AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
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2025
·Vol. 93
·期 5
·e70084
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IF 2.4
Heng Wang,Zhaofei Liu,Xiangjun Xu,Haitao Zhang,Lei He,Ming Li
Background Chronic prostatitis (CP), a frequent male urological disease, is featured with chronic pelvic pain and various discomfort. Calycosin has anti-inflammatory effect and its exact mechanism in CP remains unknown. Objective Our research was designed to explain the underlying mechanism of calycosin in CP and illustrate our findings in the rats and LPS-ATP-induced RWPE-1 cells. Methods The pathology of prostate tissues was analyzed by HE staining and histological inflammation score. The concentration of inflammatory factors were detected via ELISA assay. Besides, the representative biomarkers of oxidative stress were measured through detection kits. The ROS production, NLRP3 and GSDMD expression were evaluated by immunofluorescence or immumohistochemical staining. Furthermore, the expression of NF-kBp65 pathway-associated proteins and pyroptosis-associated proteins were detected by western blotting. RWPE-1 cells growth and pyroptosis were assessed by CCK-8 and flow cytometry, respectively. mRNA levels of pyroptosis markers were detected by qRT-PCR analysis. Results The CP model in vivo and in vitro was successfully established by carrageenan and LPS-ATP, respectively. Calycosin substantially ameliorated the pathological damage of prostate tissue. Moreover, calycosin treatment promoted RWPE-1 cells viability and reduced pyroptosis. Calycosin remarkably reduced the inflammatory factors secretion and oxidative stress markers. Calycosin stimulation effectively suppressed the pyroptosis, which was linked with inactivation of the NF-kBp65 signaling pathway. These beneficial effects of calycosin were similar to the NLRP3 inhibitor (MCC950). Conclusion To sum up, our observations indicated that calycosin protects against CP via suppressing inflammation, oxidative stress, and pyroptosis through NF-kBp65 pathway, thereby serving as a promising therapy for CP treatment.
研究领域:
医学
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药理学
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免疫学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2025
·
IF 4.7
Jicong Lu,Yingying Guo,Zhaoyuan Yang,Mengxia Xie,Shuangyu Zhang,Keji Li,Jingjing Yang,Shanhui Xue,Da Xu,Kanglu Yan,Yuehua Liu
The prevalence of gestational diabetes mellitus (GDM) is currently on the rise globally, which heightens the risk of adverse pregnancy outcomes and subsequently increases the likelihood of cesarean delivery. GDM can induce hyperglycemic conditions in cesarean wounds, leading to delayed wound healing and complications such as itching, pain, and scarring. These complications significantly impact the quality of life and mental health of mothers. Furthermore, there is a lack of effective clinical prevention strategies. Consequently, the need to improve wound healing after cesarean sections in women with GDM is a pressing concern that warrants our attention. To maximize the therapeutic impact and extend the bioavailability of calycosin-7-glucoside (CG), it was integrated into a hybridized hydrogel (GOHA) as a drug carrier to create the GOHACG hydrogel. Bases on our tests, the GOHACG hydrogel demonstrated a strong capacity for water absorption, appropriate pore size, and good biocompatibility to adjust to the in situ surroundings of the wound. GOHACG also promoted epidermal regeneration, collagen deposition, angiogenesis, and the conversion of macrophages from the M1 to M2 phenotype. Indicating a reduction in the inflammatory response, accelerated wound repair, and minimized skin scarring in a postcesarean delivery model involving gestational diabetic mellitus mice. In brief, the GOHACG possesses significant properties that enhance wound healing in GDM model, suggesting its potential effects in treating wound healing of GDM.
