Application of 14-deoxy-11, 12-dehydrogenation-7, 8-ene-andrographolide and 15-subunit substituted derivative
A technology of andrographolide and its derivatives, which is applied in the field of medicine, and can solve the problems of prolonging the survival period of patients, ineffective organ improvement, large toxic and side effects, and easy drug resistance.
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Embodiment 1
[0074] Example 1 Compounds of the present invention inhibit the migration of human hepatic stellate cells LX-2
[0075] Under the stimulation of various inflammatory mediators, growth factors and other cytokines, hepatic stellate cells migrate to the inflammatory site of the damaged liver tissue, and then proliferate, activate, and synthesize ECM components such as collagen, which is the key to the development of liver fibrosis. Therefore, compared with andrographolide, human hepatic stellate cells LX-2 (provided by Beijing Beina Chuanglian Biotechnology Research Institute) were used to study the anti-hepatic fibrosis effect of the compound of the present invention in vitro by scratch method.
[0076] 1) Cell culture
[0077] LX-2 cells were cultured in RPMI1640 medium containing 10% (V / V) fetal bovine serum, 100 μg / mL streptomycin, and 100 IU / mL penicillin in 5% CO 2 Cultivate in an incubator at saturated humidity at 37°C. Andrographolide was produced by Sichuan Shifang Jin...
Embodiment 2
[0084] Example 2 Compounds of the present invention inhibit mesenchymal transition of human type II alveolar epithelial cells A549
[0085] The type II alveolar epithelial cells present in the alveoli are stimulated by cytokines such as inflammatory mediators and growth factors, and the cell shape changes from pebble-like to spindle-like, completing the epithelial-mesenchymal transition (EMT) and possessing the function of mesenchymal cells , and then synthesize collagen fibers, a large amount of collagen fiber deposition can aggravate the course of pulmonary interstitial fibrosis. Therefore, compared with andrographolide, human type II alveolar epithelial cells A549 were used to evaluate the anti-pulmonary fibrosis effect of the compound of the present invention in vitro by morphological observation and cell scratch (migration) experiments.
[0086] 1) Cell culture
[0087] A549 cells were cultured in RPMI1640 medium containing 10% (V / V) fetal bovine serum, 100 μg / mL strepto...
Embodiment 3
[0097] Example 3 Compounds of the present invention inhibit TGF-β1-induced mesenchymal transition of human renal cortex proximal tubule epithelial cells HK-2
[0098] Early studies have found that renal tubular epithelial cells can transdifferentiate into fibroblasts and express their marker protein fibroblast-specific protein 1 (FSP1, fibroblast-specific protein 1), renal tubular epithelial cells-mesenchymal cell transdifferentiation is the key factor for renal interstitial fibers One of the important pathogenesis of cancer. Therefore, compare with andrographolide AD, utilize human renal cortex proximal tubule epithelial cell HK-2 (provided by China Center for Type Culture Collection), adopt TGF-β1 stimulated morphological observation method and scratch experiment to study the compound of the present invention In vitro anti-renal fibrosis effect.
[0099] 1) Cell culture
[0100] HK-2 cells were cultured in DMEM / F12 medium containing 10% fetal bovine serum (V / V), 100 μg / mL ...
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