Qing`e Pill Inhibits Osteoblast Ferroptosis via ATM Serine/Threonine Kinase (ATM) and the PI3K/AKT Pathway in Primary Osteoporosis

Abstract

Osteoporosis (OP) is an aging-related disease that is the main etiology of fragility fracture. Qing’e Pill (QEP) is a mixture of traditional Chinese medicine (TCM) consisting of Eucommia ulmoides Oliv., Psoralea corylifolia L., Juglans regia L., and Allium sativum L. QEP has an anti-osteoporosis function, but the underlying mechanism remains unclear. In this study, online databases were employed to determine the chemical compounds of QEP and potential target genes in osteoporosis. Potential pathways associated with genes were defined by Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases. A compound–target–disease network was constructed. Hub genes screened through Cytoscape were intersected with the FerrDB database. The potential key genes were validated in HFOB 1.19 cells, and rat models were ovariectomized through Western blot, RT-qPCR, ELISA, HE staining, immunohistochemistry, and immunofluorescence analyses. The intersection targets of QEP and osteoporosis contained 121 proteins, whereas the target–pathway network included 156 pathways. We filtered five genes that stood out in the network analysis for experimental verification. The experiments validated that QEP exerted therapeutic effects on osteoporosis by inhibiting ferroptosis and promoting cell survival via the PI3K/AKT pathway and ATM. In conclusion, combining the application of network analysis and experimental verification may provide an efficient method to validate the molecular mechanism of QEP on osteoporosis.

Chronotherapy involving rosiglitazone regulates the phenotypic switch of vascular smooth muscle cells by shifting the phase of TNF-α rhythm through triglyceride accumulation in macrophages

“…Addressing the clock system poses significant challenges. While it is well-established that light and feeding patterns can influence circadian rhythms through neurological and hormonal mechanisms [ 32 ], these methods for modulating the body's circadian rhythms in disease treatment remain largely impractical [ [33] , [34] , [35] ]. Recently, attention has turned to the development of pharmacological compounds designed to target Rev-erb and ROR nuclear receptors within the circadian mechanism, offering potential clinical applications [ [36] , [37] , [38] ] [ [36] , [37] , [38] ] [ [36] , [37] , [38] ].…”

Modified Qing’ e Pills exerts anti-osteoporosis effects and prevents bone loss by enhancing type H blood vessel formation

“…It is currently used mainly for back pain caused by osteoporosis and is included in the Chinese osteoporosis treatment guidelines. It has various pharmacological activities, such as anti-inflammatory, anti-aging, and estrogenic properties ( 11 , 36 ). Although MQEP has been used in China for more than 1,300 years, its mechanism of action is still unclear and is only explained based on TCM theories; its clinical use relies more on the experience of TCM doctors.…”

N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3β pathway

“…The relative expressions of genes were conducted according to established protocols ( Wang and Mu, 2021 ; Hao et al, 2022 ; Liu et al, 2022 ). Total RNA from the cells was extracted using a Trizol extraction reagent (Biosharp, Guangzhou, China).…”