ACS Pharmacology & Translational Science
·
2024
·
IF 4.9
Xiao-Yi Chen,Tian-Tian Wang,Qing Shen,Hao Ma,Zhan-Hua Li,Xi-Na Yu,Xiao-Feng Huang,Lin-Sen Qing,Pei Luo
In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1β, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-β1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis.
研究领域:
药理学
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心脏病学
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肾病学
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传统中医
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2012
·Vol. 65
·期 1
·149-155
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IF 2.175
Zhang Yan-Hui,Zhang You-Jin,Guo Yan-Lei,Li Wen-Juan,Yu Chao
ObjectivesWith the growing popularity of herbal and natural medicinal products, attention has turned to possible interactions between these products and pharmaceutical drugs. In this study, we examined whether astragaloside IV (AGS-IV) could inhibit the activity of CYP1A2 in rat liver microsomes in vitro and in vivo.MethodsThe effect of AGS-IV on CYP1A2 activity was investigated using probe substrates: phenacetin in vitro and theophylline in vivo. Phenacetin was incubated in rat liver microsomes with or without AGS-IV, and the mechanism, kinetics and type of inhibition were determined. The inhibitory effect of AGS-IV on CYP1A2 activity in rats was also determined using theophylline in vivo. The pharmacokinetics of theophylline were observed after a single or week-long treatment with AGS-IV.Key findingsAGS-IV was found to be a competitive inhibitor with a Ki value of 6.29 μm in vitro. In the multiple-pretreatment rat group, it was found to have a significantly higher area under the concentration–time curve (AUC) for theophylline, as well as a lower apparent oral total body clearance value (CL/F). In contrast, no significant difference in metabolism of theophylline was found for the single pretreatment group.ConclusionsThese findings suggest that AGS-IV is a potent inhibitor of CYP1A2. This work offers a useful reference for the reasonable and safe use of clinically prescribed herbal or natural products to avoid unnecessary herb–drug interactions.
研究领域:
药理学
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中药学
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代谢酶研究
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DOI
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2025
·
IF 3.1
You Xujun,Li Honghan,Li Qixin,Zhang Qing,Cao Yiguo,Fu Wei,Wang Bin
Prostate cancer (PCa) is an epithelial malignancy affecting the prostate gland. Astragaloside IV combined with polypeptide extract from scorpion venom (PESV) has been reported to inhibit the growth of PCa. This study aimed to investigate the mechanisms by which this combination mitigates the progression of PCa. Bioinformatic analysis was utilized to investigate the correlation between zinc finger DHHC-type containing 1 (ZDHHC1) expression and PCa progression. The extent of pyroptosis in PCa cells was assessed by measuring cell viability, IL-1β and IL-18 secretion, LDH release, and HMGB1 content. PCa mouse models were constructed by subcutaneous injection of DU145 or PC-3 cells into nude mice, with subsequent monitoring of tumor weight and volume. ZDHHC1 expression was significantly lower in PCa patient tissues, which correlated with a poor prognosis. ZDHHC1 overexpression inhibited PC-3 and DU145 cell viability and increased IL-1β, IL-18, LDH, and HMGB1 levels in cell supernatants. Notably, the pyroptosis inhibitor LDC7559 partially reversed these effects. Co-IP assay demonstrated an interaction between ZDHHC1 and GSDMD. ZDHHC1 overexpression significantly enhanced GSDMD palmitoylation-mediated membrane translocation and pyroptosis; however, this effect was partially reversed by the palmitoylation inhibitor 2-BP. The combination of Astragaloside IV and PESV promoted GSDMD membrane translocation and pyroptosis in PCa cells, with ZDHHC1 knockdown partially reversing the effects of Astragaloside IV-PESV. Furthermore, treatment with Astragaloside IV-PESV significantly inhibited tumor tissue growth in tumor-bearing nude mouse models. Astragaloside IV-PESV enhances palmitoylation-mediated membrane translocation of GSDMD-N by upregulating ZDHHC1 expression, thereby facilitating pyroptosis in PCa cells and attenuating PCa progression.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2022
·
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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产品关联
DOI
高影响因子
CURRENT DRUG METABOLISM
·
2022
·Vol. 23
·期 2
·131-136
·
IF 3.408
Shi Zhongbo,Jiang Junhao,Zhao Dezhang,Xie Baogang,Li Yan,Yu Chao
Backgrond: Astragaloside IV (AST) and metoprolol are often used together to treat cardiovascular diseases, while the herb-drug interaction (HDI) between them is still unclear. Objective: This study investigates the effect of AST on the pharmacokinetics of metoprolol in rats and
its mechanism to predict the HDI. Method: First, IC50 value of AST on nine CYP450 enzymes in human liver microsomes (HLMs) was determined by the cocktail method. We explored the effect of AST on the pharmacokinetics of metoprolol (metabolized by CYP2D6) in vivo. Twelve male SD rats were
equally divided into two groups, with or without pretreatment of AST (3 mg/kg/day) for 7 days, and they received metoprolol (27 mg/kg) by oral administration. Blood samples were determined using HPLC. Finally, the mechanism of AST was explored. Results: AST exhibited a moderate inhibitory
effect on CYP2D6 with IC50 value of 32.28 μM. The pharmacokinetic parameters of metoprolol were significantly altered by AST with the increase of AUC0-∞ (538.81 ± 51.41 to 1088.34 ± 86.46 μg*min/mL, P<0.05) and Cmax
(6.21 ± 0.56 to 8.34 ± 0.87 μg/ml, P<0.05). The investigation of the mechanism showed AST to be an irreversible inhibitor of CYP2D6 with KI value of 2.9 μM and Kinact of 0.018 min−1, respectively.
