Luteolin, a flavonoid found in rosemary, thyme, parsley and citrus fruits, is an effective anti-oestrogen, according to an animal study published by researchers at Peking University Health Science Center in the Journal of Pharmacology and Experimental Therapeutics. Unlike pharmacological anti-oestrogens, luteolin also improves the cholesterol balance.
In 2013 this web magazine already wrote about the anti-oestrogenic properties of luteolin. [Structural formula shown here.] Pharmacologists at the Chinese Chengdu Institute of Biology had screened over 100 substances for their anti-oestrogenic qualities, and luteolin emerged as the most interesting. But that was in-vitro research. Now we have an animal study.
The researchers used female mice whose ovaries had been surgically removed for their experiment. A number of the animals were given androstenedione [AD] injections daily. The enzyme aromatase converts androstenedione effortlessly into estradiol.
Some animals were given luteolin [LUT] as well, administered orally. The doses used are shown in the figure below. The human equivalent of the doses varies from 45 – 450 mg luteolin per day. Some mice were also given injections of letrozole [LET], a powerful pharmacological aromatase inhibitor.
After 12 weeks, the researchers measured the estradiol concentration in the mice’s blood. The figure below shows that the anti-oestrogenic effect of the highest dose of luteolin was the same as that of letrozole.
The researchers had also injected the mice with estradiol-sensitive breast cancer cells. Both luteolin and letrozole inhibited the growth of the tumours, but letrozole performed slightly better at this than luteolin.
Long-term use of pharmacological aromatase inhibitors leads to side effects, one of which is that the cholesterol balance becomes worse. The LDL concentration increases and that of HDL decreases. Luteolin also inhibits aromatase, but this flavone has the opposite effect on cholesterol balance. Luteolin lowers the LDL concentration and raises the HDL concentration.
The figure above shows that luteolin can also cancel out the negative effect of letrozole on cholesterol levels.
Luteolin had no effect on triglyceride levels.
“Although luteolin is widely distributed in plant foods, the dosages used in the current study were above the normal levels that humans consume”, the researchers concluded. “Nevertheless, this study could provide the scientific basis for nutraceutical or pharmacological development of this flavone.”
“As a high LDL/HDL ratio is usually associated with long-term use of aromatase inhibitors, the administration of luteolin can be a potential compensation mechanism without compromising on aromatase.”
Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole.
Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the Ki values of luteolin and letrozole were estimated to be 2.44 µM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs.
Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.
PMID: 25138022 DOI: 10.1124/jpet.114.216754 [PubMed – indexed for MEDLINE]