研究领域:
医学
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药理学
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生物材料学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
·
IF 3.9
Sun Jinzhou,Chen Qianqian,Zhuang Chumeng,Li Xiaohong,Yu Li,Jin Weifeng
Develop a novel coupled PK-PD model and apply it to quantitatively evaluate the synergistic effects of Hydroxysafflor Yellow A (HSYA) combined with Calycosin (CA) in the treatment of ischemic stroke. A total of 6 rats were modelled for middle cerebral artery occlusion (MCAO). Plasma was collected from the submandibular venous plexus of rats after the administration of HSYA and CA, and was detected and analyzed by LC-MS method. The plasma expression levels of Caspase-9, IL-1β and SOD in rats were also determined by ELISA kit. Meanwhile, a coupled PK-PD model was proposed, incorporating interaction terms between drugs and coupling of pharmacodynamic effects, to quantitatively reveal their interactions. Moreover, a numerical solution technique based on optimization methods was proposed, enabling the model to be effectively applied to experimental data. Based on the coupled PK model, HSYA and CA significantly increased each other’s metabolic rates. The model also showed that CA had a larger apparent volume of distribution and clearance in rats, while HSYA had a shorter mean retention time and elimination half-life. The coupled PK-PD model indicated a synergistic effect between HSYA and CA on all three pharmacodynamic markers, with HSYA contributing more significantly. Despite individual variability among the six rats, the parameter interpretations remained consistent. The proposed coupled PK-PD model and its numerical solution algorithm successfully revealed the synergistic effects of HSYA and CA in the treatment of ischemic stroke. This model lays the foundation for future models with more complex interactions and effects.
研究领域:
药理学
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生物医学工程
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神经科学
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DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
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2022
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IF 4.885
Lingling Han,Jiaqi Song,Chaoqun Yan,Chunqiang Wang,Liwei Wang,Wen Li,Yan Du,Qingshan Li,Taigang Liang
Inhibition of α-glucosidase activity plays a key role in reducing blood glucose level of type Ⅱ diabetic patients. In study, the inhibitory activity and mechanism of Calycosin (CA) and calycosin-7- O -β- D -glucoside (CAG), active components from Astragalus membranaceus , against α-glucosidase were studied by α-glucosidase activity tests, spectral analysis and docking simulation studies. The results suggested that the α-glucosidase inhibitory activity of CA (IC 50 =39.45 μM) and CAG (IC 50 =174.04 μM) were superior to acarbose (positive drug, IC 50 =471.73 μM). Fluorescence data indicated that CA and CAG quenched the fluorescence of α-glucosidase by spontaneous forming CA-α-glucosidase and CAG-α-glucosidase complexes. Besides, results obtained from CD and FT-IR analysis showed that the binding of CA or CAG to α-glucosidase caused conformational changes of α-glucosidase. Docking simulation results further suggested that, compared with CAG, CA had higher affinity for α-glucosidase because of its tightly bound to residues in active cavity of α-glucosidase. These findings demonstrated the α-glucosidase inhibitory activity and mechanism of CA and CAG, moreover, provided the basis for structural modification of AM flavonoids in the treatment of diabetes mellitus.
研究领域:
药理学
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生物化学
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分子生物学
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糖尿病研究
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药物化学
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DOI
高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
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2019
·Vol. 166
·期 6
·H187
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IF 3.12
Bolu Sun,Chaoqun Wang,Jinying Cai,Dai Li,Wuyan Li,Xiaodan Gou,Yuqiang Gou,Fangdi Hu
In this study, a newfangled molecularly imprinted electrochemical sensor based on nanoporous carbon (NC) was constructed and applied to the sensitive determination of calycosin in complex Chinese medicine samples. Aniline as functional monomer and calycosin as template were used to assemble molecularly imprinted polymer (MIP), which was bonded to the surface of NC modified glassy carbon electrode (GCE) by electropolymerization. After characterization of the successfully prepared MIP/NC composite, the electrochemical performance of the proposed sensor (MIP/NC/GCE) was evaluated by cyclic voltammetry, electrochemical impedance spectroscopy and chronocoulometry. The results proved that the sensor could accelerate electron transfer rate and heighten specific surface area. Under optimized conditions, the proposed sensor was used to detect calycosin, which displayed good reproducibility, stability and selectivity. The method demonstrated a liner range of 4.20 × 10−7∼1.29 × 10−4 mol/L with the detection limit of 8.5 × 10−8 mol/L. Moreover, this study will provide a prospective exploration for the application of electrochemical analysis technology in the active ingredient detection of traditional Chinese medicine.
