Wogonoside has anticoagulant, anti-inflammatory, anti-angiogenic and anticancer effects, it may exert its anti-inflammatory effect via dual inhibition of NF-κB and NLRP3 inflammasome. Wogonoside induced autophagy through the MAPK-mTOR pathway, it inhibited LTB 4 production at the concentration of 100 uM.
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Toxicology. 2009 May 2;259(1-2):10-7.
Wogonoside inhibits lipopolysaccharide-induced angiogenesis in vitro and in vivo via toll-like receptor 4 signal transduction.[Pubmed: 19428938
Wogonoside, one flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported for its anti-inflammation activity; however, whether it can inhibit inflammation-induced angiogenesis is still unclear.
METHODS AND RESULTS:
In the present study, we evaluated the effect of Wogonoside on lipopolysaccharide (LPS)-induced angiogenesis in vitro and in vivo. Wogonoside suppressed the LPS-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as microvessel sprouting from rat aortic rings in vitro. Moreover, Wogonoside also inhibited LPS-stimulated vessel growth of Chicken chorioallantoic membrane (CAM) in vivo. The mechanism revealed that Wogonoside inhibited LPS-induced toll-like receptor 4 (TLR4) up-regulation and its downstream mitogen-activated protein kinases (MAPKs) activation, by decreasing the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase.
The results suggest that Wogonoside inhibits LPS-induced angiogenesis both in vitro and in vivo, and that it might have a therapeutic potential for the diseases associated with the development of both inflammation and angiogenesis progress.
Food Chem Toxicol. 2013 Jan;51:53-60.
Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway.[Pubmed: 23000445
Previous studies have demonstrated that Wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory and anti-angiogenic activities.
METHODS AND RESULTS:
In this study, we evaluated Wogonoside-induced autophagy on human breast MDA-MB-231 cells. We report that Wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells. In addition, cells treated by Wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris. The results showed that Wogonoside promotes the expression of LC3-II and Beclin-1. Furthermore, Wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration- and time-dependent manner, which was associated with Wogonoside-induced autophagy. Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway.
Taken together, these results suggest that Wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.
Biochem Pharmacol. 2015 Mar 15;94(2):142-54.
Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB and NLRP3 inflammasome activation.[Pubmed: 25677765
Previous studies have demonstrated that Wogonoside, the glucuronide metabolite of wogonin, has anti-inflammatory, anti-angiogenic and anticancer effects. However, the anti-inflammatory mechanism of Wogonoside has not been fully elucidated. Recently, NLRP3 inflammasome has been reported to be correlated with inflammatory bowel disease for its ability to induce IL-1β release. Nevertheless, there are few drug candidates targeting NLRP3 inflammasome for this disease.
METHODS AND RESULTS:
In this study, we investigated the anti-inflammatory effect of Wogonoside in dextran sulfate sodium (DSS)-induced murine colitis and further revealed the underlying mechanisms by targeting NF-κB and NLRP3 inflammasome. Wogonoside treatment dose-dependently attenuated DSS-induced body weight loss and colon length shortening. Moreover, Wogonoside prevented DSS-induced colonic pathological damage, remarkably inhibited inflammatory cells infiltration and significantly decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities. The production of pro-inflammatory mediators in serum and colon was also significantly reduced by Wogonoside. The underlying mechanisms for the protective effect of Wogonoside in DSS-induced colitis may be attributed to its inhibition on NF-κB and NLRP3 inflammasome activation in colons. Furthermore, Wogonoside markedly decreased production of IL-1β, TNF-α and IL-6 and suppressed mRNA expression of pro-IL-1β and NLRP3 in phorbol myristate acetate (PMA)-differentiated monocytic THP-1 cells via inhibiting the activation of NF-κB and NLRP3 inflammasome.
In conclusion, our study demonstrated that Wogonoside may exert its anti-inflammatory effect via dual inhibition of NF-κB and NLRP3 inflammasome, suggesting that Wogonoside might be a potential effective drug for inflammatory bowel diseases.
Blood. 2013 May 2;121(18):3682-91.
Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells.[Pubmed: 23487022
Wogonoside is the main flavonoid component derived from the root of Scutellaria baicalensis Georgi. It is a popular Chinese herbal medicine with the potential to treat hematologic malignancies.
METHODS AND RESULTS:
In this study, we investigated the anticancer effects of Wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted antiproliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through the induction of G1 phase arrest and the promotion of differentiation. We also demonstrated that Wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle- and differentiation-related genes, including the upregulation of p21waf1/cip1 and downregulation of the oncogenic protein c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1,4,5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked Wogonoside-induced cell cycle arrest and differentiation and disturbed the Wogonoside-associated molecular events.
The results of this study therefore suggest that Wogonoside may represent a therapeutic candidate for the treatment of AML.
Fitoterapia. 2014 Oct;98:27-35.
Antithrombotic activities of wogonin and wogonoside via inhibiting platelet aggregation.[Pubmed: 25020199
Wogonin (WGN), a flavonoid extracted from Scutellaria baicalensis Georgi, has several biological effects including antioxidant, anti-inflammatory, antiviral, neuroprotective, anxiolytic, and anticancer activities, and the flavonoid Wogonoside (WGNS) can be derived from S. baicalensis, as it is a metabolite of wogonin.
METHODS AND RESULTS:
Here, the anticoagulant activities of WGN(S) were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin (factor IIa, FIIa) and activated factor X (FXa), and the effects of WGN(S) on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis factor (TNF)-α activated human umbilical vein endothelial cells (HUVECs). Treatment with WGN(S) resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, as well as inhibited production of thrombin and FXa in HUVECs. In addition, WGN(S) inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. WGN(S) also elicited anticoagulant effects in mice. In addition, treatment with WGN(S) resulted in significant reduction of the PAI-1 to t-PA ratio.
Collectively, WGN(S) possesses antithrombotic activities and offers a basis for development of a novel anticoagulant.
Inflammation. 2014 Dec;37(6):2006-12.
Wogonoside ameliorates lipopolysaccharide-induced acute lung injury in mice.[Pubmed: 24854163
Wogonoside has been reported to have anti-inflammatory properties. In this study, we evaluated the effect of Wogonoside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
METHODS AND RESULTS:
Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated with Wogonoside 1 h prior to LPS exposure. Mice treated with LPS alone showed significantly increased TNF-α, IL-6, and IL-1β levels in the bronchoalveolar lavage fluid (BALF). When pretreated with Wogonoside, the TNF-α, IL-6, and IL-1β levels were significantly decreased. Meanwhile, Wogonoside significantly inhibited LPS-induced increases in the macrophage and neutrophil infiltration of lung tissues and markedly attenuated myeloperoxidase activity. Furthermore, Wogonoside inhibited the TLR4 expression and the phosphorylation of NF-κB p65, and IκB induced by LPS.
In conclusion, our results indicate that Wogonoside exhibits a protective effect on LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways.