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Application of hippuric acid in preparing osteoporosis resistant drug

A technology for benzoylglycine and osteoporosis, which is applied to the application field of benzoylglycine active small molecules in the preparation of anti-osteoporosis drugs, and can solve the problems of unclear biological activity, low benzoylglycine, etc. , to increase the number of osteoblasts, increase bone mass, and reduce the number of osteoclasts

Inactive Publication Date: 2019-02-22
浙江欧谱生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] There are few previous research reports on benzoylglycine, and its biological activity is not clear

Method used

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  • Application of hippuric acid in preparing osteoporosis resistant drug
  • Application of hippuric acid in preparing osteoporosis resistant drug
  • Application of hippuric acid in preparing osteoporosis resistant drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Bone marrow ST2 stromal cells (ST2Cells), bipotential preosteoblasts (C2C12Cells), primary mouse bone marrow stromal cells (BMC Cells) were supplemented with 10% fetal bovine serum (FBS), penicillin (100 units / ml), strepto Mycin (100 μg / ml) and glutamine (4 mM) were cultured on α-MEM medium. They were then incubated with benzoylglycine at a final concentration of 60 μg / dl (1× concentration) for 12 days, and the solvent was used as a control (n=3). Use bone-specific alkaline phosphatase (ALP) staining, and then detect cell changes under a microscope, the results are as follows figure 1 Shown (data are expressed as mean ± SEM (n = 3 / group). Compared with the control group, t test was used, and significant differences are indicated by * (pfigure 1 The results showed that HA significantly promoted the proliferation and differentiation of osteoblasts.

Embodiment 2

[0029] Pre-adipocyte 3T3L1 cells (3T3L1Cells) were cultured using the same method, and then incubated with benzoylglycine at different concentrations of 30 μg / dl (0.5x), 60 μg / dl (1x), and 120 μg / dl (2x) for 3 days, and the solvent was used as a control (n=3). (Data are expressed as mean ± SEM (n=3 / group). Compared with the control group, t-test was used, and significant differences were indicated by * (p figure 2 It shows that benzoylglycine can inhibit the proliferation of adipocytes in a concentration-dependent manner (2A), and promote the differentiation of adipocytes into osteoblast-like cells (2B) (10x and 20x tables represent magnifications).

Embodiment 3

[0031] Female C57BL / 6J mice were purchased from Jackson Laboratory (Bar Harbor, Me, USA). These postnatal day (PND) 25 mice were randomly assigned to 5 groups (n=5). All five groups of mice received an AIN-93G diet formulated with casein as the sole protein source throughout the experiment. The control group was intraperitoneally injected with normal saline every day, and the other four groups were injected with HA at a dose of 0.1, 0.5, 1 or 5 mg / kg / day, named as the four HA test groups of 0.1, 0.5, 1, and 5, respectively. All groups of mice were fed in pairs, and the food and caloric intake in the five groups were strictly controlled. The mice were kept under the conditions established by the Animal Evaluation and Accreditation Committee of the Arkansas Children's Hospital Research Center, with constant humidity, a temperature of 22°C, and light hours from 6:00 am to 6:00 pm. All animal experimental procedures were approved by the Arkansas Medical College Animal Care and U...

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Abstract

The invention discloses an application of hippuric acid in preparing an osteoporosis resistant drug. The structure of the hippuric acid is shown in a formula (I). The hippuric acid can promote proliferation and differentiation of marrow ST2 matrix cells (ST2 Cells), double potential preosteoblasts (C2C12 Cells) and primary mouse marrow stroma cells (BMC) to form osteoblasts, inhibit proliferationof preadipocytes (3T3L1) and promote conversion thereof into osteoblasts, promote formation of bone trabecula in vivo, increase the quantity of osteoblasts, reduce the quantity of osteoclasts, improvethe mineralization rate of surface of the bone and the bone speed of formation and increase the bone weight, promote expression of p38 MAP kinase and osterix pathway proteins and enhance related mRNAlevel, inhibit expression of PPARgamma proteins and reduce the level of mRNA and treat osteoporosis by increasing the bone weight.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of a benzoylglycine (Hippuric Acid / HA) active small molecule in the preparation of anti-osteoporosis drugs. Background technique [0002] Osteoporosis (OP), as the most common bone disease, is one of the worldwide problems that seriously threaten human health, and the incidence of this disease increases significantly with age. Research reports have shown that about 140 million people in China suffer from osteoporosis, which seriously affects the health of Chinese people. Therefore, the prevention and treatment of osteoporosis is very urgent. However, at present, various drugs for the prevention and treatment of osteoporosis generally focus on calcium supplements and health care products, such as Merck's Fosamax and domestically produced Gubang. They can only alleviate symptoms, none of which can achieve a curative effect and all need to be taken for a long ...

Claims

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Application Information

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IPC IPC(8): A61K31/198A61P19/10A61P19/08
CPCA61K31/198A61P19/08A61P19/10
Inventor 陈尽染
Owner 浙江欧谱生物科技有限公司
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