Korean Journal of Physiology & Pharmacology最新文献

{"title":"Circular RNA circAtxn10 regulates skeletal muscle cell differentiation by targeting miR-143-3p and Chrna1.","authors":"Nakwon Choe, Anna Jeong, Hosouk Joung, Dongtak Jeong, Young-Kook Kim, Hyun Kook, Duk-Hwa Kwon","doi":"10.4196/kjpp.25.046","DOIUrl":"10.4196/kjpp.25.046","url":null,"abstract":"<p><p>Skeletal muscle differentiation is a complex process regulated by a network of genes and transcription factors. Recent studies have revealed the roles of circular RNAs (circRNAs) and microRNAs (miRNAs) in modulating gene expression during myogenesis. In this study, we focused on the functional interplay between circAtxn10, miR-143-3p, and the nicotinic acetylcholine receptor subunit alpha 1 (Chrna1) in skeletal muscle differentiation. Our results demonstrate that circAtxn10 expression increases during myogenic differentiation and acts as a sponge for miR-143-3p through direct binding. We identified Chrna1 as a direct target of miR-143-3p through three binding sites in its 3'-UTR and showed that both miR-143-3p mimic and Chrna1 knockdown significantly impair myogenesis. Notably, Chrna1 overexpression dramatically enhanced myogenic marker expression and myotube formation. Our findings establish a regulatory axis involving circAtxn10, miR-143-3p, and Chrna1 that plays a critical role in modulating skeletal muscle differentiation, providing new insights into the complex molecular mechanisms regulating myogenesis.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"637-648"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory action of citronellol on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in juvenile mice.","authors":"Thi Quy Nguyen, Thi Quynh Nhu Tran, Seon Hui Jang, Seon Ah Park, Seong Kyu Han","doi":"10.4196/kjpp.25.039","DOIUrl":"10.4196/kjpp.25.039","url":null,"abstract":"<p><p>The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) serves as the primary relay point for orofacial nociceptive inputs transmitted <i>via</i> thin myelinated Aδ and unmyelinated C primary afferent fibers. Citronellol is a monoterpenoid alcohol found in the essential oil of various medicinal plants, such as <i>Cymbopogon citratus</i>. It has been shown to be able to alleviate orofacial pain. However, the precise mechanism by which citronellol modulates SG neurons in the Vc remains unclear. To investigate this, the whole-cell patch-clamp technique was used to examine antinociceptive effects of citronellol on SG neurons in the Vc of mice. In a high-chloride pipette solution, citronellol consistently induced inward currents which persisted even in the presence of tetrodotoxin (a voltage-gated Na⁺ channel blocker), 6-cyano-7-nitroquinoxaline-2,3-dione (a non-<i>N</i>-methyl-d-aspartate glutamate receptor antagonist), and DL-2-amino-5-phosphonopentanoic acid (an <i>N</i>-methyl-d-aspartate receptor antagonist). Nevertheless, citronellol-induced inward currents were partially inhibited by picrotoxin, a GABA_A receptor antagonist, or strychnine, a glycine receptor antagonist. Citronellol-induced inward currents were almost fully blocked when both strychnine and picrotoxin were applied together. In addition, citronellol enhanced both GABA-induced inward currents and glycine-induced inward currents. These findings suggest that citronellol can mediate inhibitory effects of GABA and glycine on SG neurons in the Vc and serve as a potential herbal treatment for orofacial pain.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"603-611"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tie2 activator 4E2 ameliorates diabetic nephropathy and synergizes with dapagliflozin in a mouse model.","authors":"Da Som Jeong, Soo Min Ko, Ji-Young Lee, Hyo-Jeong Han, Yerin Lee, Weon Sup Lee, Eun-Ah Lee, Woo-Chan Son, Jinho Shin","doi":"10.4196/kjpp.24.424","DOIUrl":"10.4196/kjpp.24.424","url":null,"abstract":"<p><p>Diabetic nephropathy (DN), a primary cause of end-stage renal disease, stems from hyperglycemia-induced vascular dysfunction and aberrant angiogenesis. Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, improve glycemic control and provide renal protection yet fall short of fully halting DN progression. This study explores 4E2, a Tie2 receptor activator that mimics angiopoietin-1 to stabilize the vascular endothelium, as a novel DN therapy-both independently and in combination with dapagliflozin. In a streptozotocin (STZ)-induced DN mouse model (DBA/2J strain), male mice were treated with weekly intravenous 4E2, daily oral dapagliflozin, or a combination of both for 4 weeks following STZ administration. Dapagliflozin primarily reduced fasting blood glucose with modest renoprotective effects, whereas 4E2 significantly lowered kidney weight, blood urea nitrogen, and urinary albumin while elevating serum albumin, indicating greater renal protection. Histological analysis showed that 4E2 more effectively attenuated glomerular hypertrophy and lesions compared to dapagliflozin. Immunohistochemistry