 and Treg cells in the spleen and lymph nodes of mice was detected by flow cytometry.ResultCompared with the normal group， CIA group had obvious synovitis， disordered joint structure， severely damaged articular cartilage and bone， serious bone erosion （P<0.01）， high Th17/Treg value in joint tissue （P<0.01）， high proportion of Th17 cells in spleen and lymph nodes （P<0.01）， and low proportion of Treg cells （P<0.01）. Compared with CIA group， EMS group and MTX group had normal joint structure， mild bone erosion and bone destruction， complete and smooth joint surface， low Th17/Treg value （P<0.01）， low proportion of Th17 cells in spleen and lymph nodes （P<0.01）， and high proportion of Treg cells in spleen and lymph nodes （P<0.01）.ConclusionEMS regulates the balance of Th17/Treg， inhibits the expression of Th17 cells， and promotes the expression of Treg cells in CIA mice， thereby exerting therapeutic effect on RA.关键词：Ermiaosan;collagen-induced arthritis;T helper 17 （Th17） /regulatory T （Treg） cells;differentiation
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发布时间：2022-12-21 - 摘要：ObjectiveTo evaluate the effects of dehydrocostus lactone （DL） on the proliferation， apoptosis， and autophagy of human lung cancer cell A549 and to elucidate its related mechanism.MethodThe effect of DL with different concentrations （0， 5， 10， 15， 20， 25 μmol·L-1） on the proliferation of human lung cancer A549 cells was investigated by cell counting kit-8 （CCK-8）， and its impact on the clonogenic ability of A549 cells was studied by cell clonogenic assay. The concentrations 10， 20 μmol·L-1 were selected as DL low-dose group and high-dose group. Hoechst 33258 staining and western blot were used to observe the effect of DL on apoptosis of A549 cells. Autolysosomes were detected by acridine orange staining， and the expression level of microtubule-associated protein 1 light chain 3 （LC3） was determined by immunofluorescence and western blot. In addition， the effects of DL in combination with autophagy inhibitors bafilomycin A1 （BAF-A1） or 3-methyladenine （3-MA） on the autophagy of A549 cells was checked by CCK-8 assay. Finally， the role of DL in the regulation of A549 cell signaling pathway was explored by Western blot.ResultCompared with the conditions in the control group， the survival rate of A549 cells in the DL groups （10， 15， 20， 25 μmol·L-1） was decreased （P<0.01）， and 5 μmol·L-1 DL could inhibited the formation of A549 clone cells （P<0.01）， indicating that DL could inhibit the proliferation of human lung cancer A549 cells. The number of apoptotic cells was higher in both DL low-dose and high-dose groups than that in the control group， and the expression of apoptosis-related proteins poly （ADP ribose） polymerase （PARP） and B lymphocytoma-2 （Bcl-2）-associated X protein （Bax） were up-regulated （P<0.05， P<0.01）， while the expression of Bcl-2 was down-regulated （P<0.01） in DL high-dose group. The acridine orange staining showed that the orange fluorescence in the DL high-dose group was enhanced compared with that in the control group， indicating that DL could dramatically promote the formation of autolysosomes. Moreover， 20 μmol·L-1 DL could increase the orange fluorescent particles of LC3 and up-regulated the expression level of LC3 Ⅱ （P<0.01）. After addition of autophagy inhibitors， the sensitivity of A549 cells to the effects of DL was attenuated （P<0.01）， which suggested that autophagy was involved in DL-induced A549 cell death. Compared with the control group， DL high-dose group had increased expression of autophagy-related protein 3 （Atg3） and autophagy-related protein 5 （Atg5） while reduced phosphorylation levels of protein kinase B （Akt）， mammalian target of rapamycin （mTOR） and signal transducer and activator of transcription 3 （STAT3） （P<0.05， P<0.01）.ConclusionDL could activate apoptosis and autophagy to inhibit the proliferation and clonogenic ability of A549 cells via suppressing Akt/mTOR/STAT3 signaling pathway.关键词：dehydrocostus lactone;lung cancer;apoptosis;autophagy;protein kinase B （Akt）/mammalian target of rapamycin （mTOR）/signal transducer and activator of transcription 3 （STAT3） signaling pathway
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发布时间：2022-12-21 - 摘要：ObjectiveTo study effect of brusatol （BR） on proliferation of human gastric cancer HGC-27 cells and its mechanism.MethodCell counting kit-8 （CCK-8） was used to detect the survival rate of HGC-27 cells at different concentrations of BR. HGC-27 cells were treated with BR （7.5， 15， 30 μmol·L-1） for 24 h， and then the cell clone formation was analyzed. 2，7-Dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescent probe and lipid peroxidation sensor （C11-BODIPY） were employed to detect the levels of intracellular reactive oxygen species （ROS） and lipid peroxidation， respectively. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the messenger ribonucleic acid （mRNA） and protein expressions of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， solute carrier family 40 member 1 （SLC40A1）， transferrin， nuclear factor E2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1）， respectively.ResultThe survival rate of HGC-27 cells was decreased with the increase of BR concentration， and the IC50 was 15.34 μmol·L-1. Compared with the conditions in blank group， the cell clone formation of BR （7.5， 15， 30 μmol·L-1） groups was inhibited in a dose-dependent manner （P<0.05，P<0.01）， while the levels of intracellular ROS and lipid peroxidation， iron concentration， and lactic dehydrogenase （LDH） leakage were increased in a dose-dependent manner （P<0.05，P<0.01）. Compared with the blank group， the BR （15， 30 μmol·L-1） groups lowered the mRNA and protein expressions of SLC7A11， GPX4， SLC40A1， Nrf2 and HO-1， while elevated the mRNA and protein expression of TRF in a dose-dependent manner （P<0.05，P<0.01）.ConclusionBR suppressed the proliferation of HGC-27 cells through inducing ferroptosis via inhibiting Nrf2/HO-1 pathway.关键词：brusatol;gastric cancer;ferroptosis;reactive oxygen species;lipid peroxidation
