Liposomal Oxymatrine in Hepatic Fibrosis Treatment: Formulation, In Vitro and In Vivo Assessment

Zhang, Shujuan; Wu, Jun; Wang, Hua; Wang, Tiechuang; Jin, Lina; Shu, Dandan; Shan, Wei‐Guang; Xiong, Sheng

doi:10.1208/s12249-014-0086-y

Cited by 23 publications

(10 citation statements)

References 27 publications

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“…Oxymatrine (OMT) has numerous pharmacological activities 27 – 31 in cardiovascular protection 32 and anti-cancer properties 33 – 35 via suppression of tumor growth and invasion, induction of cycle arrest and apoptosis, and reduction of chemotherapy-induced cell toxicity. 36 We previously confirmed the inhibitory effects of OMT on vascular and lymph node invasion in GC.…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine exhibits anti-tumor activity in gastric cancer through inhibition of IL-21R-mediated JAK2/STAT3 pathway

Huang

Zhang

Wang

et al. 2018

Int J Immunopathol Pharmacol

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Oxymatrine (OMT) as a type of alkaloids collected from Sophora flavescens Ait exerts some biological functions including anticancer properties. Here, we investigated the therapeutic effects of OMT in gastric cancer cells (HGC 27 and AGS). As a result, the exposure of gastric cancer (GC) cells to OMT contributed to the suppression of cell proliferation and invasion. Interleukin 21 receptor (IL-21R) was identified to be differentially expressed between OMT treatment group (4 mg/mL) and control group (0 mg/mL), and knockdown of IL-21R repressed cell proliferation and invasion via inactivation of the JAK2/STAT3 pathway. The rescue experiment showed that IL-21R overexpression attenuated the anti-tumor effects of OMT through activation of the JAK2/STAT3 pathway. Moreover, the expression of IL-21R was significantly upregulated in GC samples compared with the adjacent normal tissues and associated with overall survival (OS) and tumor recurrence of GC patients. Taken together, in this study, we evaluated the anti-tumor effects of OMT on GC by investigating proliferation and invasion ability changes, and our findings show that OMT exhibits effects via regulation of JAK/STAT signaling pathway. Through the mechanism study, we may enlighten the potential therapeutic target for treatment of GC.

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Section: Introductionmentioning

confidence: 99%

Oxymatrine exhibits anti-tumor activity in gastric cancer through inhibition of IL-21R-mediated JAK2/STAT3 pathway

Huang

Zhang

Wang

et al. 2018

Int J Immunopathol Pharmacol

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“…Liver fibrosis is a common pathological process of all chronic liver diseases, which can be caused by a number of factors, including long-term alcohol abuse, viral infection, fatty liver disease, metabolic disease, and cholestasis[1,2]. The mechanisms of liver fibrosis and cirrhosis are considered similar; fibrosis occurs via a non-specific mechanism involving excessive accumulation of extracellular matrix proteins, including collagen.…”

Section: Introductionmentioning

confidence: 99%

Dynamic changes of key metabolites during liver fibrosis in rats

Chen

et al. 2019

WJG

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BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease. Established non-invasive tests for monitoring fibrosis are lacking, and new biomarkers of liver fibrosis and function are needed. AIM To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression. METHODS CCl 4 was used to establish the rat liver fibrosis model. Liver fibrosis process was measured by liver chemical tests, liver histopathology, and Masson’s trichrome staining. The expression levels of two fibrotic markers including α-smooth muscle actin and transforming growth factor β1 were assessed using immunohistochemistry and real-time polymerase chain reaction. Dynamic changes in metabolic proﬁles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS To investigate the dynamic changes of metabolites during the process of liver fibrosis, sera from control and fibrosis model rats based on pathological results were analyzed at five different time points. We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine, L-threonine, indoleacrylic acid, β-muricholic acid (β-MCA), cervonoyl ethanolamide (CEA), phosphatidylcholines, and lysophosphatidylcholines. Two metabolites, CEA and β-MCA, differed significantly in the fibrosis model rats compared to controls ( P < 0.05) and showed prognostic value for fibrosis. ROC curve analyses performed to calculate the area under the curve (AUC) revealed that CEA and β-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8, and can clearly differentiate early stage from late stage fibrosis or cirrhosis. CONCLUSION This study identified two novel biomarkers of fibrosis, CEA and β-MCA, which were effective for diagnosing fibrosis in an animal model.

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“…The deposition of ECM proteins substitute for functional tissues and disrupt the normal liver architecture, which in turn leads to pathophysiological damage ( 2 ). The primary causes of liver fibrosis include chronic high alcohol ingestion and infection with hepatitis B and C. Less common causes include viral infection, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, helminth infection, autoimmune diseases and nonalcoholic steatohepatitis ( 3 ). Hepatic fibrosis is a vital stage that occurs during the development of chronic liver disease.…”

Section: Introductionmentioning

confidence: 99%

Detecting serum and urine metabolic profile changes of CCl4-liver fibrosis in rats at 12 weeks based on gas chromatography-mass spectrometry

Gao

Qin

Jiang

et al. 2017

Experimental and Therapeutic Medicine

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Liver fibrosis is caused by liver injury induced by a number of chronic liver diseases, including schistosome infection, hepatitis infection, metabolic disease, alcoholism and cholestasis. The tissue damage occurring after injury or inflammation of the liver is a reversible lesion; however, liver fibrosis has become a worldwide problem and poses a threat to human health. The development of an effective drug for the prevention and treatment of liver fibrosis is ongoing and uses information from different occurrences of liver fibrosis. In the present study, carbon tetrachloride (CCl4)-induced metabonomic changes in serum and urine at 12 weeks were analyzed using gas chromatography-mass spectrometry (GC/MS) to investigate potential biomarkers. Liver fibrosis was induced in rats by subcutaneous injections of CCl4 twice a week for 12 consecutive weeks. Histopathological changes were used to assess the successful production of a CCl4-induced liver fibrosis model. Serum and urine samples from the two groups were collected at 12 weeks. The metabolic profile changes were analyzed by GC/MS alongside principal component analysis and orthogonal projections to latent structures. Metabolic profile studies indicated that the clustering of the two groups could be separated and seven metabolites in serum and five metabolites in urine were identified. In serum, the metabolites identified included isoleucine, L-malic acid, α-copper, carnitine, hippuric acid, glutaric acid and glucose. In urine 2-hydroxy butyric acid, isoleucine, N-acetyl-β-alanine, cytidine and corticoid were identified. The present study demonstrated that the pathogenesis of liver fibrosis may be associated with the dysfunction of a number of metabolic pathways, including glucose, amino acid, P450, fatty acid, nucleic acid, water-electrolyte and glutathione biosynthesis. Assessing potential biomarkers may therefore provide novel targets and theories for the innovation of novel drugs to prevent and cure liver fibrosis.

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Liposomal Oxymatrine in Hepatic Fibrosis Treatment: Formulation, In Vitro and In Vivo Assessment

Cited by 23 publications

References 27 publications

Oxymatrine exhibits anti-tumor activity in gastric cancer through inhibition of IL-21R-mediated JAK2/STAT3 pathway

Oxymatrine exhibits anti-tumor activity in gastric cancer through inhibition of IL-21R-mediated JAK2/STAT3 pathway

Dynamic changes of key metabolites during liver fibrosis in rats

Detecting serum and urine metabolic profile changes of CCl4-liver fibrosis in rats at 12 weeks based on gas chromatography-mass spectrometry

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