Shu-Di-Huang and Gan-Cao Herb Pair Restored the Differentiation Potentials of Mesenchymal Stem Progenitors in Treating Osteoporosis via Downregulation of NF-κB Signaling Pathway

Abstract

Background. Shu-Di-Huang (Radix Rehmanniae Praeparata, RR) and Gan-Cao (liquorice, L) are frequently used traditional Chinese herb pair in treating osteoporosis (OP). However, the exact mechanism of the RR and L herb pair (RR-L) remains unclear. To explore the efficacy and possible mechanisms of RR-L in treating OP, in silico, in vitro, and in vivo experiments were conducted in the current study. Methods. In silico, potential therapeutic target genes and active chemical compounds of RR-L herb pair were predicted and constructed into a network. In vivo, 30 Sprague Dawley rats were divided into 3 groups, including the sham group, the OP model group, and the RR-L-treated OP group. Micro-CT and pathological sections were conducted to validate the therapeutic effects of RR-L in treating OP. MSCs of rats were isolated and cultured in vitro to validate the mesenchymal stem cells (MSCs) related phenotype changes, including Alizarin red staining, Oil red staining, and immunofluorescence. In vitro, cell proliferation analysis, Alizarin red staining, Oil red staining, immunofluorescence of NF-κB, and protein expression of PPARγ, RUNX2, OCN, and p65 were conducted on MSCs to explore the RR-L containing serum in vitro. Also, activator and inhibitor of NF-κB signaling pathway were introduced to determine the possible mechanism of RR-L in the treatment of OP via enhancing MSCs proliferation and differentiation. Results. In silico, 168 chemical compounds with a property of oral bioavailability ≥30% and drug-likeness ≥0.18 were recognized as potentially active compounds in RR-L and 249 genes were found to be the targets of which. Among them, 120 genes were found to be therapeutic genes of RR-L in treating OP and KEGG and GO analysis of which demonstrated that RR-L involves in lipid metabolism and multiple inflammation-related signaling pathways. In vivo, ovariectomy- (OVX-) induced OP phenotypes in Sprague Dawley rats include bone mineral density and microarchitecture damaging, abnormal bone metabolism, upregulation of inflammation markers, and damaged differentiation potential of MSCs. Treatment of RR-L reversed the trend and restored the differentiation potential of MSCs. In vitro, RR-L containing serum promoted the osteogenic differentiation and suppressed adipogenic differentiation of MSCs via downregulation of the NF-κB signaling pathway. Also, RR-L containing serum inhibited the tumor necrosis factor-α (TNF-α) induced activation of the NF-κB signaling pathway. On the opposite, the addition of the NF-κB specific inhibitor significantly reduced the effect of RR-L on MSCs. Conclusions. In the current study, network pharmacology prediction and experimental validation elucidated that the RR-L herb pair restored damaged MSC differentiation potential via the NF-κB signaling pathway; this could be the possible mechanism of RR-L in treating OP. This finding provides an alternative option in OP therapy.

Casticin promotes osteogenic differentiation of bone marrow stromal cells and improves osteoporosis in rats by regulating nuclear factor‐κB/mitogen‐activated protein kinase

“…26 Shu-Di-Huang and Gan-Cao inhibits the NF-κB signaling pathway to mediate mesenchymal stem progenitors differentiation. 27 Although CAS was identified to play a part in bladder cancer, 16 skin wound healing 17 and nephrotoxicity, 18 its role and function in osteoporosis maintains to be elucidated. In the current study, we established a rat model of osteoporosis through DEX treatment.…”

“…Arbutin modulates autophagy in osteoblasts to suppress the glucocorticoid‐triggered osteoporosis 26 . Shu‐Di‐Huang and Gan‐Cao inhibits the NF‐κB signaling pathway to mediate mesenchymal stem progenitors differentiation 27 . Although CAS was identified to play a part in bladder cancer, 16 skin wound healing 17 and nephrotoxicity, 18 its role and function in osteoporosis maintains to be elucidated.…”

Si-Wu Water Extracts Protect against Colonic Mucus Barrier Damage by Regulating Muc2 Mucin Expression in Mice Fed a High-Fat Diet

“…Dang gui and chuan xiong are rich in essential oil, which has been adopted to promote blood circulation and dispel blood stasis [ 22 ]. Every single plant in si-wu has also been widely marketed as a health food for women’s care in countries where Asian medicine is used, and si-wu is also beneficial for gastrointestinal health [ 23 , 24 , 25 , 26 ]. In addition, the combination of Puerariae Lobatae Radix and Chuanxiong Rhizoma could improve intestinal permeability, and relieve gut microbiota dysbiosis and gut barrier disruption [ 27 ].…”

Jiawei Yanghe Decoction Regulates Bone-Lipid Balance through the BMP-SMAD Signaling Pathway to Promote Osteogenic Differentiation of Bone Mesenchymal Stem Cells

“…Therefore, enhancing osteogenesis and reducing adipogenesis can increase bone formation by shifting the adipogenesis of BMSCs to osteogenesis. BMSCs have become a hot target for the prevention and treatment of osteoporosis because of the multidirectional differentiation potential, especially the ability to differentiate into osteogenesis [ 12 – 14 ].…”