CN110075104A - Kuwanon H在制备抗骨质疏松药物中的应用 - Google Patents
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- APPXYONGBIXGRO-AIQWNVMPSA-N kuwanone G Chemical compound O=C([C@H]1[C@@H](CC(C)=C[C@@H]1C1=C2OC(=C(C(C2=C(O)C=C1O)=O)CC=C(C)C)C=1C(=CC(O)=CC=1)O)C=1C(=CC(O)=CC=1)O)C1=CC=C(O)C=C1O APPXYONGBIXGRO-AIQWNVMPSA-N 0.000 description 1
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Abstract
本发明公开了一种天然产物在制备抗骨质疏松药物中的应用。本发明所涉及到的化合物为Kuwanon H，中文名称为：桑皮酮H，分子式为：C45H44O11，分子量为：760.82。体外细胞试验表明该化合物能促进MC3T3‑E1Subclone 14细胞的增殖，体内动物试验表明其对泼尼松诱导的斑马鱼骨质疏松具有显著的治疗作用。
Description
技术领域
本发明涉及一种天然产物，更具体地说，是涉及Kuwanon H在制备抗骨质疏松药物中的应用。
背景技术
骨质疏松症是多种原因引起的一种以骨组织含量减少，骨的微观结构退化为特征，致使骨的脆性增加、强度降低而导致易于发生骨折的一种全身性骨骼疾病。随着人类社会逐渐进入老龄化，骨质疏松症的患病率逐年增加。骨质疏松不仅严重威胁着人们的健康，由此带来的骨折也给人们带来了沉重的负担。
骨重塑是一个复杂的生物学过程，在这一过程中，破骨细胞完成骨的吸收功能，成骨细胞主导骨的形成功能，二者生成及活性的协调是骨重塑过程维持骨骼结构完整的关键。健康骨骼处于骨形成与骨吸收动态平衡的状态，这种平衡一旦被打破可导致骨质疏松、骨硬化病等多种骨代谢性疾病。
越来越多的研究表明，传统中药里有许多活性物质具有抗骨质疏松作用，如黄酮类、皂苷类、生物碱类、香豆素类、苯丙酸类化合物等，因此从传统中药里寻找具有抗骨质疏松活性的有效物质，是开发抗骨质疏松药物的重要途径。Kuwanon H是桑科植物当中所含的一种黄酮类化合物，研究表明该化合物具有降血压、降血脂、抗HIV等作用，但未见其抗骨质疏松方面的研究报道。
发明内容
本发明的目的是：发现Kuwanon H在制备抗骨质疏松药物中的应用。
本发明是这样实现的：Kuwanon H在制备抗骨质疏松药物中的应用，中文名称为：桑皮酮H，分子式为：C45H44O11，分子量为：760.82，该化合物具体结构如下式。
为了明确Kuwanon H的抗骨质疏松活性，发明人进行了如下实验：
培养MC3T3-E1Subclone 14细胞，采用MTT法研究该化合物对成骨细胞增殖的影响，结果表明，该化合物能促进MC3T3-E1Subclone 14细胞的增殖。
随机选取3dpf野生型AB品系斑马鱼于6孔板中，给予泼尼松处理建立骨质疏松症模型。28℃培养箱处理5天后，用0.2％钙黄绿素对斑马鱼进行染色，染色后拍照并采集数据，以斑马鱼前三节脊椎骨的荧光强度评价该化合物对斑马鱼骨质疏松症的治疗作用。结果显示，该化合物能显著增加斑马鱼的骨密度，对泼尼松诱导的骨质疏松症具有显著的治疗作用。
本发明首次公开了该化合物对成骨细胞的活性作用，并对斑马鱼骨质疏松症的治疗作用进行了研究，说明此化合物可用于防治骨质疏松等骨丢失性疾病。该化合物能促进成骨前体细胞增殖，具有逆转骨丢失，提高骨密度的作用。能将其作为制备抗骨质疏松药物的有效成分。
具体实施方式
本发明通过下面的实施例予以进一步说明，但实施例并不限定本发明的范围。
实施例1：Kuwanon H对成骨细胞活性作用的研究
将MC3T3-E1Subclone l4细胞以5000个/孔的密度接种到96孔板中，24h后换含药培养基，48h后每孔加入10μL MTT(5mg/mL)，继续孵育4h后，吸弃各培养孔上清液，分别加入150μL二甲基亚砜，振荡10min，用酶标仪在490nm波长处测定OD值，计算增殖率，结果见表1。
表1 Kuwanon H对MC3T3-E1Subclone 14细胞增殖的影响
与空白组比较，**p<0.01
结果表明，Kuwanon H各浓度组吸光度与空白对照组相比，均具有显著性差异(p<0.01)，表明Kuwanon H具有促成骨细胞增殖作用。
实施例2：Kuwanon H对斑马鱼骨质疏松治疗作用评价
随机选取3dpf野生型AB品系斑马鱼于6孔板中，水溶给予泼尼松处理以建立斑马鱼骨质疏松症模型。对骨质疏松模型斑马鱼分别水溶给予1μM Kuwanon H，阳性对照药依替膦酸二钠300μg/mL浓度，同时设置正常对照组(养鱼用水处理正常斑马鱼)和模型对照组。28℃培养箱处理5天后，用0.2％钙黄绿素对斑马鱼进行染色，染色后进行拍照并分析统计斑马鱼前三节脊椎骨累积光密度，统计学处理结果用mean±SE表示。
结果表明，模型对照组的斑马鱼脊椎骨累积光密度与正常对照组比较p<0.01，提示模型构建成功；阳性对照药依替膦酸二钠组的斑马鱼脊椎骨累积光密度(43625像素)与模型对照组(14294像素)比较p<0.01，其斑马鱼骨质疏松治疗作用为113％，提示阳性药对泼尼松诱导的斑马鱼骨质疏松症具有显著的治疗作用。Kuwanon H组的斑马鱼脊椎骨累积光密度，与模型对照组比较有显著性差异(p<0.01)，说明Kuwanon H对泼尼松诱导的斑马鱼骨质疏松症具有显著的治疗作用。详见表2。
