1.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.
2.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
3.Multi-component Quality Consistency Evaluation of Leonuri Herba Granules Based on HPLC-DAD-CAD Multi-detector Technique and Chemometrics
Shuangyan LI ; Jun ZHANG ; Cong GUO ; Siyuan LI ; Jipeng DI ; Jiangmin SU ; An LIU ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):174-181
ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules, reveal the quality fluctuation patterns of products from the same and different manufacturers, providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector(HPLC-DAD-CAD) was employed to determine the contents of 4 components(syringic acid, leonurine hydrochloride, ferulic acid, and stachydrine hydrochloride) in samples from 19 manufacturers(53 batches, 159 boxes). Additionally, fingerprint profiles were constructed, and the fingerprint dissimilarity(PS) and relative standard deviation(RSD) of different samples from the same manufacturer were calculated. A principal component analysis(PCA) model was established with PS and the RSD values of the 4 components as variables to classify the manufacturers. Finally, samples from 5 manufacturers(M1-M5) covering three consistency groups were selected to calculate three quality consistency parameters, namely intra-batch consistency(PA), inter-batch consistency(PB), and PS. Then, PCA was performed with PA, PB, and PS of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them, the content of stachydrine hydrochloride(a pharmacopoeial quality control component) was 32.46-72.70 mg per bag, all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China, with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows:syringic acid of 1.43-41.92 mg per bag, leonurine hydrochloride of 0.67-11.85 mg per bag, and ferulic acid of 0.11-3.81 mg per bag. Notably, leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer(RSD of 4.8%-59.2%). PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers(M2, M6, M7, M8, M10, M15, M17, M18) demonstrated relatively high consistency, five manufacturers(M3, M9, M12, M13, M14) showed moderate consistency, six manufacturers(M1, M4, M5, M11, M16, M19) exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers, verifying the reliability of the proposed method. Among these, manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories, and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.
4.Multi-component Quality Consistency Evaluation of Leonuri Herba Granules Based on HPLC-DAD-CAD Multi-detector Technique and Chemometrics
Shuangyan LI ; Jun ZHANG ; Cong GUO ; Siyuan LI ; Jipeng DI ; Jiangmin SU ; An LIU ; Xiaodi KOU ; Yan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):174-181
ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules, reveal the quality fluctuation patterns of products from the same and different manufacturers, providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector(HPLC-DAD-CAD) was employed to determine the contents of 4 components(syringic acid, leonurine hydrochloride, ferulic acid, and stachydrine hydrochloride) in samples from 19 manufacturers(53 batches, 159 boxes). Additionally, fingerprint profiles were constructed, and the fingerprint dissimilarity(PS) and relative standard deviation(RSD) of different samples from the same manufacturer were calculated. A principal component analysis(PCA) model was established with PS and the RSD values of the 4 components as variables to classify the manufacturers. Finally, samples from 5 manufacturers(M1-M5) covering three consistency groups were selected to calculate three quality consistency parameters, namely intra-batch consistency(PA), inter-batch consistency(PB), and PS. Then, PCA was performed with PA, PB, and PS of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them, the content of stachydrine hydrochloride(a pharmacopoeial quality control component) was 32.46-72.70 mg per bag, all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China, with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows:syringic acid of 1.43-41.92 mg per bag, leonurine hydrochloride of 0.67-11.85 mg per bag, and ferulic acid of 0.11-3.81 mg per bag. Notably, leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer(RSD of 4.8%-59.2%). PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers(M2, M6, M7, M8, M10, M15, M17, M18) demonstrated relatively high consistency, five manufacturers(M3, M9, M12, M13, M14) showed moderate consistency, six manufacturers(M1, M4, M5, M11, M16, M19) exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers, verifying the reliability of the proposed method. Among these, manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories, and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.