Conclusion: AST was found to increase the plasma exposure of metoprolol in rats. AST reduced the metabolism of metoprolol by inhibiting CYP2D6 activity. The HDI might enhance when metoprolol and AST will be applied in combination.
研究领域:
药理学
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临床医学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Wanting Qin,Shaoling Li,Ziji Cheng,Wenlong Xue,Mingyue Tian,Fangfang Mou,Haidong Guo,Shuijin Shao,Baonian Liu
Sunitinib (SU) is widely used to treat solid tumors but it can be cardiotoxic and often leads to drug withdrawn or discontinuation. Astragaloside IV (ASIV) is the essential active component of the Chinese herb Astragalus membranaceus which shows potential cardioprotective effects. Herein, we investigated the effect of ASIV on SU-associated cardiotoxicity and its mechanisms. We showed that ASIV significantly ameliorated SU-induced myocardial injury in mice, as evidenced by an improvement in left ventricular ejection fraction (EF) and a decrease in blood pressure and serum concentration of myocardial injury markers. ASIV attenuated SU-induced myocardial inflammatory infiltration and fibrotic lesions. In addition, ASIV suppressed SU-induced myocardial oxidative stress and apoptosis both in vitro and in vivo . Furthermore, SU increased COUP-TFII expression both in mRNA and protein levels in mice myocardial tissue, primary neonatal rat cardiomyocytes (NRCMs) and H9c2 cell lines, and this effect was rescued by ASIV. Knockdown of COUP-TFII reduced the oxidative stress and apoptosis induced by SU in NRCMs and H9c2 cell lines. However, the overexpression of COUP-TFII blocked the protective effects of ASIV on SU-treated cardiomyocytes. Thus, our results demonstrated that ASIV ameliorated SU-indued cardiotoxicity by inhibiting COUP-TFII, suggesting that ASIV might be a potential therapeutic strategy for the prevention of SU-associated cardiotoxicity.
研究领域:
药理学
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心脏病学
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肿瘤学
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DOI
PubMed
高影响因子
Current Molecular Pharmacology
·
2024
·Vol. 17
·期 1
·e18761429267000
·
IF 2.4
Fengyan Tang,Bo Zhao,Li Zhang,Faisal Raza,Hajra Zafar,Shao Zhong,Lin Li,Wenhua Zhu,Lingna Fang,Bing Lu,Liwen Shen,Ping Guo,Nengxing Yu,Quanmin Li
Objective: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. Methods: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. Results: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert anti-oxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin–angiotensin–aldosterone system, and promotion of β-cell sensitivity to insulin. Conclusion: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.
研究领域:
药理学
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内分泌学
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Chengyu Cai,Shuohui Gao,Bingmei Wang,Tong Zhao,Hang Gao,Yan Shi,Xuerui Guo,Yueshan Xu,Yun Sun,Dongbin Guo,Jinlong Zhang,Fei Gao,Quan Liu,Zeze Fu,Liang Zhu,Xiaolei Liu,Li Wang,Yicheng Zhao
The rising threat of multidrug-resistant (MDR) pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of novel antiinfective strategies. Staphylococcus aureus ( S. aureus ), a significant foodborne pathogen, secretes virulence factors that are crucial to its pathogenicity. Unlike conventional antibiotics, antivirulence strategies offer a promising approach by targeting these factors without inhibiting bacterial growth, thereby reducing selective pressure for resistance. Among these factors, von Willebrand factor-binding protein (vWbp) is a key contributor to S. aureus pathogenesis, mediating prothrombin activation and subsequent blood coagulation, which is vital for pathogen survival in the host. This study identified astragaloside IV (As-IV) a bioactive compound from traditional Chinese medicine, as a potent inhibitor of vWbp coagulase. As-IV effectively prolongs coagulation time and reduces S. aureus biotic matrix formation on surfaces relevant to food safety, such as catheters, in vitro . Mechanistic studies, including thermal shift assays (TSAs) and fluorescence quenching, revealed that As-IV directly binds to vWbp, attenuating its activity without altering protein expression levels. In vivo , As-IV exhibited protective effects in infection models, underscoring its potential as a virulence-targeted therapeutic. These findings significantly contribute to the advancement of antivirulence strategies and underscore the potential of As-IV in combating S. aureus infections. This paves the way for its broader application in enhancing public health measures and promoting innovative therapeutic approaches.
