Applied Biological Chemistry
·
2026
·Vol. 69
·期 1
·68
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IF 4.2
Wang Yujie,Wang Jiajie,Cai Maoxuan,Ren Jie,Jia Fang,Jiang Wenjie,Su Dan,Yang Hao,Chen Guilin
Diabetic nephropathy (DN) ranks as the primary contributor to end-stage renal disease across the globe, characterized by progressive glomerular mesangial proliferation and tubular interstitial fibrosis, which poses a severe threat to public health. Pinocembrin is a major flavonoid compound that has been reported to exhibit a variety of prominent biological effects. However, its dual regulatory effects on glomerular and tubular injuries in DN remain unclear. The present study aims to investigate the potential role of pinocembrin in alleviating the progression of DN, providing a combination therapeutic strategy. In vivo experiments were performed to verify its efficacy in improving renal injury and fibrosis of pinocembrin in Lep db /Lep db ( db/db) mice. Pinocembrin-related targets were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP), Comparative Toxigenomics Database (CTD), Swiss Target Prediction, and Symmap databases. Differentially expressed genes in DN tubules and glomeruli were obtained from Gene Expression Omnibus (GEO) dataset GSE30122. Overlapping targets between pinocembrin and DN tissues were identified, followed by Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Molecular docking predicted potential binding interactions between pinocembrin and key targets. In vitro experiments demonstrated that in HG-induced HK-2 cells, pinocembrin might target HSP90AB1 to suppress inflammatory response and epithelial-mesenchymal transition, thereby alleviating tubular fibrosis injury. In HG-treated SV40 cells, pinocembrin downregulated expression of VEGFR, thereby inhibiting cell proliferation and extracellular matrix deposition to improve glomerular pathological damage. This study clarifies the dual protective mechanism of pinocembrin on DN via regulatory pathways. These findings provide experimental foundation and theoretical insight for the application of pinocembrin as a functional food ingredient for the prevention and treatment of DN.
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2017
·
IF 3.791
Yi Cai,Wanqing Ma,Yichuan Xiao,Bo Wu,Xiaobing Li,Fengrong Liu,Jianhua Qiu,Genshui Zhang
Baicalin is a major flavonoid compound purified from Scutellariae radix , which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600 mg/kg/day) induced significantly kidney injury and fibrosis . The collagen synthesis and fibrosis-related protein expression were increased in the kidney of Sprague-Dawley (SD) rats after treatment with high doses of baicalin. We further investigated the potential molecular mechanism of baicalin-mediated renal fibrosis and revealed that baicalin activated the transforming growth factor-β (TGF-β)/Smad signaling pathway in a dose-dependent manner. Moreover, we also observed that baicalin induced Smad3 interaction with transcriptional coactivator p300 accompanying with increment of Smad3 acetylation . Our results may contribute to better understanding of the future pharmacological and toxicological studies of Scutellaria baicalensis Georgi and its active compounds on the human disease.
研究领域:
药理学
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毒理学
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分子生物学
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PubMed
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
·
2024
·
IF 6.9
Hu Wenjie,Wang Yujie,Yang Huiling,Zhang Leiming,Liu Bo,Ji Yunxia,Song Xiaodong,Lv Changjun,Zhang Songzi
Pulmonary fibrosis is a chronic and irreversible progressive lung disease caused by various factors, such as age and environmental pollution. With countries stepping into an aging society and the seriousness of environmental pollution caused by global industrialization, the incidence of pulmonary fibrosis is annually increasing. However, no effective drug is available for pulmonary fibrosis treatment. C-phycocyanin (C-PC), extracted from blue-green algae, has good water solubility and antioxidation. This study elucidated that C-PC reinforces autophagy to block pulmonary fibrogenesis by inhibiting long noncoding RNA (lncRNA) biogenesis in vivo and in vitro. Cleavage under targets and release using nuclease (CUT & RUN)-PCR, co-immunoprecipitation (Co-IP), and nuclear–cytoplasmic separation experiments clarified that C-PC blocked the nuclear translocation of activating transcription factor 3 (ATF3) to prevent the binding between ATF3 and transcription factor Smad3, thereby hindering lncIAPF transcription. Human antigen R (HuR) truncation experiment and RNA binding protein immunoprecipitation (RIP) were then performed to identify the binding domain with lncIAPF in the 244–322 aa of HuR. lncIAPF exerted its profibrogenic function through the binding protein HuR, a negative regulator of autophagy. In summary, C-PC promoted autophagy via down-regulating the lncIAPF–HuR-mediated signal pathway to alleviate pulmonary fibrosis, showing its potential as a drug for treating pulmonary fibrosis. Exploring how C-PC interacts with biological molecules will help us understand the mechanism of this drug and provide valuable target genes to design new drugs.
