Corylifol A protects against ovariectomized-induced bone loss and attenuates RANKL‐induced osteoclastogenesis via ROS reduction, ERK inhibition, and NFATc1 activation

Xu, Yongfu; Song, Dezhi; Lin, Xiaofeng; Su, Yuangang; Liang, Jiamin; Hai, Na; Zhao, Jinmin; Liu, Qian

doi:10.1016/j.freeradbiomed.2023.01.017

Cited by 10 publications

(5 citation statements)

References 63 publications

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“…However, prolonged use of these agents may cause side effects leading to drug discontinuation, which highlights the need for a safe, efficacious alternative (Zhang et al, 2023). Recently, numerous herbal extracts have been researched as potential anti-osteoporosis therapeutic options owing to their potent effects and few side effects (Takagi et al, 2022;Zheng et al, 2022;Xu et al, 2023). This study presents novel findings showing that NBP suppresses osteoclast differentiation and bone resorption in vitro through reducing RANKL-induced ROS levels and blocking the MAPK signaling pathway.…”

Section: Discussionmentioning

confidence: 84%

Unveiling the potential of Butylphthalide: inhibiting osteoclastogenesis and preventing bone loss

Yanbin,

Yilin,

Yaomin

et al. 2024

Front. Pharmacol.

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Osteoporosis, resulting from overactive osteoclasts and leading to elevated fracture risk, has emerged as a global public health concern due to the aging population. Therefore, inhibiting osteoclastogenesis and bone resorption function represents a crucial approach for preventing and treating osteoporosis. The purpose of this study was to examine the effects and molecular mechanisms of Butylphthalide (NBP) on the differentiation and function of osteoclasts induced by RANKL. Osteoclastogenesis was assessed through TRAP staining and bone slice assay. An animal model that underwent ovariectomy, simulating postmenopausal women’s physiological characteristics, was established to investigate the impact of Butylphthalide on ovariectomy-induced bone loss. To delve deeper into the specific mechanisms, we employed Western blot, PCR, immunofluorescence, and immunohistochemical staining to detect the expression of proteins that are associated with the osteoclast signaling pathway. In this study, we found that Butylphthalide not only suppressed osteoclastogenesis and bone resorption in vitro but also significantly decreased TRAcP-positive osteoclasts and prevented bone loss in vivo. Further mechanistic experiments revealed that Butylphthalide reduces intracellular ROS in osteoclasts, inhibits the MAPK and NFATc1 signaling pathways, and downregulates the key genes and proteins of osteoclasts. This inhibits osteoclast formation and function. The reduction in ROS in osteoclasts is intricately linked to the activity of Butylphthalide-modulated antioxidant enzymes. Overall, NBP may offer a alternative treatment option with fewer side effects for skeletal diseases such as osteoporosis.

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Section: Discussionmentioning

confidence: 84%

Unveiling the potential of Butylphthalide: inhibiting osteoclastogenesis and preventing bone loss

Yanbin,

Yilin,

Yaomin

et al. 2024

Front. Pharmacol.

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“…Previous studies with antioxidant compounds such as the peptides PIISVYWK and FSVVPSPK from Mytilus edulis [55], the adipokine Apelin-13 [56], Ginkgolide B from Ginkgo biloba [57], polyphenolic extract from melon (Cucumis melo L.) [58], Orientin, a C-glycosyl flavonoid [18], and Resveratrol, a polyphenolic compound from grapes [59], demonstrated a protective effect on the bone microarchitecture of OVX mice or rats similarly to that of ASSNAC. Furthermore, the antioxidants Corylifol A [60] and lycopene [61] were shown to target the femur trabecular but not cortical bone microarchitecture in OVX mice similarly to the ASSNAC effect on the trabecular but not the cortical bone.…”

Section: Discussionmentioning

confidence: 90%

S-Allylmercapto-N-Acetylcysteine (ASSNAC) Attenuates Osteoporosis in Ovariectomized (OVX) Mice

