Concentrations Of Matrine Research Articles

Matrine attenuating cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity through improved mitochondrial membrane potential and activation of mitochondrial respiratory chain Complex I pathway

The study aimed to demonstrate that matrine can reduce apoptosis in H9c2 cells induced by the cardiotoxic anticancer drug doxorubicin (DOX).The researchers pretreated H9c2 cells with different concentrations of matrine before exposing them to DOX and cultured them for 24 h. They assessed cell survival rates using cell counting kit-8 and MTT assay. Hoechst 33258 dye kits were used to determine apoptosis, while laser confocal JC-1 method was applied to test the mitochondrial membrane potential (MMP). Complex I activities were detected following the manufacturer's protocol. The results indicated that matrine pretreatment significantly increased the survival rate of H9c2 cells injured by DOX. Additionally, matrine reduced apoptosis in H9c2 cells through the improvement of MMP and activity of Complex I, which were damaged by DOX.

Matrine Targets BTF3 to Inhibit the Growth of Canine Mammary Tumor Cells.

The canine mammary tumor model is more suitable for studying human breast cancer, and the safety concentrations of matrine and the biotin-labeled matrine probe were determined in canine primary mammary epithelial cells, and then selected canine mammary tumor cell lines CHMm and CHMp were incubated with matrine, and cell viability was detected by CCK-8. The biotin-labeled matrine probe was used to pull-down the targets of matrine in canine mammary tumor cells, and the targets were screened in combination with activity-based protein profiling (ABPP) and Genecards database, and verified by qPCR and western blot. The results showed that the maximum non-cytotoxic concentrations of matrine and biotin-labeled matrine probe in canine primary mammary epithelial cells were 250 μg/mL and 500 μg/mL, respectively. Matrine and biotin-labeled matrine probe had a proliferation inhibitory effect time-dependently on CHMm and CHMp cells within a safe concentration range, and induced autophagy in cells. Then BTF3 targets were obtained by applying ABPP and Genecards screening. Cellular thermal shift assay (CETSA) findings indicated that matrine could increase the heat stability of BTF3 protein. Pull-down employing biotin-labeled matrine probe with CHMm and CHMp cell lysates revealed that BTF3 protein was detected in the biotin-labeled matrine probe group and that BTF3 protein was significantly decreased by the addition of matrine. The qPCR and western blot findings of CHMm and CHMp cells treated with matrine revealed that matrine decreased the expression of the BTF3 gene and protein with the extension of the action time, and the impact was more substantial at the protein level, respectively.

Matrine exerts an anti-tumor effect via regulating HN1 in triple breast cancer both in vitro and in vivo.

The treatment of triple-negative breast cancer (TNBC) cannot meet medical needs, and it is urgent to find new drugs for intervention. This study aimed to investigate the anti-tumor effect of matrine on the proliferation and apoptosis of TNBC cells based on HN1 regulation in vitro and in vivo. TNBC cell lines (MDA-MB-453 and HCC-1806) were treated with varying concentrations of matrine (0, 1.0, 2.0, 3.0, 4.0, and 5.0 mM). CCK-8, colony formation assay, transwell assay, and flow cytometry assay were employed to detect proliferation, clone formation, invasion, and apoptosis of TNBC cells. Western blot analysis was applied to detect the protein expression of apoptosis HN1. The effects of matrine on tumor growth, protein expression of HN1, and apoptosis in vivo were validated by xenograft tumor models and histology. It was found that matrine inhibited proliferation, colony formation, and invasion and promoted apoptosis of TNBC cells in vitro. HN1 expression was suppressed by matrine. HN1 overexpression perceptibly reversed the above-mentioned additive effect in vitro. In vivo experiments found that matrine inhibited tumor growth and the expression of HN1 protein but promoted the protein expression of Cleared-Caspase-3. Above all, this study demonstrated that matrine inhibited proliferation and promoted apoptosis of TNBC cells via suppressing HN1 expression. Targeting HN1 by matrine may provide new insights into the therapeutic management of patients with TNBC.