revealed that 4E2 markedly increased VE-cadherin and CD31 expression while decreasing PDGFR-β, reflecting enhanced endothelial stability and reduced vascular remodeling through Tie2-mediated mechanisms. Combination therapy synergistically enhanced these outcomes, achieving superior reductions in glucose levels, glomerular damage, and vascular pathology compared to either treatment alone. In contrast to anti-VEGF therapies, which can worsen proteinuria, 4E2-mediated Tie2 activation normalizes vascular stability without disrupting physiological angiogenesis, providing a safer therapeutic option. These findings establish 4E2 as a promising treatment for DN, especially when combined with dapagliflozin, by leveraging Tie2-driven stabilization and synergistic benefits to meet this critical unmet need.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"613-623"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agmatine decreases long-term potentiation <i>via</i> α2-adrenergic receptor and imidazoline type 1 receptor in the hippocampus.","authors":"Wonseok Chang, Jihua An, Sang Hyun Jang, Moonil Kim, Sun Seek Min","doi":"10.4196/kjpp.24.399","DOIUrl":"10.4196/kjpp.24.399","url":null,"abstract":"<p><p>Agmatine, a decarboxylation product of L-arginine, has been proposed as a novel neurotransmitter/neuromodulator with diverse neuroprotective and antidepressant-like effects. Although its therapeutic potential has been explored, the precise mechanisms by which agmatine modulates synaptic transmission and plasticity in the hippocampus remain unclear. In this study, we investigated the effects of agmatine on the induction and maintenance of long-term potentiation (LTP) in the CA1 region of mouse hippocampal slices, its ability to counteract amyloid-β (Aβ1-42)-induced LTP impairment, and the receptor systems involved. Bath application of agmatine significantly suppressed the maintenance phase of LTP. Notably, agmatine reversed Aβ-induced deficits in LTP, suggesting a protective effect against synaptic dysfunction. Pharmacological experiments demonstrated that these effects were mediated <i>via</i> α2-adrenergic and imidazoline type I receptors. Paired-pulse facilitation and input-output analyses revealed that agmatine did not alter presynaptic release probability but selectively modulated postsynaptic transmission, particularly under AMPA receptor blockade, indicating a potential regulation of NMDA receptor-mediated signaling. Together, these findings suggest that agmatine modulates hippocampal synaptic plasticity through receptor-specific, postsynaptic mechanisms, and highlight its potential as a therapeutic agent against synaptic impairments in neurodegenerative diseases.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"593-601"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of β-adrenoceptor antagonist and 5-HT_1A and 5-HT_1B receptor antagonist alprenolol on human Kv1.3 currents.","authors":"Eunseo Kim, Su-Hyun Jo","doi":"10.4196/kjpp.25.098","DOIUrl":"10.4196/kjpp.25.098","url":null,"abstract":"<p><p>Alprenolol is a nonselective β-adrenoceptor antagonist used in treating cardiovascular diseases by stabilizing elevated heart rates and myocardial contractility through the inhibition of sympathetic nerve transmissions alongside its role as an antagonist of 5-HT_1A and 5-HT_1B receptors. This study aimed to examine whether alprenolol can affect human Kv1.3 channel (hKv1.3) currents, which contribute to the proliferation and activation of T lymphocytes by regulating the driving force of Ca²⁺ influx. We investigated the acute effects of alprenolol on hKv1.3 channel currents using two-microelectrode voltage clamp recordings in <i>Xenopus</i> oocytes. Alprenolol exhibited concentration-dependent biphasic effects on hKv1.3 currents: it increased the current amplitudes at 1-100 μM but decreased them at 300-1,000 μM during a +50 mV depolarization step. A significant difference was found in alprenolol's effects on the peak and steady-state currents after 6 min of treatment with 10 μM, 50 μM, and 100 μM and 12 min of treatment with 10 μM and 50 μM. Furthermore, alprenolol affected the time constants of intrinsic inactivation and ultrarapid activation. However, no significant changes in <i>V_1/2</i> and <i>k</i> value were found for steady-state activation and inactivation curves, except for the <i>k</i> value between 50 μM and 1,000 μM of the inactivation curve. At 1,000 μM, alprenolol suppressed hKv1.3 currents more rapidly during 5 sec inter-stimulus intervals compared to 15 sec intervals, indicating use-dependent blockade. Therefore, the effects of alprenolol on the biphasic and various biophysical properties of hKv1.3 channels could cause drug concentration-dependent changes in immune function.