Oxymatrine suppresses colorectal cancer progression by inhibiting NLRP3 inflammasome activation through mitophagy induction in vitro and in vivo

Abstract

Chinese herb Radix sophorae tonkinensis extract oxymatrine shows anticancer effects.This study evaluated the role of oxymatrine in colorectal cancer (CRC) and the underlying molecular events in vitro and in vivo. CRC cells were treated with different doses of oxymatrine to assess cell viability, reactive oxygen species production, gene expression, and gene alterations. Meanwhile, mouse xenograft and liver metastasis models were used to assess the effects of oxymatrine using histology examination, transmission electron microscopy, and Western blot, respectively. Our results showed that oxymatrine treatment triggered CRC cell mitophagy to inhibit CRC cell growth, migration, invasion, and metastasis in vitro and in vivo. At the gene level, oxymatrine inhibited LRPPRC to promote Parkin translocation into the mitochondria and reduce the mitophagy-activated NLRP3 inflammasome. Thus, oxymatrine had an anticancer activity through LRPPRC inhibition, mitophagy induction, and NLRP3 inflammasome suppression in the CRC cell xenograft and liver metastasis models. In conclusion, the study demonstrates the oxymatrine anti-CRC activity through its unique role in regulating CRC cell mitophagy and NLRP3 inflammasome levels in vitro and in vivo.

Traditional Chinese medicine treats ulcerative colitis by regulating gut microbiota, signaling pathway and cytokine: Future novel method option for pharmacotherapy

“…OMT is an alkaloid mainly extracted from Sophorae Flavescentis Radix [ 96 ]. OMT effectively increased muribaculaceae, bifidobacterium abundance, lachnospiraceae, and ruminococcaceae, inhibited staphylococcaceae and bacteroides growth and regulated the intestinal flora structure in DSS-induced colitis [ 97 ].…”

Oxymatrine Modulation of TLR3 Signaling Pathway: A Dual-Action Mechanism Against H9N2 Avian Influenza Virus and Immune Regulation

“…OMT, an established bioactive monomer (Bi et al, 2012, Liang et al, 2023, was sourced from Shanghai Yuan-ye Biotechnology Co., Ltd., with its chemical structure illustrated in (Fig. 1A).…”

“…Traditional Chinese Medicine (TCMs) holds promise in antiviral strategy development due to its mild nature and low likelihood of inducing drug resistance. Oxymatrine (OMT), an active monomer extracted from various TCMs including Sophora avescens Ait and Radix Sophorae Tonkinensis (Bi et al, 2012, Liang et al, 2023, has demonstrated e cacy in managing chronic hepatitis B (Lu et al, 2004). Besides its hepatoprotective role, OMT exhibits potential against tumorigenesis, in ammation, and bacterial infections (Li et al, 2022, Cao et al, 2023, Zhang et al, 2023a.…”

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation

“…OMT [16,17] was procured from Shanghai Yuan-ye Biotechnology Co., Ltd. (Shanghai, China) The chemical structure of OMT is delineated in Figure 1A. To assess cytotoxicity, PMVECs were initially seeded in a 96-well polypropylene plate at a density of 10,000 cells per mL, using 100 µL of medium per well, and incubated at 37 • C in an atmosphere containing 5% CO 2 .…”

“…Traditional Chinese medicine (TCM) offers a distinct perspective on antiviral therapy, emphasizing treatments that are less likely to induce drug resistance. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the roots of Sophora flavescens Aiton and Sophora tonkinensis Gagnep (Fabaceae) [16,17], exhibits a broad spectrum of biological activities [18], including hepatoprotection, anti-tumorigenesis, anti-inflammation, and antibacterial effects [19][20][21]. Its capacity to modulate the immune response and inhibit viral replication of hepatitis B virus (HBV) in transgenic mice underscores its potential as an immunomodulatory agent [22].…”