5.A Multi-dimensional Indicator-based Approach for Quality Evaluation of Chinese Patent Medicines
Shuangyan LI ; Siyuan LI ; Sha CHEN ; Yue GUO ; Jun ZHANG ; Cong GUO ; Yan LIU ; An LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):229-237
Chinese patent medicines are the core preparations for disease prevention and treatment in clinical traditional Chinese medicine (TCM). Their quality is the key to ensuring safe and effective medication and promoting the high-quality development of the TCM industry. At present, the quality evaluation of Chinese patent medicines faces prominent problems, such as inadequate control of quality consistency, over-reliance on single indicators, one-sided evaluation dimensions, unstable statistical methods, and poor implementability of research findings. These defects lead to insufficient scientificity of evaluation results, making it difficult to support the implementation of policies including centralized procurement, high quality, and favorable prices for Chinese patent medicines. According to the core requirements of quality evaluation for Chinese patent medicines, this study established a four-dimensional comprehensive evaluation system encompassing consistency index(CI), content index(MI), effect index(EI), and preparation index(PI). All evaluation indicators were normalized to achieve horizontal comparability. Meanwhile, an improved radar chart was introduced to realize the visualization of evaluation results. This method can systematically integrate four types of core quality attributes: Quality consistency, component content, biological activity, and preparation characteristics. It can effectively distinguish quality differences among products of the same specification from different manufacturers. The evaluation results are unique, stable, and not affected by the addition or reduction of samples, which takes scientificity, objectivity, and operability into account. This method can provide scientific and technical support for screening high-quality Chinese patent medicines and implementing policies of centralized procurement, high quality, and favorable prices. Moreover, it has important practical significance for improving the quality evaluation system of Chinese patent medicines and advancing the standard and modern development of TCM.
6.Visualization of Wallerian Degeneration of The Corticospinal Tract and Glial Pathological Changes After Ischemic Stroke in Mice
Meng MENG ; Jiao MU ; Mei-Yu LI ; Jun-Yan GAO ; Xiao-Min ZHU ; Liang-Liang LIU ; Ying GUO ; Guo-Hui ZHANG
Progress in Biochemistry and Biophysics 2026;53(10):2808-2819
ObjectiveStroke remains the leading cause of acquired disability in adults worldwide, imposing a substantial socioeconomic burden on patients, families, and healthcare systems. Among the various neurological deficits caused by stroke, motor dysfunction——particularly contralateral hemiplegia——is the most common and debilitating consequence, and it predominantly results from damage to the cortical motor conduction pathways. When motor cortex neurons or their projecting fibers are damaged, the distal axons and their associated myelin sheaths undergo a series of progressive, programmed degeneration, fragmentation, and eventual phagocytic clearance. This pathological process is termed Wallerian degeneration (WD). However, the temporal progression of WD following ischemic stroke and the associated alterations in the local glial microenvironment remain incompletely understood. The present study was designed to systematically elucidate the time course of corticospinal tract (CST) axonal WD after ischemic stroke in mice, and to simultaneously characterize the dynamic pathological changes of astrocytes, microglia, oligodendrocyte lineage cells, and myelinating oligodendrocytes during the WD process. MethodsEight-week-old male C57BL/6J mice were randomly assigned to control and ischemic stroke groups. A focal cortical ischemic stroke model was established in the right sensorimotor cortex using the photothrombotic method. This method induces localized intravascular thrombosis in the target cortical region through precisely controlled interaction between the photosensitizer and laser light of specific wavelength. At day 1 post‑surgery, 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate infarct volume, hematoxylin and eosin (HE) staining for histopathological examination, and Nissl staining for assessment of neuronal injury. For axonal degeneration time-course analysis, rAAV-CAG-mCherry anterograde viral tracing was employed to specifically label CST neurons. Cervical spinal cord sections at the CST region were collected at day 3, 5, 7, 14, and 60 post-injury. Morphological changes of mCherry-positive CST fibers were observed under fluorescence microscopy, and the fluorescence signal area fraction within the defined region was quantitatively analyzed to evaluate the dynamic process of axonal degeneration. For glial response assessment, immunofluorescence staining against Iba1 (microglia), GFAP (astrocytes), Olig2 (oligodendrocyte lineage cells), and APC (myelinating oligodendrocytes) was performed at day 7, 14, and 60 post‑surgery. The numbers of positive cells were counted to quantitatively analyze the dynamic changes in each glial population at different time points after ischemia, thereby revealing the evolution of the glial microenvironment during WD. ResultsThe photothrombotic method stably and reliably established an ischemic brain injury model confined to the sensorimotor cortex. Viral tracing revealed that the proportion of mCherry‑positive CST fibers was significantly reduced at day 7 after ischemic injury to the neuronal soma. Immunofluorescence staining demonstrated that during WD, the numbers of microglia and astrocytes in the CST region were significantly increased, whereas the numbers of oligodendrocyte lineage cells and myelinating oligodendrocytes showed no significant changes. ConclusionWD of CST axons is observed at day 7 post-ischemic stroke in a delayed manner. This degenerative process selectively activates microglia and astrocytes, while leaving the number of oligodendrocyte lineage cells largely unaffected.