表2 Kuwanon H对斑马鱼骨质疏松症的治疗作用(n＝10)
与模型对照组比较，**p<0.01
结果显示，该化合物能显著增加斑马鱼的骨密度，对泼尼松诱导的骨质疏松症具有显著的治疗作用。
此外，发明人解释，本申请的化合物的研究是发明人在实验过程的真实研究发现，本申请与另一件同日提交的专利申请《Kuwanon G在制备抗骨质疏松药物中的应用》虽然看起来相似，而且在实验方法上采用了相同的实验方法，但是对这两种化合物的研究都、实验以及实验产生的数据都是真实的，而不是为了专利数量而进行数据编造的虚假申请。所有实验的进行均有委托实验单位的合同、证明文件等手续，如果审查需要，可以随时提供。
Claims (1)
1.一种天然产物在制备抗骨质疏松药物中的应用，其特征在于：该化合物为KuwanonH，中文名称为：桑皮酮H，分子式为：C45H44O11，分子量为：760.82，具体结构如下式：
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181168A (zh) * | 2021-05-31 | 2021-07-30 | 西南大学 | 桑皮酮h在制备抗阿尔兹海默症药物中的应用 |
| CN114539282A (zh) * | 2022-02-25 | 2022-05-27 | 南京中医药大学 | 一种具有抗骨质疏松功效的化合物及其制备方法和应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105452269A (zh) * | 2013-06-17 | 2016-03-30 | 尤妮金公司 | 用于关节健康的组合物和方法 |
| CN106588947A (zh) * | 2016-12-07 | 2017-04-26 | 江西中医药大学 | 波罗蜜中的异戊烯基黄酮类化合物及其抗骨质疏松新用途 |
| CN107206040A (zh) * | 2014-06-16 | 2017-09-26 | 尤尼根公司 | 用于管理或改进骨病症、软骨病症或二者的组合物和方法 |
| US20180064779A1 (en) * | 2014-06-16 | 2018-03-08 | Unigen, Inc. | Compositions and Methods for Managing or Improving Bone Disorders, Joint Disorders, Cartilage Disorders, or a Combination Thereof |
-
2019
- 2019-06-14 CN CN201910513956.4A patent/CN110075104A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105452269A (zh) * | 2013-06-17 | 2016-03-30 | 尤妮金公司 | 用于关节健康的组合物和方法 |
| CN107206040A (zh) * | 2014-06-16 | 2017-09-26 | 尤尼根公司 | 用于管理或改进骨病症、软骨病症或二者的组合物和方法 |
| US20180064779A1 (en) * | 2014-06-16 | 2018-03-08 | Unigen, Inc. | Compositions and Methods for Managing or Improving Bone Disorders, Joint Disorders, Cartilage Disorders, or a Combination Thereof |
| CN106588947A (zh) * | 2016-12-07 | 2017-04-26 | 江西中医药大学 | 波罗蜜中的异戊烯基黄酮类化合物及其抗骨质疏松新用途 |
Non-Patent Citations (3)
| Title |
|---|
| HUIJUAN WANG等: "Sanggenon C Stimulates Osteoblastic Proliferation and Differentiation, Inhibits Osteoclastic Resorption,and Ameliorates Prednisone-Induced Osteoporosis in Zebrafish Model", 《MOLECULES》 * |
| 张静等: "桑白皮不同部位对实验性高脂糖尿病小鼠的影响", 《中药新药与临床药理》 * |
| 肖川云等: "波罗蜜根中的异戊烯基黄酮类成分", 《药学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113181168A (zh) * | 2021-05-31 | 2021-07-30 | 西南大学 | 桑皮酮h在制备抗阿尔兹海默症药物中的应用 |
| CN114539282A (zh) * | 2022-02-25 | 2022-05-27 | 南京中医药大学 | 一种具有抗骨质疏松功效的化合物及其制备方法和应用 |
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