PHYTOMEDICINE
·
2023
·
IF 7.9
Yanghao Li,Xu Yang,Tiantian Bao,Xiaojuan Sun,Xiang Li,Huilin Zhu,Bo Zhang,Tonghui Ma
Background The therapeutic efficacy of liver injuries heavily relies on the liver's remarkable regenerative capacity, necessitating the maintenance of glycose/lipids homeostasis and oxidative eustasis during the recovery process. Astragali Radix, an herbal tonic widely used in China and many other countries, is believed to have many positive effects, including immune stimulation, nourishing, antioxidant, liver protection, diuresis, anti-diabetes, anti-cancer and expectorant. Astragali Radix is widely integrated into hepatoprotective formulas as it is believed to facilitate liver regeneration. Nevertheless, the precise molecular pharmacological mechanisms underlying this hepatoprotective effect remain elusive. Purpose To investigate the improving effects of Astragali Radix on liver regeneration and the underlying mechanisms. Methods A mouse model of 70% partial hepatectomy (PHx) was employed to investigate the impact of Radix Astragali decoction (HQD) on liver regeneration. HQD was orally administered for 7 days before the PHx procedure and throughout the experiment. N-acetylcysteine (NAC) was used as a positive control for liver regeneration. Liver regeneration was assessed by evaluating the liver-to-body weight ratio (LW/BW) and the expression of representative cell proliferation marker proteins. Oxidative stress and glucose metabolism were analyzed using biochemical assays, Western blotting, dihydroethidium (DHE) fluorescence, and periodic acid-Schiff (PAS) staining methods. To understand the role of AQP9 as a potential molecular target of HQD in promoting liver regeneration, td-Tomato-tagged AQP9 transgenic mice (AQP9-RFP) were employed to determine the expression pattern of AQP9 protein. AQP9 knockout mice (AQP9 −/− ) were used to assess the specific targeting of AQP9 in the promotion of liver regeneration by HQD. Results HQD significantly upregulated hepatic AQP9 expression, alleviated liver injury and promoted liver regeneration in wild-type (AQP9 +/+ ) mice after 70% PHx. However, the beneficial impact of HQD on liver regeneration was absent in AQP9 gene knockout (AQP9 −/− ) mice. Moreover, HQD facilitated the uptake of glycerol by hepatocytes, enhanced gluconeogenesis, and concurrently reduced H 2 O 2 content and oxidative stress levels in AQP9 +/+ but not AQP9 −/− mouse livers. Additionally, main active substance of Radix Astragali, astragaloside IV (AS-IV) and cycloastragenol (CAG), demonstrated substantial upregulation of AQP9 expression and promoted liver regeneration in AQP9 +/+ but not AQP9 −/− mice. Conclusion This study is the first to demonstrate that Radix Astragali and its main active constituents (AS-IV and CAG) improve liver regeneration by upregulating the expression of AQP9 in hepatocytes to increase gluconeogenesis and reduce oxidative stress. The study revealed novel molecular pharmacological mechanisms of Radix Astragali and provided a promising therapeutic target of liver diseases.
研究领域:
药理学
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肝病学
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分子生物学
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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
✓ 已验证
产品关联
DOI
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2017
·Vol. 183
·期 4
·1488-1502
·
IF 1.751
Wang Liming,Chen Yan
Cycloastragenol (CA), an exclusive telomerase activator, was derived from the Astragali Radix which is widely distributed in Turkey. Until now, there is no report to produce CA with effective and environment-friendly methods. Biotransformation is considered to be a promising technology. Thus, the present study was aimed to establish a biotransformation technology that could efficiently produce CA. In this paper, a microorganism, LG-502, was used to successfully transform astragaloside IV (ASI) to CA by analysis of thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The phylogenetic analysis of the 16S rRNA indicated that this strain belongs to Bacillus sp. Three metabolites were separated during the fermentation and characterized to be cyclogaleginoside B, CA, and 20 R , 24 S -epoxy-6 α , 16 β , 25-trihydroxy-9, 19-cycloartan-3-one based on NMR and MS spectroscopic analyses. The conversion rate of ASI and yield rate of CA were achieved as high as 89 and 84%, respectively, under optimized conditions. Enzymatic analysis showed that the glycosidases were mainly located inside the bacterial body, and the activities of glucosidases were much higher than the xylosidases under the experimental conditions. This study provides a feasible, effective, and eco-friendly way to prepare CA from ASI, which might greatly contribute to the applications of ASI.
研究领域:
药学
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生物技术
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微生物学
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有机化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
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2018
·Vol. 44
·期 2
·251-259
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IF 1.362
Qing Lin-Sen,Chen Ting-Bo,Sun Wen-Xia,Chen Li,Luo Pei,Zhang Zhi-Feng,Ding Li-Sheng
Background and Objectives Astragaloside IV (AGS IV) is the most important bioactive constituent of Radix Astragali. However, its disappointing clinical application is mainly caused by its very low solubility in biologic fluids, resulting in poor bioavailability after oral administration. We recently obtained a novel water-soluble derivative of AGS IV (astragalosidic acid, LS-102) that displayed significant cardioprotective potential against hypoxia-induced injury. The objective of this study was to investigate the intestinal absorption, main pharmacokinetic parameters and acute toxicity of LS-102 in rodents compared with AGS IV. Methods An oral dose of LS-102 and AGS IV (20 mg/kg) was administered to Sprague-Dawley (SD) rats, and blood samples were collected at predetermined time points. The plasma concentrations were detected by a validated UHPLC-MS/MS method, and pharmacokinetic parameters were calculated using a compartmental model. In the intestinal permeability study, the transport of LS-102 across Caco-2 cell monolayers was investigated at six concentrations from 6.25 to 250 µM. Moreover, the acute toxicity of LS-102 (40–5000 mg/kg) via a single oral administration was investigated in BALB/c mice. Results LS-102 was rapidly absorbed, attaining a maximum concentration of 248.7 ± 22.0 ng/ml at 1.0 ± 0.5 h after oral administration. The relative bioavailability of LS-102 was twice that of AGS IV. LS-102 had a P app (mean) of 15.72–25.50 × 10 −6 cm/s, which was almost 500-fold higher than that of AGS IV, showing that LS-102 had better transepithelial permeability and could be better absorbed in the intestinal tract. The acute toxicity study showed no abnormal changes or mortality in mice treated with LS-102 even at the single high dose of 5000 mg/kg body weight. Conclusions Oral LS-102 produced a pharmacokinetic profile different from AGS IV with higher bioavailability, while the toxic tolerance was similar to previous estimates. Thus, we speculated that LS-102 might provide better clinical efficacy and be a potential candidate for the new drug development of Radix Astragali.
研究领域:
药理学
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毒理学
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药学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zong-hui Xu,Man Li,Lin Liu,Shu-jing Wu,Ruo-an Wei,Mpofu Uphakeme Inobubele Sitholumusa,Xiao-ping Zhao,Jun-qiu Liu,Guo-yin Kai
Astragaloside IV (AS-IV), derived from Astragalus membranaceus , exhibits significant anti-inflammatory properties in a variety of diseases. However, the specific anti-inflammatory mechanism of AS-IV depends on the different organs and doses. Its protective effect is still unknown in acute lung injury (ALI). This study aims to investigate the potential anti-inflammatory mechanism of AS-IV in ALI. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were utilized to form pyroptosis models in MH-S and RAW264.7 cells. Mouse model of ALI was induced by intranasal LPS administration. In addition, the anti-pyroptosis effect of AS-IV was evaluated by using the C5aR1 agonists BM-213, the C5aR1 overexpression plasmids and C5aR1 siRNA. AS-IV significantly reduced pulmonary edema, improved histopathological injury, and decreased inflammatory factors. Meanwhile, AS-IV reduced ROS level and the amount of NLRP3 and GSDMD-N in vitro and in vivo . Inhibiting C5aR1 can effectively and significantly alleviate the pyroptosis of alveolar macrophages. Further studies found that BM-213 and C5aR1 overexpression plasmids partially reversed the anti-pyroptosis effect of AS-IV. The anti-pyroptosis effect of AS-IV was significantly inhibited when C5aR1 was knocked down. Our study demonstrate that AS-IV has anti-inflammatory protective effects on LPS-induced ALI, indicating that AS-IV may be a potential therapeutic agent for the treatment of ALI. This effect may be achieved by reducing the content of C5a, lowering the expression of C5aR1, and inhibiting cell pyroptosis.
