An 8-O-4′ norlignan exerts oestrogen-like actions in osteoblastic cells via rapid nongenomic ER signaling pathway

Xiao, Huihui; Gao, Quan-Gui; Ho, Ming-Xian; Zhang, Yan; Wong, Ka-Chun; Dai, Yi; Yao, Xin‐Sheng; Wong, Man-Sau

doi:10.1016/j.jep.2015.05.012

Cited by 14 publications

(10 citation statements)

References 47 publications

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“…The stems and branches of Sambucus williamsii Hance (SWH) (North China red elder) have been used for thousands of years in China as a Traditional Chinese medicine (TCM) for the treatment of bone fractures, rheumatoid arthritis, gout, Kaschin–Beck disease, inflammation-related gastrointestinal disorders, and kidney diseases, as well as wounds. − Specifically, an aqueous EtOH extract of SWH exhibits protective effects on trabecular bone mass and the mechanical strength of cortical bone of ovariectomized (OVX) rats and mice, , a well-established animal model used for the study of estrogen-deficiency-induced bone loss . Further chromatographic separation of the aqueous EtOH fraction led to the isolation, identification, and structure determination of 34 lignans, several phenolic acids, and several triterpenoids. − In vitro bioactivity screening confirmed that several individual lignans possessing either the hydroxy- or oxybenzyl carbons are bioactive and account for much of the bone protective effects of the SWH extract. ,, One representative example is compound 5 , (7 R ,8 S )-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol (Figure ). Compound 5 exhibits estrogen-like effects in osteoblast-like UMR 106 cells, MC3T3-E1 cells, and BMSC cells and exerts actions in osteoblast-like cells via a ligand-independent, estrogen response element (ERE)-independent, and mitogen-activated protein (MAP) kinase-mediated rapid nongenomic ER signaling pathway …”

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NMR Applications for Botanical Mixtures: The Use of HSQC Data to Determine Lignan Content in Sambucus williamsii

Mok

et al. 2019

J. Nat. Prod.

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Lignans found in the botanical extract of the Traditional Chinese Medicine Sambucus williamsii Hance exhibit protective effects on trabecular bone mass and mechanical strength of cortical bone of ovariectomized rats. A novel approach was adapted using HSQC NMR methods to estimate the total amount of these bioactives in a complex mixture. It was determined that lignans possessing the hydroxy- or oxybenzyl carbon signal were bioactive. These compounds were readily identified and assigned in a defined region of the 13C NMR spectrum at 80–90 ppm and calculated as 10–15% of the lignan-rich fraction of S. williamsii. Comparison of the peak heights of the oxybenzyl-substituted carbon resonance signals of the lignans in the botanical extract was made against those of a standard lignan pinoresinol. The application of this simple and reliable NMR method can be used to estimate amounts of related compounds and chemical families in complex mixtures or botanical extracts and offers measurable scientific evidence in quality processes. This is of particular importance for registration requirements of botanical drugs and in complex mixtures of botanical extracts.

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confidence: 99%

NMR Applications for Botanical Mixtures: The Use of HSQC Data to Determine Lignan Content in Sambucus williamsii

Mok

et al. 2019

J. Nat. Prod.

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“…as such, the regulation of estrogen signaling has been explored as a potential treatment for promoting bone formation. For example, a previous study found that 8-o-4'norlignan was able to activate an endoplasmic reticulum signaling pathway in osteoblast-like cells in a ligand-independent, estrogen response element-independent and MaPK-dependent manner (27). another study determined that estrogen receptor-α was expressed in both osteoblasts and osteoclasts, and they further found that estrogen-mediated activation of this receptor within osteoblast progenitor cells promoted cortical bone accrual (28).…”

