Evaluation of in vivo estrogenic potency of natural estrogen-active chemical, puerarin, on pituitary function in gonadectomized female rats

Loutchanwoot, Panida; Vortherms, Tina; Jarry, Hubertus

doi:10.1016/j.lfs.2016.09.002

Cited by 10 publications

(8 citation statements)

References 48 publications

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“…In the present study, both 17β-estradiol (2) and puerarin (1), at high doses, were found to significantly increase uterine weights and volumes in OVX animals, suggesting that puerarin (2) exhibits estrogenic-like activity, in a similar manner to 17β-estradiol (2). Our finding is in agreement with the previous reports which demonstrated that puerarin (2) exerted uterotrophic effects in OVX mice after long-term treatment [19,20]. Moreover, in the MCF-7 cell proliferation assay, puerarin (2) was found to bind to both estrogen receptors (ERs) and exhibited estrogenic activity [21].…”

Section: Discussionsupporting

confidence: 93%

Effects of Puerarin on the Ovariectomy-Induced Depressive-Like Behavior in ICR Mice and Its Possible Mechanism of Action

et al. 2019

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Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17β-estradiol attenuated ovariectomy-induced depression-like behavior, as indicated by a decrease in immobility times in the tail suspension test (TST) and the forced swimming test (FST), an increase in the uterine weight and volume, a decrease in serum corticosterone levels, and dose-dependently normalized the downregulated transcription of the brain-derived neurotrophic factor (BDNF) and estrogen receptor (Erβ and Erα) mRNAs. Like 17β-estradiol, puerarin also inhibited ovariectomy-induced suppression of neurogenesis in the dentate gyrus of the hippocampus (increased the number of doublecortin (DCX)-immunosuppressive cells). These results suggest that puerarin exerts antidepressant-like effects in OVX animals, possibly by attenuating the OVX-induced hyperactivation of the HPA axis and/or normalizing the downregulated transcription of BDNF and ER mRNA in the brain.Molecules 2019, 24, 4569 2 of 15 depression. These symptoms can be reversed by supplementation with estrogen. A body of evidence suggests that such estrogen replacement therapy (ERT) can exert anxiolytic and antidepressant effects in menopausal females by modulating the hypothalamic-pituitary-adrenal (HPA) axis functions [3,4]. However, the drawback of ERT is its adverse effects, such as an increased risk of breast and endometrial cancers, as well as thromboembolic events [5,6]. Consequently, the long-term usage of ERT to ameliorate emotional and cognitive deficits has an obvious limitation in women. Thus, the search for new phytoestrogens, with a weak effect on reproductive organs, from natural sources continues to be an important field of research.Pueraria candollei var. mirifica is a medicinal plant used in Thai traditional medicine for its rejuvenating and estrogenic effects [7]. For this reason, this plant has been widely investigated for its constituents and pharmacological activities. Peerakam et al. [8] found that the 95% ethanol extract of this plant contained puerarin (1), as a major compound, and other isoflavonoids, such as daidzin, daidzein, genistin, and genistein, in addition to the phytoestrogens miroestrol and deoxymiroestrol. Suthon et al.[9] evaluated the anti-osteoporotic effects of the crude extract of P. candollei var. mirifica and puerarin (1) in ovariectomized (OVX) mice and found that only the crude extract at 50 mg/kg (body weight) per day caused a significant increase in the trabecular bone mineral densities of tibia metaphysis when compared to the control group. On the other hand, the pharmacological activities of puerarin (1) (Figure 1), a major isoflavonoid from P. candollei var. mirifica, have been extensively investigated. Puerarin (1) has been widely used in the treatment of diabetes, dyslipidemia, liver fibrosis, cardiovascular diseases, neurotoxicity, and Alzheimer's disease [10]. This compound was also found to exhibit various protective effects against fever, hyper...

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Section: Discussionsupporting

confidence: 93%

Effects of Puerarin on the Ovariectomy-Induced Depressive-Like Behavior in ICR Mice and Its Possible Mechanism of Action

et al. 2019

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“…We subsequently examined how puerarin induced SUMO2 expression and protected cardiomyocytes against hypoxia/reoxygenation challenge. Like many other naturally occurring flavonoids, puerarin is classified as an estrogen receptor modulator and predominantly exhibits estrogenic activity for health benefits ( Loutchanwoot et al, 2016 ; Hou et al, 2021 ). Figure 5 showed that puerarin was well bound to ER protein with the binding energy of −7.3 kcal/mol and induced the expression of reporter luciferase through an ER-mediated mechanism.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Small Ubiquitin-Like Modifier 2 and Protein SUMOylation as a Cardioprotective Mechanism Against Myocardial Ischemia-Reperfusion Injury

Zhao

Zhang

et al. 2021

Front. Pharmacol.

