Study of pharmacokinetic profiles and characteristics of active components and their metabolites in rat plasma following oral administration of the water extract of Astragali radix using UPLC–MS/MS

Shi, Jian; Zheng, Liang; Lin, Zhufen; Hou, Chuqi; Liu, Wenqin; Yan, Tingting; Zhu, Lijun; Wang, Ying; Lu, Linlin; Liu, Zhongqiu

doi:10.1016/j.jep.2015.04.019

Cited by 70 publications

(53 citation statements)

References 41 publications

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“…This pathway mainly causes low bioavailability of isoflavonoid glucosides. However, in our previous study, we found that the absorption characteristic of the main isoflavonoid glucoside in Astragali Radix differs from that of other soy isoflavonoid glucosides (Shi et al, 2015).…”

Section: Introductionmentioning

confidence: 71%

“…CG, calycosin, and daidzin ($98%, HPLC grade) were purchased from Chengdu Must Biotechnology Co., Ltd. (Chengdu, China) and used to prepare standard solutions of phase II metabolites in our laboratory (Shi et al, 2015). Glucurolactone, CaCl 2 , MgSO 4 , KCl, KH 2 PO 4 , NaCl, Na 2 HPO 4 , NaHCO 3 , DMSO, uridine diphosphate glucuronic acid, alamethicin, MgCl 2 , MK571, ko143, D-saccharic-1,4-lactone monohydrate, HEPES, and Hanks' balanced salt solution (HBSS) were purchased from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group studied the pharmacokinetic profiles of the active components of Astragali Radix and found that CG and its glucuronide were rapidly absorbed, with a peak concentration of about 100 ng/ml, after oral administration of the water extract of this herb (Shi et al, 2015). This suggested that CG could traverse the enterocytes intact.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O- -D-Glucoside in Rats

Shi

Zheng

et al. 2015

Drug Metabolism and Disposition

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Hydrolysis by lactase-phloridzin hydrolase (LPH) is the first and critical step in the absorption of isoflavonoid glucosides. However, the absorption characteristics of calycosin-7-O-b-D-glucoside (CG) slightly differ from other isoflavonoid glucosides. In this study, we used the rat intestinal perfusion model and performed pharmacokinetic studies and in vitro experiments to determine the factors influencing CG absorption and disposition. After oral administration of isoflavonoid glucosides, LPH was found to play minimal or no role on the hydrolysis of CG, in contrast to that of daidzin. CG was mainly transported into the small intestinal cells by sodium-dependent glucose transporter 1 (SGLT-1) as intact. This pathway could be the main mechanism underlying the high permeability of CG in the small intestine. CG was likely to be hydrolyzed in enterocytes to its aglycone calycosin by broad-specific b-glucuronides (BSbG) and glucocerebrosidase or rapidly metabolized. Calycosin was also rapidly and extensively metabolized to 39-glucuronide in the enterocytes and liver, and the glucuronidation rates of calycosin and CG were much higher in the former. The metabolites were also transported into lumen by breast cancer resistance protein and multidrug resistance-associated protein 2. In conclusion, the enterocytes could be an important site for CG absorption, deglycosylation, and metabolism in rats. This study could contribute to the theoretical foundation and mechanism of absorption and disposition of flavonoid compounds.

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Section: Introductionmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O- -D-Glucoside in Rats

Shi

Zheng

et al. 2015

Drug Metabolism and Disposition

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“…The main active metabolites in SYFSF probably include astragaloside IV [24], ferulic acid [25], emodin [26], angelica [27], and astragalus polysaccharide (APS) [28, 29], which have showed anti-inflammation, antioxidant, and controlling lipid effects in many studies, respectively. Therefore, SYFSF likely works through polypharmacology and network pharmacology to produce an overall systemic effect.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective Effect of the Shen-Yan-Fang-Shuai Formula by Inhibiting TNF-α/NF-κB Signaling Pathway in Diabetic Rats

