1.Rutaecarpine Attenuates Monosodium Urate Crystal-Induced Gouty Inflammation via Inhibition of TNFR-MAPK/NF-κB and NLRP3 Inflammasome Signaling Pathways.
Min LI ; Zhu-Jun YIN ; Li LI ; Yun-Yun QUAN ; Ting WANG ; Xin ZHU ; Rui-Rong TAN ; Jin ZENG ; Hua HUA ; Qin-Xuan WU ; Jun-Ning ZHAO
Chinese journal of integrative medicine 2025;31(7):590-599
OBJECTIVE:
To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro.
METHODS:
In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets.
RESULTS:
RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding.
CONCLUSION
RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals
;
NF-kappa B/metabolism*
;
Male
;
Indole Alkaloids/therapeutic use*
;
Signal Transduction/drug effects*
;
Mice, Inbred C57BL
;
Inflammation/complications*
;
Uric Acid
;
Quinazolines/therapeutic use*
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Humans
;
Gout/chemically induced*
;
Inflammasomes/metabolism*
;
Cytokines/metabolism*
;
THP-1 Cells
;
Mitogen-Activated Protein Kinases/metabolism*
;
Mice
;
Molecular Docking Simulation
;
Lipopolysaccharides
;
Quinazolinones
2.Yiqi Yangyin Huazhuo Tongluo Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Kelei GUO ; Yingli LI ; Chenguang XUAN ; Zijun HOU ; Songshan YE ; Linyun LI ; Liping CHEN ; Li HAN ; Hua BIAN
Journal of Southern Medical University 2025;45(1):27-34
OBJECTIVES:
To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism.
METHODS:
Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.
RESULTS:
MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera.
CONCLUSIONS
YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals
;
MicroRNAs/genetics*
;
Podocytes/pathology*
;
Drugs, Chinese Herbal/pharmacology*
;
Autophagy/drug effects*
;
Rats, Wistar
;
Protein Kinases/metabolism*
;
Rats
;
Forkhead Box Protein O1
;
Mice
;
Mitochondria/drug effects*
;
Ubiquitin-Protein Ligases/metabolism*
;
Glucose
;
Diabetic Nephropathies
;
Male
;
Membrane Proteins/metabolism*
;
Intracellular Signaling Peptides and Proteins
3.Epidemiological characteristics of respiratory syncytial virus infection in children in Hebei Province.
Xuan WANG ; Su-Kun LU ; Jian-Hua LIU ; Jin-Feng SHUAI ; Kun-Ling HUANG ; Bo NIU ; Li-Jie CAO ; Xiao-Wei CUI
Chinese Journal of Contemporary Pediatrics 2025;27(10):1199-1204
OBJECTIVES:
To study the epidemiological characteristics of respiratory syncytial virus (RSV) infection in hospitalized children with community-acquired pneumonia (CAP) in Hebei Province.
METHODS:
Hospitalized children with CAP who tested positive for RSV and were admitted to Hebei Children's Hospital from various cities and counties across Hebei Province between January 2019 and December 2023 were included in the study. Clinical data were collected and analyzed to assess epidemiological characteristics.
RESULTS:
The clinical data of 43 978 children with CAP were collected, with an overall RSV detection rate of 25.98%. The detection rate was higher during the implementation of non-pharmaceutical interventions (NPIs) (30.60%) than in the non-NPIs period. Winter and spring were the primary epidemic seasons for RSV each year except in 2022. The detection rate in males (26.62%) was higher than in females (25.06%) (P<0.001). The highest detection rate (59.18%) was found in infants aged 29 days to <1 year. Single RSV infection was more common, with rhinovirus being the most frequent co-infection.
CONCLUSIONS
The overall RSV detection rate in Hebei Province is influenced by NPIs, being higher during their implementation. RSV predominantly circulates in winter and spring. The detection rate of RSV is higher in males and infants. RSV infection is primarily single, most often co-occurring with rhinovirus.
Humans
;
Respiratory Syncytial Virus Infections/epidemiology*
;
Female
;
Male
;
Infant
;
Child, Preschool
;
Seasons
;
China/epidemiology*
;
Infant, Newborn
;
Community-Acquired Infections/epidemiology*
;
Child
4.A Retrospective Study of Pregnancy and Fetal Outcomes in Mothers with Hepatitis C Viremia.
Wen DENG ; Zi Yu ZHANG ; Xin Xin LI ; Ya Qin ZHANG ; Wei Hua CAO ; Shi Yu WANG ; Xin WEI ; Zi Xuan GAO ; Shuo Jie WANG ; Lin Mei YAO ; Lu ZHANG ; Hong Xiao HAO ; Xiao Xue CHEN ; Yuan Jiao GAO ; Wei YI ; Yao XIE ; Ming Hui LI
Biomedical and Environmental Sciences 2025;38(7):829-839
OBJECTIVE:
To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development.
METHODS:
A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected.
RESULTS:
Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ 2 = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006).
