Drynaria fortunei improves lipid profiles of elderly patients with postmenopausal osteoporosis via regulation of Notch1-NLRP3 inflammasome-mediated inflammation

Abstract

Background

Dyslipidemia is a common comorbidity in elderly patients with postmenopausal osteoporosis (PMOP). Drynaria fortunei (Rhizoma drynariae) is well-known in traditional Chinese medicine for its ability to improve bone mineral density (BMD). However, whether and how Drynaria fortunei improves plasma lipid profiles in elderly PMOP patients remains unclear.

Methods

Eighty elderly female patients with concurrent PMOP and hyperlipemia were randomly assigned to Drynaria fortunei 2(n = 40) or control (n = 40) groups. The clinical efficacies of Drynaria fortunei were evaluated. At 0, 3-, 6-, 9-, and 12-month of follow-up, plasma levels of IL-1β, IL-18, TNF-α, IL-6, IL-8, and IL-10 were measured using ELISA, whereas PBMC levels of NLRP3, ASC, caspase-1, NF-κB, SIRT1, and Notch1 were measured using RT-qPCR. PBMC isolated from PMOP patients were cultured and treated with Drynaria fortunei to determine its influence on NLRP3 inflammasome and associated cytokines.

Results

Drynaria fortunei effectively improved patients’ BMD and lipid profiles. IL-1β, IL-18, TNF-α, IL-6, IL-8 levels, as well as inflammasome-molecules of NLRP3, ASC, caspase-1, and NF-κB increased over time in the control group, but were significantly attenuated with Drynaria fortunei administration. In vitro, Drynaria fortunei suppressed NLRP3 inflammasome and associated cytokines by increasing SIRT1 or decreasing Notch1. Drynaria fortunei had inhibitory effects on NLRP3 inflammasome and Notch1 even when SIRT1 expression was suppressed.

Conclusions

Drynaria fortunei has been demonstrated to significantly improve lipid profiles for elderly PMOP patients. Drynaria fortunei may down-regulate Notch1 independently of SIRT1 to suppress NLRP3 inflammasome-mediated inflammation, thus improving plasma lipid profile.

骨碎补通过调节Notch1-NLRP3炎症小体介导的炎症改善老年绝经后骨质疏松症患者的血脂谱 摘要

背景：血脂异常是老年绝经后骨质疏松症(PMOP)患者常见的合并症。骨碎补是一种可提高骨密度(BMD)的著名中药。然而, 骨碎补可否以及如何改善老年PMOP患者的血脂谱仍不清楚。

方法：80例老年PMOP合并高脂血症的女性患者随机分为骨碎补2(n=40)和对照组(n=40)。评价骨碎补的临床疗效。分别于0、3、6、9、12个月随访, 用ELISA法检测血浆IL-1b、IL-18、TNF-α、IL-6、IL-8和IL-10水平, 用RT-qPCR法检测PBMC中NLRP3、ASC、caspase-1、NF-κB、SIRT1和Notch1水平。分离培养PMOP患者PBMC并观察骨碎补对NLRP3炎性小体及相关细胞因子的影响。

结果：骨碎补能有效改善患者的骨密度和血脂水平。对照组IL-1b、IL-18、TNF-α、IL-6、IL-8水平以及炎症分子NLRP3、Asc、caspase-1和NF-κB水平随时间延长而升高, 但经骨碎补治疗后明显减弱。在体外, 骨碎补通过增加SIRT1或降低Notch1抑制NLRP3炎症小体及其相关细胞因子。骨碎补在SIRT1表达受抑制时, 对NLRP3炎症小体和Notch1也有抑制作用。

结论：骨碎补能显著改善老年PMOP患者的血脂状况。骨碎补可能不依赖于SIRT1下调Notch1, 从而抑制NLRP3炎症小体介导的炎症, 从而改善血脂谱。

Keywords:

• Postmenopausal osteoporosis
• Drynaria fortunei (Rhizoma drynariae)
• hyperlipemia
• elderly
• NLRP3-inflammasome
• inflammation

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Wuhan Hospital of Traditional Chinese Medicine (WZ20Q09). Written informed consents were given for all participants.

Disclosure statement

All authors declared that they have no conflict of interests.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the Scientific Research Project of Wuhan Health and Family Planning Commission (WZ20Q09) of Traditional Chinese Medicine and integrated Chinese and Western Medicine.