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Chinmedomics facilitated quality-marker discovery of sijunzi decoction to treat spleen qi deficiency syndrome

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Frontiers of Medicine 2020年第3期14卷 335-356页

作者： Qiqi Zhao Xin Gao Guangli Yan Aihua Zhang Hui Sun Ying Han Wenxiu Li Liang Liu Xijun Wang National Chinmedomics Research Center Sino-America Chinmedomics Technology Collaboration CenterNational TCM Key Laboratory of Serum PharmacochemistryLaboratory of MetabolomicsDepartment of Pharmaceutical AnalysisHeilongjiang University of Chinese MedicineHarbin 150040China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyAvenida Wai LongTaipaMacaoChina National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials Guangxi Botanical Garden of Medicinal PlantNanning 530023China

sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of ***,the quality control (QC) standards of SJZD are *** has been designed to discover and verify bioactive compounds of a variety of *** this study,we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall *** preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of *** to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy.

关键词： traditional Chinese medicine sijunzi decoction spleen qi deficiency syndrome Chinmedomics quality-marker

Effects and mechanisms of Bazhen decoction,Siwu decoction,and sijunzi decoction on 5-fluorouracil-induced anemia in mice

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Journal of Traditional Chinese Medicine 2016年第4期36卷 486-495页

作者： Tian Yunan Xiang Yuke Wan Guoran Wan Dong Zhu Huifeng Wang Tao Yang Xian School of Pharmaceutical Sciences&School of Chinese Medicine Southwest UniversityChongqing 400715China Tong Liang High School Chongqing 400715China Department of Emergency the First AffiliatedHospital of Chongqing Medical UniversityChongqing400016China

OBJECTIVE:To investigate the effects of Bazhen decoction(BZD),Siwu decoction(SWD) and sijunzi decoction(SJZD) in mice with anemia induced by5-fluorouracil(5-FU) and discussed the possible pharmacological hematopoietic mechanism to provide experimental evidence for the clinical use of the three classical prescriptions in the treatment of ***:Anemia was induced by intravenous injection of 5-FU and 80 female Kunming mice were randomly,assigned to oral administration of SWD,SJZD,or BZD daily for 10 *** blood cells count and bone marrow cell cycle were monitored to evaluate anti-anemia *** cytokines,interferon-γ(IFN-γ),interleukin-3(IL-3),erythropoietin(EPO),granulocyte-macrophage colonystimulating factor(GM-CSF),and tumor necrosis factor-α(TNF-α) were *** m RNA expression was assayed in kidney and liver tissue ***:BZD and SWD significantly increased the number of red blood cells,hemoglobin concentration,and hematocrit,promoted bone marrow cells to enter the cell cycle,proliferate and differentiate,significantly increased IL-3 secretion,and significantly inhibited IFN-γ *** stimulated transcription of EPO m RNA in the kidney and liver and enhanced serum EPO expression.A therapeutic effect of SJZD was not ***:BZD and SWD treatment specifically enhanced hematopoietic function and mediated myelopoiesis by altering serum cytokines levels and accelerating entry of bone marrow cells into the cell *** curative effects were achieved via nourishing both Qi and blood(BZD) than by enriching the blood(SWD) or invigorating Qi(SWZD)alone.

关键词： Anemia Blood-deficiency Fluorouracil Bazhen decoction Siwu decoction sijunzi decoction

Effects of sijunzi decoction and Yupingfeng powder on expression of janus kinase-signal transducer and activator of transcription signal pathway in the brain of spleen-deficiency model rats

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Journal of Traditional Chinese Medicine 2013年第1期33卷 78-84页

作者： Bin Xiong Huinan Qian College of Basic Medicine Beijing University of Traditional Chinese Medicine Journal of Hubei University of Chinese Medicine

OBJECTIVE： To observe the influence of sijunzi decoction and Yupingfeng powder on the expression of the relevant DNAs of janus kinase （JAK）-signal transducer and activator of transcription （STAT） sig- nal pathway of the brain in spleen-deficiency mod- el rats. METHODS： Eighty male Wistar rats of sanitary degree were divided randomly into four groups： nor- mal group, model group, treatment group 1, treatment group 2. Besides the rats in the normal group, all the rats in other 3 groups were prepared as spleen deficiency model. The treatment group 1 were treated with sijunzi decoction and the treat- ment group 2 were treated with Yupingfeng powder. After treatment for 6 weeks, perfusion was given and the brain was taken for detection of the ex- pression of the relevant DNAs of JAK-STAT signal pathwayofthe brain in SD rats bygene chip method. RESULTS： Spleen deficiency could lead to increase expression of JAKI, STATI and Interleukin 4 （IL-4） in the brain, but the decrease expression of Suppres- sor of cytokine signaling I （SOCSI）, prolactin recep- tor （PRLR） and binding protein 3 （GATA 3）. sijunzi decoction could increase expression of STAT3, Pro- lactin （PRL） and GATA3, but decrease expression of JAKI, STAT, STAT4, Interleukin 10 receptor, alpha （ILIORA）, Coagulation factor II （F2）, PRLR, MAD homolog 3 （SMAD3） and IL-4. Yupingfeng powder could decrease expression of JAKI, STATI, STAT4, SOCS4_ predicted, Epidermal growth factor receptor （EGFR）, PRLR, High mobility group AT-hook I （HMGAI 0）, IL-4. CONCLUSION： sijunzi decoction and Yupingfeng powder can improve immune function of the rat through influencing the genetic expression of JAK-STAT signal pathway.