CONCLUSIONS
Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans
;
Female
;
Pregnancy
;
Adult
;
Pregnancy Complications, Infectious/epidemiology*
;
Retrospective Studies
;
Pregnancy Outcome
;
Infant, Newborn
;
Viremia/virology*
;
Hepatitis C
;
Hepacivirus/physiology*
;
Hepatitis C, Chronic/virology*
;
Young Adult
;
Alanine Transaminase/blood*
5.Mechanism of Gegen Qinlian Decoction in treatment of ulcerative colitis through affecting bile acid synthesis.
Yi-Xuan SUN ; Jia-Li FAN ; Jing-Jing WU ; Li-Juan CHEN ; Jiang-Hua HE ; Wen-Juan XU ; Ling DONG
China Journal of Chinese Materia Medica 2025;50(10):2769-2777
Gegen Qinlian Decoction(GQD) is a classic prescription for the clinical treatment of ulcerative colitis(UC). This study, based on the differences in efficacy observed in UC mice under different level of bile acids treated with GQD, aims to clarify the impact of bile acids on UC and its therapeutic effects. It further investigates the expression of bile acid receptors in the liver of UC mice, and preliminarily reveals the mechanism through which GQD affects bile acid synthesis in the treatment of UC. A UC mouse model was established using dextran sulfate sodium(DSS) induction. The efficacy of GQD was evaluated by assessing the general condition, disease activity index(DAI) score, colon length, and histopathological changes in colon tissue via hematoxylin and eosin(HE) staining. ELISA and Western blot were used to evaluate the inflammatory response in colon tissue. The total bile acid(TBA) level and liver damage were quantified using an automatic biochemistry analyzer. The expression levels of bile acid receptors and bile acid synthetases in liver tissue were detected by Western blot and RT-qPCR. The results showed that compared with the model group, GQD treatment significantly improved the DAI score, colon shortening, and histopathological damage in UC mice. The levels of pro-inflammatory factors TNF-α and IL-6 in the colon were significantly reduced. Serum TBA levels were significantly decreased, while alkaline phosphatase(ALP) levels significantly increased. After administration of cholic acid(CA), UC symptoms in the CA + GQD group were significantly aggravated compared with the GQD group. The DAI score, degree of weight loss, colon injury, serum TBA, and liver injury markers all increased significantly. However, compared with the CA group, the CA + GQD group showed a marked reduction in TBA levels and a significant improvement in UC-related symptoms, indicating that GQD can alleviate UC damage exacerbated by CA. Further investigation into the expression of bile acid receptors and synthetases in the liver showed that under GQD treatment, the expression of farnesoid X receptor(FXR) and small heterodimer partner(SHP) significantly increased, while the expression of G protein-coupled receptor 5(TGR5) and cholesterol 7α-hydroxylase(Cyp7A1) significantly decreased. These findings suggest that GQD may affect bile acid receptors and synthetases, inhibiting bile acid synthesis through the FXR/SHP pathway to treat UC.
Animals
;
Colitis, Ulcerative/genetics*
;
Bile Acids and Salts/biosynthesis*
;
Drugs, Chinese Herbal/administration & dosage*
;
Mice
;
Male
;
Humans
;
Receptors, Cytoplasmic and Nuclear/metabolism*
;
Colon/metabolism*
;
Disease Models, Animal
;
Liver/metabolism*
;
Mice, Inbred C57BL
6.Yiqi Yangyin Huazhuo Tongluo Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy
Kelei GUO ; Yingli LI ; Chenguang XUAN ; Zijun HOU ; Songshan YE ; Linyun LI ; Liping CHEN ; Li HAN ; Hua BIAN
Journal of Southern Medical University 2025;45(1):27-34
Objective To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula(YYHT)against high glucose-induced injury in mouse renal podocytes(MPC5 cells)and the possible mechanism.Methods Adult Wistar rats were treated with 19,38,and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose(30 mmol/L)prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic.The changes in miR-21a-5p expressions and the mRNA levels of FoxO1,PINK1,and Parkin in the treated cells were detected with qRT-PCR,and the protein levels of nephrin,podocin,FoxO1,PINK1,and Parkin were detected with Western blotting.Autophagic activity in the cells were evaluated with MDC staining.The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.Results MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression,lowered expressions of FoxO1,PINK1,and Parkin1 mRNAs,and reduced levels of FoxO1,PINK1,parkin,nephrin,and podocin proteins and autophagic activity.Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin,inhibited the expression of miR-21a-5p,increased the mRNA and protein expressions of FoxO1,PINK1 and Parkin,and upregulated autophagic activity of the cells.Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells,and these effects were obviously attenuated by treatment with YYHT-medicated sera.Conclusion YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
7.Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury (version 2025)
Kai HUANG ; Lunhao BAI ; Qing BI ; Hong CHEN ; Jiwu CHEN ; Xuesong DAI ; Wenyong FEI ; Weili FU ; Zhizeng GAO ; Lin GUO ; Yinghui HUA ; Jingmin HUANG ; Suizhu HUANG ; Xuan HUANG ; Jian LI ; Qiang LI ; Shuzhen LI ; Yanlin LI ; Yunxia LI ; Zhong LI ; Ning LIU ; Yuqiang LIU ; Wei LU ; Hongbin LYU ; Haile PAN ; Xiaoyun PAN ; Chao QI ; Weiliang SHEN ; Luning SUN ; Jin TANG ; Zimin WANG ; Bide WANG ; Ru WANG ; Shaobai WANG ; Licheng WEI ; Weidong XU ; Yongsheng XU ; Jizhou YANG ; Liang YANG ; Rui YANG ; Hongbo YOU ; Tengbo YU ; Jiakuo YU ; Bing YUE ; Hua ZHANG ; Hui ZHANG ; Qingsong ZHANG ; Xintao ZHANG ; Jiajun ZHAO ; Lilian ZHAO ; Qichun ZHAO ; Song ZHAO ; Jiapeng ZHENG ; Jiang ZHENG ; Zhi ZHENG ; Jingbin ZHOU ; Jinzhong ZHAO
Chinese Journal of Trauma 2025;41(4):325-338
With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.