Matrine inhibits inflammatory response induced by TNF-α in human umbilical vein endothelial cells through miR-25-3p-mediated Klf4 pathway

This study aimed to analyze the effect of matrine on tumor necrosis factor-α(TNF-α)-induced inflammatory response in human umbilical vein endothelial cells(HUVECs) and explore whether the underlying mechanism was related to the miR-25-3p-mediated Krüppel-like factor 4(Klf4) pathway. The HUVEC cell inflammation model was induced by TNF-α stimulation. After 24 or 48 hours of incubation with different concentrations of matrine(0.625, 1.25, and 2.5 mmol·L~(-1)), CCK-8 assay was used to detect cell proliferation. After treatment with 2.5 mmol·L~(-1) matrine for 48 h, the expression of TNF-α, interleukin-6(IL-6), interleukin-1β(IL-1β), and Klf4 mRNA and miR-25-3p was detected by real-time fluorescence-based quantitative PCR, and the protein expression of TNF-α, IL-6, IL-1β, and Klf4 was detected by Western blot. The anti-miR-25-3p was transfected into HUVECs, and the effect of anti-miR-25-3p on TNF-α-induced cell proliferation and inflammatory factors was detected by the above method. The cells were further transfected with miR-25-3p and incubated with matrine to detect the changes in proliferation and expression of related inflammatory factors, miR-25-3p, and Klf4. The targeting relationship between miR-25-3p and Klf4 was verified by bioinformatics analysis and dual luciferase reporter gene assay. The results displayed that matrine could inhibit TNF-α-induced HUVEC proliferation, decrease the mRNA and protein expression of TNF-α, IL-6, and IL-1β, increase the mRNA and protein expression of Klf4, and reduce the expression of miR-25-3p. Bioinformatics analysis showed that there were specific complementary binding sites between miR-25-3p and Klf4 sequences. Dual luciferase reporter gene assay confirmed that miR-25-3p negatively regulated Klf4 expression in HUVECs by targeting. The inhibition of miR-25-3p expression can reduce TNF-α-induced cell proliferation and mRNA and protein expression of TNF-α, IL-6, and IL-1β. MiR-25-3p overexpression could reverse the effect of matrine on TNF-α-induced cell proliferation and the mRNA and protein expression of TNF-α, IL-6, IL-1β, and Klf4. This study shows that matrine inhibits the inflammatory response induced by TNF-α in HUVECs through miR-25-3p-mediated Klf4 pathway.

Effect of matrine in MAC-T cells and their transcriptome analysis: A basic study.

Matrine, an alkaloid derived from herbal medicine, has a wide range of biological activities, including antibacterial. Matrine was toxic to multiple cells at high concentrations. Bovine mammary epithelial cells (MAC-T) could be used as model cells for cow breast. Matrine was a feasible option to replace antibiotics in the prevention or treatment of mastitis against the background of prohibiting antibiotics, but the safe concentration of matrine on MAC-T cells and the mechanism of action for matrine at different concentrations were still unclear. In this study, different concentrations of matrine (0.5, 1, 1.5, 2, 2.5 and 3 mg/mL) were used to treat MAC-T cells for various time periods (4, 8, 12, 16 and 24 h) and measure their lactic dehydrogenase (LDH). And then the optimal doses (2 mg/mL) were chosen to detect the apoptosis at various time periods by flow cytometry and transcriptome analysis was performed between the control and 2 mg/mL matrine-treated MAC-T cells for 8 hours. The results showed that matrine was not cytotoxic at 0.5 mg/mL, but it was cytotoxic at 1~3 mg/mL. In addition, matrine induced apoptosis in MAC-T cells at 2 mg/mL and the proportion of apoptosis cells increases with time by flow cytometry. RNA-seq analysis identified 1645 DEGs, 676 of which were expressed up-regulated and 969 were expressed down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the following pathways were linked to matrine-induced toxicity and apoptosis, including cytokine-cytokine receptor interaction pathway, viral protein interaction with cytokine and cytokine receptor, P53 and PPAR pathway. We found 7 DEGs associated with matrine toxicity and apoptosis. This study would provide a basis for the safety of matrine in the prevention or treatment of mastitis.

