Isopsoralen regulates PPAR‑γ/WNT to inhibit oxidative stress in osteoporosis

Abstract

The present study aimed to examine the effects of isopsoralen against postmenopausal osteoporosis in an ovariectomized rat model. The ovariectomized rats were treated with three days 10 mg/kg isopsoralen or with three days 20 mg/kg isopsoralen. Alkaline phosphatase, the oxidative stress indicators and caspase‑3/9 were measured using ELISA assay kits. Reverse transcription‑quantitative polymerase chain reaction was used to measure collagen type I (Col I), osteocalcin and osteoprotegerin mRNA levels. Wnt, β‑catenin and peroxisome proliferators‑activated receptor γ (PPAR‑γ) were analyzed using western blot analysis. Isopsoralen suppressed mature adipocyte differentiation of C2C12 cells, inhibited serum calcium and urinary calcium levels, and reduced the structural scores of articular cartilage and cancellous bone in the proximal tibia metaphysis of mice with postmenopausal osteoporosis. Isopsoralen also promoted the activity of alkaline phosphatase and the mRNA expression levels of Col 1, osterix and osteopontin in mice with postmenopausal osteoporosis. Oxidative stress and activities of caspase‑3/9 in the mice with postmenopausal osteoporosis were effectively suppressed by isopsoralen treatment, which upregulated the protein expression of Wnt/β‑catenin and downregulated the protein expression of PPAR‑γ. These findings demonstrated that isopsoralen prevented osteoporosis through the regulation of PPAR‑γ/WNT, inhibiting oxidative stress by targeting the PPAR‑γ/WNT pathway. These results provide evidence of the potential targeted therapy for isopsoralen in the clinical treatment of postmenopausal osteoporosis.

Angelicin—A Furocoumarin Compound With Vast Biological Potential

“…Further analysis of the calcium/creatine levels in the urine, calcium and leptin levels in the serum and measurement of the bone mineral density of the rats indicates positive osteogenic differentiation in the rats (Wang et al, 2018). Wnt and b-catenin proteins were also upregulated as well in the cartilage tissue which suggests the activation of Wnt/b-catenin pathway while downregulation PPARg protein expression indicates suppression of adipogenesis (Wang et al, 2018). Angelicin also dosedependently inhibited the upregulation of OCN, COL-1, and osteoprotegerin (OPN)-a soluble decoy receptor that inhibits the function and differentiation of osteoclasts-in the cartilage tissues of the rats with osteoporosis, bringing them back to almost normal levels as compared with the healthy rats (Udagawa et al, 2000;Wang et al, 2018).…”

“…Wnt and b-catenin proteins were also upregulated as well in the cartilage tissue which suggests the activation of Wnt/b-catenin pathway while downregulation PPARg protein expression indicates suppression of adipogenesis (Wang et al, 2018). Angelicin also dosedependently inhibited the upregulation of OCN, COL-1, and osteoprotegerin (OPN)-a soluble decoy receptor that inhibits the function and differentiation of osteoclasts-in the cartilage tissues of the rats with osteoporosis, bringing them back to almost normal levels as compared with the healthy rats (Udagawa et al, 2000;Wang et al, 2018). Based on the in vitro and in vivo analysis, angelicin may potentially be exhibiting proosteogenesis properties by inhibiting ROS in bone resorption.…”

“…In addition, in vivo studies on female Sprague Dawley rats showed similar results concerning angelicin's ability to attenuate oxidative stress. Antioxidants such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) activity in the blood were increased after the treatment with 10 and 20mg/kg angelicin while lipid peroxidation marker malondialdehyde (MDA) was reportedly reduced (Del Rio et al, 2005;Wang et al, 2018). Apart from that, apoptosis markers caspase3/9 were also downregulated in the bone of the rats, suggesting a suppression of cell apoptosis in the bone.…”

“…Significant increase in b-catenin protein expression: ≥ 10 mg/kg angelicin 13. Significant decrease in PPARg protein expression: ≥ 10 mg/kg angelicin (Wang et al, 2018) Antiperiondontitis week old male C57BL/6 mice stimulation with P. gingivalis-derived lipopolysaccharide (Pg-LPS) (e) Treatment for 9 days on hPDLCs in osteogenic induction assay. On the 3rd day, the expression of osteogenic proteins was analyzed via measurement of concentration in BCA protein assay kit.…”

“…Hence, the decrease of ALP in the blood of the rats indicates that there is a decrease in bone turnover rate by angelicin. Further analysis of the calcium/creatine levels in the urine, calcium and leptin levels in the serum and measurement of the bone mineral density of the rats indicates positive osteogenic differentiation in the rats (Wang et al, 2018). Wnt and b-catenin proteins were also upregulated as well in the cartilage tissue which suggests the activation of Wnt/b-catenin pathway while downregulation PPARg protein expression indicates suppression of adipogenesis (Wang et al, 2018).…”