关键词： sijunzi decoction Yupingfeng powder Spleen deficiency JAK-STAT signal pathway

Identification of anti-inflammatory components in Panax ginseng of sijunzi decoction based on spectrum-effect relationship

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Chinese Herbal Medicines 2023年第1期15卷 123-131页

作者： Hong Kan Dongxue Zhang Weijia Chen Shihan Wang Zhongmei He Shifeng Pang Shuai Qu Yingping Wang College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118China Institute of Special Animal and Plant Sciences of Chinese Academy of Agricultural Sciences Changchun 130112China Jilin Institute of Biology Changchun 130012China

Objective: This study aimed to identify the main medicinal active components of Panax ginseng(P. ginseng) in the compatibility environment of clinical application. For this purpose, the anti-inflammatory ingredients of P. ginseng were investigated based on its therapeutic effect in sijunzi decoction(SJD) which is a widely used traditional Chinese ***: The fingerprints of 10 batches of SJD consisting of different sources of P. ginseng were established by UPLC technique to investigate the chemical components. At the same time, the antiinflammatory effects of these components were evaluated by dextran sulfate sodium-induced ulcerative colitis mouse model. Grey relational analysis was applied to explore the correlation degree between fingerprints and anti-inflammatory effects in SJD. Lipopolysaccharide-stimulated RAW264.7 murine macrophages were established to evaluate the anti-inflammatory action of the screened effective substances of P. ***: According to grey relational analysis, notoginsenoside R1, ginsenoside Rg2 and ginsenoside Rb3of P. ginseng were the major anti-inflammatory contributions in SJD. They had been proven to be closely associated with the anti-inflammatory process of SJD and displayed a close effect compared with SJD by LPS-stimulated RAW264.7 murine ***: Our work provides a general strategy for exploring the pharmacological ingredients of P. ginseng in traditional Chinese formulas which is beneficial for establishing the quality standards of traditional herbs in traditional Chinese medicine prescription based on their clinical therapeutic effect.

关键词： anti-inflammation ginsenosides Panax ginseng C.A.Mey sijunzi decoction spectrum-effect relationship ulcerative colitis

Efficacy of sijunzi decoction(四君子汤) on limb weakness in spleen Qi deficiency model rats through adenosine monophosphate-activated protein kinase/unc-51 like autophagy activating kinase 1 signaling

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Journal of Traditional Chinese Medicine 2021年第4期41卷 617-623页

作者： LIU Wenjun XU Xinzhu DUAN Zhiyuan LIANG Xicai MA Dan LI Gege XIE Xin CHAI Jiyan CHEN Jing SHAN Dehong Teaching and Experimental Center Liaoning University of Traditional Chinese MedicineShenyang 110847China College of Integrated Traditional and Western Medicine Liaoning University of Traditional Chinese MedicineShenyang 110847China Animal Laboratory Center Liaoning University of Traditional Chinese MedicineShenyang 110847China College of Acupuncture Liaoning University of Traditional Chinese MedicineShenyang 110847China

OBJECTIVE:To investigate the efficacy of sijunzi decoction(四君子汤)on limb weakness in a rat model of spleen Qi deficiency(SQD),and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase(AMPK)/unc-51 like autophagy activating kinase 1(ULK1)***:SQD model rats were produced by fasting combined with forced swimming method for15 *** model assessment,rats were randomly divided into four groups of 10[low/middle/high(L/M/H)sijunzi decoction dose groups and a normal saline(S)group].Limb holding power(HP)and body mass(BM)were measured after 2 weeks of *** euthanasia,quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy(TEM).Mitochondrial membrane potential(MMP),adenosine triphosphatase(ATP)and reactive oxygen species(ROS)levels were determined using colorimetric methods,and immunoblot analysis of Microtubule-associated protein light chain 3(LC3)and Sequestosome 1(p62)was performed to monitor mitophagy and AMPK/ULK1 ***:Compared with control(C)group rats,in the S group,HP was reduced,the myofiber Z line was disordered,mitochondria were scattered,and numerous vacuoles and mitophagy were *** and ATP levels were reduced,ROS levels were elevated,and LC3B expression,and p-AMPKα(Thr172)/AMPKα,p-ULK1(Ser555)/ULK1,and p-Raptor(Ser792)/Raptor ratios were increased,while p62 expression and p-mT OR(Ser2448)/mT OR and p-ULK1(Ser757)/ULK1 ratios were *** treatment,compared with the S group,HP was improved in M and H groups but not in the L *** was reduced in M,H and L groups but the Z line was disordered and vacuolization remained in the L *** levels were elevated in M,H and L groups,and MMPs were elevated in M and H groups but not in the L *** levels were decreased in M,H and L groups,as were LC3B expression and p-Raptor(Ser792)/Raptor ratios,while p62 expression and p-mT OR(