Functional analysis of 3 genes in xenobiotic detoxification pathway of Bursaphelenchus xylophilus against matrine

Bursaphelenchus xylophilus is the causative agent of pine wilt disease. It has caused devastating damage to ecosystems worldwide, owing to the characteristic of being widely spread and uncontrollable. However, the current methods of control are mainly based on pesticides, which can cause irreversible damage to the ecosystem. Therefore, the search for new drug targets and the development of environmentally friendly nematicides is especially valuable. In this study, three key genes of the xenobiotic detoxification pathways were cloned from B. xylophilus, which were subsequently subjected to bioinformatic analysis. The bioassay experiment was carried out to determine the concentration of matrine required for further tests. Subsequently, enzyme activity detection and three gene expression pattern analysis were performed on matrine treated nematodes. Finally, RNA interference was conducted to verify the functions carried out by the three genes in combating matrine. The results indicated that cytochrome P450 and glutathione S-transferase of B. xylophilus were activated by matrine, which induced high expression of BxCYP33C4, BxGST1, and BxGST3. After RNA interference of three genes of B. xylophilus, the sensitivity of B. xylophilus to matrine was increased and the survival rate of nematodes was reduced to various degrees in comparison to the control group. Overall, the results fully demonstrated that BxCYP33C4, BxGST1, and BxGST3 are valuable drug targets for B. xylophilus. Furthermore, the results suggested that matrine has value for development and exploitation in the prevention and treatment of B. xylophilus.

Effects of matrine combined with LY294002 on proliferation, apoptosis and cell cycle of human myeloid leukemia K562 cells

To investigate the effects of matrine combined with LY294002 on proliferation, apoptosis and cell cycle of human myeloid leukemia K562 cells and explore the underlying mechanism. The effects of different concentrations of matrine alone and in combination with LY294002 on the proliferation of K562 cells were examined with CCK-8 assay. The changes in morphology of K562 cells were observed following treatment for 48 h with 0.4 g/L matrine and 10 μmol/L Y294002, either alone or in combination, and cell apoptosis was detected using flow cytometry with annexin V-FITC/PI double labeling; the changes in cell cycle was detected with PI labeling. Western blotting was performed to examine the effect of matrine combined with LY294002 on expressions of p-mTOR, p-PI3K, Akt, p-Akt, cyclinD1, Bcl-2 and caspase-9 in the cells. Treatment with different concentrations of matrine, both alone and in combination with LY294002, inhibited the proliferation of K562 cells in a time- and concentration-dependent manner. Compared with matrine treatment alone, the combined treatment caused more obvious morphological changes of the cells, significantly increased cell apoptosis (P < 0.01), and induced cell cycle arrest in G0/G1 (P < 0.01). Western blotting showed that the protein expression levels of p-mTOR, cyclinD1, p-PI3K, p-Akt and Bcl-2 in K562 cells increased while the expression level of caspase-9 decreased significantly after the combined treatment (P < 0.01). Matrine combined with LY294002 produces a synergistic inhibitory effect on K562 cells possibly by down-regulating the p-Akt expression in PI3K/Akt signaling pathway, reducing the expressions of p-mTOR, cyclinD1 and Bcl-2, and increasing the expression of caspase-9.

Matrine Promotes Dendritic Cell Activation and Enhances Anti-tumor Effect of Human Gastric Carcinoma Dendritic Cells Vaccine in Vitro

Objective: The purpose of this study was to investigate whether matrine can affect the phenotypes and functional maturation of dendritic cells (DC), and to secrete many cytokines, as well as the cytotoxic T lymophocyte (CTL) specific killing effect induced by gastric carcinoma dendritic cells vaccine in vitro. Materials and methods: The experimental groups consisted of three concentrations of matrine (0.5, 1.0, and 2.0 mg/mL). The DC maturation was detected by flow cytometry. The proliferation of T cells was detected by cell counting kit-8 (CCK-8) method. The secretions of cytokines by CTLs were detected by enzyme-linked immunosorbent assay (ELISA). The specific killing capacity of CTLs to target MKN45 gastric cancer cells was detected by lactate dehydrogenase (LDH) release assay. Results: The results showed that matrine could increase the expressions of CD86 and CD83 in a dose-dependent manner. Matrine could promote T cell proliferation (P&lt;0.05). Moreover, matrine also significantly increased the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-12p70 (IL-12p70), respectively (P&lt;0.05). The therapeutic vaccination with DCs vaccine treated with lipopolysaccharide (LPS) plus matrine resulted in improved killing effect as compared to that observed with DCs treated with LPS alone (P&lt;0.05). Conclusion: These findings define matrine as an immune adjuvant that enhances the DC activation and demonstrate a new pharmacological approach to improve the therapeutic effect of autogenous DC vaccines.

Matrine exerts antitumor activity in cervical cancer by protective autophagy via the Akt/mTOR pathway in vitro and in vivo.