Wang

et al. 2017

Journal of Diabetes Research

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Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and satisfactory therapeutic strategies have not yet been established. The Shen-Yan-Fang-Shuai Formula (SYFSF) is a traditional Chinese formula composed of Astragali radix, Radixangelicae sinensis, Rheum officinale Baill, and four other herbs. It has been widely used as an effective treatment for DKD patients in China. However, little is known about the molecular mechanisms underlying SYFSF's renoprotection. In this study, we compared the protective effect of SYFSF to irbesartan on the histology and renal cells in type 2 DKD rat model and high-glucose (HG) cultured mesangial cells, respectively. We found that SYFSF could significantly decrease urinary albumin, cholesterol, and triglyceride. And a decrease in serum creatinine was also found in SYFSF-treated group compared with irbesartan-treated rats. In addition, SYFSF inhibited the interstitial expansion and glomerulosclerosis in diabetic rats. Notably, SYFSF markedly downregulated the expression of MCP-1, TGF-β1, collagen IV, and fibronectin in diabetic rat models and HG-induced mesangial cell models. The renoprotection was closely associated with a reduced expression of TNF-α and phosphorylated NF-κBp65. Our study suggests that SYFSF may ameliorate diabetic kidney injury. The observed renoprotection is probably attributable to an inhibition of inflammatory response and extracellular matrix (ECM) accumulation mediated by TNF-α/NF-κBp65 signaling pathway.

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“…Astragali Radix , the monarch drug of PRM, is reported to possess several medicinal functions including antitumor, immunostimulating and antiaging effects 10, 11 . In addition, the isoflavonoid compounds of PRM, such as calycosin, calycosin-7-O-glucoside, formononetin, ononin and mangiferin, are effective medicinal ingredients due to their pharmacological activities and therapeutic efficacies 12–15 .…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic and pharmacokinetic assessment of pulmonary rehabilitation mixture for the treatment of pulmonary fibrosis

Zhao

Ren

et al. 2017

Sci Rep

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Pulmonary rehabilitation mixture (PRM), a Chinese herbal medicine formula, has been used to treat pulmonary fibrosis for decades. In this study, we systematically evaluated the pharmacodynamic and pharmacokinetic performance of PRM. The pharmacodynamic results showed that PRM could improve the condition of CoCl2-stimulated human type II alveolar epithelial cells, human pulmonary microvascular endothelial cells, human lung fibroblasts and pulmonary fibrosis rats induced by bleomycin, PRM treatment reduced the expression of platelet-derived growth factor, fibroblast growth factor, toll-like receptor 4, high-mobility group box protein 1 and hypoxia-inducible factor 1α. In the pharmacokinetic study, an accurate and sensitive ultra-high performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of calycosin, calycosin-7-O-glucoside, formononetin, ononin and mangiferin of PRM in the rat plasma for the first time. The method was then successfully applied to the comparative pharmacokinetic study of PRM in normal and pulmonary fibrosis rats. The five constituents could be absorbed in the blood after the oral administration of PRM and exhibited different pharmacokinetic behaviors in normal and pulmonary fibrosis rats. In summary, PRM exhibited a satisfactory pharmacodynamic and pharmacokinetic performance, which highlights PRM as a potential multi-target oral drug for the treatment of pulmonary fibrosis.

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Study of pharmacokinetic profiles and characteristics of active components and their metabolites in rat plasma following oral administration of the water extract of Astragali radix using UPLC–MS/MS

Cited by 70 publications

References 41 publications

SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O- -D-Glucoside in Rats

SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O- -D-Glucoside in Rats

Renoprotective Effect of the Shen-Yan-Fang-Shuai Formula by Inhibiting TNF-α/NF-κB Signaling Pathway in Diabetic Rats

Pharmacodynamic and pharmacokinetic assessment of pulmonary rehabilitation mixture for the treatment of pulmonary fibrosis

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