Ginsenoside Rg1 interferes with the progression of diabetic osteoporosis by promoting type H angiogenesis modulating vasculogenic and osteogenic coupling

Abstract

Ginsenoside Rg1 (Rg1) has been demonstrated to have antidiabetic and antiosteoporotic activities. The aim of this study was to investigate the protective effect of Rg1 against diabetic osteoporosis and the underlying mechanism. In vitro, we found that Rg1 increased the number of osteoprogenitors and alleviated high glucose (HG) induced apoptosis of osteoprogenitors by MTT assays and flow cytometry. qRT‒PCR and western blot analysis suggested that Rg1 can also promote the secretion of vascular endothelial growth factor (VEGF) by osteoprogenitors and promote the coupling of osteogenesis and angiogenesis. Rg1 can also promote the proliferation of human umbilical vein endothelial cells (HUVECs) cultured in high glucose, enhance the angiogenic ability of endothelial cells, and activate the Notch pathway to promote endothelial cells to secrete the osteogenesis-related factor Noggin to regulate osteogenesis, providing further feedback coupling of angiogenesis and osteogenesis. Therefore, we speculated that Rg1 may have similar effects on type H vessels. We used the Goto-Kakizaki (GK) rat model to perform immunofluorescence staining analysis on two markers of type H vessels, Endomucin (Emcn) and CD31, and the osteoblast-specific transcription factor Osterix, and found that Rg1 stimulates type H angiogenesis and bone formation. In vivo experiments also demonstrated that Rg1 promotes VEGF secretion, activates the Noggin/Notch pathway, increases the level of coupling between type H vessels and osteogenesis, and improves the bone structure of GK rats. All of these data reveal that Rg1 is a promising candidate drug for treating diabetic osteoporosis as a potentially bioactive molecule that promotes angiogenesis and osteointegration coupling.

Herbal Extracts of Ginseng and Maqui Berry Show Only Minimal Effects on an In Vitro Model of Early Fracture Repair of Smokers

“…The effect of MBE on vessels in the fracture environments is not known from the current literature, but anthocyanins have been reported to suppress CD31 expression in tumor environments and platelets [51,71]. On the contrary, type H vessel formation in rodents as well as the expression of CD31 and Endomucin in endothelial cells have been shown to be supported by different ginseng root extracts and ginsenosides, including P. quinquefolium saponin (PQS, from American ginseng), saponin Ophiogonin D, or ginsenoside Rg1 [47,72,73].…”

Role of miRNA-regulated type H vessel formation in osteoporosis

“…In addition to identifying the type H vessels, Kusumbe and colleagues found that the number of type H endothelial cells and osteoblasts decreases in experimental mice with aging, indicating that age-related OP may be related to the reduction of type H endothelial cells (17). Other scholars also found that type H endothelial cells decreased in other rodent models of different types of OP, such as postmenopausal OP (23), glucocorticoid-induced OP (24), disuse OP (25), and diabetic OP (26). In human subjects, Wang and colleagues first demonstrated the type H vessel is present in the proximal femur near the greater trochanter and coupled with osteoprogenitors.…”

Bone Aging and Osteoporosis: Recent Evidence Focusing on Plant-Based Natural Products

“…Curcumin prevents bone loss and promotes angiogenesis in diabetic OP mice by suppressing the hyper glucose-activated NF-κB pathway to restore osteogenic and angiogenic coupling of BMSC in hyperglycemia (147). In addition, Ginsenoside Rg1 facilitates the secretion of VEGF, triggers the Noggin/Notch signaling pathway, and enhances the interaction between H-type blood vessels and bone formation, leading to an improvement in bone structure in a mouse model of diabetic OP (148). Besides, Salvianolic acid B and Salidroside were also reported to prevent bone loss by enhancing angiogenesis in Glucocorticoidinduced and OVX-induced OP model, respectively, (149,150).…”