Matrine is a quinazoline alkaloid extracted from Sophora flavescens. The aim of the present study was to determine whether matrine can induce autophagy in the human HeLa and SiHa cervical cancer cell lines in vitro and in vivo. Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of HeLa and SiHa cells. A total of 28 4-week-old female BALB/c nude mice were used for the in vivo study. Autophagy and protein expression were observed via transmission electron microscopy, monodansylcadaverine and immunohistochemical staining and western blotting. The inhibitory effect of matrine on the proliferation of cervical cancer cells was time- and dose-dependent. The combination of matrine and cisplatin synergistically inhibited the proliferation of cervical cancer cells in vitro and in vivo. Transmission electron microscopy showed that after the addition of matrine, numerous autophagosomes and autophagolysosomes were observable in HeLa and SiHa cells, as demonstrated by monodansylcadaverine staining. Western blotting and immunohistochemical staining showed that as the concentration of matrine increased, the expression of the autophagy marker LC3A/B-II also increased significantly in vitro and in vivo. These findings suggested that matrine inhibited the proliferation of cervical cancer cells and induced autophagy by inhibiting the Akt/mTOR signaling pathway. Thus, matrine may represented a potential candidate in combination therapy for cervical cancer as an inducer of autophagy.

Matrine induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells via miR-122 mediated CG1/livin/survivin signal axis

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To study the impact of matrine on cell cycle and apoptotic changes in hepatoma cells, and the mechanism involved.&#x0D; Methods: Human hepatoma cell line HepG2 was treated with different concentrations of matrine. The blank control cells were maintained in 1640 medium only. The influence of matrine on proliferative ability was determined with 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) method. Flow cytometry was used to determine its effect on cell cycle and apoptosis; RT-PCR (reverse transcription-polymerase chain reaction) was applied to assay the mRNA expressions of miR-122, cyclin G1 (CG1), livin and survivin mRNA, while the protein expressions of CG1, livin and surviving were assayed by Western blotting.&#x0D; Results: Matrine time- and dose-dependently suppressed the proliferative capacity of the cells. At a concentration of 0.5 mg/mL, matrine had no significant effect on the cell cycle. However, 1.0 mg/mL matrine blocked the cell cycle in G1 phase, while 1.5 mg/mL matrine blocked HepG2 cells in G2/M phase (p &lt; 0.05). Moreover, matrine induced apoptosis in HepG2 cells, and markedly downregulated the expressions of miR-122 concentration- time-reliantly (p &lt; 0.05). In addition, matrine markedly and concentration-dependently reduced mRNA and protein expression levels of CG1, livin and survivin, with the strongest inhibitory effect at a level of 1.5 mg/mL.&#x0D; Conclusion: Matrine induces cell cycle block and apoptotic changes in hepatoma cells through a mechanism related to regulation of the CG1/livin/survivin signal axis mediated by miR-122. Matrine may be a potential treatment for liver cancer. However, clinical trials are needed to confirm this potential.&#x0D; &#x0D; &#x0D; &#x0D;

Pharmacokinetic Characterization and Bioavailability Barrier for the Key Active Components of Botanical Drug Antitumor B (ATB) in Mice for Chemoprevention of Oral Cancer.

This study aims to characterize the pharmacokinetic (PK) profiles and identify important bioavailability barriers and pharmacological pathways of the key active components (KACs) of Antitumor B (ATB), a chemopreventive agent. KACs (matrine, dictamine, fraxinellone, and maackiain) of ATB were confirmed using the antiproliferative assay and COX-2 inhibition activities in oral cancer cells. The observed in vitro activities of KACs were consistent with their cell signaling pathways predicted using the in silico network pharmacology approach. The pharmacokinetics of KACs were determined after i.v., i.p., and p.o. delivery using ATB extract and a mixture of four KACs in mice. Despite good solubilities and permeabilities, poor oral bioavailabilities were estimated for all KACs, mostly because of first-pass metabolism in the liver (for all KACs) and intestines (for matrine and fraxinellone). Multiple-dose PK studies showed 23.2-fold and 8.5-fold accumulation of dictamine and maackiain in the blood, respectively. Moreover, saliva levels of dictamine and matrine were found significantly higher than their blood levels. In conclusion, the systemic bioavailabilities of ATB-KACs were low, but significant levels of dictamine and matrine were found in saliva upon repeated oral administration. Significant salivary concentrations of matrine justified its possible use as a drug-monitoring tool to track patient compliance during chemoprevention trials.