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发布时间：2022-12-21 - 摘要：ObjectiveTo explore the effect of Weiwei Tongtiao decoction （WTD） on chronic atrophic gastritis （CAG） rats and the underlying mechanism.MethodA total of 90 SD rats were randomized into normal control group， model group， high-dose， medium-dose， and low-dose WTD groups （18， 9， 4.5 g·kg-1·d-1 WTD， respectively， ig）， and weifuchun control group （0.45 g·kg-1·d-1 weifuchun aqueous solution， ig）， with 15 rats in each group. The N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was employed to induced CAG in rats. After the modeling （identified by histopathological examination）， the administration began and lasted 12 weeks. Then， gastric mucosa tissues of the rats were collected and stained with hematoxylin and eosin （HE）， and the pathological changes of gastric mucosa were observed under the optical microscope. Real-time PCR， immunohistochemistry （IHC）， and Western blotting were applied to examine the mRNA and protein expression of indexes in nuclear factor kappa-B （NF-κB） signaling pathway in the gastric mucosa of rats.ResultCAG rats showed irregular arrangement and morphology of the inherent glands in gastric mucosa and the glands decreased or disappeared. In addition， inflammatory cell infiltration was observed in the lamina propria of CAG rats， and about 48.4% presented intestinal metaplasia. WTD significantly alleviated the reduction of the glands and intestinal metaplasia in a dose-dependent manner. Compared with the normal control group， the model group demonstrated increase in the mRNA expression of cyclooxygenase-2 （COX-2）， NF-κB p65， interleukin （IL）-1α， IL-1β， IL-10， IL-8α， and IL-8β， and protein expression of COX-2， NF-κB p65， and IL-10 （P<0.01）. WTD and weifuchun lowered the mRNA expression of COX-2， NF-κB p65， IL-1α， IL-1β， IL-10， IL-8α， and IL-8β， and the protein expression of COX-2， NF-κB p65， and IL-10 in gastric mucosa of CAG rats （P<0.01）. The expression of the above indexes after the intervention with high-dose WTD was close to that of the normal control group.ConclusionWTD can improve or even reverse the diseased gastric mucosa of CAG rats， and the mechanism is the likelihood that WTD down-regulates the mRNA and protein expression of the indexes in NF-κB signaling pathway in gastric mucosa of CAG rats.关键词：chronic atrophic gastritis（CAG）;Weiwei Tongtiao decoction;nuclear factor kappa-B（NF-κB） signaling pathway
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发布时间：2022-12-21 - 摘要：ObjectiveTo explore the effect and regulatory mechanism of notoginseng total saponins on apoptosis of mammary gland cells in rats with mammary gland hyperplasia.MethodSixty female non-pregnant SD rats were randomly divided into control group， model group， Notoginseng total saponins low-， medium- and high-dose （10， 20， 40 mg·kg-1， respectively） groups and tamoxifen group （1.8 mg·kg-1）， 10 rats per group. Rat model of mammary gland hyperplasia was established by intramuscular injection of estradiol benzoate and progesterone. Oral administration was performed according to the experimental dose of each group， once a day for 30 consecutive days. The rats in the control group and the model group were given equal volume of normal saline by gavage every day. After administration， the diameter of the second pair of nipples of the rats was measured with vernier calipers， and breast tissue samples were collected and stained with hematoxylin and eosin （HE） to observe the pathological changes. Immunohistochemistry was used to determine the expression of apoptosis regulators B-cell lymphoma-2 （Bcl-2）-associated X （Bax） and Bcl-2， and Western blot was conducted to detect the expression of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway-related proteins.ResultCompared with the control group， the model group had increased diameter of the second pair of nipples （P<0.05）， elevated volume of mammary lobules and number of acinus， diffuse mammary gland hyperplasia， and up-regulated expression of Bcl-2 protein， increased ratio of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR （P<0.05） and decreased expression of Bax in the mammary gland （P<0.05）. Compared with the conditions in the model group， the diameter of the second pair of nipples of the rats in the notoginseng total saponins low-， medium- and high-dose groups and tamoxifen group was decreased （P<0.05）， and the number of mammary lobules and acinus and the amount of secretions were reduced. In addition， the mammary gland hyperplasia was alleviated， and a decrease was observed in the expression of Bcl-2 protein and the ratio of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR （P<0.05）， and an increase in the expression of Bax （P<0.05）.ConclusionNotoginseng total saponins could improve mammary gland hyperplasia in rats， and its mechanism was related to regulating PI3K/Akt/mTOR pathway and promoting apoptosis of mammary gland cells.关键词：Notoginseng total saponins;mammary gland hyperplasia;phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）;apoptosis;rat
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发布时间：2022-12-21 - 摘要：ObjectiveTo observe the effects of Cuscutae Semen on the learning and memory ability， N6-methyladenosine （m6A）-related modification enzymes and total m6A level in hippocampus of the offspring of fear-damaged pregnant rats.MethodForty-five pregnant rats were randomly divided into blank group， model group and Cuscutae Semen group. From the 1st day to the 19th day of pregnancy， rats in the model group and the Cuscutae Semen group were induced by observing electric shock of other rats. The Cuscutae Semen group was treated with 5 g·kg-1·d-1 Cuscutae Semen decoction （ig）， while the other two groups were treated with the same amount of purified water. The offspring were assigned following the grouping method of their maternal generation. The behavioral changes of the offspring were tested by Morris water maze on 21st day after birth， and the development of hippocampal neurons was observed by transmission electron microscopy. The mRNA and protein expression levels of methyltransferase-like 3 （METTL3）， METTL14， Wilms tumor 1 associated protein （WTAP）， fat mass and obesity-associated protein （FTO） and Alk B homologue 5 （ALKBH5） were detected by Real-time polymerase chain reaction （Real-time PCR）， Western blot and immunohistochemistry （IHC）. The total content of m6A in hippocampus was determined by high performance liquid chromatography tandem mass spectrometry （LC-MS/MS）.ResultCompared with the conditions in the blank group， the average latency duration in the model group was prolonged， and the number of entries in the target quadrant， the target quadrant duration and the number of crossing the platform were decreased （P<0.01）. Additionally， the model group had seriously damaged structure of hippocampal CA1 and CA3 neurons， swollen mitochondria， expanded endoplasmic reticulum， and small number of synapses with some having blurred structure， and the expression levels of METTL3， METTL14， FTO， ALKBH5 as well as the total m6A level were lower than those in the blank group （P<0.05，P<0.01）. Compared with the model group， the Cuscutae Semen group had shortened average latency duration， increased number of entries in the target quadrant， target quadrant duration and number of crossing the platform （P<0.01）， alleviated damage of hippocampal CA1 and CA3 neurons， fine structure of mitochondrial and endoplasmic reticulum， and clear， intact and dense synapses. And the expression levels of METTL3， METTL14， FTO as well as the total level of m6A were up regulated， while the expression level of ALKBH5 was down regulated in the Cuscutae Semen group （P<0.05，P<0.01）.ConclusionCuscutae Semen improved the learning and memory ability of the offspring of the rats affected by fear damaging kidney during pregnancy， protected hippocampal neurons， and up-regulated the expression levels of METTL3， METTL14， FTO and the total m6A level in hippocampus.