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"649-658"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Procyanidin B2-induced LKB1-AMPK activation mitigates vascular smooth muscle cell proliferation through inhibition of mTOR signaling.","authors":"Hee Young Park, Seul Gi Kim, Gyeong Ju Bae, Jin Young Sung, Hyoung Chul Choi","doi":"10.4196/kjpp.25.108","DOIUrl":"10.4196/kjpp.25.108","url":null,"abstract":"<p><p>Vascular smooth muscle cell (VSMC) proliferation contributes to intimal thickening in atherosclerosis and restenosis diseases. As a proanthocyanidin type B, procyanidin B2 (PB2) is abundantly found in cocoa, apples, and grapes and is reported to have vascular protective effects. However, the mechanisms by which PB2 inhibits proliferation of VSMCs are not clearly understood. Therefore, the purpose of this study was to investigate the underlying mechanism of PB2-induced inhibition of cell proliferation in VSMCs. We found that PB2 dose- and time-dependently increased phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK) in VSMCs. AMPK is a serine-threonine kinase and serves as a key sensor of cellular energy. PB2 induced LKB1 translocation from nucleus to cytosol which led to AMPK activation. In addition, PB2-induced AMPK activation decreased cell proliferation and cell cycle progression by inhibiting mammalian target of rapamycin signaling pathway. Transfection with LKB1 or AMPK siRNA and transduction of dominant-negative isoforms of the α1 and α2 subunits of AMPK eliminated anti-proliferative effects of PB2. These results demonstrate that PB2 might be a preventive agent for cardiovascular disorders such as atherosclerosis and hypertension.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"659-667"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals as promising agents in Axl-targeted cancer treatment.","authors":"ChuHee Lee","doi":"10.4196/kjpp.25.006","DOIUrl":"10.4196/kjpp.25.006","url":null,"abstract":"<p><p>Axl, a receptor tyrosine kinase, plays a critical role in various cellular processes, such as survival, proliferation, migration, and immune response regulation. Dysregulation of Axl, particularly its overexpression and activation, is implicated in several cancers, where it has been found to facilitate tumor growth, metastasis, and the development of resistance to chemotherapy. Consequently, the inhibition of Axl has garnered significant interest as a potential strategy for cancer treatment. Natural compounds, known for their structural diversity and inherent bioactivity, are a valuable resource for drug discovery. These compounds offer a vast array of chemical structures that can serve as potential inhibitors of Axl, thereby providing novel approaches to modulate its activity. Researchers have identified various natural compounds that exhibit inhibitory effects on Axl, which underscore their potential for developing effective therapies. This review strives to provide a comprehensive overview of natural compounds that have been identified as Axl inhibitors. It will examine the mechanisms through which these natural compounds exert their inhibitory effects on Axl and discuss their potential applications in therapeutic settings. By compiling and analyzing existing research, this review seeks to advance the understanding of natural compounds as viable candidates in the development of effective Axl-targeted therapies, ultimately contributing to improved outcomes in diseases marked by Axl dysregulation.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"533-545"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in diurnal expression of inflammatory mediators in the brain and peripheral blood of male and female mice.","authors":"Eun-Mi Lee, Hyun-Jung Kim, Yelin Park, Jihee Lee Kang, Eun-Mi Park","doi":"10.4196/kjpp.24.372","DOIUrl":"10.4196/kjpp.24.372","url":null,"abstract":"<p><p>Several molecules in human body exhibit light-dependent diurnal expression rhythms, and their disruption impairs physiological functions and health. Normal aging alters these rhythms, contributing to aging processes and age-related brain disorders. Chronic low-grade inflammation is a hallmark of aging (inflammaging), and age-related changes in the diurnal expression of proinflammatory cytokines have been reported in the suprachiasmatic nucleus (SCN) and peripheral blood. However, it remains unclear which genes show diurnal expression changes in brain with the SCN regions removed (extra-SCN) and whether these changes are reflected in peripheral blood. To address this, we analyzed the diurnal expression of genes in extra-SCN brain regions and cytokines in the peripheral blood of young and aged male and female mice. Samples were collected during the light (10 AM) and the dark (10 PM) phases and analyzed using RNA sequencing and cytokine array analysis. In the aged brain, the number of genes displaying diurnal variation in expression was reduced, whereas genes related to inflammation and immune responses, especially <i>Ccl21</i>, were upregulated regardless of phase, suggesting age-associated immune dysregulation. However, peripheral blood levels of CCL21 protein did not differ between age groups. Instead, CXCL13 and IGFBP1 showed age-related diurnal alterations in the blood, but their expression patterns in the aged brain differed from those in the blood. These findings indicate that diurnal expression of inflammation-related molecules is altered with aging in both the brain and blood, with differences observed. These diurnal changes may contribute to the underlying mechanism of inflammaging and age-related diseases.