Matrine protects against DSS-induced murine colitis by improving gut barrier integrity, inhibiting the PPAR-α signaling pathway, and modulating gut microbiota

Matrine is a naturally occurring quinolizidine alkaloid with various bioactivities. However, little is known of its function on ulcerative colitis (UC). Here, we investigated the effect and underlying mechanisms of matrine on dextran sulfate sodium (DSS)-induced UC mice. In this study, different concentrations of matrine were given to mice with DSS-induced colitis for a week. The symptoms of colitis, colonic pathology, inflammation-related indicators, and intestinal mucosal barrier function were detected and analyzed. Moreover, RNA-seq analysis in colon tissues was conducted, and 16S rDNA sequencing was carried out to evaluate the gut microbiota of colon contents. The results showed that matrine significantly alleviated clinical activity and histological changes of UC mice, inhibited the production of the pro-inflammatory cytokines, and improved gut barrier integrity. Moreover, RNA-seq analysis and experimental verification showed that matrine significantly inhibited the peroxisome proliferator-activated receptor-α (PPAR-α) signaling pathway. 16S rDNA sequencing revealed that matrine altered the composition and functions of gut microbiota, increased the abundance of Barnesiella intestinihominis and decreased the abundance of Helicobacter ganmani at the species level. In conclusion, matrine ameliorated DSS‐induced colitis by improving gut barrier integrity, inhibiting the PPAR-α signaling pathway, and modulating gut microbiota. These suggested that matrine may be a therapeutic agent for UC treatment.

Synergistic Interaction between the Entomopathogenic Fungus Akanthomyces attenuatus (Zare &amp; Gams) and the Botanical Insecticide Matrine against Megalurothrips usitatus (Bagrall)

The excessive use of synthetic chemicals for Megalurothrips usitatus (Bagrall) management has resulted in the development of insecticide resistance as well as adverse effects to the natural ecosystem. This has driven the need to develop alternative pest control strategies. This study reports a synergistic interaction between the entomopathogenic fungus Akanthomyces attenuatus (Zare & Gams) and the botanical insecticide matrine against M. usitatus. The results revealed that the germination rate and colony growth of A. attenuatus were inhibited by higher matrine concentrations. Percentage mortalities of M. usitatus following application of A. attenuatus and matrine showed a dose mortality effect. After five days of treatment, all concentrations of matrine combined with different concentrations of A. attenuatus, except one combination (matrine 0.25 mg/mL + 1 × 107 conidia/mL), showed synergistic effect. The activities of acetylcholinesterase and antioxidant enzymes (superoxide dismutase, catalase and peroxidase) in M. usitatus, in response to individual or combined application of A. attenuatus and matrine at the end of the experimental period, were significantly lower than controls. The findings confirm the synergistic action of A. attenuatus and matrine against M. usitatus along with the biochemical phenomenon possibly regulating the synergistic effect.

Anti-tumor and Phenotypic Regulation Effect of Matrine on Dendritic Cells through Regulating TLRs Pathway.

To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect. Different concentrations (0, 1, 2, 4, 8 and 16 µ g/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay. Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and I κ B kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-II, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 µg/mL, all indices had significant difference (P<0.01 or P<0.05). Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway, promoting the secretion of inflammatory cytokines and enhancing immune function.

Matrine Inhibits Proliferation, Invasion, and Migration and Induces Apoptosis of Colorectal Cancer Cells Via miR-10b/PTEN Pathway.