关键词：Cuscutae Semen;fear damaging kidney;learning and memory;hippocampus;N6-methyladenosine （m6A）
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发布时间：2022-12-21 - 摘要：ObjectiveBased on the hemodynamic indicators of transcranial Doppler （TCD），this study aimed to analyze the correlations of visual analogue scale（VAS） and Hamilton depression rating scale 24-item（HAMD-24） scores with mean blood velocity （Vm） of the anterior cerebral artery （ACA），the middle cerebral artery （MCA）， and the posterior cerebral artery （PCA），and the correlation between VAS score of headache and HAMD-24 score，and explore the clinical efficacy of Xiaoyaosan combined with paroxetine tablets in the treatment of migraine with liver depression and blood deficiency syndrome and depression.MethodSixty-two outpatients treated in the encephalopathy department， the First Afffiliated Hospital of Anhui University of Chinese Medicine between January 2019 to June 2020 who were in line with the diagnostic criteria were enrolled and divided into a treatment group （32 cases） and a control group （30 cases）. All patients were treated with paroxetine tablets，while those in the treatment group received additional Xiaoyaosan. The changes in relevant indicators in the two groups before and after treatment were observed. The effects of Xiaoyaosan on the TCD indicators （VmACA， VmMCA， and VmPCA）， scores of migraine and depression ［including VAS score， Headache Impact Test-6 （HIT-6） score，and HAMD-24 score］， and the traditional Chinese medicine （TCM） syndrome score were analyzed.ResultVAS and HAMD-24 scores were positively correlated with VmACA， VmMCA， and VmPCA （P<0.01）. VAS scores were positively correlated with HAMD-24 scores. Compared with the conditions before treatment， the levels of TCD indicators （VmACA， VmMCA， and VmPCA） in the two groups decreased after treatment （P<0.01）， and the scores of HIT-6， VAS， and HAMD-24 in the two groups were significantly improved （P<0.01）. Compared with the control group after treatment， the treatment group showed decreased levels of TCD indicators （VmACA， VmMCA， and VmPCA） （P<0.01） and superior improvement of HIT-6， VAS， and HAMD-24 scores （P<0.01）. The effective rate in the treatment group was 90.6% （29/32）， higher than 63.3% （19/30） in the control group （χ2=5.13，P<0.05）. There was no significant difference in adverse reactions between the two groups.ConclusionTCD indicators can effectively reflect the cerebral blood flow of patients with migraine and depression co-morbidity，and migraine is correlated with the onset and severity of depression. The comprehensive analysis showed that the efficacy of Xiaoyaosan combine paroxetine tablets was better than that of paroxetine tablets alone in the treatment of migraine with liver depression and blood deficiency syndrome and depression. This therapeutic protocol can significantly improve cerebral blood flow and the symptoms and degree of migraine and depression and can provide references for clinical treatment.关键词：migraine;depression;transcranial Doppler（TCD）;Xiaoyaosan;paroxetine tablets
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发布时间：2022-12-21 - 摘要：ObjectiveTo investigate the efficacy and safety of Shengxiantang in the treatment of early Parkinson's disease with autonomic dysfunction of Qi deficiency pattern.MethodA total of 82 eligible patients were randomized into control group （41 cases） and traditional Chinese medicine （TCM） group （41 cases）. On the basis of standardized treatment of western medicine， TCM group was prescribed Shengxiantang while control group were treated with placebo for 12 consecutive weeks additionally. Scale for Outcomes in Parkinson's Disease-Autonomic （SCOPA-AUT） questionnaire， Unified Parkinson's Disease Rating Scale （UPDRS）， Traditional Chinese Medicine Qi Deficiency Symptom Score of Parkinson's Disease （TCMQDSSPD）， serum levels of glutathione peroxidase （GPx） and superoxide dismutase （SOD）， daily dosage of pramipexole and levodopa and benserazide hydrochloride， and safety index were evaluated both before and after treatment.ResultAfter treatment， the total score of SCOPA-AUT， gastrointestinal score， urinary score， and thermoregulatory score in the control group were higher than those before treatment （P<0.01）， while the above sores in the TCM group were lower than those before treatment （P<0.05， P<0.01）. In addition， the cardiovascular score， pupillomotor score， and sexual score in two groups showed no significant difference from those before treatment. After treatment， the total score of SCOPA-AUT， gastrointestinal score， urinary score， and thermoregulatory score in the TCM group were lower than those in the control group （P<0.05， P<0.01）， and cardiovascular score， pupillomotor score， and sexual score showed no significant difference between two groups. After treatment， the total score of TCMQDSSPD， main symptom scores， and minor symptom scores in the control group had no significant difference from those before treatment. The total score of TCMQDSSPD and minor symptom scores of TCM group were lower than those before treatment （P<0.01）， while the main symptom scores of the TCM group showed no significant difference from those before treatment. After treatment， the UPDRS score， serum GPx and SOD levels， and daily dosage of pramipexole and levodopa and benserazide hydrochloride demonstrated no significant difference from those before treatment in the two groups and between the two groups. No abnormality was found in the safety indexes.ConclusionBased on the standardized treatment of western medicine， Shengxiantang can effectively and safely improve the autonomic symptoms of gastrointestinal system， urinary system， and thermoregulation， as well as the symptoms of Qi deficiency syndrome in early Parkinson's disease with autonomic dysfunction.关键词：Parkinson's disease;autonomic dysfunction;integrated traditional Chinese and western medicine;Shengxiantang
