Water extract of Er-xian decoction selectively exerts estrogenic activities and interacts with SERMs in estrogen-sensitive tissues

Wong, K.P.; Zhou, Liping; Yu, Wenxuan; Poon, Chi‐Ming; Xiao, Huihui; Chan, Chi-On; Mok, Daniel Kam Wah; Wong, Man Sau

doi:10.1016/j.jep.2021.114096

Cited by 7 publications

(8 citation statements)

References 33 publications

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“…The most general mechanisms contributing to anti-osteoporosis are estrogen-like effects. In previous studies, many TCMs have this effect, including Rhizoma drynaria (Zhou et al, 2022), QingYan formula (Zhao F. et al, 2021), and Er-xian decoction (Wong et al, 2021). QEP is already widely used in the clinic which also has estrogen-like activity (Xiong et al, 2022).…”

Section: Discussionmentioning

confidence: 97%

Qing`e Pill Inhibits Osteoblast Ferroptosis via ATM Serine/Threonine Kinase (ATM) and the PI3K/AKT Pathway in Primary Osteoporosis

Hao

Bei

et al. 2022

Front. Pharmacol.

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Osteoporosis (OP) is an aging-related disease that is the main etiology of fragility fracture. Qing’e Pill (QEP) is a mixture of traditional Chinese medicine (TCM) consisting of Eucommia ulmoides Oliv., Psoralea corylifolia L., Juglans regia L., and Allium sativum L. QEP has an anti-osteoporosis function, but the underlying mechanism remains unclear. In this study, online databases were employed to determine the chemical compounds of QEP and potential target genes in osteoporosis. Potential pathways associated with genes were defined by Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases. A compound–target–disease network was constructed. Hub genes screened through Cytoscape were intersected with the FerrDB database. The potential key genes were validated in HFOB 1.19 cells, and rat models were ovariectomized through Western blot, RT-qPCR, ELISA, HE staining, immunohistochemistry, and immunofluorescence analyses. The intersection targets of QEP and osteoporosis contained 121 proteins, whereas the target–pathway network included 156 pathways. We filtered five genes that stood out in the network analysis for experimental verification. The experiments validated that QEP exerted therapeutic effects on osteoporosis by inhibiting ferroptosis and promoting cell survival via the PI3K/AKT pathway and ATM. In conclusion, combining the application of network analysis and experimental verification may provide an efficient method to validate the molecular mechanism of QEP on osteoporosis.

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Section: Discussionmentioning

confidence: 97%

Qing`e Pill Inhibits Osteoblast Ferroptosis via ATM Serine/Threonine Kinase (ATM) and the PI3K/AKT Pathway in Primary Osteoporosis

Hao

Bei

et al. 2022

Front. Pharmacol.

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“…These results suggested the estrogen-like effect of RD and tamoxifen in osteoporotic rats, in which RD acted mainly on bone formation while tamoxifen governed both bone formation and resorption. Also, our previous study demonstrated a positive correlation between BMD and serum E2 and a negative correlation between BMD and serum FSH or LH at the distal femur in OVX rats (15). FSH has also been reported to regulate osteoclastogenesis, bone resorption, and bone turnover biomarkers in postmenopausal women (16,17).…”

Section: Discussionmentioning

confidence: 83%

Water Extract of Rhizoma Drynaria Selectively Exerts Estrogenic Activities in Ovariectomized Rats and Estrogen Receptor-Positive Cells

et al. 2022

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Our previous study demonstrated that the bone protective actions of herbal medicine Rhizoma Drynariae (Gusuibu, RD) were mainly mediated by flavonoid phytoestrogens via estrogen receptors, raising concerns about the safety of using RD as it may induce estrogen-like risk-benefit profile and interact with other ER ligands, such as selective estrogen receptor modulators (SERMs), when coadministered. The present study evaluated the estrogenic activities of RD and its potential interaction with tamoxifen, a SERM, in estrogen-sensitive tissues by using mature ovariectomized (OVX) rats and ER-positive cells. Similar to but weaker than tamoxifen, RD at its clinical dose dramatically ameliorated OVX-induced changes in bone and dopamine metabolism-related markers in OVX rats. However, tamoxifen, but not RD, induced uterotrophic effects. No significant alteration in mammary gland was observed in OVX rats treated with RD, which was different from the inhibitory actions of tamoxifen. The two-way ANOVA results indicated the interactions between RD and tamoxifen in the bone, brain, and uterus of OVX rats while RD did not alter their responses to tamoxifen. Our results demonstrate that RD selectively exerts estrogenic actions in a different manner from tamoxifen. Moreover, RD interacts with tamoxifen without altering its effects in OVX rats.

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“…TCM are characterized by their synergistic effects on multiple pathways, targets, and signaling pathways through various active ingredients. The mechanism of action against osteoporosis includes: 1. inhibiting osteoclast resorption activity ( 31 – 33 ); 2. promoting bone trabecular maturation and osteoblast increase ( 34 – 39 ) ( 32 , 40 , 41 ); 3. accelerating osteoclast metabolic activity ( 42 ); 4. protecting gonads and increasing sex hormone levels; restoring the amount of bone lost due to the decline in the level of sex hormones ( 43 , 44 ). We took the representative traditional Chinese patent medicine (Xianling Gubao capsule) and decoction (Erxian decoction) with high recommendation frequency and many research materials as examples to further analyze their active ingredients and mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

Osteoporosis guidelines on TCM drug therapies: a systematic quality evaluation and content analysis

Zhang,

Li,

Xie

et al. 2024

Front. Endocrinol.

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ObjectiveThe aims of this study were to evaluate the quality of osteoporosis guidelines on traditional Chinese medicine (TCM) drug therapies and to analyze the specific recommendations of these guidelines.MethodsWe systematically collected guidelines, evaluated the quality of the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool, and summarized the recommendations of TCM drug therapies using the Patient-Intervention-Comparator-Outcome (PICO) model as the analysis framework.Results and conclusionsA total of 20 guidelines were included. Overall quality evaluation results revealed that four guidelines were at level A, four at level B, and 12 at level C, whose quality needed to be improved in the domains of “stakeholder involvement”, “rigor of development”, “applicability” and “editorial independence”. Stratified analysis suggested that the post-2020 guidelines were significantly better than those published before 2020 in the domains of “scope and purpose”, “stakeholder involvement” and “editorial independence”. Guidelines with evidence systems were significantly better than those without evidence systems in terms of “stakeholder involvement”, “rigor of development”, “clarity of presentation” and “applicability”. The guidelines recommended TCM drug therapies for patients with osteopenia, osteoporosis and osteoporotic fracture. Recommended TCM drugs were mainly Chinese patent medicine alone or combined with Western medicine, with the outcome mainly focused on improving bone mineral density (BMD).

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Water extract of Er-xian decoction selectively exerts estrogenic activities and interacts with SERMs in estrogen-sensitive tissues

Cited by 7 publications

References 33 publications

Qing`e Pill Inhibits Osteoblast Ferroptosis via ATM Serine/Threonine Kinase (ATM) and the PI3K/AKT Pathway in Primary Osteoporosis

Qing`e Pill Inhibits Osteoblast Ferroptosis via ATM Serine/Threonine Kinase (ATM) and the PI3K/AKT Pathway in Primary Osteoporosis

Water Extract of Rhizoma Drynaria Selectively Exerts Estrogenic Activities in Ovariectomized Rats and Estrogen Receptor-Positive Cells

Osteoporosis guidelines on TCM drug therapies: a systematic quality evaluation and content analysis

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