研究领域:
肺病学
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分子生物学
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药理学
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遗传学
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DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2021
·Vol. 12
·期 1
·167-179
·
IF 4.617
Wang Shuanghu,Tan Xueying,Zhou Quan,Geng Peiwu,Wang Jinhui,Zou Ping,Deng Aiping,Hu Jingbo
Multidrug resistance (MDR) is considered as a critical limiting factor for the successful chemotherapy, which is mainly characterized by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2. In this study, folate-targeted polymeric micellar carrier was successfully constructed to co-delivery of doxorubicin (DOX) and SIS3 (FA/DOX/SIS3 micelles), a specific Smad3 inhibitor which sensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic agents. The ratio of DOX to SIS3 in polymeric micelles was determined based on the anti-tumor activity against resistant breast cells. In addition, FA/DOX/SIS3 micelles exhibited a much longer circulation time in blood and were preferentially accumulated in resistant tumor tissue. Pharmacodynamic studies showed that FA/DOX/SIS3 micelles possessed superior anti-tumor activity than other DOX-based treatments. Overall, FA/DOX/SIS3 micelles are a promising formulation for the synergistic treatment of drug-resistant tumor. Graphical abstract
研究领域:
肿瘤学
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药剂学
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化疗
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药物递送系统
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Dan Wang,Yimeng Zou,Tianqi Zhao,Weiyue Cao,Jiachi Han,Qing Wu,Zhitong Li,Xinyu Li,Peijing Liu,Lin Bai,Guiping Ren
Background The blood FGF21 expression has been previously suggested to increase in patients developing atopic dermatitis (AD) and asthma. However, its impact on atopic march is rarely analyzed. The present work focused on investigating the role of Fibroblast Growth Factor 21(FGF21) in atopic march mice and its underlying mechanisms. Methods The models were induced with Diisononyl phthalate (DINP) and OVA in wild-type C57BL/6 and FGF21 −/− mice. RAW264.7 cells were induced by LPS with/without FGF21 or KLB-SiRNA for in vitro analyses. Results The data indicated that there were more severe allergic reactions including IgE levels and the proportion of mast cells in the blood of FGF21 −/− mice in relative to WT model mice during the progression from AD to asthma. However, exogenous administration of FGF21 inhibited allergies. In this study, we reported that FGF21 mitigated AD-like lesions and Th1/2 or Th17/Treg cell imbalance in AD mice, and significantly decreased TSLP, IL-33, IL-4, IL-5, IL-13 and IL-17A expression on skin. During the asthma phase, FGF21 improved airway remodeling by downgrading inflammatory factors IL-4, IL-5, IL-13 and IL-17A; fibrotic markers α-SMA and Collagen I; and oxidative products MDA and ROS in wild-type model mice. Compared with WT model mice, the adverse consequences were aggravated in FGF21 −/− asthmatic mice. From the mechanistic perspective, FGF21 suppressed NF-κB/NLRP3, TGF-β1/Smad3 and JNK signaling pathways and increased Nrf2 expression in vivo and in vitro. In addition, β-Klotho knockdown attenuated the ameliorative impact of FGF21 on cellular damage. Blocking AMPKα in the LPS-treated RAW264.7 cells inhibited the reduction of FGF21 and the phosphorylation of JNK. Conclusions To conclude, FGF21 alleviated atopic march by inhibiting Th2/17 immune response, and reduced airway remodeling by regulating NF-κB/NLRP3, TGF-β1/Smad3 and AMPKα/JNK pathways. Moreover, this study provides a rationale and novel ideas for applying FGF21 in treating AD and asthma.
