Escin CAS 6805-41-0

The anti-inflammatory effect of Escin is similar to that of dexamethasone, but its action time is longer, and it has an effect on the spleen index (SI), thymus index (TI), splenocyte proliferation ability (PS), lymphocyte count (LC) of experimental animals. , Serum tumor necrosis factor-α (TNF-α) level had no significant effect. Aescin does not significantly increase the secretion of corticosteroids in serum, nor does it promote the apoptosis of immune cells in the spleen and thymus, so its anti-inflammatory effect does not depend on the secretion of corticosteroids.

When studying the effect of aescin on the survival rate of lipopolysaccharide-induced endotoxemia mice, it was found that Escin can inhibit the release of high mobility group box B1 (HMGB1) from macrophages, and reduce the levels of TNF-α and IL in macrophages. -1β, IL-6 levels, inhibit the activation of NF-κB, and improve the survival rate of mice. In addition, the antioxidant activity of aescin can enhance its anti-inflammatory ability. Aescin can increase the activity of myeloperoxidase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduce serum NO, TNF-α and IL-1β inflammatory factors Increase the expression and function of glucocorticoid receptor, greatly reduce the degree of lung injury in endotoxemia mice, and prolong their survival time. External application of aescin can significantly inhibit carrageenan-induced paw edema in rats, and the effect is more obvious after pretreatment with dexamethasone; it can significantly inhibit xylene-induced ear edema in mice, and the curative effect is better than that of dexamethasone alone; it can inhibit The improvement of skin vascular permeability caused by histamine, but the curative effect is worse than that of dexamethasone; the subacute granulomatous inflammation induced by cotton balls is obviously inhibited, and the curative effect is better than that of dexamethasone. Experiments show that aescin can significantly inhibit PGE2, The increase of TNF-α and IL-1β inflammatory factors may be related to the participation of glucocorticoid receptors.

Escin can significantly inhibit the exudation of inflammatory tissue, reduce its permeability, and has a significant effect on the edema and damage of various tissues. Studies have confirmed that large doses of aescin can significantly inhibit the increase in blood-retinal barrier permeability caused by ischemia/reperfusion in rats, reduce retinal edema, and effectively inhibit retinal edema and vision loss; the combination of aescin and triamcinolone acetonide The application has a synergistic protective effect on the blood-retinal barrier ischemia/reperfusion injury, and the combined use of the two can significantly reduce the permeability of the blood-retinal barrier after ischemia, while a small dose of aescin or triamcinolone acetonide alone has no such effect In addition, the combined application can promote the expression of the tight junction protein occludin, resist the damage of the blood-retinal barrier, and significantly improve the curative effect.

In the treatment of allergic inflammation, the experiment found that the treatment of small doses of prednisone combined with aescin can significantly reduce paw swelling in animal models of arthritis, reduce synovial inflammatory cell infiltration, inhibit synovial hyperplasia and bone erosion, and reduce serum TNF-α, IL-1β and IL-6 levels, and reduce the side effects of high-dose hormones. Aescin can inhibit the skin allergic reaction in a dose-dependent manner. The allergic skin reaction of experimental animals administered orally at 5 mg/kg aescin was significantly inhibited on the second day, and the range of skin redness and swelling was significantly reduced. Its anti-allergic effect may be Associated with the glucocorticoid receptor pathway. In terms of airway allergic inflammation, β-escin sodium can inhibit the activation and degranulation of mouse mast cells in the skin, prevent fluid from penetrating into tissues, and reduce type I hypersensitivity reactions; inhibit lung tissue inflammation and reduce white blood cells , eosinophils, IL-5 and IL-13 in the alveolar accumulation, reduce airway inflammation, reduce the intensity of delayed type Ⅰ hypersensitivity.

There is increasing evidence that numerous small molecules such as various inflammatory molecules, transcription factors, adhesion molecules, activating protein 1 (AP-1), chemokines, CRP, COX-2, ILs, 5-lipoxygenase (5-LOX), MMPs, NF-κB, signal transducer and activator of transcription 3 (STAT3), TNF, VEGF play an important role in the occurrence of chronic diseases such as inflammation and tumors. Escin can prevent or delay the occurrence of chronic diseases such as tumors by inhibiting these inflammatory pathways. A number of basic studies have confirmed that aescin can kill cancer cells through various mechanisms.