研究领域:
药理学
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免疫学
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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 Journal of Environmental Science and Technology
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2016
·Vol. 13
·期 10
·2449-2458
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IF 2.344
Shang J. G.,Kong X. R.,He L. L.,Li W. H.,Liao Q. J. H.
Thermally carbonization biochar produced from a traditional Chinese herbal medicine waste ( Astragalus mongholicus residue) was investigated for its performance in ciprofloxacin adsorption. Batch sorption experiments were conducted, and scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and Brunauer–Emmett–Teller surface area analyses were employed to characterize the biochar. The results demonstrated that thermal activation process improves the adsorbent characteristics. Biochar produced at 800 °C had the best adsorption capacity, a better pore structure and the largest surface areas. The adsorption process fit well to a pseudo-second-order kinetics model. The adsorption isothermal model results revealed that the adsorption process of ciprofloxacin is described better by the Freundlich isotherm and the type of adsorption is a chemical process. The maximum adsorption of ciprofloxacin occurred at pH 7. The present research demonstrated that A. mongholicus biochar might be an attractive and cost-effective adsorbent with good adsorption performance for removing ciprofloxacin from water solution.
研究领域:
环境科学
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药用植物学
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产品关联
DOI
高影响因子
ACS Pharmacology & Translational Science
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2024
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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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
·
IF 2.65
Yuan Yue,Xinjun Liu,Lan Pang,Yue Liu,Yuzhu Lin,Ting Xiang,Jie Li,Shiqin Liao,Yunlan Jiang
Delayed wound healing is a common and serious complication in diabetic patients, especially the slow healing of foot ulcers, which seriously affects the quality of life of patients and is also the most important risk factor for lower limb amputation. The multifunctional novel dressing prepared by loading the polymer nanofibers with anti-inflammatory and prohealing plant extracts can promote the wound repair of these ulcers by electrospinning technology. Liposomes are nanoparticles prepared from phospholipids and have been widely used as drug delivery systems. Liposomes can be combined with electrospun nanofibrous webs to facilitate local and sustained delivery of loaded bioactive substances. In this study, liposomes were prepared with astragaloside IV (AS) by employing a modified ethanol injection method and conducting the physical and chemical characterization (e.g., the particle size, polydispersity index, zeta potential, and entrapment efficiency). Astragalus polysaccharides were extracted from Astragalus membranaceus. Subsequently, we prepared the electrospun polyvinyl alcohol (PVA)/astragalus polysaccharide (APS)/astragaloside IV (AS) nanofibers. The morphology of the produced ASL/APS/PVA, APS/PVA, and PVA nanofibers were analyzed by scanning electron microscopy (SEM), and it turns out that the addition of astragalus extract made the fiber diameter smaller and the fibers arranged neatly with no dripping. An induced diabetic rat model was built, and a diabetic ulcer model was built by total cortical resection to assess the prorepair ability of the prepared nanofibers. According to in vivo animal experiments, the nanofibrous membrane loaded with APS and ASL was reported to inhibit the occurrence of wound inflammation, enhance the deposition of collagen fibers () and the repair of regenerated epithelium (), and effectively strengthen the wound healing of diabetic rats (). In brief, PVA-loaded APS/ASL nanofibrous membranes refer to a prominent wound healing dressing material, which can effectively facilitate the healing of diabetic wounds, and they are demonstrated to be highly promising for application in diabetic wound dressings and tissue engineering.
