Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway

Abstract

Background. Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods. Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results. In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1β. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion. Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.

The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis

“…When exploring the mechanism, we focused on the PI3K–AKT pathway. PI3K is a crucial lipoprotein kinase controlling the proliferation, survival, and movement of cells after ligand activation [ 59 ], while AKT is a direct downstream target of PI3K [ 60 ]. The PI3K–AKT signaling pathway is crucial to osteoblast survival and differentiation [ 61 ].…”

“…P-AKT expression was also reduced after using the PI3K inhibitor, demonstrating that AKT acts as a downstream signal for PI3K, consistent with previous research [ 53 ]. The PI3K–AKT signaling pathway has been suggested as an effective OP therapeutic target [ 60 , 65 ]. Our results indicated that ZGP and ED-71 could synergistically affect T2DOP by upregulating the PI3K–AKT signaling pathway.…”

Exploring the molecular mechanism of Ling-Gui-Zhu-Gan decoction for the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking: A review

“…[32] The PI3K/Akt signaling pathway of key downstream factors is closely related to the regulation of glucose and lipid metabolism, [33] and data suggesting a reduction in the occurrence of diabetic osteoporosis with further upregulation of PI3K/Aktrelated protein levels. [34] In turn, activation of the HIF-1 signaling pathway is associated with inflammatory and fibrotic processes in the renal unit and vascular calcification in patients with T2DM. [35,36] In conclusion, the pharmacological process of LGZG decoction for the treatment of T2DM may be a synergistic combination of multiple active ingredients, multiple action targets, and multiple signaling pathways.…”