RESUMEN
Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.
Asunto(s)
Chalcona , Glucocorticoides , Osteoporosis , Quinonas , Ratas Sprague-Dawley , Animales , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control , Osteoporosis/metabolismo , Osteoporosis/tratamiento farmacológico , Ratas , Quinonas/farmacología , Chalcona/análogos & derivados , Chalcona/farmacología , Glucocorticoides/efectos adversos , Antiinflamatorios/farmacología , Densidad Ósea/efectos de los fármacos , Masculino , Femenino , Dexametasona/farmacologíaRESUMEN
Intervertebral disc degeneration (IDD) is a major cause of a number of spinal diseases, resulting in serious public health problems. Evodiamine (Evo) is an indole quinazoline alkaloid extracted from Evodia rutaecarpa, which has antioxidant, antiapoptosis and antiinflammatory effects. The purpose of the present study was to investigate lipopolysaccharide (LPS)induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism. The viability and apoptosis of NPCs were detected by Cell Counting Kit8 (CCK8) and TUNEL staining, respectively. Western blotting was used to detect the expression levels of proteins, cell transfection was performed to knockdown Sirtuin 1 (SIRT1) and the expression of tumor necrosis factoralpha (TNFα) and interleukin 6 (IL6) was detected by enzymelinked immunosorbent assay kits. The results showed that Evo effectively alleviated LPSinduced NPCs apoptosis and caspase3 activation and Evo treatment reversed the upregulation of matrix metalloproteinase13, as well as the downregulation of collagen type II (collagen II), Srytype highmobilitygroup box 9 and aggrecan and reduced the production of proinflammatory factors TNFα and IL6 in LPSstimulated NPCs. In addition, treatment with Evo upregulated SIRT1 and activated the PI3K/Akt pathway, knockdown of SIRT1 inhibited the phosphorylation of Akt and PI3K in LPSstimulated NPCs. In general, Evo upregulated SIRT1 and inhibited LPSinduced NPCs apoptosis, extracellular matrix degradation and inflammation by activating the PI3K/Akt pathway.