Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway

Xiao, Yi; Ma, Dawei; Wang, Honglei; Wu, Duoming; Chen, Ying; Kun, Ji; Tao, Qianshan; Wu, Langping

doi:10.1002/ptr.5785

Cited by 17 publications

(12 citation statements)

References 38 publications

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“…Literature has reported that Matrine has anti-apoptotic effect through endoplasmic reticulum pathway and Osthole also has anti-apoptotic effects respectively [18,25,26]. In this study, the synergistic inhibitory effect of Matrine combined with Osthole on PCV2-induced apoptosis was demonstrated and the result was consistent with the conclusion that Matrine and Osthole alone have anti-apoptosis effects.…”

Section: Discussionsupporting

confidence: 88%

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

Sun

Wan

et al. 2020

Preprint

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Background: Porcine circovirus type 2 (PCV2) is an important DNA pathogen commonly in pig farms, which can cause immunosuppression and induce apoptosis. To evade clearance by the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, it is difficult to eradicate complex PCV2 infection by relying on vaccine immunity and one compound. At present, there is no literature report on the effective prevention and treatment of PCV2 infection by the combined a of two or more compounds through multiple pathways and multiple targets. We have previously demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further studied. Many literatures have proved that Osthole has a variety of pharmacological activities. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and the synergistic anti-apoptosis mechanism in the same pathway and targets.Results: It was first demonstrated that Osthole alone had anti-PCV2 effect and the synergistic anti-PCV2 effect combined with Matrine was better than Matrine and Osthole alone by qPCR, IFA and Western blot results. Subsequently, demonstrated that the reduction of endoplasmic reticulum PERK apoptosis induced by PCV2 was mainly contributed the mechanism of anti-PCV2 using these two extracts by Annexin V-FITC/PI, JC-1 and Western blot results. Finally, it was further demonstrated that Matrine combined with Osthole could inhibit the expression of Cap in cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. In this study, Ribavirin was used as the positive control.Conclusions: It was proved that the synergistic anti-PCV2 effect of Matrine combined with Osthole was significantly better than that of Matrine and Osthole alone. And the two ombined, with Cap and GRP78 as potential targets of anti-PCV2, further inhibited PERK apoptosis induced by PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The results formed a basis for further studies on the mechanism of anti-PCV2 in vivo using Matrine combined with Osthole and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets.

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Section: Discussionsupporting

confidence: 88%

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

Sun

Wan

et al. 2020

Preprint

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“…On the one hand, hepatitis B and atherosclerosis are considered to be associated with excessive ER stress, and Mat has a good therapeutic effect on these two diseases [ 45 – 48 ]. On the other hand, some researchers have discovered that Mat also exerts anti-cancer effects by aggravating ER stress [ 49 ]. The increase of SERCA2 activity was demonstrated in cancer cells and is considered to protect cancer cells from apoptosis [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Matrine attenuates endoplasmic reticulum stress and mitochondrion dysfunction in nonalcoholic fatty liver disease by regulating SERCA pathway

et al. 2018

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BackgroundEndoplasmic reticulum (ER) stress, which can promote lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Calcium (Ca2+) homeostasis is considered to play a key role in ER stress. Matrine (Mat) has been applied for the treatment of hepatitis B, but its effect on NAFLD is still unknown, and there is no unified view of Mat on the regulation of ER stress in the previous literature.MethodsThe pharmacological effects were studied in high-fat-diet or methionine–choline-deficient diet induced C57BL/6J mice models and in palmitic acid (PA) induced L02 human liver cell model. Calcium fluorescence experiments, computational virtual docking analysis and biochemical assays were used in identifying the locus of Mat.ResultsThe results showed that Mat-treated mice were more resistant to steatosis in the liver than vehicle-treated mice and that Mat significantly reduced hepatic inflammation, lipid peroxides. The beneficial effect of Mat was associated with suppressing ER stress and restoring mitochondrial dysfunction. Additionally, Mat decreased the PA-induced lipid accumulation, ER stress and cytosolic calcium level ([Ca2+]c) in hepatocyte cell lines in low and middle dose. However, the high dose Mat did not show satisfactory results in cell model. Calcium fluorescence experiments showed that Mat was able to regulate [Ca2+]c. By computational virtual docking analysis and biochemical assays, Mat was shown to influence [Ca2+]c via direct inhibition of SERCA.ConclusionsThe results showed that the bi-directional regulation of Mat to endoplasmic reticulum at different doses was based on the inhibition of SERCA. In addition, the results also provide a theoretical basis for Mat as a potential therapeutic strategy in NAFLD/NASH.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1685-2) contains supplementary material, which is available to authorized users.

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“…Shao et al (2013) reported that matrine can inhibit the proliferation of breast cancer MCF7, BT-474, and MDA-MB-231 cells, which may be related to the inhibition of inhibitory k B kinase b (IKKb) regulation of nuclear factor k B (NF-kB) signaling pathway. Matrine can induce endoplasmic reticulum stress in MCF-7 cells, downregulate the expression of hexokinase II, inhibit energy metabolism, promote apoptosis (Xiao et al, 2017), and reverse the drug resistance of MCF-7/ADR cells. Adriamycin (ADR) accumulates in cells and induces apoptosis in MCF-7/ADR cells by modulating the PI3K/AKT signaling pathway (Zhou B. G. et al, 2018).…”

Section: Lung Cancermentioning

confidence: 99%

Matrine: A Promising Natural Product With Various Pharmacological Activities

et al. 2020

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Matrine is an alkaloid isolated from the traditional Chinese medicine Sophora flavescens Aiton. At present, a large number of studies have proved that matrine has an anticancer effect can inhibit cancer cell proliferation, arrest cell cycle, induce apoptosis, and inhibit cancer cell metastasis. It also has the effect of reversing anticancer drug resistance and reducing the toxicity of anticancer drugs. In addition, studies have reported that matrine has a therapeutic effect on Alzheimer's syndrome, encephalomyelitis, asthma, myocardial ischemia, rheumatoid arthritis, osteoporosis, and the like, and its mechanism is mainly related to the inhibition of inflammatory response and apoptosis. Its treatable disease spectrum spans multiple systems such as the nervous system, circulatory system, and immune system. The antidisease effect and mechanism of matrine are diverse, so it has high research value. This review summarizes recent studies on the pharmacological mechanism of matrine, with a view to providing reference for subsequent research.

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Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway

Cited by 17 publications

References 38 publications

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2

Matrine attenuates endoplasmic reticulum stress and mitochondrion dysfunction in nonalcoholic fatty liver disease by regulating SERCA pathway

Matrine: A Promising Natural Product With Various Pharmacological Activities

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