LICOCHALCONE-A CAS 58749-22-7

1.1 Induction of tumor cell apoptosis

Apoptosis, also known as programmed cell death, is an active cell suicide behavior. Under normal circumstances, cell proliferation and apoptosis maintain a balance relationship. Once this balance relationship is disrupted, it may lead to tumorigenesis. Tumor cells can be induced to mutate and apoptosis by chemical drugs. Licochalcone A acts on human ovarian cancer OVCAR-3 and SK-OV-3 cells, can down-regulate Bid, Bcl-2, Bcl-xL and survivin protein levels, and up-regulate Bax protein levels; it can cause a decrease in mitochondrial membrane potential and promote Cytochrome C releases, activates Caspases (-8, -9, -3); promotes the cleavage of PARP-1; up-regulates the expression level of the tumor suppressor gene p53, thereby promoting apoptosis. Similar studies found that licochalcone A can induce the human breast cancer cell line MCF-7 cells and human promyelosomes by down-regulating the expression of the anti-apoptotic protein Bcl-2, reducing the Bcl-2/Bax ratio, and promoting the cleavage of PARP protein. The leukemia cell line HL-60 cells apoptosis; recent studies also show that licochalone A can induce the apoptosis of gastric cancer cells, the mechanism may be related to the cleavage of PARP protein, down-regulation of Caspase-3, Bcl-2 protein expression, and up-regulation of Bax protein expression related. In vivo experiments showed that licochalcone A could significantly inhibit tumorigenesis in BALB/c mice subcutaneously inoculated with colorectal cancer CT-26 cells. Immunohistochemical TUNEL staining found that with the increase of licochalcone A dose, the proportion of apoptotic cells increased. gradually increase.

1.2 Prevention of chemical carcinogenesis, inhibition of tumor invasion and metastasis

Metastasis of malignant tumor cells is one of the characteristics that distinguish them from normal cells, and is its own biological feature. Tumor metastasis is the main reason for endangering the life of the host and affecting the therapeutic effect. Licochalcone A has obvious preventive effect on the tumor induced by chemical drugs. C57BL/6 colon cancer mice induced by azomethane chemical method were orally administered 5, 15, 30 mg·kg-1 licochalone A, The incidence of tumor was significantly reduced and was dose-dependent. In addition, a study on the prevention of metastasis by licochalone A found that licochalone A could significantly improve the survival rate of nude mice injected with CT-26 cells in the spleen, and at the same time inhibit liver metastasis.

1.3 Induction of tumor cell differentiation

Malignant tumor cells are similar to undifferentiated embryonic cells in morphology and function, and have the characteristics of high division. Induction of differentiation refers to the reversal of the re-differentiation of malignant tumors towards normal maturation in the presence of a differentiation-inducing agent. At present, tumor induction and differentiation therapy is a new idea and new method for tumor treatment. In vitro studies of licorice chalcone A have shown that it has inhibitory effects on a variety of tumor cells. Glycochalcone A acts on human promyelocytic leukemia HL-60 cells, which can induce an increase in the expression of non-specific esterase (NSE). Blue tetrazolium (NBT) reducing ability has no effect, NSE is a marker of macrophage (monocyte) formation, and NBT reducing ability is a marker of granulocyte formation, it is speculated that licochalone induces HL-60 cells to monocytes Cells differentiate instead of granulocytes.

1.5 Inhibition of angiogenesis

Tumor growth and metastasis depend on angiogenesis. Studies have found that licochalone A can inhibit angiogenesis both in vitro and in vivo. In vitro studies have found that licochalone A can significantly inhibit the proliferation (20μmol·L-1), migration (5-20μmol·L-1) and lumen formation (10-20μmol·L-1) of human umbilical cord vascular endothelial cells (HUVECs). 1), and the growth of rat aortic ring microvessels (10～20μmol·L-1) in a dose-dependent manner. In vivo studies showed that licochalcone A significantly inhibited the growth of colorectal cancer CT-26 cells inoculated in BALB/c mice. With the increase of concentration, CD31 and Ki-67 positive cells in tumor tissue decreased, but the apoptosis rate increased significantly. Its anti-angiogenic mechanism may be related to down-regulating vascular endothelial growth factor receptor (VEGFR)-2 activation and blocking VEGF/VEGFR-2 signaling pathway.