Bleichman,

Hiram-Bab,

Gabet

et al. 2024

Antioxidants

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Osteoporosis is a bone-debilitating disease, demonstrating a higher prevalence in post-menopausal women due to estrogen deprivation. One of the main mechanisms underlying menopause-related bone loss is oxidative stress. S-allylmercapto-N-acetylcysteine (ASSNAC) is a nuclear factor erythroid 2-related factor 2 (Nrf2) activator and cysteine supplier, previously shown to have anti-oxidation protective effects in cultured cells and animal models. Here, we studied the therapeutic potential of ASSNAC with and without Alendronate in ovariectomized (OVX) female mice. The experimental outcome included (i) femur and L3 lumbar vertebra morphometry via Micro-Computed Tomography (μCT); (ii) bone remodeling (formation vs. resorption); and (iii) oxidative stress markers in bone marrow (BM) cells. Four weeks after OVX, there was a significant bone loss that remained evident after 8 weeks, as demonstrated via µCT in the femur (cortical and trabecular bone compartments) and vertebra (trabecular bone). ASSNAC at a dose of 50 mg/Kg/day prevented bone loss after the four-week treatment but had no significant effect after 8 weeks, while ASSNAC at a dose of 20 mg/Kg/day significantly protected against bone loss after 8 weeks of treatment. Alendronate prevented ovariectomy-induced bone loss, and combining it with ASSNAC further augmented this effect. OVX mice demonstrated high serum levels of both C-terminal cross-linked telopeptides of type I collagen (CTX) (bone resorption) and procollagen I N-terminal propeptide (P1NP) (bone formation) after 2 weeks, and these returned to control levels after 8 weeks. Alendronate, ASSNAC and their combination decreased CTX and increased P1NP. Alendronate induced oxidative stress as reflected by decreased glutathione and increased malondialdehyde (MDA) levels, and combining it with ASSNAC partially attenuated these changes. These results portray the therapeutic potential of ASSNAC for the management of post-menopausal osteoporosis. Furthermore, ASSNAC ameliorates the Alendronate-associated oxidative stress, suggesting its potential to prevent Alendronate side effects as well as improve its bone-protective effect.

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“…Culturing and treatment of BMMs were done with Ppg (0, 40, and 80) in 96-well plates. As previously described [ 51 ], staining, detection, and imaging of mature osteoclasts were done using RGB and DAPI channels with the aid of a Biotek microscope.…”

Section: Methodsmentioning

confidence: 99%

Periplogenin attenuates LPS-mediated inflammatory osteolysis through the suppression of osteoclastogenesis via reducing the NF-κB and MAPK signaling pathways

Gan,

Lian,

Yang

et al. 2024

Cell Death Discov.

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The key target for treating inflammatory osteolysis is osteoclasts. In an inflammatory environment, osteoclast differentiation increases, and bone resorption is enhanced. Periplogenin (Ppg) is a traditional Chinese medicine. It has anti-inflammatory and antitumor effects, but its impact on inflammatory osteolysis is unknown. This study found that Ppg prevented LPS-induced skull osteolysis by inhibiting the expression of inflammatory cytokines and osteoclast production. In vitro, Ppg blocked the RANKL-induced generation of osteoclasts, the development of pseudopodia bands, and bone resorption. Ppg also attenuated the expression of NFATc1, c-Fos, CTSK, and Atp6v0d2 proteins by inhibiting the NFATc1 signaling pathway. In addition, Ppg inhibited the expression of osteoclast-specific genes, including NFATc1, c-Fos, CTSK, Atp6v0d2, and Mmp9. Moreover, Ppg also inhibited NF-κB and MAPK pathways. In vivo, Ppg reduced the number of osteoclasts on the surface of the bone and suppressed LPS-induced osteolysis of the skull. These outcomes suggest that Ppg can serve as a new alternative therapy for treating inflammatory osteolysis by inhibiting inflammation and osteoclasts.

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Corylifol A protects against ovariectomized-induced bone loss and attenuates RANKL‐induced osteoclastogenesis via ROS reduction, ERK inhibition, and NFATc1 activation

Cited by 10 publications

References 63 publications

Unveiling the potential of Butylphthalide: inhibiting osteoclastogenesis and preventing bone loss

Unveiling the potential of Butylphthalide: inhibiting osteoclastogenesis and preventing bone loss

S-Allylmercapto-N-Acetylcysteine (ASSNAC) Attenuates Osteoporosis in Ovariectomized (OVX) Mice

Periplogenin attenuates LPS-mediated inflammatory osteolysis through the suppression of osteoclastogenesis via reducing the NF-κB and MAPK signaling pathways

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