2.1 Anti-tumor effect of synergistic chemotherapy drugs Studies have found that Escin can enhance the anti-tumor effect of chemotherapy drugs and reverse multidrug resistance. Aescin can increase the sensitivity of cancer cells to cytokines and chemotherapeutic drugs, induce cell cycle arrest, promote apoptosis of pancreatic cancer cells, enhance the inhibitory effect of gemcitabine on the growth of pancreatic cancer cells, effectively inhibit the proliferation and invasion of cancer cells , and its mechanism may be related to inhibiting the activation of NF-κB and its regulated gene products. Aescin can also improve the chemotherapy effect of chemotherapy drugs on extrahepatic cholangiocarcinoma through the glycogen synthase kinase-3β/β-catenin (GSK3β/β-catenin) pathway, and reverse P-glycoprotein-dependent multidrug resistance .

2.2 Inducing tumor cell cycle arrest and apoptosis Escin can increase the production of reactive oxygen species, reduce the mitochondrial membrane potential and increase the release of cytochrome C, induce apoptosis of bladder cancer cells, and inhibit the growth of bladder tumors. In addition, it can block STAT3 signaling pathway, inhibit upstream JAK1 and JAK2 activation, and downregulate STAT3-regulated gene products such as cyclin D1 (cyclin D1), B-cell lymphoma/leukemia-2 gene (Bcl-2), B cell Lymphoma/Leukemia-XL (Bcl-XL), Survivin (Survivin), Myeloid Leukemia Gene-1 (Mcl-1), and VEGF, Promote Cleavage of Poly ADP-ribose Polymerase (PARP), Inhibit Progen Proliferation of primary liver cancer cells and promotion of apoptosis of cancer cells. Aescin can induce apoptosis of cholangiocarcinoma cells by interfering with the cell cycle and mitochondrial caspase-dependent pathways, increasing the ratio of Bax/Bcl-2, and enhancing the activity of reactive oxygen species. Aescin can block the G2-M phase transition of cells, increase the aggregation of cancer cells in the pre-G1 phase and annexin Ⅴ binding, activate caspase-9/3, increase PARP cleavage and Bax protein levels, and reduce anti-apoptotic proteins such as The levels of Bcl-2, apoptosis inhibitory protein and survivin can also induce the generation of reactive oxygen species (ROS), lead to abnormal mitochondrial membrane potential, and finally induce apoptosis of human renal cancer cells.

2.3 Inhibition of tumor angiogenesis Sodium aescinate can inhibit the proliferation and migration of endothelial cells, inhibit the vitality of endothelial cells, and induce apoptosis of endothelial cells. Its anti-angiogenesis effect is probably related to the direct effect on endothelial cells. Aescin can effectively induce the synthesis of cholesterol in endothelial cells, resulting in a decrease in the integrity of the actin cytoskeleton. This change can significantly reduce the response of cells to TNF-α stimulation, which can reduce cell migration and reduce monolayer Endothelial cell permeability inhibits the transcription of NF-κB signaling pathway, which in turn leads to a decrease in the expression of TNF-α-induced effector proteins.

2.4 Inhibition of tumor invasion and metastasis Escin can inhibit the invasion and metastasis of triple-negative breast cancer and other cancer cells. Aescin can inhibit the invasion and metastasis of melanoma cells, significantly reduce the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), and inhibit the expression of NF-κB and inhibitor of nuclear transcription factor κB (IκB). Exogenous supplementation of macrophage chemokine ligand 16 (CXCL16) can reduce the inhibitory effect of aescin on cancer cell migration, and aescin can inhibit focal adhesion kinase (FAK)/serine/threonine protein kinase (Akt) phosphorylation, reduce the activation of CXC-type chemokine receptor 6 (CXCR6)/CXCL16, reduce the expression level of CXCL16, inhibit the expression of TM-CXCL16 induced by sCXCL16 secretion, and finally inhibit the migration and invasion of gastric adenocarcinoma AGS cells .

Escin can also scavenge oxygen free radicals, protect nerve tissue from ischemia/reperfusion injury, and promote the recovery of its function. Sodium aescinate combined with basic fibroblast growth factor can increase the expression of Bcl-2, inhibit the apoptosis of nerve cells, reduce the damage of neurons, nerve axons and myelin sheath, promote the functional recovery after spinal cord injury, and improve motor function. Spinal nerve injury has a synergistic protective effect. Escin can reduce the levels of TNF-α, MMP-9, COX-2 and prostaglandin E2 (PGE2), improve the permeability of the blood-brain barrier, reduce the brain water content, and also have a certain effect on cerebral edema in mice with acute omethoate poisoning Good therapeutic effect.