JOURNAL OF SEPARATION SCIENCE
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2020
·Vol. 43
·期 12
·2290-2300
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IF 2.878
Guanghui Ren,Huili Chen,Mei Zhang,Nan Yang,Hui Yang,Chuanru Xu,Jiaming Li,Chen Ning,Zhongjin Song,Shiyu Zhou,Siliang Zhang,Xiaoqian Wang,Yang Lu,Ning Li,Yongjie Zhang,Xijing Chen,Di Zhao
Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi , is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra-high-performance liquid chromatography–tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0–500.0, 5.0–500.0, and 1.881–940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate after single-dose intravenous and oral administration of Oroxylin A in beagle dogs.
研究领域:
药物分析
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药理学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2020
·
IF 2.527
Guanghui Ren,Huili Chen,Mei Zhang,Nan Yang,Hui Yang,Chuanru Xu,Jiaming Li,Chen Ning,Zhongjin Song,Shiyu Zhou,Yueying Bian,Yang Lu,Ning Li,Yongjie Zhang,Xijing Chen,Di Zhao
Oroxylin A (OA), as a natural flavonoid extracted from the root of Scutellaria baicalensis Georgi, is a candidate drug with multiple pharmacological activities . However, pharmacokinetic studies of OA have rarely been reported up to now. The present study aim to conduct a systemic evaluation on the pharmacokinetics, tissue distribution and excretion of OA in rats, with quantification of both OA and its two metabolites, Oroxylin A 7-O-glucuronide (OG) and Oroxylin A sodium sulfonate (OS) by the sensitive and rapid UPLC-MS/MS methods. The results show that OA was rapidly eliminated in vivo after a single–dose (2 mg/kg) i.v. administration of OA. The relative bioavailability of OA in all three i.g. administration groups (40, 120, and 360 mg/kg) were <2%. The AUC 0−t values of OA, OG, and OS in rats show an apparent dose-proportionality. OA, OG, and OS all underwent a rapid and widespread tissue distribution after i.g. administration (120 mg/kg) of OA. Except for stomach and intestine, the major distribution tissues of OA and its two metabolites in rats were liver, kidney, respectively. And OA was more widely distributed in tissue than its metabolites. After i.g. administration (120 mg/kg) of OA, it was mainly excreted from the feces, and OG mainly excreted from bile and urine, while OS almost free of excretion. This work present a comprehensive pharmacokinetics information for further investigation of OA and its two metabolites.
研究领域:
药理学
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中药学
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DOI
高影响因子
FEBS LETTERS
·
2016
·Vol. 590
·期 16
·2619-2628
·
IF 3.519
Yu-Ying Zhang,Rui-Xue Xu,Shuai Gao,Ai-Xia Cheng
Oroxylin A and hispidulin, compounds which are abundant in both Scutellaria and liverwort species, are important lead compounds for the treatment of ischemic cerebrovascular disease. Their enzymatic synthesis requires an O -methyltransferase able to interact with the related flavonoid's 6-OH group, but such an enzyme has yet to be identified in plants. Here, the gene encoding an O -methyltransferase (designated PaF6OMT) was isolated from the liverwort species Plagiochasma appendiculatum . A test of alternative substrates revealed that its strongest preferences were baicalein and scutellarein, which were converted into, respectively, oroxylin A and hispidulin. Allowed a sufficient reaction time, the conversion rate of these two substrates was, respectively, 90% and 100%. PaF6OMT offers an enzymatic route to the synthesis of oroxylin A and hispidulin.
研究领域:
植物学
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生物化学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2023
·
IF 2.4
Jinxia ZHU,Hongxiu CHEN,Jianjiao CUI,Xiaorui ZHANG,Guangwei LIU
Autoimmune hepatitis (AIH) is a kind of autoimmune disease mediated by T cells, and its incidence is gradually increasing in the world. Oroxylin A (OA) is one of the major bioactive flavonoids that has been reported to inhibit inflammatory. Here, an AIH model of mouse was induced by Concanavalin A (Con A). It found that serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in mice with the treatment of OA. Hematoxylin-eosin staining showed that the liver injury was attenuated by OA, and TUNEL staining indicated that the cells apoptosis of liver was weakened in mice with OA treatment. ELISA analysis of cytokines and chemokines suggested that OA reduced the expression of IL-6, IL-17A, CCL2, CXCL1 and CXCL10, but promoted the expression of IL-10 and TGF-β in mice. The mRNA levels of IL-17A in liver and spleen tissues were also significantly decreased, on the contrary, the mRNA levels of IL-10 in liver and spleen tissues were increased. The proportion of Treg/Th17 detected by flow cytometry revealed that OA promoted the differentiation of Treg and inhibited the differentiation of Th17 both in the liver and spleen. The results of this study demonstrated the inhibitory effects of OA on AIH-induced liver injury and the inflammatory response of AIH, and revealed that OA affected the balance of Treg/Th17 and shifted the balance toward Treg differentiation. It provided new potential drugs for the prevention of AIH.