8.Key technologies and challenges in online adaptive radiotherapy for lung cancer.
Baiqiang DONG ; Shuohan ZHENG ; Kelly CHEN ; Xuan ZHU ; Sijuan HUANG ; Xiaobo JIANG ; Wenchao DIAO ; Hua LI ; Lecheng JIA ; Feng CHI ; Xiaoyan HUANG ; Qiwen LI ; Ming CHEN
Chinese Medical Journal 2025;138(13):1559-1567
Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.
Humans
;
Lung Neoplasms/radiotherapy*
;
Radiotherapy Planning, Computer-Assisted/methods*
9.Mini-barcode development based on chloroplast genome of Descurainiae Semen Lepidii Semen and its adulterants and its application in Chinese patent medicine.
Hui LI ; Yu-Jie ZENG ; Xin-Yi LI ; ABDULLAH ; Yu-Hua HUANG ; Ru-Shan YAN ; Rui SHAO ; Yu WANG ; Xiao-Xuan TIAN
China Journal of Chinese Materia Medica 2025;50(7):1758-1769
Descurainiae Semen Lepidii Semen, also known as Tinglizi, originates from Brassicaceae plants Descurainia sophia or Lepidium apetalum. The former is commonly referred to as "Southern Tinglizi(Descurainiae Semen)", while the latter is known as "Northern Tinglizi(Lepidii Semen)". To scientifically and accurately identify the origin of Tinglizi medicinal materials and traditional Chinese medicine products, this study developed a specific DNA mini-barcode based on chloroplast genome sequences. By combining the DNA mini-barcode with DNA metabarcoding technology, a method for the qualitative and quantitative identification of Tinglizi medicinal materials and Chinese patent medicines was established. In this study, chloroplast genomes of Southern Tinglizi and Northern Tinglizi and seven commonly encountered counterfeit products were downloaded from the GenBank database. Suitable polymorphic regions were identified to differentiate these species, enabling the development of the DNA mini-barcode. Using DNA metabarcoding technology, medicinal material mixtures of Southern and Northern Tinglizi, as well as the most common counterfeit product, Capsella bursa-pastoris seeds, were analyzed to validate the qualitative and quantitative capabilities of the mini-barcode and determine its minimum detection limit. Additionally, the mini-barcode was applied to Chinese patent medicines containing Tinglizi to authenticate their botanical origin. The results showed that the developed mini-barcode(psbB) exhibited high accuracy and specificity, effectively distinguishing between the two authentic origins of Tinglizi and commonly encountered counterfeit products. The analysis of mixtures demonstrated that the mini-barcode had excellent qualitative and quantitative capabilities, accurately identifying the composition of Chinese medicinal materials in mixed samples with varying proportions. Furthermore, the analysis of Chinese patent medicines revealed the presence of the adulterant species(Capsella bursa-pastoris) in addition to the authentic species(Southern and Northern Tinglizi), indicating the occurrence of adulteration in commercially available Tinglizi-containing products. This study developed a method for the qualitative and quantitative identification of multi-origin Chinese medicinal materials and related products, providing a model for research on other multi-origin Chinese medicinal materials.
DNA Barcoding, Taxonomic/methods*
;
Drugs, Chinese Herbal/chemistry*
;
Drug Contamination
;
Genome, Chloroplast
;
Medicine, Chinese Traditional
10.UPLC-Q-TOF-MS combined with network pharmacology reveals effect and mechanism of Gentianella turkestanorum total extract in ameliorating non-alcoholic steatohepatitis.
Wu DAI ; Dong-Xuan ZHENG ; Ruo-Yu GENG ; Li-Mei WEN ; Bo-Wei JU ; Qiang HOU ; Ya-Li GUO ; Xiang GAO ; Jun-Ping HU ; Jian-Hua YANG
China Journal of Chinese Materia Medica 2025;50(7):1938-1948
This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals
;
Non-alcoholic Fatty Liver Disease/genetics*
;
Mice
;
Network Pharmacology
;
Male
;
Drugs, Chinese Herbal/administration & dosage*
;
Chromatography, High Pressure Liquid
;
Liver/metabolism*
;
Mice, Inbred C57BL
;
Humans
;
Mass Spectrometry
;
Tumor Necrosis Factor-alpha/metabolism*
;
Disease Models, Animal
;
Molecular Docking Simulation

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