Matrine

The root of Sophora japonica

IC50 Value: 540 μg/ml (inhibit gastric cancer cell line MNK45, MTT) [1] Matrine is an alkaloid found in plants from the Sophora genus. It has a variety of pharmacological effects, including anti-cancer effects, and action as a kappa opioid receptor and ?-receptor agonist. in vitro: MTT assay showed that the matrine was able to inhibit gastric cancer cell line MNK45 in a dose-dependent manner. The concentration required for 50% inhibition (IC50) was found to be 540 μg/ml. This anti-tumor function was achieved through modulation of the NF-κB, XIAP, CIAP, and p-ERK proteins expression in cell line MNK45. Matrine induces apoptosis of human NSCLC cells with anti-apoptotic factors inhibited and dependent on caspase activity. In addition, we found that matrine increases the phosphorylation of p38 but not its total protein, and inhibition of the p38 pathway with SB202190 partially prevents matrine-induced apoptosis. Furthermore, matrine generates reactive oxygen species (ROS) in a dose- and time-dependent manner, which is reversed by pretreatment with N-acetyl-L-cysteine (NAC) [2]. in vivo: Oral administration of matrine (200, 100 and 50 mg/kg) significantly attenuated isoproterenol-induced cardiac necrosis and left ventricular dysfunction [3]. high dose of matrine significantly reduced the mortality rate of mice with LPS administration. Treatment with matrine improved LPS-induced lung histopathologic changes, alleviated pulmonary edema and lung vascular leak, inhibited MPO and MDA activity,and reduced the production of inflammatory mediators including TNF-α, IL-6 and HMGB1 [4]. Toxicity: N/A Clinical trial: N/A

Matrine induces mitochondrial apoptosis in cisplatin-resistant non-small cell lung cancer cells via suppression of beta-catenin/survivin signaling.[Pubmed:25760455]

Oncol Rep. 2015 May;33(5):2561-6.

Matrine is an alkaloid isolated from Sophora flavescens and shows anticancer activities. The present study was carried out to determine the cytotoxic effects of Matrine on cisplatin-resistant non-small cell lung cancer (NSCLC) cells and the associated molecular mechanisms. Parental and cisplatin-resistant A549 and H460 NSCLC cells were treated with 1 or 2 g/l of Matrine for 48 h, and cell viability and apoptosis were assessed. beta-catenin-mediated transcriptional activity, mitochondrial membrane potential (DeltaPsim) changes, activation of caspases, and survivin expression were examined. The effect of overexpression of survivin on the anticancer activity of Matrine was investigated. Compared to the parental cells, cisplatin-resistant NSCLC cells showed increased beta-catenin transcriptional activity. Matrine treatment resulted in a significant reduction in beta-catenin activation and survivin expression in the cisplatin-resistant cells. Matrine caused apoptotic death in the cisplatin-resistant NSCLC cells, coupled with loss of DeltaPsim and activation of caspase-9 and -3. Matrine-induced apoptosis of the cisplatin-resistant NSCLC cells was significantly reversed by overexpression of survivin. In conclusion, Matrine exposure induces mitochondrial apoptosis in cisplatin-resistant NSCLC cells, which is largely mediated through inactivation of beta-catenin/survivin signaling. Further investigation of the therapeutic benefit of Matrine in overcoming cisplatin resistance in NSCLC is warranted.

Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine.[Pubmed:19426721]

Chem Biol Interact. 2009 Sep 14;181(1):15-9.

Matrine (Mat), a component extracted from Sophora flavescens Ait, has a wide spectrum of pharmacological effects. Glycyrrhizin (Gly), a major active constituent of licorice (Glycyrrhiza glabra) root, has various pharmacological effects. Gly and Mat are ancillary drugs used clinically in China for protection of liver function and treatment of tumors. However, habitual administration of Gly may cause adverse effects marked by the development of pseudohypercorticosteroidism. This work was designed to see whether combination use of Gly and Mat could offer better liver protective and anti-hepatocarcinogenic effects than Gly or Mat alone, and whether it could reduce the adverse effects of Gly alone by acetaminophen-induced hepatotoxicity, diethylnitrosamine-induced hepatocarcinogenesis, induction of immunosuppression, albumen-induced swelling of rat hind paws. The results showed that compared with Gly or Mat alone, Gly+Mat reduced the mortality of acetaminophen overdosed mice more effectively, attenuate acetaminophen-induced hepatotoxicity, and reduced the number and area of gamma-GT positive foci, thus protecting liver function and preventing HCC from occurring. In addition, Gly+Mat had a protective effect on immunosuppression, a strong non-specific anti-inflammatory effect, and an effect of reducing the incidence of sodium and water retention.

Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblasts.[Pubmed:19346587]

Biofactors. 2008;33(2):121-8.

Matrix metalloproteinase-1 (MMP-1) plays an important role in the maintenance and turnover of extracellular matrix (ECM) macromolecules. Remodelling of extracellular matrix by MMPs is a hallmark feature of physiological and pathological processes. In this study, in order to establish the therapeutic potential of Matrine, we investigated its effect on MMP-1 expression in human dermal fibroblast cells. We found that Matrine inhibited both MMP-1 mRNA and protein expression induced by PMA (phorbol myristate acetate). Therefore, we characterized the inhibitory mechanism of Matrine on PMA-induced MMP-1 expression. Matrine inhibited PMA-induced activation of the AP-1 promoter, an important nuclear transcription factor in MMP-1 expression. Additionally, we detected that Matrine suppressed the PMA-induced phosphorylation of two mitogen-activated protein kinases, extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but did not suppress the PMA-induced phosphorylation of p38 kinase. These results suggest that Matrine suppresses PMA-induced MMP-1 expression through inhibition of the AP-1 signaling pathway and also may be beneficial for treatment of some inflammatory skin disorders.