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发布时间：2022-12-21 - 摘要：ObjectiveTo investigate the changes of intestinal microbiota in type 2 diabetic diarrhea （T2DD） patients with dampness-heat syndrome and spleen-kidney deficiency syndrome.MethodT2DD patients who were admitted to the Department of Endocrinology Ⅰ of the Affiliated Hospital of Shaanxi University of Chinese Medicine from March 2020 to May 2021 were selected， including 14 patients with type 2 diabetes mellitus （T2DM）， 12 T2DD patients with dampness-heat syndrome， and 13 T2DD patients with spleen-kidney deficiency syndrome. Twelve healthy subjects receiving medical examination were selected as control group. Their body mass index （BMI）， fasting plasma glucose （FPG）， 2 h postprandial blood glucose （2 h PBG） and glycosylated hemoglobin （HbA1c） were compared. Fecal samples were collected for DNA extraction to build a database. High-throughput 16S rDNA sequencing was used to compare the composition of intestinal microbiota and the differential bacteria among the four groups.ResultCompared with the conditions in control group， the levels of FPG， 2 h PBG and HbA1c in the other groups were increased （P<0.05）. Alpha diversity showed no significant difference in species richness， evenness and diversity of intestinal microbiota among the groups. Beta diversity indicated that intestinal microbiota tended to be consistent in each group， and there was no marked difference between groups. The top 5 phylum by relative abundance were Bacteroidetes，Proteobacteria， Firmicutes， Actinobacteria， and Fusobacteria， among which，Bacteroidetes， Proteobacteria and Firmicutes were dominant. Compared with the control group， the three diabetic groups had elevated relative abundance of Bacteroidetes while decreased relative abundance of Firmicutes. The relative abundance of Actinomycetes in spleen-kidney deficiency T2DD group was significantly higher than that in the other groups， and the relative abundance of Firmicutes and Fusobacteria in the dampness-heat T2DD group was significantly lower than that in the other groups. At the genus level， the top 10 bacteria by relative abundance were Phocaeicola， Bacteroides， Pseudescherichia， Prevotella， Bifidobacterium， Faecalibacterium， Fusobacterium， Roseburia， Citrobacter， and Cetobacterium. LEfSe analysis revealed that the relative abundance of Prevotella， Mediterraneibacter， Parabacteroides， and Fusicatenibacter in diabetic patients was remarkably higher than that in healthy patients. Bacteroides and Sutterella might be the characteristic microbiota of T2DD patients with dampness-heat syndrome， while Faecalibacterium， Limosilactobacillus， Eubacterium， Gemmiger， Enterocloster， Alistipes， Parasutterella and Oscillibacter might be the characteristic microbiota of T2DD patients with spleen-kidney deficiency syndrome.ConclusionBacteroides and Parasutterella might be the characteristic microbiota of T2DD patients with dampness-heat syndrome and spleen-kidney deficiency syndrome， respectively. This paper provided reference for studying the mechanism， diagnosis and treatment of modern traditional Chinese medicine for T2DD of dampness-heat type and spleen-kidney deficiency type.关键词：type 2 diabetic diarrhea;dampness-heat syndrome;spleen-kidney deficiency syndrome;intestinal microbiota;high-throughput 16S rDNA sequencing
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发布时间：2022-12-21 - 摘要：ObjectiveTo identify the members of the Rehmannia glutinosa miR166 gene family and clarify the response mode under adversity.MethodHigh-throughput sequencing technology was employed to obtain a small RNA database and the miR166 family members of R. glutinosa were screened out. The precursor structures were analyzed by RNAfold. DNAMAN and MEGA were used for conservative and evolutionary analyses， respectively. TargetFinder software was used to predict the target genes of R. glutinosa miR166 family members. The expression of miR166 family members in response to abiotic stress was analyzed by real-time polymerase chain reaction（Real-time PCR）.ResultFive miR166s were identified with precursors possessing complete stem-loop structures. As revealed by sequence alignment results， the precursors and matures were both highly conserved. Forty-eight target genes of miR166s were predicted， which were mainly annotated to the HD-ZIP Ⅲ family transcription factors. The expression characteristics showed that the expression of miR160s was up-regulated after R. glutinosa was infected by endophytic fungi， which was different from the expression of the family members under abiotic stress. The expression level of rgl-miR166b-5p in the drought-flood treatment group and the high-low temperature treatment group was significantly down-regulated compared with that in the control group， and the expression pattern was opposite under the endophytic fungal infection.ConclusionThe results of this study preliminarily clarified the expression patterns of R. glutinosa in response to biotic and abiotic stresses and provided a theoretical basis for future breeding and improvement of R. glutinosa.关键词：Rehmannia glutinosa;miR166;real-time polymerase chain reaction（Real-time PCR）;stress;expression
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发布时间：2022-12-21 - 摘要：ObjectiveTo optimize and establish a multiplex polymerase chain reaction （PCR） system to simultaneously identify Ziziphi Spinosae Semen （ZSS），Hovenia acerba semen （HAS），and Ziziphi Mauritianae Semen （ZMS）， etermine their content to solve the problem of adulteration of ZSS pieces and its preparations.MethodAfter the analysis and comparison of the internal transcribed spacer （ITS） sequence differences of ZSS and its adulterants，specific single nucleotide polymorphism （SNP） sites were found，and specific primers for identification were designed. The samples of ZSS，HAS， and ZMS from different sources were specifically amplified under the conditions of optimized annealing temperature，the number of cycles， and concentration of primers，as well as different polymerases and PCR systems after evaluation. Identification was carried out according to the size of specific amplification bands，and the lower limit of detection （LOD） and adulteration LOD were studied.ResultWhen the annealing temperature was 63 ℃ and the number of cycles was 23，549，169，389 bp specific bands were amplified from ZSS，HAS， and ZMS. The lower LOD of this method was 0.24 ng and 1.2 ng for ZSS and HAS， respectively. The adulteration LOD for ZSS，HAS， and ZMS was 0.5%，2%， and 2% respectively.ConclusionThe established multiplex allele-specific PCR identification method can accurately identify ZSS，HAS， and ZMS at the same time，which can provide a basis for solving the problem of adulteration of ZSS and references for controlling the quality，security， and clinical application of ZSS.关键词：Ziziphi Spinosae Semen;Hovenia acerba semen;Ziziphi Mauritianae Semen;multiplex allele-specific polymerase chain reaction（PCR）;identification;adulteration
