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Biochem Biophys Res Commun. 2014 Aug 22;451(2):282-7. doi: 10.1016/j.bbrc.2014.07.115. Epub 2014 Aug 1.

Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina.

Author information

1
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyung-Heedaero, Seoul 130-701, Republic of Korea.
2
Department of Medical Zoology, Kyung Hee University School of Medicine, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
3
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyung-Heedaero, Seoul 130-701, Republic of Korea; Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: dsjang@khu.ac.kr.
4
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyung-Heedaero, Seoul 130-701, Republic of Korea. Electronic address: innks@khu.ac.kr.

Abstract

Extracts of Prunella vulgaris have been shown to exert antiestrogenic effects. To identify the compounds responsible for these actions, we isolated the constituents of P. vulgaris and tested their individual antiestrogenic effects. Rosmarinic acid, caffeic acid, ursolic acid (UA), oleanolic acid, hyperoside, rutin and betulinic acid (BA) were isolated from the flower stalks of P. vulgaris var. lilacina Nakai (Labiatae). Among these constituents, UA and BA showed significant antiestrogenic effects, measured as a decrease in the mRNA level of GREB1, an estrogen-responsive protein; the effects of BA were stronger than those of UA. UA and BA were capable of suppressing estrogen response element (ERE)-dependent luciferase activity and expression of estrogen-responsive genes in response to exposure to estradiol, further supporting the suppressive role of these compounds in estrogen-induced signaling. However, neither UA nor BA was capable of suppressing estrogen signaling in cells ectopically overexpressing estrogen receptor α (ERα). Furthermore, both mRNA and protein levels of ERα were reduced by treatment with UA or BA, suggesting that UA and BA inhibit estrogen signaling by suppressing the expression of ERα. Interestingly, both compounds enhanced prostate-specific antigen promoter activity. Collectively, these findings demonstrate that UA and BA are responsible for the antiestrogenic effects of P. vulgaris and suggest their potential use as therapeutic agents against estrogen-dependent tumors.

KEYWORDS:

Antiestrogenic effect; Betulinic acid; Estrogen; Estrogen receptor; Prunella vulgaris var. lilacina; Ursolic acid

PMID:
25088993
DOI:
10.1016/j.bbrc.2014.07.115
[Indexed for MEDLINE]

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