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confidence: 99%

Identification of key microRNAs and target genes for the diagnosis of bone nonunion

et al. 2020

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a number of recent studies have highlighted the causes of bone nonunion (Bn), however, the rate of Bn incidence continues to rise and available therapeutic options to treat this condition remain limited. Thus, to prevent disease progression and improve patient prognosis, it is vital that BN, or the risk thereof, be accurately identified in a timely manner. in the present study, bioinformatics analyses were used to screen for the differentially expressed genes (deGs) and differentially expressed mirnas (deMs) between patients with Bn and those with bone union, using data from the Gene expression omnibus database. Furthermore, clinical samples were collected and analyzed by reverse transcription-quantitative Pcr and western blotting. In vitro and in vivo experiments were carried out to confirm the relationship between Bn and the deGs of interest, in addition to being used to explore the underlying molecular mechanism of Bn. Functional enrichment analysis of the downregulated deGs revealed them to be enriched for genes associated with 'ecM-receptor interactions', 'focal adhesion', 'and the calcium signaling pathway'. When comparing deM target genes with these DEGs, nine DEGs were identified as putative deM targets, where hsa-microrna (mir)-1225-5p-ccnl2, hsa-mir-339-5p-PrcP, and hsa-mir-193a-3p-mitogen-activated protein kinase 10 (MaPK10) were the only three pairs which were associated with decreased gene expression levels. Furthermore, hsa-mir-193a-3p was demonstrated to induce Bn by targeting MaPK10. collectively, the results of the present study suggest that hsa-mir-193a-3p may be a viable biomarker of Bn.

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“…It is well recognized that naturally occurring phytoestrogens have fewer side effects compared with synthetic oestrogen (Xiao et al. 2015). Seeking effective phytoestrogen is an important and urgent issue in the prevention and treatment of postmenopausal syndrome.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of genistein and 8-prenylgenistein on reproductive tissues in immature female mice

Sui

Lin

et al. 2019

Pharmaceutical Biology

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Context: We identified an active prenylated derivative of genistein, 8-prenylgenistein (8PG) from Erythrina variegata L. (Leguminosae) and found that 8PG increased osteoprotective effects of genistein in oestrogen-deficient mice. Objective: This study investigated and compared the oestrogenic effects of genistein and 8PG on uterus and vagina of immature mice. Materials and methods: Immature female CD-1 mice were orally treated with vehicle (Control, n = 10) or genistein (75 mg/kg, n = 10) or 8PG with low (8PG-L, 75 mg/kg, n = 10) and high dose (8PG-H, 150 mg/kg, n = 10) for 7 consecutive days by intragastric gavage. The uterus and vagina were harvested for histological and molecular measurements. Results: Treatment with genistein and 8PG-H significantly increased uterus index (1.98 ± 0.21 & 1.49 ± 0.16 mg/g) and vagina index (3.83 ± 0.11 & 3.13 ± 0.25 mg/g) as compared to untreated control (uterus, 1.12 ± 0.13 mg/g; vagina, 2.32 ± 0.18 mg/g). Accordingly, both genistein and 8PG-H made vaginal cells keratinized and induced uterine and vaginal hypertrophy associated with the endometrial proliferation. 8PG-L did not affect oestrus cycle and histology of uterus and vagina. Treatment of immature mice with genistein or 8PG-H upregulated protein expression of oestrogen receptor-α (ER-α) and proliferating cell nuclear antigen (PCNA), but 8PG-L did not alter ER-α and PCNA expression in uterus and vagina. Conclusion: This study indicated that 8-prenylgenistein exerted oestrogenic effects in immature female mice. The efficacy and safety of 8-prenylgenistein when applied in improving oestrogen deficiency-induced syndrome requires further elucidation.

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An 8-O-4′ norlignan exerts oestrogen-like actions in osteoblastic cells via rapid nongenomic ER signaling pathway

Cited by 14 publications

References 47 publications

NMR Applications for Botanical Mixtures: The Use of HSQC Data to Determine Lignan Content in Sambucus williamsii

NMR Applications for Botanical Mixtures: The Use of HSQC Data to Determine Lignan Content in Sambucus williamsii

Identification of key microRNAs and target genes for the diagnosis of bone nonunion

Differential effects of genistein and 8-prenylgenistein on reproductive tissues in immature female mice

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