Isosinensetin alleviates estrogen deficiency-induced osteoporosis via suppressing ROS-mediated NF-κB/MAPK signaling pathways

Qin, Yiwu; Song, Dezhi; Liao, Shijie; Chen, Junchun; Xu, Minglian; Su, Yuangang; Lian, Haoyu; Wei, Linhua; Chen, Kai; Xu, Jiake; Zhao, Jinmin; Liu, Qian

doi:10.1016/j.biopha.2023.114347

Cited by 16 publications

(8 citation statements)

References 56 publications

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“…A recent study showed how a flavonoid, isosinensetin (used at low micromolar concentrations, not present in our library screen), can rescue estrogen deficiency-induced osteoporosis through ER pathway activation in murine bone assays. 61 In our high throughput, high content screen, we confirmed many known ER-active compounds (genistein, daidzein, apigenin), and determined that within our 85 hits, 49 (57.6%) had no scientific literature attributing the compound to ERα activation, thus justifying the screening approach with an HT amenable mechanistic HCA-based screen. Interestingly, out of all the hits only two of the compounds induced ER recruitment to the PRL array but suppressed transcription (P276-00 and irigenin).…”

Section: Discussionmentioning

confidence: 70%

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta

Bolt,

Oceguera,

Singh

et al. 2024

iScience

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Section: Discussionmentioning

confidence: 70%

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta

Bolt,

Oceguera,

Singh

et al. 2024

iScience

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“…Additionally, GO and KEGG enrichment analysis utilizing the Metascape database (Zhou et al, 2019) identified numerous signaling pathways, such as the ROS, NF‐κB, and MAPK pathways, that are implicated in osteoclast differentiation. It was shown that RANKL‐induced osteoclastogenesis generates ROS and activates downstream signaling pathways NF‐κB and MAPK (Qin et al, 2023; Zhang et al, 2022). Therefore, the hypothesized mechanism by which CA reduces osteoclast differentiation most likely includes these pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Through this mechanism, NF‐κB is set free and is able to go into the nucleus where it activates target genes important for osteoclastogenesis. ROS are essential in fostering this process because they activate the IκB kinase complex (Sá‐Pessoa et al, 2023; Wang, Wang, et al, 2022), which in turn causes IκBα to degrade and makes it easier for NF‐κB to translocate into the nucleus (Li, Liang, et al, 2022; Qin et al, 2023). In this study, we discovered that CA inhibited the phosphorylation and the nuclear translocation of P65 with less degradation of IkBa.…”

Section: Discussionmentioning

confidence: 99%

“…Among the obtained targets, TNF, EGFR, MMP9, JUN, and CASP3 showed the highest relevance. Additionally, GO and KEGG enrichment analysis utilizing the Metascape database (Zhou et al, 2019) activates downstream signaling pathways NF-κB and MAPK (Qin et al, 2023;Zhang et al, 2022). Therefore, the hypothesized mechanism by which CA reduces osteoclast differentiation most likely includes these pathways.…”

Section: Discussionmentioning

confidence: 99%

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Cichoric acid targets RANKL to inhibit osteoclastogenesis and prevent ovariectomy‐induced bone loss

Xian,

Gao,

et al. 2024

Phytotherapy Research

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Background and AimOsteoporosis, a systemic metabolic bone disease, is characterized by the decline of bone mass and quality due to excessive osteoclast activity. Currently, drug‐targeting osteoclasts show promising therapy for osteoporosis. In this study, we investigated the effect of cichoric acid (CA) on receptor activator of nuclear kappa‐B ligand (RANKL)‐induced osteoclastogenesis and the bone loss induced by ovariectomy in mice.Experimental ProcedureMolecular docking technologies were employed to examine the interaction between CA and RANKL. CCK8 assay was used to evaluate the cell viability under CA treatment. TRAcP staining, podosome belt staining, and bone resorption assays were used to test the effect of CA on osteoclastogenesis and osteoclast function. Further, an OVX‐induced osteoporosis mice model was employed to identify the effect of CA on bone loss using micro‐CT scanning and histological examination. To investigate underlying mechanisms, network pharmacology was applied to predict the downstream signaling pathways, which were verified by Western blot and immunofluorescence staining.Key ResultsThe molecular docking analysis revealed that CA exhibited a specific binding affinity to RANKL, engaging multiple binding sites. CA inhibited RANKL‐induced osteoclastogenesis and bone resorption without cytotoxic effects. Mechanistically, CA suppressed RANKL‐induced intracellular reactive oxygen species, nuclear factor‐kappa B, and mitogen‐activated protein kinase pathways, followed by abrogated nuclear factor activated T‐cells 1 activity. Consistent with this finding, CA attenuated post‐ovariectomy‐induced osteoporosis by ameliorating osteoclastogenesis.Conclusions and ImplicationsCA inhibited osteoclast activity and bone loss by targeting RANKL. CA might represent a promising candidate for treating osteoclast‐related diseases, such as osteoporosis.

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“…Tetramethoxyluteolin (MOL007879) can inhibit the focal inflammation in the brain caused by the cytokine of mast cells and microglia, which results from the co-stimulation of CRH in cooperation with IL-33, to exert neuroprotective effects [46]. Isosinensetin (MOL013277) also inhibits the NF-κB pathway through the MAPK pathway to attenuate inflammatory damage [47].…”

Section: Active Components Of Zhishimentioning

confidence: 99%

Research Progress on the Pharmacodynamic Mechanisms of Sini Powder against Depression from the Perspective of the Central Nervous System

Shen

Dong

2023

Medicina

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Depression is a highly prevalent emotional disorder characterized by persistent low mood, diminished interest, and loss of pleasure. The pathological causes of depression are associated with neuronal atrophy, synaptic loss, and neurotransmitter activity decline in the central nervous system (CNS) resulting from injuries, such as inflammatory responses. In Traditional Chinese Medicine (TCM) theory, patients with depression often exhibit the liver qi stagnation syndrome type. Sini Powder (SNP) is a classic prescription for treating such depression-related syndrome types in China. This study systematically summarized clinical applications and experimental studies of SNP for treatments of depression. We scrutinized the active components of SNP with blood–brain barrier (BBB) permeability and speculated about the corresponding pharmacodynamic pathways relevant to depression treatment through intervening in the CNS. Therefore, this article can enhance our understanding of SNP’s pharmacological mechanisms and formula construction for depression treatment. Moreover, a re-demonstration of this classic TCM prescription in the modern-science language is of great significance for future drug development and research.

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Isosinensetin alleviates estrogen deficiency-induced osteoporosis via suppressing ROS-mediated NF-κB/MAPK signaling pathways

Cited by 16 publications

References 56 publications

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta

Cichoric acid targets RANKL to inhibit osteoclastogenesis and prevent ovariectomy‐induced bone loss

Research Progress on the Pharmacodynamic Mechanisms of Sini Powder against Depression from the Perspective of the Central Nervous System

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