The molecular conformation differs between helenalin and its derivatives, which affects the lipophilicity and the accessibility of the Michael addition sites.

[citation needed] Helenalin can target the p65 subunit (also called RelA) of the transcription factor NF-κB.

The levels of glutathione, which contains sulfhydryl groups, are reduced in helenaline-treated cells, further increasing the toxicity of helenalin.

It was also seen that helenalin increase CPK and LDH activities in serum and that it inhibits multiple enzymes of the liver involved in triglyceride synthesis.

[8] Helenalin also suppresses essential immune functions, such as those mediated by activated CD4+ T-cells, by multiple mechanisms.

The efficacy of helenalin for treatment of pain and swelling, when applied topically, is not supported by the current available evidence at doses of 10% or lower.

[13] In former times, plant extracts containing helenalin were used as a herbal medicine for the treatment of sprains, blood clots, muscle strain and rheumatic complaints.

Oral administration of large doses of helenalin can cause gastroenteritis, muscle paralysis, and cardiac and liver damage.

[19] Helenalin has been shown to selectively inhibit the transcription factor NF-κB, which plays a key role in regulating immune response, through a unique mechanism.

[20] In vitro, it is also a potent, selective inhibitor of human telomerase[7]—which may partially account for its antitumor effects—has anti-trypanosomal activity,[21][22] and is toxic to Plasmodium falciparum.