7.Potential utility of albumin-bilirubin and body mass index-based logistic model to predict survival outcome in non-small cell lung cancer with liver metastasis treated with immune checkpoint inhibitors.
Lianxi SONG ; Qinqin XU ; Ting ZHONG ; Wenhuan GUO ; Shaoding LIN ; Wenjuan JIANG ; Zhan WANG ; Li DENG ; Zhe HUANG ; Haoyue QIN ; Huan YAN ; Xing ZHANG ; Fan TONG ; Ruiguang ZHANG ; Zhaoyi LIU ; Lin ZHANG ; Xiaorong DONG ; Ting LI ; Chao FANG ; Xue CHEN ; Jun DENG ; Jing WANG ; Nong YANG ; Liang ZENG ; Yongchang ZHANG
Chinese Medical Journal 2025;138(4):478-480
8.The historical evolution of Chinese physiology textbooks.
Yan FENG ; Xiao ZHAI ; Xin WANG ; Feng YANG ; Liang ZHU ; Guo-Chao SUN ; Ning WANG ; Jun ZHANG ; Jing XIAO ; Wei-Wei LIU ; You-Fei GUAN
Acta Physiologica Sinica 2025;77(1):1-12
This article systematically reviews the characteristics and trends of the writing, editing, publication and promotion of physiology textbooks in China from the late 19th century to the present, focusing on the introduction, development and innovation of Chinese physiology textbooks. The development of physiology textbooks in China is divided into four main stages: the introduction and initial development of physiology textbooks from the late 19th century to 1925; the localization and diversification of textbooks from 1926 to 1949, after the establishment of the Chinese Physiological Society; the exploratory phase of textbook construction after the founding of the People's Republic of China from 1949 to 1976; the formation and innovation of the textbook development process from 1977 to the present, following the restoration of the college entrance examination. For each phase, the article not only records the historical development of physiology textbooks, but also analyzes the evolution of their content, writing styles and the interaction with the social and political contexts. The article summarizes the characteristics and experiences of all these four phases. Special attention is given to the comprehensive statistical analysis of physiology textbooks published since the restoration of the college entrance examination and Economic Reform and Opening-up in 1977, revealing the changes in the number, publication trends and academic features of textbooks during this period. Finally, the article presets the future development of physiology textbooks in China, proposing that textbook writing should integrate aspects such as ideological and political education, medical humanities, basic and clinical medicine, health education, scientific research and international exchange and collaboration. The article also advocates for the application of new technologies and methods, such as artificial intelligence, virtual teaching models and knowledge graphs, to support "personalized learning". This research provides a systematic reference for the study of the history of medical education and offers theoretical support for the future innovation of physiology textbook in China.
Humans
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China
;
History, 19th Century
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History, 20th Century
;
History, 21st Century
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Physiology/education*
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Textbooks as Topic/history*
9.Synergistic neuroprotective effects of main components of salvianolic acids for injection based on key pathological modules of cerebral ischemia.
Si-Yu TAN ; Ya-Xu WU ; Zi-Shu YAN ; Ai-Chun JU ; De-Kun LI ; Peng-Wei ZHUANG ; Yan-Jun ZHANG ; Hong GUO
China Journal of Chinese Materia Medica 2025;50(3):693-701
This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism*
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Neuroprotective Agents/pharmacology*
;
Animals
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Drugs, Chinese Herbal/administration & dosage*
;
Benzofurans/pharmacology*
;
Mice
;
Drug Synergism
;
Caffeic Acids/pharmacology*
;
Polyphenols/pharmacology*
;
Humans
;
Alkenes/pharmacology*
;
Endothelial Cells/drug effects*
;
Depsides
10.Berberine promotes expression of AQP4 in astrocytes by regulating production of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance.
Xue-Ling LIN ; Ying LI ; Meng-Qing GUO ; Yan-Jun ZHANG ; Qing-Sheng YIN ; Peng-Wei ZHUANG
China Journal of Chinese Materia Medica 2025;50(3):768-775
This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans
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MicroRNAs/metabolism*
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Berberine/pharmacology*
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Hep G2 Cells
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Exosomes/genetics*
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Aquaporin 4/metabolism*
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Insulin Resistance
;
Astrocytes/drug effects*

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