研究领域:
分析化学
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中药学
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生物医学工程
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DOI
高影响因子
Nanoscale
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2025
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IF 5.1
Bin Lu,Kun Zhang,Qingrong Dong,Lan Wei,Jia Shi,Fang Liu,Taigang Liang,Jiangfeng Du
Sepsis is a heterogeneous disease with high morbidity and mortality due to the limited therapeutic. Calycosin (CA), one of the main active ingredients of Astragalus, can potentially treat sepsis, but its therapeutic effect is limited by low blood circulation concentration and poor bioavailability. To address this challenge, we have successfully prepared BSA@Se-CA nanocomposite system （BSC） through self-assembly loading calycosin (CA) onto BSA@Se nanoparticles (BS). Compared to CA, BSC enhances the scavenging of ROS more effectively than CA alone by enhancing the activity of glutathione peroxidase (GPX). Notably, BSC reducing the expression level of inflammatory factors (NO, IL-6, IL-1β, and TNF-α) in inflammatory macrophages by synergistically inhibit the NF-κB signaling pathway. Moreover, the in vitro experiments demonstrated that BSC can also effectively alleviate RAW264.7 cells and HUVEC cells damage caused by oxidative stress, which can maintain the normal cells physiological function. In vivo, BSC exhibit significantly improve the therapeutic effect of sepsis by intraperitoneal injection, such as increase the survival rate of sepsis mice, and alleviate normal organ damage. Thus, this study provides a new strategy for improving the utilization efficiency of natural products with poor treatment effect and provides a reference for improving the therapeutic effect of sepsis.
研究领域:
药理学
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纳米医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2024
·Vol. 28
·期 7
·e18157
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IF 4.3
Hui Jiang,Yang Wang,Zhao Tang,Xianjiang Peng,Chan Li,Yangjie Dang,Rui Ma
Periprosthetic osteolysis (PPO) caused by wear particles is one of the leading causes of implant failure after arthroplasty. Macrophage polarization imbalance and subsequent osteogenic inhibition play a crucial role in PPO. Calycosin (CA) is a compound with anti-inflammatory and osteoprotective properties. This study aimed to evaluate the effects of CA on titanium (Ti) particle-induced osteolysis, Ti particle-induced macrophage polarization and subsequent osteogenic deficits, and explore the associated signalling pathways in a Ti particle-stimulated calvarial osteolysis mouse model using micro-CT, ELISA, qRT-PCR, immunofluorescence and western blot techniques. The results showed that CA alleviated inflammation, osteogenic inhibition and osteolysis in the Ti particle-induced calvarial osteolysis mouse model in vivo. In vitro experiments showed that CA suppressed Ti-induced M1 macrophage polarization, promoted M2 macrophage polarization and ultimately enhanced osteogenic differentiation of MC3T3-E1 cells. In addition, CA alleviated osteogenic deficits by regulating macrophage polarization homeostasis via the NF-κB signalling pathway both in vivo and in vitro. All these findings suggest that CA may prove to be an effective therapeutic agent for wear particle-induced osteolysis.
研究领域:
骨科
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药理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2021
·Vol. 26
·期 22
·6998
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IF 4.412
Nilupaier Tayier,Ning-Yi Qin,Li-Nan Zhao,Yi Zeng,Yu Wang,Guang Hu,Yuan-Qiang Wang
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin can lead to a variety of skin disorders. Calycosin is an isoflavone from Astragali Radix, which is a traditional Chinese medicine that exhibits several pharmacological activities including skin whitening. In our study, the inhibitory effect of calycosin on melanin production is confirmed in a zebrafish in vivo model by comparing with hydroquinone, kojic acid, and arbutin, known as tyrosinase inhibitors. Moreover, the inhibitory kinetics of calycosin on tyrosinase and their binding mechanisms are determined using molecular docking techniques, molecular dynamic simulations, and free energy analysis. The results indicate that calycosin has an obvious inhibitory effect on zebrafish pigmentation at the concentration of 7.5 μM, 15 μM, and 30 μM. The IC50of calycosin is 30.35 μM, which is lower than hydroquinone (37.35 μM), kojic acid (6.51 × 103μM), and arbutin (3.67 × 104μM). Furthermore, all the results of molecular docking, molecular dynamics simulations, and free energy analysis suggest that calycosin can directly bind to the active site of tyrosinase with very good binding affinity. The study indicates that the combination of computer molecular modeling and zebrafish in vivo assay would be feasible in confirming the result of the in vitro test and illustrating the target-binding information.Keywords:calycosin;tyrosinase;melanin;zebrafish;molecular docking
研究领域:
药理学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
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2025
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IF 1.2
Junling Zhu,Rilian Lai,Qin Zheng,Shuying Huang,Shenghua Hu,Zhangfei Xu,Huixia Sun