研究领域:
微生物学
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药理学
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传染病学
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DOI
PubMed
高影响因子
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
·
2018
·
IF 4.841
Suixin Wang,Jiao Jiao,Xinyu Wang,Qingyan Gai,Ping Kou,Wenjing Xu,Meng Luo,Chunjian Zhao,Yu-Jie Fu
Integrated and environmentally friendly methods for extraction and enrichment of natural products have gained increasing interests. The proposed preparation process provides the possibility that extraction and pre-concentration for astragalosides from Radix Astragali roots can be conducted with the surfactant aqueous system in one single procedure. The formulated surfactant system composing of 2% TX-114 as surfactant and 0.03% (w/v) of Gemini 16-5-16 as co-surfactant showed higher extraction efficiency with ultrasonic-assisted method and four astragalosides could be enriched by the cloud point phenomenon of surfactant. This work represents a valuable alternative for the eco-friendly extraction and enrichment of secondary metabolites from plants.
研究领域:
天然产物化学
·
植物化学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Natural Medicines
·
2025
·
IF 2.5
Luo Ye,Xu Chang-jun,Ai Xing-hui,Li Yu-ping,Zhu Xing,Yang Chang-fu
This study aimed to investigate the effects of astragaloside IV(AS-IV) and quercetin (QCT) on autophagic activity, pyroptosis, and epithelial-mesenchymal transdifferentiation (EMT) in the context of idiopathic pulmonary fibrosis (IPF), utilizing both in vivo and in vitro models. In the in vivo component of the research, C57BL/6 J mice were subjected to bleomycin (BLM) modeling, followed by AS-IV + QCT intervention at low, medium, and high doses for 14 and 28 days. Pathological changes in lung tissue were assessed through HE and Masson staining. Additionally, the expression levels of autophagy and pyroptosis-related proteins in serum and bronchoalveolar lavage fluid were examined via Western blot analysis. In the in vitro experiment, RAW264.7 macrophage cells were co-cultured with MLE-12 alveolar epithelial cells (3:1 ratio), implementing BLM and NLR family pyrin domain-containing protein (NLRP3) + BLM models to induce IPF. The effects of AS-IV and QCT on these cells were evaluated by electron microscopy to observe structural changes, while Western blot and ELISA were used to measure the expression of autophagy and pyroptosis-related proteins. Results showed that AS-IV and QCT significantly enhanced autophagic activity, evidenced by increased levels of LC3II and beclin-1 and decreased levels of P62. Additionally, both compounds reduced the expression of pyroptosis-related proteins (NLRP3, Caspase-1, IL-1β, and IL-18) and slowed the progression of EMT in alveolar epithelial cells. These findings propose that AS-IV and QCT inhibit the EMT process in IPF by activating autophagic mechanisms while suppressing pyroptosis, thereby underscoring their potential as innovative therapeutic strategies for IPF and highlighting the promising implications of herbal compounds in its prevention and treatment. Graphical
研究领域:
药理学
·
呼吸病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2016
·
IF 2.551
Xiaochun Luo,Ping Huang,Baohong Yuan,Tao Liu,Fang Lan,Xiaoyan Lu,Liangcheng Dai,Yunjun Liu,Hui Yin
Astragaloside IV (AS-IV), one of the major active compounds extracted from Astragali Radix , has been used experimentally for its potent antiinflammatory and immunoregulatory activities. In this study, we further investigate the potential efficacy of AS-IV on impaired wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was produced on the back of diabetic mice and treated with AS-IV or vehicle topically. Our results showed that AS-IV application promoted diabetic wound repair with wounds gaping narrower and exhibiting augmented reepithelialization . AS-IV enhanced the collagen deposition and the expression of extracellular matrix (ECM)-related genes such as fibronectin and collagen IIIa, which implies a direct effect of AS-IV on matrix synthesis. AS-IV also improved the new blood vessel formation in wound tissue with increased numbers of endothelial cells and enhanced expression of VEGF and vWF. Moreover, the beneficial effect of AS-IV was related to the development of polarized alternatively activated macrophages, which involved in resolution of inflammation and facilitation of wound repair. All together, these findings suggest that AS-IV may play a potential effect on maintenance of cutaneous homeostasis and acceleration of diabetic wound healing.
研究领域:
药理学
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免疫学
·
糖尿病研究
✓ 已验证
DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Xiaoyu Zhu,Fangze Tao,Li Zhang,Yajie Yu,Yanchao Xu,Gang Yang,Zhifeng Wei,Yidong Cheng,Xuelai Yin,Xinyuan Zhang,Wu Wei,Anxi Wang
Aims. Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process. Methods. Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies. Results. Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway. Conclusion. Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way.
研究领域:
药理学
·
泌尿科
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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