Matrine: A Promising Natural Product With Various Pharmacological Activities

Abstract

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.

Keywords: apoptosis; autophagy; cancer; cell cycle; inflammation; matrine; natural product.

Figure 1

Anticancer mechanisms of matrine. For tumor cells, matrine can induce caspase-mediated exogenous apoptosis by activating Fas/Fas-L and TRAIL. Matrine can also induce mitochondrial damage by promoting the proapoptotic genes Bax, Bid, Bad, Bim, and downregulating the apoptosis-inhibiting genes Bcl-2, Mcl-1, Bcl-XL, and release Cyt-C and AIF to promote endogenous Apoptosis. Matrine can inhibit tumor cell proliferation through the GP130/JAK/STAT pathway, and can also induce apoptosis and inhibit proliferation by downregulating the expression of survivin through wnt/β-catenin and LEF1/TCF1. Matrine can inhibit insulin-like growth factor (IGF1) and GF and then affect the expression of phosphatidylinositol 3-kinase (PI3k)/AKT, nuclear factor κB (NF-κB) signaling pathway, and p53, thereby promoting tumor cell apoptosis, inhibiting proliferation and invasion. Matrine can also induce autophagy through PI3K/AKT/mTOR signaling pathway, causing autophagy related cell death and inhibiting the expression of EGF and vascular endothelial growth factor (VEGF). Matrine can also upregulate E-cadherin, downregulate MMP2, MMP9, and vimentin to inhibit invadopodia, slug, and snail, so as to inhibit epithelial-mesenchymal transition (EMT) and prevent tumor cell invasion. In addition, matrine can also promote the expression of NKG2DL in tumor cells to promote the recognition and killing of NK cells to tumor cells.

Figure 2

Non-anticancer mechanisms of matrine. For normal cells, matrine can promote cell survival under various stress environments. Under oxidative stress conditions, matrine can inhibit reactive oxygen species (ROS) production, thus inhibiting high mobility group protein box 1 (HMGB1), nod-like receptor protein 3 (NLRP3)/ASC/CASP1 pathway and nuclear factor κ B (NF-κB pathway)–mediated inflammation. Matrine can also inhibit tumor necrosis factor (TNF)-α and IL-1 induced NF-κB and TAK/JNK/AP1 pathway-mediated inflammation. In addition, TGFβ/Smad/FOXP3/RORγt is also a pathway for matrine to inhibit inflammation. Matrine can also block CASP8 mediated exogenous apoptosis by inhibiting TLR4/MyD88 pathway, eIF2α/ATF4/CHOP mediated mitochondrial damage, Cyt-C release and CASP9 mediated endogenous apoptosis by inhibiting ER stress. Matrine can also inhibit GP130/JAK/STAT pathway mediated apoptosis. TGFβ/Smad, NOTCH/NICD, and miR455/ATF6 mediated fibrosis can also be inhibited by matrine. In addition, matrine can promote cell proliferation by activating Hsp90.

Figure 3

Summary of signal pathways and diseases related to the actions of matrine. For tumor cells, matrine can inhibit proliferation and invasion, promote apoptosis and autophagic cell death, and enhance the cytotoxicity of NK cells. These effects are related to the inhibition of nuclear factor κ B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, Wnt/β-catenin, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and cell cycle pathways, and promotion of PTEN, death receptor pathways. For normal cells, matrine can promote proliferation, inhibit apoptosis, inflammation and fibrosis. These effects are related to matrine inhibiting NF-κB, JAK/STAT, Hsp90, MAPK/ERK, TGFβ/Smad, death receptor, toll like receptor pathways, promoting PI3K/AKT, NOTCH pathways.