1.Pathogenesis Evolution and Stage-based Treatment of Gout: An Exploration Based on Theory of ''Endogenous Dampness Leading to Bi Syndrome''
Yingjie ZHANG ; Fan YANG ; Ruifang YANG ; Zhuoming ZHENG ; Siwei PENG ; Yan XIAO ; Peng CHEN ; Youxin SU ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):74-83
Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia, recurrent joint swelling and pain, and tophus formation. The disease course is divided into three stages: The hyperuricemia stage, acute attack stage, and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology, but traditional Chinese medicine (TCM) lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms, making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory, clinical practice, and modern medical understanding, and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber, our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities, it manifests as ''spleen deficiency with impaired transport and transformation'', resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels, serum uric acid levels rise. When it stagnates in the viscera and limbs, monosodium urate crystals deposit in the joints. Triggered by precipitating factors, this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory, the stage-specific pathogenic characteristics of gout are proposed: The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation, internal retention of pathogenic dampness-turbidity'', the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints'', while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity, intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage, treatment focuses on ''strengthening the spleen, draining dampness, and eliminating turbidity''. In the acute attack stage, the treatment should "strengthen the spleen, drain dampness, clear heat, eliminate turbidity, alleviate swelling, and relieve pain''. In the chronic stage, the treatments emphasizes to ''strengthen the spleen, drain dampness, transform turbidity, clear heat, resolve phlegm, and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root, dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research, providing systematic theoretical guidance and a practical framework for the precise TCM management of gout, thereby promoting the modernization of TCM pathogenesis theory related to gout.
2.Analysis of Chronic Gouty Arthritis Animal Models Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Yan XIAO ; Siyuan LIN ; Fan YANG ; Qianglong CHEN ; Xiaohua CHEN ; Meiling WANG ; Zhen ZHANG ; Jiali LUO ; Youxin SU ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):84-92
ObjectiveBased on the clinical characteristics of chronic gouty arthritis (CGA) in both traditional Chinese and western medicine, this study aims to systematically evaluate the clinical concordance of existing CGA animal models, providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure, Wanfang, VIP Chinese Science and Technology Periodical Database (VIP), and PubMed, all relevant literature on CGA animal models was collected. Based on the guidelines, the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes, and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction, high-protein diet induction (poultry lack urate oxidase), and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature, the traditional Chinese and western medicine scoring data of each model were extracted, and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%, respectively. Among them, the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection, achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA, they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore, in the future, it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria, providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.
3.Mechanism of Huazhuo Sanjie Chubi Presciption in Regulating Macrophage Polarization and Improving Low-grade Inflammation in Rats with Chronic Gouty Arthritis
Yuwan LI ; Yingjie ZHANG ; Siyuan LIN ; Xiaohua CHEN ; Qianglong CHEN ; Fan YANG ; Jun LIU ; Bingyan CHEN ; Peng CHEN ; Jiemei GUO ; Youxin SU ; Yan XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):93-104
ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption (HSCD) on chronic gouty arthritis (CGA) rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated, using the random number table, to a normal group (n=8) and a model group (n =33). CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate (250 mg·kg-1·d-1) and hypoxanthine (300 mg·kg-1·d-1), combined with intra-articular injection of a monosodium urate (MSU) crystal suspension (50 μL, 25 g·L-¹) into the left ankle twice weekly. After 4 weeks of modeling, 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group, an HSCD group (10.35 g·kg-1·d-1, gavage once daily), an M1 polarization agonist group (L-methionine sulfoximine, 300 mg·kg-1, subcutaneous injection every other day), an M1 polarization agonist + HSCD group, an M2 polarization inhibitor group (PD0325901, 10 mg·kg-1·d-1, gavage once daily), and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment, whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium (CMC-Na) vehicle (10.35 g·kg-1·d-1, gavage once daily). All interventions were continued for four weeks. During the intervention period, except for the normal group, potassium oxonate (250 mg·kg⁻¹) and hypoxanthine (300 mg·kg-1) were co-administered by gavage every other day to maintain the model. At the end of treatment, serum uric acid (SUA), ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), chemokine C-C motif ligand 2 (CCL2), S100 calcium-binding protein A8/A9 (S100A8/A9), interleukin-10 (IL-10) and arginase-1 (Arg-1) in serum and joint fluid were determined by enzyme-linked immunosorbent assay (ELISA). High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin (HE) staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase (iNOS) and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 (CD163) in synovial tissue. ResultsCompared with the normal group, the model group showed significantly elevated SUA level and joint swelling index, and increased levels of pro-inflammatory cytokines, CCL2, and S100A8/A9 in both serum and joint fluid (P<0.05), accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated (P<0.05). Compared with model group, rats in HSCD group had significantly lower SUA levels, attenuated joint swelling, reduced serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid, accompanied with alleviated MSU deposition and synovial inflammation (P<0.05). HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS (P<0.05), whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group, the M1 polarization agonist + HSCD group showed significantly reduced joint swelling, lower serum levels of pro-inflammatory cytokines, and decreased levels of CCL2 and S100A8/A9 in joint fluid (P<0.05). In addition, synovial inflammatory cell infiltration and angiogenesis were attenuated, and iNOS mRNA and protein expression levels were significantly reduced (P<0.05). Compared with the M2 polarization inhibitor group, the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling, decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation (P<0.05), whereas the levels of anti-inflammatory mediators (IL-10, Arg-1) and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats, at least in part, by inhibiting macrophage polarization toward the M1 phenotype.
4.Effect and Action Mechanism of Huazhuo Sanjie Chubi Prescription on Gouty Bone Erosion Model Rats Based on PI3K/Akt Signaling Pathway
Zhuoming ZHENG ; Jun LIU ; Meiling WANG ; Xiaohua CHEN ; Yuwan LI ; Siwei PENG ; Yingjie ZHANG ; Ruifang YANG ; Youxin SU ; Yan XIAO ; Jiemei GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):105-117
ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription (HSCD) on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg-1·d-1 and potassium oxonate solution at 250 mg·kg-1·d-1, combined with intra-articular injection of 200 μL monosodium urate (MSU) crystal suspension at 25 g·L-1 into the right ankle joint (joint injection once every three days), so as to induce the gouty bone erosion model. After four weeks of modeling, three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group, HSCD group (10.35 g·kg-1·d-1), allopurinol group (20 mg·kg-1·d-1), and inhibitor group (LY294002, 10 mg·kg-1·d-1), with six rats per group. Except for the blank group, rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg-1 and potassium oxonate solution at 250 mg·kg-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline (10.35 g·kg-1·d-1) by gavage for four consecutive weeks. After administration, ankle joint swelling of the rats in all groups was observed, and the diameters were measured. Bone volume fraction (BV/TV) and bone surface area to bone volume (BS/BV) were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin (HE) staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of receptor activator of nuclear factor-κB ligand (RANKL) and phosphorylated (p)-phosphatidylinositol-3-kinase (PI3K) in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion, including RANKL, tartrate-resistant acid phosphatase
5.Genetic analysis and reproductive intervention for 46 Chinese pedigrees affected with Hereditary multiple exostoses.
Lilan SU ; Xiao HU ; Jing DAI ; Zhengxing WAN ; Duo YI ; Shuangfei LI ; Liang HU ; Yueqiu TAN ; Fei GONG ; Ge LIN ; Guangxiu LU ; Qianjun ZHANG ; Juan DU ; Wenbin HE
Chinese Journal of Medical Genetics 2026;43(4):253-258
OBJECTIVE:
To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention.
METHODS:
Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010).
RESULTS:
In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born.
