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Application of helvolic acid to preparation of osteoporosis treating drug

A technology for osteoporosis and fumagillic acid, which is used in drug combinations, pharmaceutical formulations, bone diseases, etc.

Active Publication Date: 2018-11-20
GUANGXI MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effect of fumagic acid on bone metabolism, especially the effect on osteoclasts, has not been reported at home and abroad so far.

Method used

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  • Application of helvolic acid to preparation of osteoporosis treating drug
  • Application of helvolic acid to preparation of osteoporosis treating drug
  • Application of helvolic acid to preparation of osteoporosis treating drug

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Experimental program
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Embodiment Construction

[0016] 1. Materials

[0017] Fumonic acid was purchased from Shanghai Zhenzhun Biotechnology Co., Ltd. and prepared at a concentration of 1 mmol / L in phosphate-buffered saline (PBS). d-minimal essential medium (α-MEM), fetal bovine serum (FBS), osteoclast F ring stain RhodaminePhalloidin, reactive oxygen species (ROS) probe (Fluo-4and 2', 7'-dichlorodihydrofluoresceindiacetate, H 2 DCFDA) was purchased from Thermo Fisher Scientific, Australia. NFATC1, Cathepsin K, c-Fos, IκB-α, ERK, phosphorylated ERK and β-actin antibodies in western blot experiments were purchased from Santa Cruz Biotechnology, USA. MTS kit and luciferase detection kit were purchased from Promega (Sydney, Australia). The expression and purification of the recombinant RANKL protein used in the laboratory was completed in the laboratory of Professor Xu Jiake, School of Medicine, University of Western Australia. Macrophage colony-stimulating factor (M-CSF) was purchased from R&D Company.

[0018] 2. Method ...

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Abstract

The invention discloses an application of helvolic acid to preparation of an osteoporosis treating drug. It is discovered with a tartrate-resistant acid staining method that helvolic acid can effectively inhibit osteoclast formation and is dose-dependent; functional identification shows that the bone absorption function of osteoclasts in a hydroxyapatite plate is also effectively inhibited under obvious drug effect. Besides, a real-time quantitative PCR detection result proves that characteristic genes such as Ctr, Acp5, Ctsk and Atp6v0d2 of the osteoclasts are all inhibited by helvolic acid.Based on the phenomena, further mechanism research indicates that helvolic acid finally affects NFATcl signals and further affects formation and functions of the osteoclasts by affecting EPK phosphorylation, c-Fos signaling pathway, calcium ion oscillation and antioxidative stress effect. Therefore, it is proved that helvolic acid as an effective drug for inhibiting the osteoclasts has great potential in treatment of osteoporosis.

Description

technical field [0001] The invention belongs to the technical field of bone disease treatment, and in particular relates to the application of fumagic acid in the preparation of medicines for treating osteoporosis. Background technique [0002] In the process of life development and growth, bone, as a highly active organ, continuously undergoes two independent and coupled events of bone resorption and bone formation, and the dynamic balance between the two maintains the structure and function of bone . Among them, osteoclasts, as the main players in bone resorption, mediate the occurrence of rare bone resorption-related diseases under normal physiological conditions. For example, excessive osteoclast differentiation and activation is the main cause of osteoporosis in menopausal women. reason. With the increasing aging, osteoporosis has become a worldwide health problem. Osteoporosis is a metabolic bone disease characterized by decreased bone mass and degeneration of bone ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/575A61P19/10
CPCA61K31/575A61P19/10
Inventor 徐家科陈凯赵劲民刘倩宋方茗
Owner GUANGXI MEDICAL UNIVERSITY