1. To study the effects of calycosin on palmitic acid-induced HepG2 cells, as well as the potential mechanisms of action.2. Potential targets of calycosin for the alleviation of insulin resistance were predicted by network pharmacology. Glucose concentration in the culture medium was determined by the GOD-POD method. The model of insulin resistance was established by palmitic acid-induced HepG2 cells. Effects of palmitic acid and calycosin on HepG2 cell activity were determined using an MTT assay kit. The expression levels of AKT1 and FOXO3a were detected by western blot.The expression level of hsa-miR-324-3p was detected by RT-qPCR. Dual luciferase reporter assay to detect targeting of AKT1 by hsa-miR-324-3p.3. AKT1 was predicted and validated as a potential target of calycosin for treatment of insulin resistance. The model of insulin resistance was successfully established by palmitic acid-induced HepG2 cells. Up-regulation of AKT1 expression inhibits FOXO3a entry into the nucleus. Calycosian was demonstrated to concentration-dependently increase the sensitivity of insulin resistance cells to insulin. The hsa-miR-324-3p was proven to exist in insulin-resistant cells. Hsa-miR-324-3p was found to target AKT1 involved in the alleviation of insulin resistance.4. Calycosin inhibits FOXO3a nuclear translocation by regulating the hsa-miR-324-3p/AKT pathway, thus alleviating insulin resistance.
研究领域:
药理学
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分子生物学
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内分泌学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
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2021
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IF 2.479
Xue Liu,Yumeng Shao,Xinyue Zhang,Xiang Ji,Min Xie,Huaman Liu
The precise etiology and pathogenesis of idiopathic pulmonary fibrosis are not completely understood, and no satisfactory treatment exists. This work aimed to examine the effects of calycosin (CA, an isoflavone compound) on pulmonary fibrosis (PF) and explore the underlying mechanism. In this study, we established a mice model of PF induced by 5 mg/mL bleomycin (BLM), and mice were orally administrated with 7 mg/kg or 14 mg/kg CA once a day for three weeks. In vitro , after pretreated with 80 μM CA, MLE-12 cells were stimulated with 10 ng/mL transforming growth factor-β1 (TGF-β1) for inducing epithelial-mesenchymal transition (EMT). The results showed that CA treatment ameliorated the severity of fibrosis and the lung tissue damage, as well as suppressed the secretion of inflammation factors in a dose-dependent manner of the PF mice model induced by BLM. Subsequently, CA inhibited the BLM-induced PF progression by repressing EMT, evidenced by the reverse of the downregulation of E-cadherin and the upregulation of vimentin, α-SMA, and fibronectin. Moreover, the elevated phosphorylation of AKT and GSK3β induced by BLM (or TGF-β1) was decreased by CA treatment, leading to the rescue of the high expression of β-catenin. CA prevented the translocation of β-catenin from the cytoplasm to the nucleus. The repressed effects of CA on the TGF-β1-induced EMT and the AKT/GSK3β/β-catenin axis, as well as the translocation of β-catenin were all reversed by a AKT activator SC79. Taken together, CA ameliorated PF by the EMT inhibition upon suppressing the AKT/GSK3β/β-catenin signaling pathway.
研究领域:
药理学
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肺科学
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细胞生物学
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信号传导
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
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IF 5.6
Xiuying Li,Fengyuan Zhang,Xin Wang,Xizhu Chen,Qinqing Li,Yandong Li,Fan Zeng,Caixia Liu
Macrophage polarization imbalance is closely implicated in the pathogenesis of rheumatoid arthritis (RA). Triptolide (TP) can effectively regulate macrophage polarization but is severely limited by its high toxicity and narrow therapeutic window. Calycosin (CAL) not only alleviates TP-induced toxicity but also exhibits anti-inflammatory and chondroprotective effects, making their combination a promising strategy for safer and more effective RA therapy. However, this free combined therapy suffers from high dosage requirements and nonspecific systemic distribution in vivo . Herein, we developed a high drug-loading, lesion-targeted, and stimuli-responsive delivery system for co-delivery of TP and CAL. Using polyamidoamine (PAMAM) as the carrier, we fabricated a locked (LD)-type folate-targeted PAMAM nanomicelle (LD-PAMAM-TP&CAL) by coating a matrix metalloproteinases (MMPs)-responsive detachable PEG shell, based on MMPs overexpression in RA microenvironment. This engineered nanomicelle showed uniform morphology, high encapsulation efficiency, and MMPs-triggered conversion from a locked (LD) state to an open state for intelligent drug release. In vitro , it achieved folate receptor (FR)-mediated targeted macrophage uptake, regulated M1/M2 polarization, protected chondrocytes, and effectively resolved the toxicity-efficacy paradox of TP. In vivo , it significantly enhanced drug accumulation in arthritic joints, alleviated joint swelling and bone destruction in CIA rats, modulated inflammatory and bone-related factor expression, balanced synovial macrophage function, and ensured systemic safety. Collectively, this “Lock-and-Release” nanomicelle integrates functional carrier innovation, drug synergy, and inflammatory microenvironment-responsive intelligent lock-to-release behavior. It successfully overcomes the clinical bottlenecks of TP and enables high-efficiency, low-toxicity RA therapy via regulating macrophage polarization, providing a promising functional nanoplatform for clinical RA treatment.