Background: Colorectal cancer (CRC) is the third most common malignancy worldwide. Matrine can act as a potential antitumor drug, and its antitumor activities have been tested in various cancers, including CRC. However, the effect of matrine and the related mechanisms on CRC cells remains poorly defined. Materials and Methods: CRC cells were treated with different concentrations of matrine, and then MTT, flow cytometric, and transwell assays were used to assess cell proliferation, apoptosis, invasion, and migration. MiR-10b-5p and Phosphatase and tensin homolog (PTEN) expression levels were measured by quantitative real-time polymerase chain reaction and Western blot assay. The binding interaction of miR-10b-5p and PTEN were predicted by TargetScan and verified by a dual-luciferase reporter and RIP assay. The effect of matrine, miR-10b-5p, and PTEN on CRC cell proliferation, apoptosis, migration, and invasion was detected by MTT, flow cytometric, and transwell assays severally. Results: Matrine notably restrained proliferation, invasion, and migration and boosted apoptosis of CRC cells, as well as downregulated miR-10b-5p expression and upregulated PTEN protein level. PTEN was a direct target of miR-10b-5p in CRC cells. MiR-10b-5p knockdown and matrine treatment inhibited cell proliferation, migration, and invasion and induced apoptosis, and reintroduction of si-PTEN partly regained the inhibiting effect. Besides, MiR-10b-5p knockdown and matrine treatment repressed CRC growth in vivo. Conclusion: Matrine could suppress proliferation, migration, and invasion and induce apoptosis of CRC cells via the miR-10b/PTEN pathway, providing the potential molecular mechanism of matrine in blocking CRC progression.

Effect of matrine on JAK2/STAT3 signaling pathway and brain protection in rats with cerebral ischemia-reperfusion.

Ischemic encephalopathy is a common clinical disease. The main treatment goal is to achieve vascular recanalization. However, after vascular recanalization, the reperfusion of fresh blood can change local cell metabolism, thus adversely affecting cell structure and function, which can result in reperfusion injury. To explore the effect of matrine intervention of different concentrations on JAK2/STAT3 signaling pathway and brain protection in rats with cerebral ischemia-reperfusion. Healthy male Sprague Dawley rats were divided into a blank control group (20 rats), a model group (80 rats) and a sham group (20 rats). In the model group, the middle cerebral artery was occluded with suture method to establish cerebral ischemia-reperfusion model rats, which were subdivided into cerebral ischemia-reperfusion group, and 5, 10 and 20 mg/kg matrine groups, with 20 rats in each group. Indicators including neurological function score, brain infarct size, brain water content, lactic dehydrogenase activity, protein expressions of p-JAK2 and p-STAT3, as well as superoxide dismutase activity and malondialdehyde content were evaluated. Compared with cerebral ischemia-reperfusion group, all the indicators were significantly improved in the 3 matrine treatment groups in a dose-dependent manner, and protein expressions of p-JAK2 and p-STAT3 in the brain tissue and brain cell apoptosis rate were decreased with the increase of matrine concentration (all p < 0.05). Matrine can significantly ameliorate the neurological function and brain edema of rats with cerebral ischemia-reperfusion, and improve superoxide dismutase, malondialdehyde and lactic dehydrogenase levels in the brain tissue and brain cell apoptosis rate. The mechanism of matrine may be related to the inhibition of abnormal JAK2/STAT3 signaling pathway activation.

Evaluation of the Effect of Matrine on Human Laryngeal Squamous Cell Carcinoma Cell Line

Aim of study: to evaluate the possible anticancer potential of Matrine, one of the main active components extracted from dry roots of Sophora flavescens Ait (Leguminosae), on human laryngeal squamous cell carcinoma cell line (Hep-2). Material and methods: Prepared (Hep-2) cell line was treated with different concentrations of Matrine for 48 hours. The effect of Matrine on cell line was investigated using MTT assay, cytological examination and nuclear morphometric analysis of treated cells to explore the effect of the drug on cell proliferation and induction of apoptosis. The results were analyzed statistically. P value ≤ 0.05 was considered significant. Results: MTT assay showed that the proliferation of Matrine treated cells (in relation to control cells) decreased in a dose dependent manner. Morphometric analysis showed a decrease in nuclear area factor (NAF), which is an indicator of apoptosis, as concentrations increased. The results were statistically significant. Conclusion: Matrine has a cytotoxic effect on Hep-2 cell line through induction of apoptosis.

Fabrication and characterization of matrine-loaded konjac glucomannan/fish gelatin composite hydrogel as antimicrobial wound dressing