CONCLUSION
This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans
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Female
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Male
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Pedigree
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Exostoses, Multiple Hereditary/diagnosis*
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N-Acetylglucosaminyltransferases/genetics*
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Adult
;
Exostosin 1
;
Asian People/genetics*
;
Genetic Testing
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Exostosin 2
;
Mutation
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China
;
Prenatal Diagnosis
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Pregnancy
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Genetic Counseling
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Preimplantation Diagnosis
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Exome Sequencing
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East Asian People
6.Clinical Advantages of Traditional Chinese Medicine in Treatment of Childhood Simple Obesity: Insights from Expert Consensus
Qi ZHANG ; Yingke LIU ; Xiaoxiao ZHANG ; Guichen NI ; Heyin XIAO ; Junhong WANG ; Liqun WU ; Zhanfeng YAN ; Kundi WANG ; Jiajia CHEN ; Hong ZHENG ; Xinying GAO ; Liya WEI ; Qiang HE ; Qian ZHAO ; Huimin SU ; Zhaolan LIU ; Dafeng LONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):238-245
Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance, while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine (TCM) has a long history in the prevention and management of this condition, demonstrating eight distinct advantages, including systematic theoretical foundation, diversified therapeutic approaches, definite therapeutic efficacy, high safety profile, good patient compliance, comprehensive intervention strategies, emphasis on prevention, and stepwise treatment protocols. Additionally, TCM is characterized by six distinctive features: the use of natural medicinal substances, non-invasive external therapies, integration of medicinal dietetics, simple exercise regimens, precise syndrome differentiation, and diverse dosage forms. By combining internal and external treatments, TCM facilitates individualized regimen adjustment and holistic regulation, demonstrating remarkable effects in improving obesity-related metabolic indicators, regulating constitutional imbalance, and promoting healthy behaviors. However, challenges remain, such as inconsistent operational standards, insufficient high-quality clinical evidence, and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment, conducting multicenter randomized controlled trials, and fostering interdisciplinary integration, so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.
7.Chemical and pharmacological research progress on Mongolian folk medicine Syringa pinnatifolia.
Kun GAO ; Chang-Xin LIU ; Jia-Qi CHEN ; Jing-Jing SUN ; Xiao-Juan LI ; Zhi-Qiang HUANG ; Ye ZHANG ; Pei-Feng XUE ; Su-Yi-le CHEN ; Xin DONG ; Xing-Yun CHAI
China Journal of Chinese Materia Medica 2025;50(8):2080-2089
Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional
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Humans
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Drugs, Chinese Herbal/pharmacology*
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Animals
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Syringa/chemistry*
8.Correlation between differences in starch gelatinization, water distribution, and terpenoid content during steaming process of Curcuma kwangsiensis root tubers by multivariate statistical analysis.
Yan LIANG ; Meng-Na YANG ; Xiao-Li QIN ; Zhi-Yong ZHANG ; Zhong-Nan SU ; Hou-Kang CAO ; Ke-Feng ZHANG ; Ming-Wei WANG ; Bo LI ; Shuo LI
China Journal of Chinese Materia Medica 2025;50(10):2684-2694
To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry*
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Starch/chemistry*
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Multivariate Analysis
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Water/chemistry*
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Terpenes/analysis*
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Plant Roots/chemistry*
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Plant Tubers/chemistry*
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Drugs, Chinese Herbal/chemistry*
9.Identification of tissue distribution components and mechanism of antipyretic effect of famous classical formula Dayuanyin.
Yu-Jie HOU ; Kang-Ning XIAO ; Jian-Yun BI ; Xin-Rui LI ; Ming SU ; Li-Jie WANG ; Yu-Qing WANG ; Dan-Dan SUN ; Hui ZHANG ; Xin-Jun ZHANG ; Shan-Xin LIU
China Journal of Chinese Materia Medica 2025;50(10):2810-2824
Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Rats
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Molecular Docking Simulation
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Male
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Antipyretics/metabolism*
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Rats, Sprague-Dawley
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Tissue Distribution
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Mass Spectrometry
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Chromatography, High Pressure Liquid
;
Hypothalamus/metabolism*
10.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
;
Mice, Inbred BALB C

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