研究领域:
免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Hanghang Wang,Chen Chen,Mingzhen Xue,Yu Zhang,Keming Chen,Bingjie Sun,Peipei Wang,Xinyi Tong,Xiong Yu,Han Li,Jia Li,Lihong Hu,Yi Zang,Linguo Zhao,Xiachang Wang,Yinan Zhang
Gynostemma pentaphyllum ( Thunb. ) Makino has been traditionally utilized as medicinal herb and function food in traditional Chinese medicine for treating chronic hepatic disorders. Sweet variants of G. pentaphyllum collected from different regions of China are cultivated as the primary resources for the preparation of curative products. We and other groups identified a series of dammarane-type triterpenoids enriched in the plant, such as gypenosides LVI and XLVI, as the bioactive components responsible for the hepatoprotective effect. However, their therapeutic potential may be constrained by low oral bioavailability and complex metabolic pathways. This study applied an in vitro analysis of gut microbiome-based metabolism to determine the major pathway of the gypenosides. Structure-activity relationships, pharmacokinetic studies, and pharmacodynamic results revealed that the removal of the C-3 saccharide chain is not only the main metabolic pathway in the intestinal tract but also generates the active hepatoprotective ingredient with higher bioavailability and potency than the proteotype. Notably, the investigation of underlying the mechanism demonstrated that the compounds inhibited the activation of hepatic stellate cells via the AMPK/P300/Smad3 signaling pathway. Collectively, these findings demonstrate that in vivo metabolism is critical for unlocking the therapeutic potential of orally administered sweet variant G. pentaphyllum , as this metabolic process releases active ingredients that overcome the bioavailability limitations of the parent gypenoside.
研究领域:
中药学
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天然产物化学
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肝脏病学
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分子药理学
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药物代谢
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肠道微生物组学
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药代动力学
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DOI
PubMed
高影响因子
FEBS Open Bio
·
2023
·
IF 2.6
Yu Zhu,Longmei Wang,Rui Liu,Xiurong Ding,Song Yin,Yuankun Chen,Chuanlong Zhu,Zheng Wang,Wenting Li
Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In this study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation (CLP). The expression and localization of PRMT1 and molecules involved in the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were detected in mouse kidney tissues by western blot, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were further verified in vitro in mouse renal tubular epithelial cells (mRTECs). CLP caused epithelial-mesenchymal transition (EMT), apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of sIL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mRTECs restricted the expression of Cox-2, E-cad, Pro-caspase3 and p-Smad3 (involved in the TGF-β1-mediated signaling pathway), and blocked IL-6/sIL-6R, inducing the expression of Cox-2 and p-STAT3. In conclusion, our findings suggest inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-β1/Smad3 pathway in the cortex and IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.
研究领域:
肾病学
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免疫学
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分子生物学
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病理生理学
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jianchao Li,Zhenxv Wu,Zixue Jiao,Yu Wang,Zongliang Wang,Min Guo,Gang Li,Liqiang Wang,Peibiao Zhang
Postoperation adhesion, as a worldwide problem, are often accompanied by serious complications and cause severe pain to patients, and traditional medicines and commercial anti-adhesion barriers have limited protective effects. So, we designed a novel injective, antifouling and photo-crosslinked polygalacturonic acid (PGA) hydrogel barrier composed of PGA methacrylate (PGAMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) with excellent effect of covering the wound and preventing adhesion. The product termed, as PGAMA-MPC, enhanced hydration as expected with the introduction of abundant MPC, showing an obvious resistance to protein, cell, and microorganism. Simultaneously, as injectable medical materials, stable attachment to the wound and low invasiveness for tissue were provided by photo-crosslinking of PGAMA-MPC hydrogel during Minimally invasive surgery. In the rat model of cecal injury, the PGAMA-MPC hydrogel effectively prevented the postoperative peritoneal adhesion, showing an obvious protective effect within 7 d and the excellent ability to repair of cecum and abdominal wall after 14 d. Compared with the control group, the rats treated with PGAMA-MPC3 almost recovered to the level of the normal level. Furthermore, we found that PGAMA-MPC3 hydrogel significantly reduced the expression of inflammation and deposition of fibrin. The underlying mechanism of anti-adhesion was subsequently confirmed by analyzing the signaling pathway TGF-β1. The PGA-MPC3 hydrogel promoted fibrinolysis by blocking the activation of TGF-β1/Smad3 pathway. In conclusion, we developed an available polysaccharide hydrogel for rapid repair of peritoneum and prevention of postoperative adhesion, possessing an extensive application as medical materials.