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发布时间：2022-12-21 - 摘要：ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology.MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language.ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on.ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.关键词：Mori Ramulus;Mori Cortex;Mori Fructus;Mori Folium;insulin resistance;ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）;molecular docking;material basis
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发布时间：2022-12-21 - 摘要：ObjectiveTo study the modeling elements and detection indexes of type 2 diabetes mellitus （T2DM） animal models， to provide a reference for establishing animal models with related pathogenesis in a cost-effective and simple manner， and to lay a basis for the research on relevant pathogenesis and pharmacological mechanism.MethodPapers on animal experiment of T2DM which were published from January 1， 2011 to December 31， 2021 were retrieved from China Knowledge Network， Wanfang Data， and PubMed. Data on the types and genders of animals， modeling methods， and evaluation indexes and methods were collected used to establish a database. Then， Excel and SPSS 18.0 were employed for data analysis.ResultA total of 249 eligible papers were included and male SD rats were mainly used for the modeling. The combination of chemical and diet was mainly adopted for the modeling， with streptozotocin （STZ） as the main chemical and high-fat and high-sugar diet as the main diet. The evaluation indexes of serum biochemical indexes， histopathology， and related indexes were frequently used.ConclusionIn animal experiment on T2DM， male SD rats are mainly adopted for modeling. The frequently used modeling method is the combination of high-fat and high-sugar diet （containing 10% lard and 20% sucrose） or high-fat diet （containing 40%-60% fat） with small dose of STZ （30-40 mg·kg-1， intraperitoneal injection， once）. This method is characterized by ease of implementation and high success rate， and the yielded animal model has the disease pathogenesis. The models are often evaluated based on blood glucose， blood lipid profile， serum insulin， glucose tolerance test or insulin tolerance test. The findings are expected to serve as a reference for research on basic animal experiment on T2DM.关键词：type 2 diabetes mellitus;animal models;data mining;modeling elements;detection indexes
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发布时间：2022-12-21 - 摘要：ObjectiveTo study the modeling characteristics of primary dysmenorrhea models in animals and to provide references for the standardization of the primary dysmenorrhea animal models.MethodThe research articles on animal models of primary dysmenorrhea were retrieved to establish a database. The types of experimental animals， modeling methods， modeling cycle， drug dosage， drug injection methods， high-frequency detection indicators， positive drug types， etc.， were summarized and analyzed.ResultA total of 171 research articles that met the criteria were included. The animals for primary dysmenorrhea model induction were mainly SD rats， Wistar rats， and Kunming mice. Most of them were prepared by combining estradiol and oxytocin with the modeling cycle of 9 d≤t≤12 d. In terms of drug dosage for rats， estradiol benzoate was 0.5 mg·d-1 on the 1st and 10th days and 0.2 mg·d-1 on the 2nd to 9th days， while oxytocin at 2 U·d-1 was the most common. In terms of drug dosage for mice， diethylstilbestrol at 2 mg·kg-1·d-1 and oxytocin at 20 U·kg-1·d-1 were the most common. In terms of injection methods， oxytocin was mainly administered by intraperitoneal injection and estradiol （estradiol benzoate and diethylstilbestrol） by subcutaneous injection. The detection indicators were mainly behavioral indicators of the writhing assay or the related biochemical indicators in the uterus or serum by enzyme-linked immunosorbent assay. The positive western medicines were dominated by ibuprofen and Chinese medicines by Tongjingbao.ConclusionAlthough primary dysmenorrhea animal models have become a hot topic， the existing reviews are not comprehensive， and the modeling standards and traditional Chinese medicine （TCM） syndrome evaluation are inadequate. By summarizing and analyzing the big data of the animal models， this study proposed some specific views to provide guidance and references for establishing the standard and ideal animal models of primary dysmenorrhea， so as to carry out research on this disease.关键词：data mining;primary dysmenorrhea;animal model
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发布时间：2022-12-21 - 摘要：The development of famous classical formula compound preparations has been a research hotspot in recent years， carrying great expectations from the government， academia and industry. During the process of its research and development， it reflects many problems related to traditional Chinese medicine （TCM） industry and deserves deep consideration by the academic community. Based on the current status of development of famous classical formulas， this paper summarizes the key problems and made an in-depth analysis. The results show that three key issues should be paid attention. The first is the weakness of basic research in TCM， which affect the healthy development of TCM. The second is the understanding of development of famous classical formula compound preparations is not in-depth， and the formulation of relevant policies needs to be more reasonable. Thirdly， the expectation for the development of famous classical formula compound preparations is too high， which affects the research and development process of the compound preparations. It is hoped that the TCM industry can take this opportunity to face the problems， propose solutions， and form new breakthroughs to promote the development and progress of TCM.关键词：famous classical formulas;compound preparations;hot inspiration of development;cool-minded ideas;influencing factors;traditional Chinese medicine;policy