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"559-570"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amorfrutin A ameliorates cerebral ischemia/reperfsion injury <i>in vivo</i> and <i>in vitro via</i> modulating Nrf2/HO-1 signaling pathway.","authors":"Youxi Yang, Liying Shi, Xiaoting Xu, Bilan Luo, Xing Cui, Lei Tang, Jianta Wang","doi":"10.4196/kjpp.24.304","DOIUrl":"10.4196/kjpp.24.304","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of death and disability worldwide. Amorfrutin A (AA), a small molecule compound found in <i>Amorpha fruticosa</i> L. (bastard indigo), possesses various activities, including blood glucose regulation, antiinflammatory, analgesic, and tumor suppression. In this study, we used the middle cerebral artery occlusion/reperfusion (MCAO/R) model and the oxygen glucose deprivation/ reoxygenation (OGD/R) model to mimic the ischemia/reperfusion process <i>in vivo</i> and <i>in vitro</i>, respectively. The role of AA in ischemic stroke was evaluated by CCK-8 assay, ELISA, TTC staining, hematoxylin-eosin staining and Western blot assay. AA increased the survival of BV2 or PC12 cells following OGD/R injury. Meanwhile, AA effectively suppressed the release of reactive oxygen species, nitric oxide, and tumor necrosis factor-α (TNF-α) in BV2 or PC12 cells subjected to OGD/R. After 24 h of MCAO/R surgery, AA significantly reduced the neurological deficit score, diminished the cerebral infarct volume, and attenuated brain pathological injury in rats. AA administration significantly increased superoxide dismutase and glutathione peroxidase levels, reduced malondialdehyde production, and inhibited the release of inflammatory cytokines interleukin-1β and TNF-α in the ischemic brain tissue of MCAO/R rats. In addition, AA suppressed Kelch-like ECH-associated protein 1 expression and promoted nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1, and heme oxygenase 1 (HO-1) expression in rat ischemic brain. AA may be a potential drug for the treatment of ischemic stroke. Its antioxidant and anti-inflammatory effects in cerebral ischemia-reperfusion injury may be related to Nrf2/HO-1 signaling pathway.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"547-557"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Xuefu Zhuyu decoction in treating diabetic kidney disease-induced renal fibrosis: UPLC-Q/TOF-MS, network pharmacology, and experimental validation.","authors":"Yifei Zhang, Shuaixing Zhang, Zeyu Zhang, Zijing Cao, Xuehui Bai, Shujiao Zhang, Mengqi Zhou, Jingyi Tang, Yiran Xie, Zhongjie Liu, Weijing Liu, Yuning Liu","doi":"10.4196/kjpp.24.330","DOIUrl":"10.4196/kjpp.24.330","url":null,"abstract":"<p><p>Xuefu Zhuyu decoction (XFZY) has therapeutic effects on diabetic kidney disease (DKD)-induced renal interstitial fibrosis (RIF), but the mechanisms are unclear. This study investigates XFZY's molecular mechanisms through network pharmacology and experimental validation. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and database screening was used to identify XFZY bioactive compounds. Common targets between these compounds and DKD-induced RIF were analyzed. A protein-protein interaction network was constructed, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Molecular docking validated interactions between XFZY compounds and targets. <i>In vivo</i>, a mouse model of DKD-induced RIF was established using streptozotocin and a high-fat diet. <i>In vitro</i>, human kidney-2 cells were treated with advanced glycation end products. Renal function and pathology were assessed, along with key protein expression levels. Using UPLC-Q-TOF-MS technology and database screening, seven bioactive components of XFZY were identified. Network pharmacology identified 61 common targets, including core targets like AKT1, MTOR, ULK1, and MMP9. Enrichment analysis indicated the AMPK signaling pathway is closely related to XFZY's therapeutic effects on DKD-induced RIF. Molecular docking demonstrated the seven bioactive components exhibited high binding affinities with key targets in the AMPK pathway (AMPK, mTOR, ULK1). <i>In vivo</i>, XFZY improved renal function, ameliorated renal pathology, reduced tubular injury, and alleviated RIF. Both <i>in vivo</i> and <i>in vitro</i>, XFZY increased phosphorylated AMPK and phosphorylated ULK1 expression, decreased phosphorylated MTOR, and reduced LC3 and p62 expression in the autophagy pathway. XFZY may alleviate DKD-induced RIF by modulating autophagy via the AMPK/MTOR/ULK1 pathway.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"571-597"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}