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Background: Small ubiquitin-like modifier (SUMO) proteins modify proteins through SUMOylation as an essential protein post-translational modification (PTM) for regulating redox status, inflammation, and cardiac fibrosis in myocardial infarction. This study aimed to investigate whether natural product puerarin could alleviate myocardial ischemia/reperfusion injury (MI-RI) by targeting protein SUMOylation.Methods: Mouse MI-RI model was induced by ligating the left anterior descending (LAD) coronary artery and subsequently treated with puerarin at the dose of 100 mg/kg. Rat cardiomyocyte H9c2 cells were challenged by hypoxia/reoxygenation and treated with puerarin at concentrations of 10, 20, and 40 μM. The infarction area of mouse hearts was assessed by 2% TTC staining. Cell damage was analyzed for the release of lactate dehydrogenase (LDH) in serum and cell culture medium. Western blot technique was employed to detect the expression of SUMO2, phospho-ERK, pro-inflammatory biomarker COX2, fibrosis index galectin-3, apoptosis-related protein cleaved PARP-1. The activation of the estrogen receptor (ER) pathway was assayed by the dual-luciferase reporter system.Results: The present study validated that puerarin effectively reduced myocardial infarct size and LDH release in the mouse MI-RI model. In the cell culture system, puerarin effectively decreased the release of LDH and the protein level of COX2, galectin-3, and cleaved PARP-1. Mechanistic studies revealed that puerarin increased the expression of SUMO2, SUMOylation of proteins and the activation of ER/ERK pathway in cardiomyocytes. ER, ERK and SUMO2 inhibitors attenuated the cardioprotective effects of puerarin.Conclusion: Puerarin may alleviate myocardial injury by promoting protein SUMOylation through ER/ERK/SUMO2-dependent mechanism.

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“…Also, 17β-estradiol has been recognized as an inhibitor of IDD by downregulating MMP-3 and MMP-13 and upregulating type II collagen [20]. Similarly, though PUR has not been reported yet in treating IDD, this medicine, as a phytoestrogen [21], is likely to be potentially favorable in suppression of IDD. To be more specific, PUR is greatly associated with modification of autophagy [22], decreased reactive oxygen species (ROS) production [23], and anti-inflammation effects [23].…”

Section: Introductionmentioning

confidence: 99%

Puerarin Relieved Compression-Induced Apoptosis and Mitochondrial Dysfunction in Human Nucleus Pulposus Mesenchymal Stem Cells via the PI3K/Akt Pathway

Huang

Peng

et al. 2020

Stem Cells International

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Puerarin (PUR), an 8-C-glucoside of daidzein extracted from Pueraria plants, is closely related to autophagy, reduced reactive oxygen species (ROS) production, and anti-inflammatory effects, but its effects on human nucleus pulposus mesenchymal stem cells (NPMSCs) have not yet been identified. In this study, NPMSCs were cultured in a compression apparatus to simulate the microenvironment of the intervertebral disc under controlled pressure (1.0 MPa), and we found that cell viability was decreased and apoptosis level was gradually increased as compression duration was prolonged. After PUR administration, apoptosis level evaluated by flow cytometry and caspase-3 activity was remitted, and protein levels of Bas as well as cleaved caspase-3 were decreased, while elevated Bcl-2 level was identified. Moreover, ATP production detection, ROS, and JC-1 fluorography as well as quantitative analysis suggested that PUR could attenuate intercellular ROS accumulation and mitochondrial dysfunction. Besides, the rat tail compression model was utilized, which indicated that PUR could restore impaired nucleus pulposus degeneration induced by compression. The PI3K/Akt pathway was identified to be deactivated after compression stimulation by western blot, and PUR could rescue the phosphorylation of Akt, thus reactivating the pathway. The effects of PUR, such as antiapoptosis, cell viability restoration, antioxidation, and mitochondrial maintenance, were all counteracted by application of the PI3K/Akt pathway inhibitor (LY294002). Summarily, PUR could alleviate compression-induced apoptosis and cell death of human NPMSCs in vitro as well as on the rat compression model and maintain intracellular homeostasis by stabilizing mitochondrial membrane potential and attenuating ROS accumulation through activating the PI3K/Akt pathway.

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Evaluation of in vivo estrogenic potency of natural estrogen-active chemical, puerarin, on pituitary function in gonadectomized female rats

Cited by 10 publications

References 48 publications

Effects of Puerarin on the Ovariectomy-Induced Depressive-Like Behavior in ICR Mice and Its Possible Mechanism of Action

Effects of Puerarin on the Ovariectomy-Induced Depressive-Like Behavior in ICR Mice and Its Possible Mechanism of Action

Upregulation of Small Ubiquitin-Like Modifier 2 and Protein SUMOylation as a Cardioprotective Mechanism Against Myocardial Ischemia-Reperfusion Injury

Puerarin Relieved Compression-Induced Apoptosis and Mitochondrial Dysfunction in Human Nucleus Pulposus Mesenchymal Stem Cells via the PI3K/Akt Pathway

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