关键词： spleen-Qi deficiency muscle skeletal mitochondria oxidative phosphorylation mitophagy AMP-activated protein kinases autophagy-related protein-1 homolog sijunzi decoction

Progress in Research on Applying sijunzi decoction (四君子汤) in Treating Digestive Malignant Tumor

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Chinese Journal of Integrative Medicine 2007年第2期13卷 156-159页

作者：吴彬宣正荣 Department of Surgery Longhua Hospital Aff iliated to Shanghai University of TCM

Patients with digestive malignant tumor always have their immune function, especially the cellular immunity, suppressed to a certain extent. Traditional Chinese medicine （TCM） holds that Pi （脾）-Wei （胃） is the essence of postnatal life, and the genesis and development of digestive tumor are chiefly due to the insufficiency of vital-qi, which makes the body open to the invasion of evil pathogens. Starting from regulating the immune function of organisms, researchers recently obtained some therapeutic effects by applying the Chinese recipe, sijunzi decoction （四君子汤）, in the treatment of digestive malignant tumors. In this paper, the related studies on the concerned basic theory and clinical application were reviewed.

关键词： sijunzi decoction immune regulation Pi-deficient syndrome digestive malignant tumor

Effect of sijunzi decoction on the Myonuclear Domain of Rat Soleus in Spleen Qi Deficiency

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Chinese Medicine 2023年第4期14卷 276-285页

作者： Linlin Zhang Dan Ma Songnan Wang Xudong Liu Lingzhi Wang Dehong Shan Department of Physiology and Psychology College of Integrated Chinese and Western medicine Liaoning University of Traditional Chinese Medicine Shenyang China

Objective: To study the mechanism of sijunzi decoction treating limb weakness in spleen Qi deficiency (SQD) based on the myonuclear domain (MND) theory. Methods: 40 male Sprague-Dawley rats were randomly divided into the normal group, SQD model group (model group), SQD+ still water group (SW group) and SQD+ sijunzi decoction group (CM group), 10 rats each group;Grip-Strength Meter was used to measure limb grip strength;transmission electron microscope was employed to observe the ultrastructural changes of the myofibers, Image Pro 6.0 was used to measure the myonuclear numbers, cross-section area (CSA) and then their ratios (the MND sizes) were calculated, immunofluorescence assay was chosen to test the expressions of paired box gene 7 (Pax7) and myogenic differentiation antigen (MyoD). Results: Compared with those in the normal group, limb grip strength was decreased, sarcomeres were abnormal, and all the myonuclear numbers, CSA and MND sizes were reduced, but the Pax7+ cell numbers were increased, significantly, in the model and SW groups;Compared with those in the model and SW groups, limb grip strength was increased, sarcomeres were basically normal, the myonuclear number and CSA were both greater, and the Pax7+ and MyoD+ cell numbers were both increased, significantly, in the CM group. Conclusion: sijunzi decoction might increase the myonuclear number by activating the MSCs to treat limb weakness in SQD.

关键词： sijunzi decoction Spleen Qi Deficiency Limb Weakness Myonuclear Domain Muscle Stem Cell

Effects of Traditional Herbal Formulae on Human CYP450 Isozymes

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Chinese Journal of Integrative Medicine 2017年第1期23卷 62-69页

作者： Seong Eun Jin Hyekyung Ha Hyeun-Kyoo Shin K-Herb Research Center Korea Institute of Oriental MedicineDaejeon 34054Republic of Korea

Objective：To assess the effects of traditional herbal formulae sijunzi decoction（四君子汤,Sagunja-tang,SJZD）,Siwu decoction（四物汤,Samul-tang,SWD）,Bawu decoction（八物汤,Palmul-tang,BWD）and Shiquan Dabu decoction（十全大补汤,Sipjeondaebo-tang,SDD）on the activities of human cytochrome P450（CYP450）,a drug-metabolizing ***：Herbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled *** activities of major human CYP450isozymes（CYP3A4,CYP2C19,CYP2D6 and CYP2E1）were measured using in vitro fluorescence-based enzyme *** inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration（IC50）***：All the tested herbal formulae inhibited CYP2C19activity（IC50：SJZD,83.28μg/m L;SWD,235.54μg/m L;BWD,166.82μg/m L;SDD,178.19μg/m L）;SJZD（IC50=196.46μg/m L）,SWD（IC50=333.42μg/m L）and SDD（IC50=163.42μg/m L）inhibited CYP2E1-mediated metabolism;whereas BWD exhibited comparatively weak inhibition of CYP2E1（IC50=501.78μg/m L）.None of the four herbal formulas significantly affected CYP3A4 or ***：These results suggest that SJZD,SWD,BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via *** addition,clinically relevant pharmacokinetic interactions could occur when SJZD,SWD or SDD is co-administered with drugs metabolized by *** findings provide information for the safety and effective clinical use of these four classic herbal formulas.

关键词： cytochrome P450 sijunzi decoction Siwu decoction Bawu decoction Shiquan Dabu decoction,herb-drug interactions