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发布时间：2022-12-21 - 摘要：The idea that Gypsum Fibrosum can release flesh has a long history， but its clinical popularization， application， and in-depth discussion are insufficient due to the problems of mineral drug dissolution and limited research means. Through the analysis of releasing flesh method （RFM）， this paper concluded that the RFM-targeted pathogenesis was deficiency of body fluid and disturbance in the exterior， and the core connotation of RFM of Gypsum Fibrosum was clearing heat to restore fluid and expelling pathogenic factors in the exterior. Based on the ancient and modern application of RFM and modern research on coordination chemistry， this paper enriched the connotation of RFM of Gypsum Fibrosum from compatibility with traditional Chinese medicine （TCM） classical prescriptions recorded in the Treatise on Cold Damage （《伤寒论》） and Synopsis of the Golden Chamber （《金匮要略》） as examples. Specifically， in addition to muscle discomfort symptoms after external contraction， RFM of Gypsum Fibrosum could also affect the function of internal organs， thereby treating internal injuries and miscellaneous diseases. Moreover， a new idea， RFM of Gypsum Fibrosum by compatibility， was proposed， that the fresh-releasing effect of Gypsum Fibrosum could be markedly exerted through compatibility with Ephedrae Herba， Puerariae Lobatae Radix， Stephaniae Tetrandrae Radix， Anemarrhenae Rhizoma， Ginseng Radix et Rhizoma， Paeoniae Radix Alba， Bambusae Caulis in Taenias， Rehmanniae Radix， Ophiopogonis Radix， and Polygonati Odorati Rhizoma by adjusting the expelling and heat-clearing intensity. A clinical case was presented to provide a reference for the clinical application of Gypsum Fibrosum and a direction for the study of drug mechanism of compatibility.关键词：releasing flesh;Gypsum Fibrosum;compatibility;classical prescriptions
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发布时间：2022-12-21 - 摘要：Renal interstitial fibrosis （RIF） is the main pathological feature of chronic kidney disease caused by a variety of factors. "Kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" is the main pathogenesis of RIF. The deficiency of healthy Qi will influence the kidney Qi， resulting in kidney deficiency and unsmooth qi transformation. As a result， phlegm， heat， stasis， toxin and other excess pathogens block the kidney collaterals， forming miniature masses. The masses accumulate in the renal collaterals， finally leading to RIF. Autophagy is a key process that keeps your body's cells in proper balance by taking aged or damaged components in a cell and recycling them. It is involved in the occurrence and development of RIF. The metabolism of excess pathogens such as phlegm， heat， stasis， and toxin in vivo is related to the degradation and reabsorption of autophagy. Autophagy is a way to eliminate phlegm， heat， stasis， toxin and other excess pathogens. Autophagy dysfunction will cause the accumulation of phlegm， heat， blood stasis， toxin and other excess pathogens， further the stasis of the kidney collaterals， miniature mass in kidney， and finally RIF. Kidney deficiency and blood stasis in collateral are the root cause of autophagy dysfunction， and the miniature mass of renal collateral is the manifestation of autophagy dysfunction. Autophagy dysfunction and miniature mass of renal collateral have the same pathological evolution. In this paper， based on the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" of RIF and RIF-autophagy relationship， this paper discusses the "kidney deficiency and blood stasis in collateral-autophagy dysfunction-miniature mass of renal collateral" relationship in RIF and comprehensively interprets the scientific connotation of the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral"， which is expected to lay a basis for explaining the role of autophagy in TCM theory and for the treatment of RIF and research on the mechanism.关键词：renal interstitial fibrosis;autophagy dysfunction;kidney deficiency and blood stasis in collateral;miniature mass of renal collateral
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发布时间：2022-12-21 - 摘要：In vitro cell experiment based on serum pharmacology is a common way to study the pharmacodynamic mechanism of Chinese medicine， and screening the optimal intervention concentration of serum containing Chinese medicine is a key step in the whole experiment. Over-diluted serum containing Chinese medicine or over-high concentration leads to false negative or positive results， while the optimal concentration of medicated serum reduces the number of groups in subsequent experiments as well as the operation error. Thus it is of great significance to screen the optimal serum concentration in studying the pharmacodynamic mechanism of Chinese medicine in in vitro cell experiments. However， there has been no unified standards for the screening methods at present. After reviewing the literature in China and abroad in the past 20 years， this paper conducted an analysis from three aspects of intragastric dose of Chinese medicine， blood collection time and serum dilution degree， and then summarized the screening methods for optimal concentration of serum containing drugs， providing guidance for the study of pharmacodynamic mechanism of Chinese medicine. The screening methods mainly included "same intragastric dose， same blood collection time， and different concentrations" "different intragastric doses， same blood collection time， and same concentration" "same intragastric dose， different blood collection time， and same concentration" "different intragastric doses， different blood collection time， and different concentrations" "serum lyophilized powder" "simulation of gradient concentration of serum containing western medicine" and "pure serum intervention". Among them， the former two were the dominant ways in current related research. The above screening methods had their own advantages and disadvantages， and researchers should make a reasonable choice according to the specific requirements and actual situation of the experiments.关键词：cell experiment;drug-containing serum;serum pharmacology of Chinese medicine;concentration
