JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2012
·Vol. 65
·期 1
·149-155
·
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
·
中药学
·
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
·
细胞生物学
·
药理学
✓ 已验证
产品关联
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
·
心脏病学
·
肿瘤学
✓ 已验证
DOI
PubMed
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
·
临床医学
·
生物化学
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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
·
传染病学
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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
✓ 已验证
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
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
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
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
Frontiers in Pharmacology
·
2021
·
IF 5.811
Gao Ping,Du Xiaoyi,Liu Lili,Xu Hua,Liu Maochang,Guan Xinlei,Zhang Chengliang
Tacrolimus-induced chronic nephrotoxicity (TIN) hinders its long-term use in patients. However, there are no drugs available in the clinic to relieve it at present. Astragaloside IV (AS-IV) is a saponin extract of the Astragalus which is widely used in the treatment of kidney disease. This study aimed to investigate the effect of AS-IV on TIN and its underlying mechanism. Herein, C57BL/6 mice were treated with tacrolimus and/or AS-IV for 4 weeks, and then the renal function, fibrosis, oxidative stress and p62-Keap1-Nrf2 pathway were evaluated to ascertain the contribution of AS-IV and p62-Keap1-Nrf2 pathway to TIN. Our results demonstrated that AS-IV significantly improved renal function and alleviated tubulointerstitial fibrosis compared with the model group. The expression of fibrosis-related proteins, including TGF-β1, Collagen I and α-SMA, were also decreased by AS-IV. Furthermore, AS-IV relieved the inhibition of tacrolimus on antioxidant enzymes. The data in HK-2 cells also proved that AS-IV reduced tacrolimus-induced cell death and oxidative stress. Mechanistically, AS-IV markedly promoted the nuclear translocation of Nrf2 and the renal protective effects of AS-IV were abolished by Nrf2 inhibitor. Further researches showed that phosphorylated p62 was significantly increased after AS-IV pretreatment. Moreover, AS-IV failed to increase nuclear translocation of Nrf2 and subsequent anti-oxidative stress in HK-2 cells transfected with p62 siRNA. Collectively, these findings indicate that AS-IV relieve TIN by enhancing p62 phosphorylation, thereby increasing Nrf2 nuclear translocation, and then alleviating ROS accumulation and renal fibrosis.
研究领域:
药理学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2015
·Vol. 7
·期 24
·10199-10206
·
IF 1.821
Li Wang,Zhan Zhang,Xinyu Yu,Hongyan Zhao,Xinyue Wu,Xiang Chen,Xinhu Zhou,Lei Li
Mainly consisting of Chinese white spirit and traditional Chinese medicine, Chinese functional spirit is a popular health food in China due to its healthy effects, such as resisting fatigue and enhancing immunity. As one of the major active constituents of Radix Astragali, astragaloside-IV (AGS-IV) commonly exists in Chinese functional spirit. However, the concentration of AGS-IV in this health food is still rarely known. We firstly report an efficient, sensitive and accurate analytical method based on ultra-performance liquid chromatography (UPLC) coupled with quadrupole-orbitrap mass spectrometry (Q Exactive MS) to determine AGS-IV in Chinese functional spirit. Conditions of UPLC and Q Exactive MS were optimized. Sample pre-treatment was done by diluting ten times to weaken the matrix effect. The limit of quantitation and the limit of detection were 0.5 and 0.25 ng mL−1, respectively. The recovery was 92.5–96.7% and the relative standard deviation was 0.8–1.6%. The regression coefficient was 0.9999. In both the selected brands, AGS-IV was at trace levels (76.7 and 59.8 ng mL−1, respectively), which is nearly thousands of times lower than in traditional Chinese medicine extracts. From this analysis method, AGS-IV in Chinese functional spirit for daily health improvement could be clearly determined, and meanwhile it could promote a more scientific and reasonable quality control of Chinese functional spirit rather than detecting the content of total saponins to represent all the efficacy components in it.
研究领域:
中药化学
·
分析化学
·
食品科学
✓ 已验证
产品关联
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2017
·Vol. 38
·期 7
·998-1008
·
IF 3.223
Zhou Bing,Zhou Dan-li,Wei Xiao-hong,Zhong Rong-yu,Xu Jie,Sun Liao
Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not completely understood, the increased influx of free fatty acids (FFAs) into the liver and the FFA-induced hepatic endoplasmic reticulum (ER) stress are two crucial pathogenic processes in the initiation and development of NAFLD. In this study we investigated the effects of astragaloside IV (AS-IV), a bioactive compound purified from Astragali Radix , on FFA-induced lipid accumulation in hepatocytes and elucidated the underlying mechanisms. Human HepG2 cells and primary murine hepatocytes were exposed to FFAs (1 mmol/L, oleate/palmitate, 2:1 ratio) with or without AS-IV for 24 h. Exposure to FFAs induced marked lipid accumulation in hepatocytes, whereas co-treatment with AS-IV (100 μg/mL) significantly attenuated this phenomenon. Notably, AS-IV (50–200 μg/mL) concentration-dependently enhanced the phosphorylation of AMPK, acetyl-CoA carboxylase (ACC) and SREBP-1c, inhibited the accumulation and nuclear translocation of mature SREBP-1 and subsequently decreased the mRNA levels of lipogenic genes including acc1 , fas and scd1 . AS-IV treatment also concentration-dependently attenuated FFA-induced hepatic ER stress evidenced by the reduction of the key markers, GRP78, CHOP and p-PERK. Pretreated the cells with the AMPK inhibitor compound C (20 μmol/L) greatly diminished these beneficial effects of AS-IV. Our results demonstrate that AS-IV attenuates FFA-induced ER stress and lipid accumulation in an AMPK-dependent manner in hepatocytes, which supports its use as promising therapeutics for hepatic steatosis.
研究领域:
药理学
·
肝病学
·
细胞生物学
·
代谢疾病
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）