Study on the treatment of postmenopausal osteoporosis with quercetin in Liuwei Dihuang Pill based on network pharmacology

Abstract

Background Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored. Methods Protein–protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry. Results Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling. Conclusion Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.

Based on network pharmacology and molecular docking to explore the molecular mechanism of Ginseng and Astragalus decoction against postmenopausal osteoporosis

“…[34] However, the current in vitro research mainly focuses on the prevention and potential mechanism of quercetin on PMO. [35] For the first time, we demonstrated the role of quercetin in PMO through the mining of drug components, construction of network targets and molecular docking verification, which well corroborated previous views and provided a good reference for the next in vivo research or clinical trials of quercetin in the treatment of PMO. With regard to the effect of kaempferol on PMO, only studies have shown that kaempferol has an inhibitory effect on bone loss in rats with osteoporosis after ovariectomy, [36] but there is still no study on its potential mechanism and clinical effect.…”

“…[51,52] Furthermore, AKT and PI3K are generally downregulated when osteoporosis occurs, illustrating that the progression of osteoporosis might be associated with cell injury. [35,53,54] There are many other studies on the role of PI3K/AKT pathway in PMO, for example, silence of miR-483-5p can alleviate postmenopausal osteoporosis through PI3K/AKT pathway [55] ; Chlorogenic acid can prevent osteoporosis in ovariectomized rats through PI3K/Akt pathway. [56] Therefore, PI3K/AKT pathway is an important pathway for the occurrence and development mechanism of PMO, and also an important medium for the treatment of PMO.…”

Pharmacological and mechanistic aspects of quercetin in osteoporosis

“…Que can reduce FAC-induced apoptosis and reactive oxygen species (ROS) production, downregulate the expression of caspase-3 and Bax, and upregulate the expression of Bcl-2 ( Xiao et al, 2023 ; Zhu et al, 2023 ). Que can attenuate chondrocyte apoptosis by modulating the Bcl-2/Bax-caspase-3 signaling pathway to reduce sodium nitroprusside-induced overproduction of intracellular ROS and restore mitochondrial membrane potential ( Hu et al, 2019 ).…”

Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/β-Catenin Signaling Pathway

“…Traditional Chinese medicine (TCM) is extensively used in China to treat various ailments, including OP. Liuwei Dihuang pills (LWDH pills) are a formulated medicine composed of six herbal ingredients: prepared Rehmannia root, Cornus officinalis , Cortex Moutan , Rhizoma Dioscoreae , Poria cocos , and Alismatis Rhizoma [ 10 ]. These herbal ingredients have been extensively recognized to confer therapeutic properties in TCM that include nourishing yin, tonifying the kidneys, replenishing the essence, and benefiting the marrow; in other words, they can promote the balance and stability of the human body’s internal environment and enhance the activity of osteoblasts.…”