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发布时间：2022-12-21 - 摘要：As a prescription for tonifying kidney yang， Youguiwan accords with the pathogenesis of osteoarthritis. Professor LIU Yuan-lu from the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine found that modified Youguiwan had a significant effect on the clinical conservative treatment of osteoarthritis pain with Chinese medicine. There are teams studying the mechanism of Youguiwan in the treatment of osteoarthritis in China， but the profound study of the compound needs the mechanism of each component as support. Youguiwan contains 10 kinds of Chinese medicine， including Rehmanniae Radix Praeparata， Aconiti Lateralis Radix Praeparata， Cinnamomi Cortex， Dioscoreae Rhizoma， Corni Fructus， Cuscutae Semen， Angelicae Sinensis Radix， Eucommiae Cortex， Cervi Cornus Colla， and Lycii Fructus. With more and more attention to the study of Chinese medicine monomer， the amount of related research in this field is increasing. Therefore， it is of great significance to summarize the mechanism of Youguiwan in the treatment of osteoarthritis. Based on the sovereign， minister， assistant， and guide of Chinese medicine in Youguiwan， this paper used China National Knowledge Infrastructure （CNKI）， Pharmacopoeia of the People's Republic of China （2020 edition Vol. 1）， and ChemicalBook platform to understand the active components of each kind of Chinese medicine， and used PubMed to search. The latest research progress of effective monomers that had an intersection with the mechanism of osteoarthritis was summarized， and there were five pharmacological effects including anti-inflammation， pain inhibition， chondrocyte apoptosis， oxidative stress， and extracellular matrix degradation， involving several signaling pathways. The theory of sovereign， minister， assistant， and guide and the molecular mechanism were integrated and discussed， respectively， and finally， they were combined with traditional Chinese medicine theory， providing theoretical references for further study in this direction.关键词：Youguiwan;active components;osteoarthritis;signaling pathways
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发布时间：2022-12-21 - 摘要：The prevalence and mortality of cancer have been on the rise， and it has been the global leading cause of death. The causes of cancer are diverse， such as heredity， radiation， and carcinogens. The abnormality of cell cycle regulation is also one of the causes. Cell cycle is a complex sequence of events through which a cell duplicates its contents and divides. Cell cycle is highly organized to ensure the integrity of genetic material. This process involves many regulatory genes and proteins. Cell cycle will be dysregulated when these proteins and genes change， resulting in the loss of control of cell proliferation， the inhibition of apoptosis， and finally the occurrence of tumor. At the moment， the therapies for cancer include traditional surgical resection， radiotherapy， chemical therapy， and targeted therapy. Chinese medicine has a wide range of sources and little side effect， which is worthy of further research and development. More and more studies have revealed that a variety of Chinese medicines play an anti-tumor role by inducing cell cycle arrest， so as to improve the quality of life and prolong the survival time of patients with advanced tumors. This article first introduces the characteristics and related regulatory factors of each phase of cell cycle， and enumerates the clinical and experimental examples of tumorigenesis caused by abnormal cell cycle. Then， we summarize the hot anti-tumor drugs targeting cell cycle in China and abroad， such as Cyclin-dependent kinase （CDK） inhibitors， cell division cycle 25 （CDC25） inhibitors， ataxia-telangiectasia-mutated-and-Rad3-related kinase （ATR） inhibitors， and checkpoint kinase 1 （CHK1） inhibitors. Finally， this article summarizes the recent research on the anti-tumor effect of Chinese medicine by inducing cell cycle arrest from the three aspects of cell cycle G0/G1 phase， S phase and G2/M phase， in order to provide some reference for the research on the anti-tumor effect of Chinese medicine.关键词：Chinese medicine;anti-tumor;cell cycle;research progress
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发布时间：2022-12-21 - 摘要：Nasopharyngeal carcinoma （NPC）， characterized by insidious onset and non-specific features at the initial stage， is usually diagnosed at middle or late stage with metastasis. The invasion and metastasis of NPC involve complex biological processes， which are affected by many factors. The regulation of gene expression is involved in the invasion and metastasis of NPC， which has become a hot topic. Micro-ribonucleic acids （miRNAs） are short （about 22 nucleotides long） non-coding ribonucleic acids （RNAs） that participate in each step of invasion and metastasis of malignant tumor cells and play an important regulatory role by modulating the transcription and translation of target genes. Abnormal expression of miRNAs has been found in NPC， which regulates the invasion and metastasis of NPC cells. This paper summarized the regulatory mechanisms of different miRNAs as tumor suppressor genes in the migration and invasion of NPC cells， including the modulation of target genes， migration-and invasion-related proteins， and important signaling pathways， which involve biological processes such as epithelial-mesenchymal transition （EMT）， neovascularization and lymphatic vessels， tumor stem cells， and resistance to radiotherapy and chemotherapy. As Chinese medicine shows remarkable efficacy in the prevention and control of NPC， especially in the alleviation of adverse reactions and reduction of metastasis rate after radiotherapy and chemotherapy， we also summed up the effect and mechanism of Chinese medicine and the active components in inhibiting the migration and invasion of NPC cells by miRNAs. Thereby， this review is expected to lay a theoretical basis for further research and development of new drugs against NPC.关键词：tumor suppressor micro-ribonucleic acid （miRNAs）;nasopharyngeal carcinoma;migration;invasion;Chinese medicine
