Screening of herbal constituents for aromatase inhibitory activity

Paoletta, Silvia; Steventon, Glyn B.; Wildeboer, Dirk; Ehrman, Thomas M.; Hylands, Peter J.; Barlow, David J.

doi:10.1016/j.bmc.2008.08.034

Cited by 44 publications

(21 citation statements)

References 30 publications

(33 reference statements)

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“…Naringenin also inhibits CYP3A4 and CYP19 (Moon et al, 2006). With an IC 50 of 0.34 mM, liquiritigenin has been identified as a potent inhibitor of CYP19 (Paoletta et al, 2008). Inhibitory effects of isosakuranetin on CYP1 enzyme isoforms require concentrations in the range of 1-3 mM (Takemura et al, 2010), and inhibition of other P450 enzymes has, to our knowledge, not been demonstrated.…”

Section: Discussionmentioning

confidence: 86%

Flavanones That Selectively Inhibit TRPM3 Attenuate Thermal Nociception In Vivo

et al. 2013

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Transient receptor potential melastatin 3 (TRPM3) is a calciumpermeable nonselective cation channel that is expressed in a subset of dorsal root (DRG) and trigeminal ganglia sensory neurons. TRPM3 can be activated by the neurosteroid pregnenolone sulfate (PregS) and heat. TRPM3 2/2 mice display an impaired sensation of noxious heat and thermal hyperalgesia. We have previously shown that TRPM3 is blocked by the citrus fruit flavanones hesperetin, naringenin, and eriodictyol as well as by ononetin, a deoxybenzoin from Ononis spinosa. To further improve the tolerability, potency, and selectivity of TRPM3 blockers, we conducted a hit optimization procedure by rescreening a focused library that was composed of chemically related compounds. Within newly identified TRPM3 blockers, isosakuranetin and liquiritigenin displayed favorable properties with respect to their inhibitory potency and a selective mode of action. Isosakuranetin, a flavanone whose glycoside is contained in blood oranges and grapefruits, displayed an IC 50 of 50 nM and is to our knowledge the most potent inhibitor of TRPM3 identified so far. Both compounds exhibited a marked specificity for TRPM3 compared with other sensory TRP channels, and blocked PregS-induced intracellular free Ca 21 concentration signals and ionic currents in freshly isolated DRG neurons. Furthermore, isosakuranetin and previously identified hesperetin significantly reduced the sensitivity of mice to noxious heat and PregS-induced chemical pain. Because the physiologic functions of TRPM3 channels are still poorly defined, the development and validation of potent and selective blockers is expected to contribute to clarifying the role of TRPM3 in vivo.

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Section: Discussionmentioning

confidence: 86%

Flavanones That Selectively Inhibit TRPM3 Attenuate Thermal Nociception In Vivo

et al. 2013

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“…In addition, Gupta et al (2005) reported that A. lebbeck inhibited the fertility of male rats which suppressed the function of Leydig cells and Sertoli cells and inhibited sperm production. Whereas Paoletta et al (2008) noted that the aglycone myricetin inhibits the aromatase enzyme. Also, Lu et al (2012) reported that myricetin inhibited oestrogen biosynthesis by 20%, although it worked via suppressing aromatase transcription rather than inhibiting the enzyme.…”

Section: Discussionmentioning

confidence: 99%

Myricitrin and bioactive extract ofAlbizia amaraleaves: DNA protection and modulation of fertility and antioxidant-related genes expression

Kassem

Ibrahim

Hussein

et al. 2016

Pharmaceutical Biology

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Context: Albizia species are reported to exhibit many biological activities including antiovulatory properties in female rats and antispermatogenic and antiandrogenic activities in male rats. Objective: The present study investigates the flavonoids of Albizia amara (Roxb.) B. Boivin (Fabaceae) leaves and evaluates their activity on gene expression of fertility and antioxidant glutathione-S-transferaserelated genes of treated female mice in addition to their effect on DNA damage. Materials and methods: Plant materials were extracted by using 70% methanol for 48 h, the extract was chromatographed on a polyamide 6S column, each isolated compound was purified by using Sephadex LH-20 column; its structure was elucidated by chemical and spectral methods. Both the leaves extract and myricitrin (200, 30 mg/kg bw/d, respectively) were assayed for their effect on DNA damage in female mice after four weeks treatment using Comet assay. Their modulatory activity on gene expression of fertility (aromatase CYP19 and luteinizing hormone LH) and antioxidant glutathione-S-transferase (GST)-related genes of treated female mice were investigated by real-time PCR (qPCR). Results: Quercetin-3-O-gentiobioside, myricitrin, quercetin-3-O-a-rhamnopyranoside, myricetin, quercetin and kaempferol were isolated and identified from the studied taxa. Myricitrin and the extract induced low rate of DNA damage (4.8% and 5%, respectively), compared with the untreated control (4.2%) and significantly down-regulated the expression of CYP19 and LH genes and up-regulated GST gene. Discussion and conclusion: Our results highlight the potential effect of the leaves extract of Albizia amara and myricitrin as fertility-regulating phytoconstituents with ability to protect DNA from damage and cells from oxidative stress. ARTICLE HISTORY

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“…Three Potential inhibitors of the human, aromatase enzyme (CYP19) myricetin, liquiritigenin, and gossypetin, were screened by random forest as well as molecular docking studies. The virtual screening results were subsequently confirmed experimentally by in vitro assay [87]. …”

Section: In Silico Methods For Ligand-protein Interactionsmentioning

confidence: 97%

Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods, and Applications

Zhao

Zhou

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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The traditional Chinese medicine (TCM), which has thousands of years of clinical application among China and other Asian countries, is the pioneer of the “multicomponent-multitarget” and network pharmacology. Although there is no doubt of the efficacy, it is difficult to elucidate convincing underlying mechanism of TCM due to its complex composition and unclear pharmacology. The use of ligand-protein networks has been gaining significant value in the history of drug discovery while its application in TCM is still in its early stage. This paper firstly surveys TCM databases for virtual screening that have been greatly expanded in size and data diversity in recent years. On that basis, different screening methods and strategies for identifying active ingredients and targets of TCM are outlined based on the amount of network information available, both on sides of ligand bioactivity and the protein structures. Furthermore, applications of successful in silico target identification attempts are discussed in detail along with experiments in exploring the ligand-protein networks of TCM. Finally, it will be concluded that the prospective application of ligand-protein networks can be used not only to predict protein targets of a small molecule, but also to explore the mode of action of TCM.

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Screening of herbal constituents for aromatase inhibitory activity

Cited by 44 publications

References 30 publications

Flavanones That Selectively Inhibit TRPM3 Attenuate Thermal Nociception In Vivo

Flavanones That Selectively Inhibit TRPM3 Attenuate Thermal Nociception In Vivo

Myricitrin and bioactive extract ofAlbizia amaraleaves: DNA protection and modulation of fertility and antioxidant-related genes expression

Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods, and Applications

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