Estrogen Receptor (ER) Subtype Selectivity Identifies 8-Prenylapigenin as an ERβ Agonist from <i>Glycyrrhiza inflata</i> and Highlights the Importance of Chemical and Biological Authentication

Hajirahimkhan, Atieh; Mbachu, Obinna; Simmler, Charlotte; Ellis, Sarah; Dong, Huali; Nikolić, Dejan; Lankin, David C.; Breemen, Richard B. van; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

doi:10.1021/acs.jnatprod.7b01070

Cited by 24 publications

(34 citation statements)

References 56 publications

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“…5B). Other studies suggest that GI has superior chemopreventive properties to GG (11)(47). GI had the greatest anti-inflammatory activity among medicinal licorice species in macrophage cells because it contains two major anti-inflammatory compounds, LicA and LigC (11).…”

Section: Discussionmentioning

confidence: 96%

“…GI had the greatest anti-inflammatory activity among medicinal licorice species in macrophage cells because it contains two major anti-inflammatory compounds, LicA and LigC (11). Also, GI contains the ERβ preferential agonist 8-prenylapigenin (47), which may have a better safety profile. Long-term studies are planned to compare the effect of GG and GI on E 2 -induced mammary carcinogenesis in ACI rats and ultimately estrogen metabolism in women.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats

Wang

Dunlap

Huang

et al. 2018

Cancer Prevention Research

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Women are increasingly using botanical dietary supplements (BDS) to reduce menopausal hot flashes. While licorice (Glycyrrhiza sp.) is one of the frequently used ingredients in BDSs, the exact plant species is often not identified. We previously showed that in breast epithelial cells (MCF-10A), Glycyrrhiza glabra (GG) and G. inflata (GI), and their compounds differentially modulated P450 1A1 and P450 1B1 gene expression, which are responsible for estrogen detoxification and genotoxicity, respectively. GG and isoliquiritigenin (LigC) increased CYP1A1, whereas GI and its marker compound, licochalcone A (LicA), decreased CYP1A1 and CYP1B1. The objective of this study was to determine the distribution of the bioactive licorice compounds, the metabolism of LicA and whether GG, GI, and/or pure LicA modulate NAD(P)H quinone oxidoreductase (NQO1) in an ACI rat model. In addition, the effect of licorice extracts and compounds on biomarkers of estrogen chemoprevention (CYP1A1) as well as carcinogenesis (CYP1B1) were studied. LicA was extensively glucuronidated and formed GSH adducts; however, free LicA as well as LigC were bioavailable in target tissues after oral intake of licorice extracts. GG, GI, and LicA caused induction of NQO1 activity in the liver. In mammary tissue, GI increased CYP1A1 and decreased CYP1B1, whereas GG only increased CYP1A1. LigC may have contributed to the upregulation of CYP1A1 after GG and GI administration. In contrast, LicA was responsible for GI-mediated downregulation of CYP1B1. These studies highlight the polypharmacological nature of botanicals and the importance of standardization of licorice BDSs to specific Glycyrrhiza species and to multiple constituents.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats

Wang

Dunlap

Huang

et al. 2018

Cancer Prevention Research

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“…8-Prenylnaringenin showed nanomolar estrogenic RP without ER selectivity ( Hajirahimkhan et al, 2013 ). A recent study identified 8-Prenylapigenin from Glycyrrhiza inflata as an ERβ agonist ( Hajirahimkhan et al, 2018 ).…”

Section: Other Estrogenic Plantsmentioning

confidence: 99%

Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause

et al. 2021

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In mammals, sexual hormones such as estrogens play an essential role in maintaining brain homeostasis and function. Estrogen deficit in the brain induces many undesirable symptoms such as learning and memory impairment, sleep and mood disorders, hot flushes, and fatigue. These symptoms are frequent in women who reached menopausal age or have had ovariectomy and in men and women subjected to anti-estrogen therapy. Hormone replacement therapy alleviates menopause symptoms; however, it can increase cardiovascular and cancer diseases. In the search for therapeutic alternatives, medicinal plants and specific synthetic and natural molecules with estrogenic effects have attracted widespread attention between the public and the scientific community. Various plants have been used for centuries to alleviate menstrual and menopause symptoms, such as Cranberry, Ginger, Hops, Milk Thistle, Red clover, Salvia officinalis, Soy, Black cohosh, Turnera diffusa, Ushuva, and Vitex. This review aims to highlight current evidence about estrogenic medicinal plants and their pharmacological effects on cognitive deficits induced by estrogen deficiency during menopause and aging.

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“…ex DC differ significantly in the ratio of liquiritigenin to isoliquiritigenin, as well as in congeneric constituents, and are therefore expected to have different bioactivities. 122,123 Characterization sufficient for the detection of such minor components, known or unknown, is therefore critical for quality control and for monitoring batch-to-batch variation and stability. 15,124 Identity and purity of all materials used, regardless of the supplier, should be verified prior to use.…”

Section: Np Specifications and Integritymentioning

confidence: 99%

Improving natural product research translation: From source to clinical trial

et al. 2019

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

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Estrogen Receptor (ER) Subtype Selectivity Identifies 8-Prenylapigenin as an ERβ Agonist from Glycyrrhiza inflata and Highlights the Importance of Chemical and Biological Authentication

Cited by 24 publications

References 56 publications

Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats

Evidence for Chemopreventive and Resilience Activity of Licorice: Glycyrrhiza Glabra and G. Inflata Extracts Modulate Estrogen Metabolism in ACI Rats

Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause

Improving natural product research translation: From source to clinical trial

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