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发布时间：2022-12-21 - 摘要：Atherosclerosis （As） is a chronic vascular disease caused by lipid deposition on the vascular wall and is characterized by lipid metabolism disorder，oxidative stress，and inflammation. It is the pathological basis of cardiovascular and cerebrovascular diseases such as coronary heart disease，heart failure，and stroke. Ferroptosis is a new type of cell death caused by iron-dependent lipid peroxidation，which is morphologically，biologically，and genetically distinct from other types of cell death. The pathogenesis of ferroptosis is complex and is mainly related to the activity of the glutathione/glutathione peroxidase 4 antioxidant system，iron metabolism，iron autophagy，lipid peroxidation，and other pathways. Ferroptosis plays an important role in the process of As and is involved in many pathological processes such as vascular endothelial cell injury，macrophage inflammation，foam cell formation，and vascular smooth muscle cell proliferation and migration. It has become a new target for As research. Traditional Chinese medicine （TCM） is a unique and valuable medical science in China，with profound theoretical and practical accumulation. Studies have shown that Chinese medicine compounds，Chinese medicine monomers，and active ingredients can regulate ferroptosis in vascular-related cells and have unique advantages in the prevention and treatment of As. This article mainly reviewed the role of ferroptosis in various pathological links of As and related Chinese medicine intervention，aiming to provide a new direction for the prevention and treatment of As by Chinese medicine from the perspective of ferroptosis.关键词：ferroptosis;atherosclerosis;lipid peroxidation;oxidative stress;Chinese medicine
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发布时间：2022-12-21 - 摘要：Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic intestinal disease characterized by abdominal pain and increased water content in stool. The pathological mechanism of this disease is complex and attributed to many factors， where the impairment of intestinal mucosal barrier is pivotal in the pathogenesis of IBS-D. The intercellular tight junction （TJ）in intestinal mucosa is mainly composed of Occludin，Claudins， and zonula occludens （ZOs），which is an important component of mechanical barrier and can significantly affect mucosal function. Since modern medicine holds that the pathogenesis of this disease is not fully revealed，symptomatic treatment is the first choice in clinical practice even though the outcomes are not satisfactory. According to traditional Chinese medicine （TCM），the epithelial barrier function in intestinal mucosa corresponds to the TCM theory of "the spleen acts as the guard". Many studies have reported that the active components of Chinese medicine and compound prescriptions can restore the intestinal epithelial barrier function of IBS-D rats by regulating TJ protein，reduce its permeability， and inhibit intestinal water and electrolyte exudation，thereby improving symptoms. This study reviewed the relationship of IBS-D with TJ and its key target proteins to clarify the key role of TJ in the pathophysiology of IBS-D and summarized the TCM treatment of IBS-D through the target regulation of TJ， with the purpose to provide a theoretical basis for the treatment of IBS-D and further drug development.关键词：diarrhea-predominant irritable bowel syndrome （IBS-D）;tight junction;traditional Chinese medicine;action mechanism
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发布时间：2022-12-21 - 摘要：Pyroptosis is a recently discovered programmed cell death mediated by cysteinyl aspartate specific proteinase （Caspase）， which may lead to the release of intracellular inflammatory substances to extracellular and induce inflammatory cascades.Autoimmune diseases （ADs） is a kind of disease in which the body's immune tolerance is impaired， and the body overproduces autoantibodies， causing damage to its tissues.The pathogenic factors of ADs are complex and the pathogenesis is still unclear. With the deepening of the research on pyroptosis， more and more results show that pyroptosis is involved in the pathogenesis of various ADs such as rheumatoid arthritis， ulcerative colitis， systemic lupus erythematosus， and psoriasis. Glucocorticoid drugs， anti-rheumatism drugs， and biological agents are mostly used in the clinical treatment of ADs， but the therapeutic effect of some drugs is limited， and there are some long-term adverse reactions. Chinese medicine in the treatment of ADs has been proven to be safe and effective in long-term clinical practice. It has the characteristics of multiple targets and few side effects and has certain advantages in controlling the course of the disease. More and more studies have found that a variety of Chinese medicine formulations， single Chinese medicine， and active ingredients of Chinese medicine treat ADs through the intervention of pyroptosis. Therefore， this paper reviewed the experimental studies on the effect of Chinese medicine on pyroptosis in ADs in recent years， hoping to provide references for clinical treatment and scientific research.关键词：Chinese medicine;autoimmune disease;pyroptosis;Experimental Studies
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发布时间：2022-12-21 - 摘要：Ulcerative colitis （UC） is a chronic non-specific digestive disease with abdominal pain， diarrhea， and blood and mucus in stool as the main clinical manifestations and inflammatory injury of colorectal mucosa and submucosa as the main pathological changes. With the change in living habits and dietary structure of people， the incidence and cancer morbidity in UC are rising rapidly all over the world， which has seriously reduced the quality of life and caused a huge social burden. Till now， the pathogenesis has not been elucidated. In western medicine， aminosalicylates， corticosteroids， and immunosuppressors are commonly used to relieve symptoms. However， the long-term application will lead to problems such as decreased efficacy and increased adverse reactions. There are more studies of traditional Chinese medicine （TCM） in the treatment of UC by reducing the inflammatory response， alleviating oxidative stress， protecting the intestinal mucosal barrier， and regulating intestinal microecological imbalance by virtue of the advantages of integrated regulation based on multiple links， levels， and targets. In view of this， the present study reviewed the effect and mechanism of active ingredients of TCM， TCM extracts， TCM pairs， classic TCM compounds， and TCM combined with chemical agents in the treatment of UC based on relevant research articles in recent 10 years to provide references for seeking effective drugs.关键词：ulcerative colitis;active ingredients of traditional Chinese medicine（TCM）;TCM extracts;TCM pairs;classic TCM compounds;combined use of TCM with chemical agents;mechanism
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发布时间：2022-12-21
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