Matrine inhibits the migratory and invasive properties of nasopharyngeal carcinoma cells.[Pubmed:25633440]

Mol Med Rep. 2015 Jun;11(6):4158-64.

Matrine is a widely used Chinese herbal medicine that has historically been used in the treatment of inflammation and cancer. However, the antimetastatic effects and associated molecular mechanisms of Matrine on nasopharyngeal carcinoma (NPC) remain to be elucidated. Therefore, the aims of the present study were to assess the antimetastatic effects of Matrine on NPC, and identify the underlying mechanisms. Matrine inhibited the proliferation of NPC cells in vitro and in vivo. Furthermore, Matrine inhibited the migration and invasion of NPC tumor cells at doses below the toxic range. Following treatment with Matrine for 24 h, there was a decrease in the protein expression levels and activities of matrix metalloproteinase (MMP)2 and MMP9 in NPC039 cells. In addition, Matrine markedly reduced the expression levels of p65 and p50 in the nuclei. Combined treatment of Matrine with helenalin, a nuclear factorkappaB (NFkappaB) inhibitor resulted in a synergistic reduction in MMP2 and MMP9 expression levels, and the invasive capabilities of the NPC039 cells were also reduced. In conclusion, Matrine inhibits NPC cell migration and invasion by suppressing the NFkappaB pathway. These results suggest that Matrine may be a potential therapeutic agent for NPC.

Matrine reduces yeast-to-hypha transition and resistance of a fluconazole-resistant strain of Candida albicans.[Pubmed:24860982]

J Appl Microbiol. 2014 Sep;117(3):618-26.

AIMS: To evaluate the potential effect of Matrine on reducing the growth of hypha and lowering the resistance of a fluconazole-resistant colony of Candida albicans. METHODS AND RESULTS: Candida albicans SC5314 and a fluconazole-resistant C. albicans 215 were used. As for C. albicans SC5314, minimal inhibitory concentration (MIC(80)) and effective concentration (EC(50)) were determined, 1 mg ml(-1) Matrine could inhibit nearly 80% of planktonic growth by inverted microscope, 2 mg ml(-1) Matrine suppressed 50% of metabolic activity of biofilm by XTT assay, vanishing hypha could be observed on spider agar containing 2 mg ml(-1) Matrine, the expressions of three hypha-related genes, namely ALS 3, SUN 41 and PBS 2, were suppressed by 29, 45 and 61% by 2 mg ml(-1) Matrine. Also, Matrine could lower the resistance of C. albicans 215, in either the free-floating form or the biofilm phenotype. CONCLUSIONS: Matrine had favourable antifungal potential and might be able to reverse the fluconazole resistance of clinical isolates at relatively high concentration. The anti-candidal performance of Matrine could be tightly associated with yeast-to-hypha transition proved by spider agar test and qRT-PCR. SIGNIFICANCE AND IMPACT OF STUDY: More efforts are needed to find new antifungal agents. Matrine could be a potential candidate to fight against Candida-related infections by regulating yeast-to-hypha transition.

Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases.[Pubmed:23002236]

Carcinogenesis. 2013 Jan;34(1):128-38.

Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, Matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by Matrine in SGC7901 cells. The accumulation of autophagic vacuoles in Matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that Matrine blocked autophagic degradation by impairing the activities of lysosomal proteases. Moreover, confocal microscopy and gradient ultracentrifugation revealed that the trafficking processes and proteolytic activation of cathepsins were inhibited by Matrine. Using a pH sensor probe, we found elevated pH values in endosomes/lysosomes in response to Matrine treatment. Therefore, Matrine seems to be a novel autophagy inhibitor that can modulate the maturation process of lysosomal proteases.

Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3.[Pubmed:19429345]

J Ethnopharmacol. 2009 May 4;123(1):91-6.

AIM OF THE STUDY: Matrine, an alkaloid purified from the chinese herb Sophora flavescens Ait, is well known to possess activities including anti-inflammation, anti-fibrotic and anticancer. In this study, the mechanism of Matrine inducing the apoptosis of gastric carcinoma cells was investigated. MATERIALS AND METHODS: Proliferation of SGC-7901 cells was examined by MTT assay. Cellular morphology was observed under transmission electron microscope. Flow cytometry (FCM) was used to observe the apoptosis of SGC-7901 cells by staining with annexinV-FITC/PI. The expression levels of Fas/FasL in SGC-7901 cells were monitored by FCM analysis using an indirect immunofluorescence method. Activity of caspase-3 enzyme was measured by spectrofluorometry. RESULTS: MTT assay showed that Matrine inhibited SGC-7901 cells proliferation in a dose-dependent and time-dependent manner. Apoptosis induction was demonstrated by morphological changes under electron microscope and FCM analysis. Fluorescence intensity levels of Fas and FasL were found to be equally up-regulated after Matrine treatment, which were both correlated with apoptosis rate. The activity of caspase-3 enzyme increased in Matrine groups, positively correlated with apoptosis rate. CONCLUSIONS: Matrine could inhibit cell proliferation and induce apoptosis of SGC-7901 cells in vitro. The apoptosis induction appears to proceed by up-regulating Fas/FasL expression and activating caspase-3 enzyme.

Matrine (Matridin-15-one) is an alkaloid found in plants from the Sophora genus. It has a variety of pharmacological effects, including anti-cancer effects, and action as a kappa opioid receptor and u-receptor agonist.

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