2.1 Inhibition of NO synthesis

Both acute and chronic inflammation are related to NO. Inducible NO synthase (iNOS) is an important enzyme that mediates inflammatory responses. In pathological conditions, iNOS catalyzes the production of excessive NO. The arachidonic acid metabolite prostaglandin (PG), as an inflammatory mediator, also plays an important role in the inflammatory response of tissues, and cyclooxygenase (COX) plays a key role in the PG synthesis pathway. COX-2 catalyzes the synthesis of large amounts of PG. Licochalcone A reduces LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in RAW264. 7 cells, thereby inhibiting cellular NO and prostaglandin (PG) E (2 ) production, while also inhibiting the production of inflammatory cytokines IL-1β and IL-6. The results of in vivo experiments showed that licochalcone A played a protective effect on LPS-induced endotoxic shock in nude mice by inhibiting the production of various inflammatory cytokines and NO.

2.2 Inhibition of NF-κB activation

NF-κB can efficiently induce inflammatory cytokines (TNF-α, IL-1, IL-6, etc.), chemokines, adhesion factors (ICM-1, VCM-1), inflammatory enzymes (iNOS, COX-2) Isogenic expression, amplifies the inflammatory response cascade, and is highly activated at sites of inflammation in a variety of inflammatory diseases. Glycochalcone A can exert anti-inflammatory effect by inhibiting the activation of NF-κB. Glycochalcone A can inhibit TNF-α-induced nuclear localization, DNA binding activity and NF-κB transcriptional activity. Its mechanism It may be related to the inhibition of IκK activation and IκB degradation by licochalone A. Glycochalcone A significantly inhibited NO production, TNF-α expression and MCP-1 expression levels in lipopolysaccharide (LPS)-induced RAW267.4 cells and macrophages. Plasma TNF-α and MCP-1 levels were also significantly reduced in C57BL/6 mice administered licochalcone A before LPS injection. Licochalcone A significantly inhibited LPS-induced TNF-α transcriptional activation, but had no effect on IκBα degradation and phosphorylation, nuclear transport and DNA binding activity of NF-κBP65, suggesting that the anti-inflammatory effect of licochalone A may be due to By inhibiting the activation of NF-κB. In addition, licochalone A can reduce the level of urinary protein in nephritis mice, significantly inhibit xylene-induced mouse ear swelling and carrageenan-induced rat foot swelling, and fight against various skin inflammations, including child-specific Dermatitis and skin inflammation caused by ultraviolet radiation.

Glycochalcone A has inhibitory effect on a variety of pathogenic bacteria. Enterotoxins produced by Staphylococcus aureus may cause a variety of diseases in the human body, including Staphylococcus aureus gastroenteritis, food poisoning, etc. The sub-inhibitory concentration of licorice chalcone A can significantly reduce methicillin-sensitive golden yellow glucose Enterotoxin A (SEA) and Enterotoxin B (SEB) secretion by cocci and methicillin-resistant Staphylococcus aureus. Licorice chalcone A can significantly down-regulate the expression of hla and agr genes in Staphylococcus aureus in vitro, inhibit the secretion of α-toxin, and inhibit its hemolytic activity, inhibit the formation of Candida albicans biofilm, and prevent it from becoming more pathogenic bacteria. Changes in silk growth status. Another study pointed out that licochalone A can inhibit the growth of Bacillus in food, and also has a good bacteriostatic effect on human pathogenic Mycobacterium species and Legionella species.