Cissus quadrangularis (Hadjod) Inhibits RANKL-Induced Osteoclastogenesis and Augments Bone Health in an Estrogen-Deficient Preclinical Model of Osteoporosis Via Modulating the Host Osteoimmune System

Abstract

Osteoporosis is a systemic skeletal disease characterised by low bone mineral density (BMD), degeneration of bone micro-architecture, and impaired bone strength. Cissus quadrangularis (CQ), popularly known as Hadjod (bone setter) in Hindi, is a traditional medicinal herb exhibiting osteoprotective potential in various bone diseases, especially osteoporosis and fractures. However, the cellular mechanisms underpinning its direct effect on bone health through altering the host immune system have never been elucidated. In the present study, we interrogated the osteoprotective and immunoporotic (the osteoprotective potential of CQ via modulating the host immune system) potential of CQ in preventing inflammatory bone loss under oestrogen-deficient conditions. The current study outlines the CQ’s osteoprotective potential under both ex vivo and in vivo (ovariectomized) conditions. Our ex vivo data demonstrated that, in a dose-dependent manner CQ, suppresses the RANKL-induced osteoclastogenesis (p < 0.001) as well as inhibiting the osteoclast functional activity (p < 0.001) in mouse bone marrow cells (BMCs). Our in vivo µ-CT and flow cytometry data further showed that CQ administration improves bone health and preserves bone micro-architecture by markedly raising the proportion of anti-osteoclastogenic immune cells, such as Th1 (p < 0.05), Th2 (p < 0.05), Tregs (p < 0.05), and Bregs (p < 0.01), while concurrently lowering the osteoclastogenic Th17 cells in bone marrow, mesenteric lymph nodes, Peyer’s patches, and spleen in comparison to the control group. Serum cytokine analysis further supported the osteoprotective and immunoporotic potential of CQ, showing a significant increase in the levels of anti-osteoclastogenic cytokines (p < 0.05) (IFN-γ, IL-4, and IL-10) and a concurrent decrease in the levels of osteoclastogenic cytokines (p < 0.05) (TNF-α, IL-6, and IL-17). In conclusion, our data for the first time delineates the novel cellular and immunological mechanism of the osteoprotective potential of CQ under postmenopausal osteoporotic conditions.

Dietary restriction‐induced alterations on estrogen receptor alpha expression in regulating fertility in male Coturnix coturnix japonica: Relevance of Withania somnifera in modulation of inflammation and oxidative stress in testis

“…Five micrometer thick paraffin sections of testes were prepared, deparaffinized by dipping the glass slides in xylene for 10−15 min followed by a rinse with tri‐chlorotrifluoroethane (C 2 Cl 3 F 3 ) and dried by solvent evaporation. The specimen was given a surface conductive coat of gold (Au) for further insights 22 . For doing this, the backscattered electron (BSE) image has been used.…”

“…The specimen was given a surface conductive coat of gold (Au) for further insights. 22 For doing this, the backscattered electron (BSE) image has been used. The images were captured at low and high magnifications using by scanning electron microscope (FEI Nova NanoSEM 450).…”

Withaferin-A attenuates T2DM-induced male reproductive dysfunction mediated by ERα in brain and testes of Swiss albino mice

“…The body weight of all mice was recorded and then anaesthetized with Ketamine (100-150 mg/kg) and Xylazine (5-16 mg/kg) 37 for collecting blood via retro-orbital sinus. For serum isolation, the blood was allowed to clot in tubes by keeping it undisturbed at RT for 20 minutes.…”

Fine‐tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis

“…It has been observed that the ethanolic extract of C. quadrangularis contains flavonoids and phenolic substances with immunomodulatory potential that significantly inhibits bone resorption postovariectomy (Banu et al, 2012). In addition, our group recently reported that via modulating the immunoporotic potential of distinct immune cells (Th1, Th2, Th17, Treg, and Breg) C. quadrangularis administration has significantly enhanced the bone health in ovariectomized mice model (Azam et al, 2023). Native to the Indian subcontinent, Moringa oleifera , a member of Moringaceae family, is a fast‐growing, drought‐resistant tree and is one of the most nutritious food supplements.…”