研究领域:
免疫学
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药理学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
·
2026
·Vol. 32
·期 6
·113529
·
IF 7.7
Mei-Yuan Zhang,Rui-Qian Sun,Qi Min,Yu-Qi Zhu,Shu-Kui Qin,Qing-Long Guo
BACKGROUND The clinical application of donafenib in advanced hepatocellular carcinoma (HCC) is restricted by its limited therapeutic efficacy and a variety of treatment-associated adverse events. These factors collectively underscore the need for more effective and well-tolerated therapeutic strategies. AIM To investigate the effects and underlying mechanisms of oroxylin A in combination with donafenib on HCC through in vivo and in vitro studies. METHODS The antitumor efficacy of oroxylin A, donafenib, and their combination was assessed in xenograft mouse models and MHCC-97H/PLC-PRF-5 cell lines. Tumor growth was monitored using fluorescence live imaging. Cell viability, colony formation, and apoptosis were assessed using Cell Counting Kit-8, clonogenic, and flow cytometry assays, respectively. Molecular mechanisms were investigated by assessing the expression of tumor protein p53 (TP53) signaling-related regulators via quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry. Public datasets and Kaplan-Meier analysis were used to analyzed the relationship between their expression and patient survival. RESULTS The combination of oroxylin A and donafenib demonstrated superior anti-tumor efficacy in vivo compared to monotherapies, without inducing significant hepatorenal toxicity. The combination therapy demonstrated a stronger anti-proliferative and pro-apoptotic effects than two monotherapies in two HCC cell lines. Mechanistically, the drug combination synergistically activated the TP53 signaling pathway. Oroxylin A primarily targeted the cyclin-dependent kinase 9-murine double minute 2 (MDM2)/MDM4 axis to stabilize TP53, while donafenib suppressed the vascular endothelial growth factor receptor/B-rapidly accelerated fibrosarcoma proto-oncogene serine/threonine kinase axis to activate TP53. Clinical data has verified that the upregulation of key components of this pathway (TP53, MDM2, MDM4, and cyclin-dependent kinase 9) in patients with HCC is associated with a poor overall survival. CONCLUSION Oroxylin A and donafenib exert a synergistic anti-tumor effect in HCC by co-activating the TP53 signaling pathway through distinct but complementary molecular axes. This combination strategy presents a promising and viable therapeutic approach to overcome the limitations of donafenib monotherapy in the treatment of HCC.
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2020
·
IF 1.813
Jingtian Qu,Fang Liu,Xuezhu Zhang,Jialong Wang
Oroxylin A, a flavonoid, is naturally produced in many medicinal plants. Our previous study identified it as a phytoestrogen. Based on this, the present study investigated its vasoconstriction reducing effects and whether the action was mediated by the estrogen receptor (ER) signal pathway. Long-term in vitro treatment with oroxylin A reduced Ach-induced vasorelaxation and NE-mediated or KCl-mediated contractile responses in rat aortic rings. These effects were interfered by an ER inhibitor ICI 182,780. Rat cardiac microvascular endothelial cells (CMECs) and aortic vascular smooth muscle cells (VSMCs) were used to study the possible underlying mechanisms. Oroxylin A activated the ER signal pathway. In CMECs, it increased NO production and eNOS protein expression. In VSMCs, it promoted NO production and iNOS protein expression. These effects were also inhibited by ICI 182,780. Besides, oroxylin A stimulated ERα and ERβ protein expression in CMECs and VSMCs. All these findings suggest that the ER signal pathway takes part in the vasoconstriction reducing effects of oroxylin A.
研究领域:
药理学
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心血管研究
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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