研究领域:
生物医学工程
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材料科学
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外科手术
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药剂学
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DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
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IF 6.543
Lijun Fang,Wei Wang,Jiazheng Chen,Anju Zuo,Hongmei Gao,Tao Yan,Pengqi Wang,Yujia Lu,Ruijuan Lv,Feng Xu,Yuguo Chen,Linmao Lyu
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of Cnidium ninidium. Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-β1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-β1/NOX4-mediated oxidative stress in lung fibroblasts.
研究领域:
药理学
·
呼吸病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Juan Chen,Zi-yun Hu,Yu Ma,Shan Jiang,Jiu-yu Yin,Yu-kai Wang,Yong-gui Wu,Xue-qi Liu
Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae ( Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-β1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-β1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.
研究领域:
药理学
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肾病学
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分子生物学
·
糖尿病
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Shengxiu Wen,Hanqiang Zhao,Ying Zhang,Dadong Cao,Meijun Liu,Hongming Yang,Weifen Zhang
Pathological scarring has been a challenge in skin injury repair since ancient times, and prophylactic treatment in the early stages of wound healing usually results in delayed wound healing. In this study, poly(ethylene oxide) (PEO) and chitosan (CTS) were used as carrier materials to construct multifunctional pirfenidone (PFD)/CTS/PEO (PCP) nanofiber membranes (NFMs) loaded with PFD by microfluidic blow-spinning (MBS). MBS is a good method for quickly, safely, and greenly constructing large-area manufacturing of inexpensive NFMs. PCP NFMs were uniform in external morphology, with diameters ranging from 200 to 500 nm. The encapsulation efficiency of the drug-loaded PCP NFMs was above 80%, which had a good slow release, visualization, water absorption, and biocompatibility. The inhibitory effect of PCP NFMs on normal human dermal fibroblasts was dose-dependent and inhibited the expression of the transforming growth factor-β1/SMAD family member 3 (TGF-β1/SMAD3) signaling pathway. PCP NFMs showed significant antibacterial effects against both Staphylococcus aureus and Escherichia coli. In the rabbit ear scar experiment, the wound healed about 70% on day 5 and almost completely on day 10 after PCP-3 NFMs treatment, with the thinnest scar tissue, skin color, tenderness close to normal tissue, and a Vancouver scar scale score of less than 5. PCP-3 NFMs had good effects on anti-inflammatory, wound healing, and collagen-I deposition reducing effects. In conclusion, PCP-3 NFMs can both promote wound healing and intervene to inhibit pathological scarring in advance, making them a potential multifunctional wound dressing for early prevention and treatment of pathological scarring.
研究领域:
材料科学
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生物医学工程
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药剂学
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伤口愈合
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组织工程
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产品关联
DOI
PubMed
高影响因子
Cancer Immunology Research
·
2024
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IF 8.1
Shi Yongjing,Zheng Xiaodong,Peng Hui,Xu Chenqi,Sun Rui,Tian Zhigang,Sun Haoyu,Wang Xianwei
Natural killer (NK) cells are the main innate antitumor effector cells but their function is often constrained in the tumor microenvironment (TME). It has been reported that the E3 ligase FBXO38 accelerates PD-1 degradation in tumor-infiltrating T cells to unleash their cytotoxic function. In this study, we found that the transcriptional levels of FBXO38 in intratumoral NK cells of cancer patients and tumor-bearing mice were significantly lower than in peritumoral NK cells. Conditional knock-out (cKO) of FBXO38 in NK cells accelerated tumor growth and increased tumor metastasis. FBXO38 deficiency resulted in impaired proliferation and survival of tumor-infiltrating NK (TINK) cells. Mechanistically, FBXO38 deficiency enhanced TGF-β signaling, including elevating expression of Smad2 and Smad3, which suppressed expression of the transcription factor Eomes and further reduced expression of surface IL-15Rβ and IL-15Rγc on NK cells. Consequently, FBXO38 deficiency led to TINK cell hyporesponsiveness to IL-15. Consistent with these observations, FBXO38 mRNA expression was positively correlated with the proliferation of TINK cells in multiple human tumors. To study the therapeutic potential of FBXO38, mice bearing human tumors were treated with FBXO38 overexpressed human primary NK cells and showed a significant reduction in tumor size and prolonged survival. In conclusion, our results suggest that FBXO38 sustains NK-cell expansion and survival to promote antitumor immunity, and have potential therapeutic implications as they suggest FBXO38 could be harnessed to enhance NK cell–based cancer immunotherapy.
研究领域:
癌症生物学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
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