Natural Luteolin An Effective Estrogen Inhibitor?
From Ergo Log
Luteolin, a flavonoid that we consume daily through our food, inhibits the body's production of estradiol. Researchers at the Chengdu Institute of Biology in China report their findings in the Journal of Agricultural and Food Chemistry. In their test tubes luteolin reduces the production of the enzyme aromatase by cells.
Estradiol is a useful hormone for both men and women, but it's also hormone that at times it would be more convenient to have less of. For example women who are breast cancer survivors or men with gyno.
There are effective pharmacological estradiol inhibitors, but they have side effects. That's why researchers are looking for naturally occurring substances that inhibit the enzymes that convert androstenedione and testosterone into estradiol, which would mean that the dose of pharmacological anti-oestrogens could be reduced.
The Chinese discovered that luteolin may indeed be one of these naturally occurring substances. They screened 1431 natural compounds and discovered that luteolin was the most powerful aromatase inhibitor.
Luteolin is a flavonoid that we consume daily via foods such as celery, green paprika and peppers, onions, parsley, cabbage and apple peel. In 1994 scientists at the University of Minnesota published the results of an in-vitro study which showed that luteolin sabotaged the synthesis of aromatase in young fat cells. [J Steroid Biochem Mol Biol. 1994 Aug;50(3-4):205-12.] Two years ago biochemists at the Chinese University of Hong Kong discovered that luteolin had the same effect in MCF-7 breast cancer cells. [Mol Cell Endocrinol. 2011 Sep 15;344(1-2):51-8.]
The way in which luteolin blocks aromatase is unclear. The researchers at the De Institute wanted to elucidate the mechanism by doing experiments with human KGN ovarian cells. The synthesis of aromatase rises in these cells as a result of promoter II activity. This then bonds with cAMP-response element binding protein (CREB) and steroidogenic factor-1. More messenger hormone activity or more cAMP, more aromatase.
The Chinese exposed their KGN cells to 10 micromols luteolin, 10 micromols forskolin [a cAMP booster that therefore boosts aromatase synthesis and/or 50 micromols formestan [an anti-oestrogen that sabotages the effect of aromatase]. And lo and behold. Luteolin works better than formestan.
The researchers discovered that luteolin doesn't actually do anything to the aromatase enzyme itself: luteolin inhibits the synthesis of aromatase.
The Chinese suspect that luteolin is a cAMP inhibitor. They base their reasoning on a Korean in-vitro study from 2008. [Arch Pharm Res. 2008 Sep;31(9):1166-71.] We on the other hand, unhindered by science, wonder whether this theory holds water. We regard luteolin as an inhibitor of the enzyme phosphodiesterase type 4 [PDE4]. PDE4 is an enzyme that cAMP deactivates, and PDE4 inhibitors prevent this from happening. PDE4 inhibitors are cAMP boosters, not inhibitors. So we suspect that the mechanism is a little more complex that the Chinese suggest.
Luteolin bears a remarkable resemblance to isorhamnetin, kaempferol, quercetin and myricetin. So the Chinese also measured the extent to which these flavonoids were capable of inhibiting estradiol synthesis in their KGN cells.
Luteolin was the best estradiol inhibitor. It inhibits estradiol synthesis at a concentration as low as 1 micromole. In second place was kaempferol.
Japanese researchers have observed a concentration of 3 micromols in rats that they had given 15 mg luteolin per kg bodyweight. [FEBS Lett. 1998 Nov 6;438(3):220-4.] This dose – human equivalent 3 mg per kg – is probably safe. According to an animal study performed at the Yong Loo Lin School of Medicine in School, rats can be given 30 mg luteolin per kg bodyweight daily without showing signs of toxicity. [Chem Biol Interact. 2006 Dec 1;164(1-2):1-14.]
J Agric Food Chem. 2012 Aug 20. [Epub ahead of print].