The phytochemical lindleyin, isolated from Rhei rhizoma, mediates hormonal effects through estrogen receptors

Abstract

Some plant compounds or herb mixtures are popular alternatives to conventional therapies and contain organic compounds that bind to some nuclear receptors, such as the estrogen receptor (ER), to exert various biological effects. We studied the effect of various herbal extracts on ER and ER isoforms. One herbal extract, Rhei rhizoma (rhubarb), acts as an agonist to both ER and ER . The phytochemical lindleyin, a major component of rhubarb, might contribute to this estrogenic activity through ER and ER . 4-Hydroxytamoxifen, an ER antagonist, completely reversed the estrogenic activity of lindleyin.Lindleyin binds to ER in vitro, as demonstrated using a fluorescent polarization assay. The in vivo effect of rhubarb extract was studied using a vitellogenin assay system in the freshwater fish, Japanese medaka (Oryzias latipes). There were marked increases in serum vitellogenin levels in male medaka exposed to rhubarb extract. We conclude that lindleyin, a component of some herbal medicines, is a novel phytoestrogen and might trigger many of the biological responses evoked by the physiological estrogens.

Botanical Modulation of Menopausal Symptoms: Mechanisms of Action?

“…3 F) with a relative binding potency of 20 000 times lower than that of estradiol for ERα. The extract increased vitelogenin (a marker of estrogenic activity) levels in the serum of Japanese Medaka [124]. These studies showed that different rhubarb species might have a weak to moderate ER-dependent estrogenic potential.…”

Botanical Modulation of Menopausal Symptoms: Mechanisms of Action?

“…3 F) with a relative binding potency of 20 000 times lower than that of estradiol for ERα. The extract increased vitelogenin (a marker of estrogenic activity) levels in the serum of Japanese Medaka [124]. These studies showed that different rhubarb species might have a weak to moderate ER-dependent estrogenic potential.…”

Acteoside and martynoside exhibit estrogenic/antiestrogenic properties

“…For example, a component of ginseng saponin (a ginsenoside), a 4-ethoxymethylphenol, some catechins, and the phytochemical lindleyin may act as agonists/antagonists of estrogens via the ER␣ and ER␤ pathway, depending on their concentration and tissue type [30][31][32][33][34]. In addition, recent studies in our laboratory revealed that plant-derived arylobenzofurans exhibit SERM-like properties [35,36].…”

Evaluation of Estrogenic/Antiestrogenic Activity of Ellagic Acid via the Estrogen Receptor Subtypes ERα and ERβ

“…Resveratrol, a polyphenol found naturally in grapes, binds ERα and ERβ with comparable affinity, but it transactivates ERα and ERβ differently in an ERE sequence-dependent manner ( − ). The phytochemical polyphenol lindleyin, on the other hand, transactivates ERβ with a higher potency than ERα, whereas glabrene, a polyphenol isolated from the licorice root, is a natural estrogen agonist that activates ERα-mediated transcription in vitro ( , ). Recently, it was reported that phytochemical glyceollins exerted antihormonal effects through ERα and ERβ ().…”

Botanical Modulation of Menopausal Symptoms: Mechanisms of Action?

“…3 F) with a relative binding potency of 20 000 times lower than that of estradiol for ERα. The extract increased vitelogenin (a marker of estrogenic activity) levels in the serum of Japanese Medaka [124]. These studies showed that different rhubarb species might have a weak to moderate ER-dependent estrogenic potential.…”

Acteoside and martynoside exhibit estrogenic/antiestrogenic properties

“…For example, a component of ginseng saponin (a ginsenoside), a 4-ethoxymethylphenol, some catechins, and the phytochemical lindleyin may act as agonists/antagonists of estrogens via the ER␣ and ER␤ pathway, depending on their concentration and tissue type [30][31][32][33][34]. In addition, recent studies in our laboratory revealed that plant-derived arylobenzofurans exhibit SERM-like properties [35,36].…”

Evaluation of Estrogenic/Antiestrogenic Activity of Ellagic Acid via the Estrogen Receptor Subtypes ERα and ERβ

“…Resveratrol, a polyphenol found naturally in grapes, binds ERα and ERβ with comparable affinity, but it transactivates ERα and ERβ differently in an ERE sequence-dependent manner ( − ). The phytochemical polyphenol lindleyin, on the other hand, transactivates ERβ with a higher potency than ERα, whereas glabrene, a polyphenol isolated from the licorice root, is a natural estrogen agonist that activates ERα-mediated transcription in vitro ( , ). Recently, it was reported that phytochemical glyceollins exerted antihormonal effects through ERα and ERβ ().…”

Botanical Modulation of Menopausal Symptoms: Mechanisms of Action?

“…3 F) with a relative binding potency of 20 000 times lower than that of estradiol for ERα. The extract increased vitelogenin (a marker of estrogenic activity) levels in the serum of Japanese Medaka [124]. These studies showed that different rhubarb species might have a weak to moderate ER-dependent estrogenic potential.…”

Acteoside and martynoside exhibit estrogenic/antiestrogenic properties

“…For example, a component of ginseng saponin (a ginsenoside), a 4-ethoxymethylphenol, some catechins, and the phytochemical lindleyin may act as agonists/antagonists of estrogens via the ER␣ and ER␤ pathway, depending on their concentration and tissue type [30][31][32][33][34]. In addition, recent studies in our laboratory revealed that plant-derived arylobenzofurans exhibit SERM-like properties [35,36].…”

Evaluation of Estrogenic/Antiestrogenic Activity of Ellagic Acid via the Estrogen Receptor Subtypes ERα and ERβ

“…Resveratrol, a polyphenol found naturally in grapes, binds ERα and ERβ with comparable affinity, but it transactivates ERα and ERβ differently in an ERE sequence-dependent manner ( − ). The phytochemical polyphenol lindleyin, on the other hand, transactivates ERβ with a higher potency than ERα, whereas glabrene, a polyphenol isolated from the licorice root, is a natural estrogen agonist that activates ERα-mediated transcription in vitro ( , ). Recently, it was reported that phytochemical glyceollins exerted antihormonal effects through ERα and ERβ ().…”