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Chemicals in Folk Medicines Found Effective Blocking Fertilization

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A new study identifies two chemicals found in anti-fertility folk medicines as effective in blocking a key step in fertilization and potential alternatives to hormone-based contraceptives.

Unlike hormone-based contraceptives, which sometimes cause side effects, the chemicals seem to have no adverse effect on egg or sperm, other than to prevent the sperm from pushing through the cells that congregate around the egg and an enveloping membrane called the zona pelucida.

    Effective at low doses, according to the study published on May 15 in the journal Proceedings of the National Academy of Sciences, they work by stopping sperm’s power kick, which is normally stimulated by the hormone progesterone secreted by cells surrounding the egg and makes the sperm’s tail whip forcefully to propel it into the egg.


    One of these chemicals is pristimerin, from the plant Tripterygium wilfordii, also known as “thunder god vine.” Leaves from the plant have been used as an anti-fertility drug in Chinese traditional medicine, though some compounds in the leaves are poisonous. It has also been used as a folk remedy for rheumatoid arthritis.

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In 2021, Medicilon established the International Discovery Service Unit (IDSU). The IDSU provides global pharmaceutical companies with high quality, efficient and cost-effective chemistry synthesis design and production and medicinal chemistry. The IDSU supports the discovery and delivery of clinical candidate compounds forglobal drug research and development.

The other chemical is lupeol, which is found in plants such as mango and dandelion root. While it has been tested as an anticancer agent, it was not suspected of having contraceptive properties.

“Because these two plant compounds block fertilization at very, very low concentrations,” said Polina Lishko, an assistant professor of molecular and cell biology, who led the team that discovered the anti-fertility properties of the two chemicals.

“They could be a new generation of emergency contraceptive we nicknamed ‘molecular condoms.’ If one can use a plant-derived, non-toxic, non-hormonal compound in lesser concentration to prevent fertilization in the first place, it could potentially be a better option.”

“The massive influx of calcium into the sperm tail changes the sperm tail’s beating pattern, making it highly asymmetrical,” said Nadja Mannowetz, first author on the study. “This asymmetrical bending gives the sperm cell enough force to drill through the tenacious egg vestment.”

Last year, Lishko, Mannowetz and and former postdoctoral fellow Melissa Miller found that the hormone progesterone is key to opening the calcium channel and triggering tail whipping. The hormone binds to a protein called ABHD2, which in turn opens the channel. They began a search for other chemicals that would bind to ABHD2, either opening the channel, like progesterone, or blocking the channel.

In the new study, Mannowetz tested three other hormones: testosterone, estrogen and cortisol, a stress hormone. All three competed with progesterone and blocked tail whipping, though only testosterone and cortisol were effective at levels typical of the hormones’ levels in the body. This suggests, she said, that stress and high testosterone levels in women decrease fertility in part by preventing sperm from penetrating the egg.

They also found a second hormone that triggers tail whipping: a steroid structurally similar to progesterone called pregnenolone sulfate.

Mannowetz found that both pristimerin and lupeol blocked progesterone binding to ADHD2, preventing sperm’s power kick. “These compounds not only blocked calcium channel activation, but also blocked sperm hyperactivated motility, reducing their activity to the level of inactivated sperm cells,” Lishko was quoted as saying in a news release.

“It doesn’t kill sperm basal motility. It is not toxic to sperm cells; they still can move. But they cannot develop this powerful stroke, because this whole activation pathway is shut down.”

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