Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model

Mousavi, Sima; Vakili, Sina; Zal, Fatemeh; Savardashtaki, Amir; Jafarinia, Morteza; Sabetian, Soudabeh; Razmjoue, Damoun; Veisi, Ali; Azadbakht, Omid; Sabaghan, Mohamad; Behrouj, Hamid

doi:10.1007/s11033-023-08311-w

Cited by 7 publications

(9 citation statements)

References 45 publications

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“…61 Enhanced osteoclast-mediated bone resorption is critical in the early stages of PMOP and rapid glucocorticoid-induced bone loss, suggesting that inhibition of osteoclastic autophagy activity may be potent in reversing bone loss. Consistent with previous studies, 42 western blot and immunofluorescence results revealed a decrease in Beclin1, LC3II/I, and an accumulation of p62, and the effect of QR alone was comparable to that of ALN. HE and TRAP staining also showed that treatment with QR resulted in a tidier arrangement of bone trabeculae, a marked decrease in fat vacuoles and osteoclasts, and an increase in osteocytes.…”

Section: Discussionsupporting

confidence: 91%

“…The recent study combined high-dose ALN (5 g/kg/day) with low-dose QR (15 mg/kg/day), and using ELISA, stereological tests, RT-PCR, and immunofluorescence found that the combination of QR and ALN improved the total number of osteoblasts and bone remodeling indexes in the femur of OVX rats better compared with ALN alone with significant downregulation of autophagy markers and apoptosis-associated genes, hypothesizing that the combination of these two may be an effective therapeutic strategy for the treatment of OP in postmenopausal women. 42 Our study simulated the daily recommended intake of QR supplements, as well as the frequency and dose of clinical ALN intake, with the addition of autophagy and NLRP3 pathway inhibitor treatment groups. Our study aimed to assess more intuitively and systematically whether QR alone as a dietary supplement could achieve similar therapeutic effects of ALN in the OVX-induced mandibular OP in female rats from the perspectives of autophagy and the NLRP pathway by micro-CT, western blotting, and other methods.…”

Section: Discussionmentioning

confidence: 99%

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Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Xiong,

Huang,

Shi

et al. 2023

Exp Biol Med (Maywood)

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With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Xiong,

Huang,

Shi

et al. 2023

Exp Biol Med (Maywood)

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“…In addition, as bone resorption increases, OC/BGP was released from the bone matrix into the blood, resulting in elevated levels in the blood of osteoporotic individuals. The measurement of serum osteocalcin demonstrates its potential as a diagnostic biomarker for postmenopausal osteoporosis in women ( Vakili et al, 2021 ; Mousavi et al, 2023 ). In the ovariectomized (OVX) rat model, there was no significant increase in the control group, and it is speculated that the rate of bone remodeling was not significantly different from that of the sham group.…”

Section: Discussionmentioning

confidence: 99%

Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats

Shi,

Lin,

Lee

et al. 2024

Front. Pharmacol.

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Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

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“…Quercetin mostly exists in the form of glycosides such as rutin, quercetin, and hyperin. Rutin can be hydrolyzed by acid to obtain quercetin. , Numerous studies have shown that quercetin can prevent various diseases, such as osteoporosis, liver cancer, tumors, and cardiovascular diseases . The antioxidant effect of quercetin plays an important role in preventing and treating these diseases. , Quercetin, as a typical flavonoid compound, has shown potential to improve human health due to its in vivo antioxidant activity in the medical field .…”

Section: Introductionmentioning

confidence: 99%

“…Rutin can be hydrolyzed by acid to obtain quercetin. 10 , 11 Numerous studies have shown that quercetin can prevent various diseases, such as osteoporosis, 12 liver cancer, 13 tumors, 14 and cardiovascular diseases. 15 The antioxidant effect of quercetin plays an important role in preventing and treating these diseases.…”

Section: Introductionmentioning

confidence: 99%

Optimization of Preparation Conditions for Quercetin Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability

Liu,

Yu,

et al. 2024

ACS Omega

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Quercetin is a flavonol compound with excellent biological activities. However, quercetin exhibits poor stability and solubility in water, which limits its application. In this study, quercetin nanoliposomes (QUE-NL-1) were prepared using an ultrasonic thinfilm dispersion method, and the preparation conditions were optimized using response surface methodology. The optimal conditions for preparing QUE-NL-1 were as follows: an evaporation temperature of 35 °C, a drug concentration of 0.20 mg/mL, and a lipid bile ratio of 4:1. The encapsulation rate of QUE-NL-1 is (63.73 ± 2.09)%, the average particle size is 134.11 nm, and the average absolute value of the zeta potential is 37.50 and PDI = 0.24. By analyzing the storage temperature, storage time, and leakage rate of QUE-NL-1 in simulated gastrointestinal fluid, it was found that quercetin exhibits good stability after embedding and can achieve sustained release in intestinal juice. In addition, the cytotoxicity of QUE-NL-1 was not significant, and the survival rate of Caco-2 cells was >90% when the concentration range of QUE-NL-1 was 0.1− 0.4 mg/mL. This study provides an efficient method for preparing QUE-NL-1 with small particle sizes, good stability, and high safety, which is of great significance for expanding the application range of quercetin.

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Quercetin potentiates the anti-osteoporotic effects of alendronate through modulation of autophagy and apoptosis mechanisms in ovariectomy-induced bone loss rat model

Cited by 7 publications

References 45 publications

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats

Optimization of Preparation Conditions for Quercetin Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability

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