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Qianqian Chen,Jiayang Wan,Yangyang Zhang,Yu He,Yida Bao,Li Yu,Jiehong Yang
Objective Astragalus and Safflower are commonly used in the treatment of stroke. Studies have shown that their two active components, hydroxysafflor yellow A (HSYA) and calycosin (CA), have protective effects on cerebral ischemia-reperfusion injury (I/R). However, the pharmacokinetic-pharmacodynamic (PK-PD) modeling study of the combination of the two components has not been reported in rats. The study aimed to perform combined PK-PD modeling of HSYA and CA in normal and cerebral ischemia model rats to explain quantitatively their time-concentration-effect relationship. Methods To make the middle cerebral artery occlusion (MCAO) model. SD rats were randomly divided into normal treated group (NTG) ( n = 6), model group (MDG) ( n = 6) and model treated group (MTG) ( n = 6). Plasma was collected from the mandibular vein after 0, 2, 5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 180, and 240 min after intravenous administration. Rats in NTG and MTG were administered the same dose of HSYA (5 mg/kg) and CA (8 mg/kg) by tail vein injection. HPLC-VWD method was used for detection and analysis. Simultaneously, ELISA was performed to detect the levels of IL-1β and caspase-9 in rat plasma at different time points. The improvement in the above indicators was compared after administration. Lastly, after combining the pharmacokinetic parameters and pharmacodynamic indicators in vivo , DAS 3.2.6 software was used to fit the PK-PD model. Results The MCAO model was successfully established. Compared to NTG, there was a significant difference ( P < 0.05) in t 1/2α , t 1/2β , V 1 , V 2 , CL 1 , CL 2 , AUC (0−t) , AUC (0-∞) , and K 12 of MTG for HSYA, and there was a significant difference ( P < 0.05) in t 1/2α , V 1 , CL 1 , AUC (0−t) , AUC (0-∞) , and K 10 of MTG for CA . Compared to NTG, the PK parameters of t 1/2α , V 1 , V 2 , CL 1 , and K 10 were higher for HSYA in MTG, while AUC (0−t) , AUC (0-∞) , K 12 , and K 21 were lower; the PK parameters of t 1/2α , V 1 , V 2 , AUC (0−t) , and AUC (0-∞) were higher for CA in MTG, while CL 1 , CL 2 , K 10 , K 12 , and K 21 were lower. Also, the results of PD showed extremely significant differences in the levels of caspase-9 and IL-1β at the different time points in MTG ( P < 0.01) compared with 0 min. The levels of caspase-9 and IL-1β in NTG rats showed little fluctuation and were relatively stable; however, their levels in MTG showed a downward trend with time. There were highly significant differences in the levels of each of the pharmacodynamic indicators at every time point between NTG and MTG ( P < 0.01). Conclusion The PK-PD model of the combined administration of HSYA and CA was successfully established in rats, and the differences in pharmacodynamic and pharmacokinetic properties between the normal and cerebral ischemic rats were evaluated. Based on comprehensive data analysis, we found that the combination of HSYA and CA may exert protective effects against I/R injury in rats via anti-apoptotic and anti-inflammatory pathways. The study provided additional insights into the development of drugs for ischemic stroke as well as the design of appropriate dosing regimens.
研究领域:
药理学
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神经科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）