研究领域:
药剂学
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材料科学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
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中药学
·
代谢酶研究
✓ 已验证
DOI
高影响因子
PROCESS BIOCHEMISTRY
·
2014
·
IF 2.524
Wenjie Sui,Hongzhang Chen
Plant extraction occupies a vital status in the fine chemical industry, and steam explosion has been confirmed to be an effective pretreatment to enhance the extraction performance. In order to reveal the extraction enhancing mechanism of steam explosion, innovatively from the view of plant porous medium, we characterized porous properties of steam exploded Radix Astragali and established the correlation of porous properties and saponins extraction performance of Radix Astragali . The results indicated that average pore diameter was the most relevant to extraction parameters with R -square > 0.99 among various porous properties, which can effectively characterize the extraction performance. Area percentage of middle and large pores (100–100,000 nm) of Radix Astragali was increased from 8.25% to 91.57% after steam explosion and the increase of these pores was the major factor for enhancing extraction performance. Based on the close correlation of extraction parameters and porous properties, the extraction mechanistic model of steam exploded Radix Astragali was proposed. Altered porous properties improved the solute–solvent accessibility and internal mass transfer in the extraction process. Such findings are anticipated to prompt the enhancing effects and widespread application of steam explosion technology in plant extraction, and further identify research directions that lead to more efficient extraction.
研究领域:
植物化学
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药用植物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Yong-Gang Xia,Si-Miao Yu,Jun Liang,Bing-You Yang,Hai-Xue Kuang
A generic strategy based on chemical fingerprinting is proposed for the differentiation of polysaccharides from Astragalus membranaceus (AEP) and A. mongholicus (AOP), using multiple chromatographic and mass spectrometric techniques. Complete and mild acid hydrolysis and Smith degradation were employed for the depolymerization of polysaccharides. The corresponding digested products were efficiently separated and detected using GC–MS, HILIC-ELSD and HR-ESI − -MS. The resulting bottom-up fingerprinting reflected the variations in native polysaccharides, which may be attributed to the three structural levels, which are monosaccharide compositions, glycosidic linkages, and skeletal structure. Similarity analysis from GC–MS and HILIC-ELSD fingerprinting showed that the correlation coefficients from homologous species were more than 0.914, whereas those from heterologous species were less than 0.796. It also noted that characteristic peak area ratio of Man/Gal in Smith fingerprinting could be used a feasible parameter for direct discrimination of AEP and AOP. Principal component analysis from m/z fingerprinting data resulted in clear clustering of AEP and AOP based on changes of oligosaccharides in mild acid hydrolyzates. By combining the accurate m/z , ESI − -MS/MS and methylation assays, the structures of a series of hexose glycopolymers in mild acid hydrolyzates were characterized by predominant 1,6 glycosidic linkages along with minor 1,4 glycosidic linkages. The established chemical fingerprinting is not only an interconnected structure mapping but also a powerful approach for the evaluation of polysaccharides from traditional Chinese medicines.
研究领域:
中药学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Horticulturae
·
2023
·Vol. 9
·期 9
·1019
·
IF 3.1
Yuan Zhang,Mina Nan,Huali Xue
Radix Astragali(RA) is the root ofAstragalus membranaceusvar. mongholicus (Bunge) P.K. Hsiao. In order to determine targeted and effective methods for treating mold infections in fresh RA, pathogenic fungi were isolated and identified using morphology and molecular biology techniques, and factors affecting the growth of the pathogenic fungi, such as temperature, pH, light, and carbon and nitrogen sources, were analyzed. Changes in the main active ingredients of RA, such as carbohydrates, flavonoids, and saponins, were detected before and after infection with pathogenic fungi. The results showed thatPenicillium polonicum,Trichothecium roseum, andFusarium equisetiwere the main pathogens causing postharvest disease in fresh RA. The optimum growth temperature for the three pathogens was 25 °C;P. polonicumwas able to grow at an alkaline pH of 8–9, whileT. roseumandF. equisetigrew better and had higher levels of sporulation under acidic conditions with pH values of 5–6. Different carbon and nitrogen sources had different effects on mycelium growth and sporulation. Darkness was favorable for the growth and sporulation of the three pathogens. Compared with healthy RA, the total carbohydrate, flavonoid, and saponin contents of the RA samples infected with the three fungi decreased. This study provides a theoretical basis for the scientific and precise control of RA postharvest disease during storage by targeting different pathogens and their growth conditions.Keywords:Radix Astragali;postharvest disease;identification;biological characteristics;active ingredients
研究领域:
药用植物学
·
真菌学
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植物病理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）