Anti‐Postmenopausal osteoporosis effects of Isopsoralen: A bioinformatics‐integrated experimental study

Abstract

Isopsoralen (IPRN), which comes from the fruit of Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proven to be effective for the treatment of osteoporosis (OP). However, the mechanisms underlying IPRN's anti‐OP effects, especially the anti‐postmenopausal osteoporosis (PMOP) effects, remain indistinct. Thus, this study aimed to investigate the effects and mechanisms of IPRN's anti‐PMOP activity. In this study, the bioinformatics results predicted that IPRN could resist PMOP by targeting EGFR, AKT1, SRC, CCND1, ESR1 (ER‐α), AR, PGR, BRCA1, PTGS2, and IGF1R. An ovariectomized (OVX) mice model and a H2O2‐induced bone marrow mesenchyml stem cells (BMSCs) model confirmed that IPRN could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation in H2O2‐induced BMSCs by inhibiting oxidative stress and apoptosis. Moreover, IPRN could significantly produce the above effects by upregulating ESR1. IPRN might be a therapeutic agent for PMOP by acting as an estrogen replacement agent and a natural antioxidant.

Multi-layered Network Analysis of Osteoking in the Treatment of Osteoporosis: Unraveling Mechanisms from Gene Expression to Molecular Docking

“…Furthermore, its correlation with the proliferation of osteoblasts underscores its pivotal role in bone health [27,28] . PTGS2 is a key protein regulating inflammatory responses and cellular apoptosis, and its modulation in bone metabolism may be related to Osteoking's anti-inflammatory and pro-survival effects on bone cells [29][30][31] . PRKCA, a protein kinase C isoform, is intricately linked to crucial biological processes such as cell proliferation, differentiation, and apoptosis [32,33] .…”

Multi-layered Network Analysis of Osteoking in the Treatment of Osteoporosis: Unraveling Mechanisms from Gene Expression to Molecular Docking

“…Furthermore, its correlation with the proliferation of osteoblasts underscores its pivotal role in bone health [27,28] . PTGS2 is a key protein regulating in ammatory responses and cellular apoptosis, and its modulation in bone metabolism may be related to Osteoking's anti-in ammatory and pro-survival effects on bone cells [29][30][31] . PRKCA, a protein kinase C isoform, is intricately linked to crucial biological processes such as cell proliferation, differentiation, and apoptosis [32,33] .…”

Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2

“…IL-17A is a classic pro-osteogenic cytokine [9][10][11][12][13]. In addition, IL-17A has the ability to inhibit autophagy; it is involved in the pro-osteogenic effect [12,13].…”

“…Remarkably, adding H 2 O 2 can construct the classic in vitro cell model for oxidative stress, especially osteoporosis-associated oxidative stress. H 2 O 2related cell models have been used in various in vitro studies of osteoporosis, including postmenopausal and senile osteoporosis [9][10][11], making it representative in exploring the solutions to oxidative stress-induced bone loss. Therefore, finding effective strategies to resist the damage of H 2 O 2 is crucial for establishing a good osteogenic environment.…”

“…IL-17A is an important pro-osteogenic factor. Previous study showed that IL-17A can promote osteoblastic differentiation, and bone regeneration and remodeling [9]. IL-17A can also exhibit strong osteogenic effects when directly intervening with bone marrow mesenchymal stem cells (MSCs) [10].…”