The konjac glucomannan (hereafter referred to simply as konjac) hydrogel has favorable gel-forming ability and swelling capacity, but the insufficient flexibility and poor water retention have limited its utilization. In this study, composite gels based on konjac and fish gelatin (FG) were prepared by alkali processing and thermal treatment subsequently. The influence of FG contents on the gel fraction, swelling behavior, biodegradation. was researched. Matrine was incorporated into the hydrogel and its effect on the hemocompatibility and antibacterial activity of gels were evaluated. According to the results, all gels presented at least 270% swelling degree and 72.7%–81.5% equilibrium water content. Pure konjac hydrogel presented 83.9% gel fraction and 96.9% water evaporation rate, while those of the composite gels were 84.8%–93.0% and 75.0%–91.9% respectively. As the doses of matrine increased from 0 to 40 mg/mL, hemolysis values decreased from 1.56% to 0.12%, indicating the improved hemocompatibility. Furthermore, the antimicrobial activity of gels was enhanced steadily with the increase of matrine concentration. When matrine concentration was 40 mg/mL, the inhibitory zones for Escherichia coli ATCC25922 and Staphylococcus aureus CMCC(B) 26003 were 12 and 11.5 mm, respectively. The overall results suggested that matrine-loaded konjac/FG hydrogel could not only maintain physiological environment for wound healing but also inhibit the growth of bacterial on the wound surface.

Matrine inhibits proliferation and migration of HepG2 cells by downregulating ERK1/2 signaling pathways

To research the effect of matrine on the proliferation and migration of HepG2 cells through extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. HepG2 cell was selected and divided into blank control group, experimental group (matrine 1, 2, and 4 mg/mL), and positive control group (PD98059, ERK1/2 inhibitor). MTT measure was used to detect the effective time and concentration which matrine inhibits HepG2 cells. After 24 h, the effect of effective concentration of matrine on the of morphological changing HepG2 cells was observed. The invasion ability was assayed by transwell method, the expression of ERK1/2 and pERK1/2 were detected through Western blot, and reverse transcription polymerase chain reaction was used to test the expression level of ERK1/2 mRNA. With the increase of matrine concentration, the number of adherent HepG2 cells gradually decreased, the morphologic changes gradually became spherical, some cell morphology was incomplete, and even cell fragments appeared. The proliferation and invasion ability of HepG2 cells decreased. The expression of ERK1/2, pERK1/2, and ERK1/2 mRNA downregulated with the increase of matrine concentration (P < 0.05). Matrine inhibits the proliferation and migration of HepG2 cells by downregulating the ERK1/2 signaling pathway.

Matrine suppresses stemness of hepatocellular carcinoma cells by regulating β-catenin signaling pathway

To explore the effects of matrine on the proliferation, tumor cell stemness, β-catenin transcriptional activity and AKT/GSK3β/β-catenin signaling pathway in human hepatocellular carcinoma (HCC) HepG2 and Huh7 cells. The proliferation and colony formation ability of HepG2 and Huh7 cells treated with 200, 400, and 800 μg/mL matrine were evaluated with MTT assay and colony formation assay, respectively. Real-time quantitative PCR was performed to detect the mRNA expressions of CD90, epithelial cell adhesion molecule (EpCAM) and CD133, and dual-luciferase assay was used to detect the transcriptional activity of β-catenin in the treated cells. The effects of matrine on the expressions of protein kinase B (AKT), P-AKT, GSK-3β, P-GSK-3β, P-β-catenin and β-catenin proteins in the Wnt/β-catenin signaling pathway were assessed using Western blotting. Matrine inhibited the proliferation of the two HCC cell lines in a time- and concentration-dependent manner. The half-inhibitory concentrations of matrine were 2369, 1565 and 909.1 μg/mL at 24, 48 and 72 h in HepG2 cells, respectively, and were 1355, 781.8, and 612.8 μg/mL in Huh7 cells, respectively. Matrine concentrationdependently suppressed colony formation of the HCC cells, producing significant inhibitory effects at 400 μg/mL P < 0.01) and 800 μg/mL P < 0.001) in HepG2 cells and at 200 μg/mL P < 0.05), 400 μg/mL P < 0.01), and 800 μg/mL P < 0.001) in Huh7 cells. Matrine at 400 and 800 μg/mL significantly inhibited the mRNA expression of CD90, EpCAM and CD133 and the transcriptional level of β-catenin in both HepG2 and Huh7 cells P < 0.05 or 0.01). Matrine at 400 and 800 μg/mL also significantly decreased the protein levels of β-catenin, P-AKT and P-GSK-3β and increased the phosphorylation level of β-catenin in both of the cell lines. Matrine inhibits the proliferation, colony formation, and the expressions of tumor stem cell markers CD90, EpCAM and CD133 in both HepG2 and Huh7 cells probably by inhibiting Wnt/β-catenin signaling pathway and the transcriptional activity ofβ-catenin.