Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone

Abstract

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis.

Diabetes Perturbs Bone Microarchitecture and Bone Strength through Regulation of Sema3A/IGF-1/β-Catenin in Rats

“…They found that Sema3A beneficially contributed to bone volume, bone-to-implant contact ratio and the maximal push-out force by improving peri-implant bone implant, osseointegration and fixation. Similarly, Ma et al demonstrated that naringin, the main active constituent of citrus fruits, improved bone development through increasing Sema3A expression and regulation of Wnt/β-catenin signaling [26, 27]. Clinically, Sema3A and its receptor plexin A2 is positively associated with osteocalcin [28] and BMD [29] in postmenopausal women.…”

Treatment of Mice with Naringin Alleviates the Doxorubicin-Induced Oxidative Stress in the Liver of Swiss Albino Mice

“…35,38,39 It has been found to be anti-inflammatory, antidiabetic, antifibortic, antiosteoporotic, antidyslipidemic and protected against lipodystrophy and iron induced toxicity. [40][41][42][43][44] Naringin may also have protective effects on cognition and oxidative damage. 45 Naringin reduced cell viability and cell proliferation by arresting the cell cycle at the G1 phase in 5637 cells and inhibited cyclin D1/CDK4 and cyclin E-CDK2 complexes by the increased expression of p21WAF1 and activation of Ras/Raf/ERK.…”

In ovo injection of flavanone on bone quality characteristics, biochemical parameters and antioxidant enzyme status of blood in daily chicks

“…Flavonone as a plant secondary metabolites can operate as phytoestrogens and show a wide range of health beneficial effects on bone quality. Flavonoid extract increased the tibial and femoral growth and as a result improved bone length (Choudhary et al, ; Ma et al, ; Xu, Li, Wooley, Yang, & Jiang, ). Examining histomorphometry of bone showed wider distal femoral and proximal tibial growth plate, increased the number and size of hypertrophic chondrocytes with subsequent improvement of longitudinal bone growth, which helped achieving the more mineralization of bone during ageing and growing (Choudhary et al, ).…”

“…The higher doses of naringin can promote the osteoblast differentiation in contrast to osteoclast differentiation. The researchers show the activity of naringin by upregulating osteocalcin (Li, Jiang, Woole, Xu, & Yang, ; Ma et al, ) osteoblast differentiation and inhibiting activity of osteoclastogenesis by downregulating of C‐terminal telopeptides of collagen type 1 (CTX‐1) an index of bone resorption activity, in plasma (Li et al, ). These results show that flavonone like naringin can act as a potent agent in bone formation and metabolism (Mandadi et al, ).…”

“…Normally occurring flavonoid, myricetin, prevents oxidative damage in osteoblastic MC3T3‐E1 cells (Lee & Choi, ), and quercetin, a plant‐derived flavonoid, protects gestational oxidative stress‐related bone damage, supporting a potential benefit of antioxidant nutrients in bone pathophysiology (Prater, Laudermilch, Liang, & Holladay, ). It has been specified that Naringin, flavanone‐7‐O‐glycoside (4′,5,7‐Trihydroxyflavanone 7‐rhamnoglucoside), in citrus fruits, stimulate the bone formation in vitro and in vivo conditions (Choudhary et al, ; Ma et al, ). It is identified that flavonoids derivatives increased Ca and P retention in the tibia (Tahmasbi, Mirakzehi, Hosseini, Agah, & Kazemi, ).…”