Silymarin, a polyphenolic flavonoid impede Plasmodium falciparum growth through interaction with heme

Abstract

A polyphenolic flavonoid, Silymarin isolated from Silybum marianum is widely known for its hepatoprotective action. In the present study anti-plasmodial activity of Silymarin has been demonstrated for the first time having IC₅₀ of 14 ± 0.33 μM against the NF-54 strain of P. falciparum with high selectivity index (>100). The parasitostatic action is exerted through inhibition of β-hematin/hemozoin formation which is due to the interaction (Kd = 3.63 ± 0.9µM) of silymarin with free heme in a Stoichiometry of 1:1 Silymarin: heme complex resulting into heme-induced membrane damage in the parasite. Silymarin could hinder the glutathione and hydrogen peroxide-induced heme detoxification. Silymarin also induces apoptosis in the parasite through the elevation of caspase-3 level in a dose-dependent manner. Results from the docking studies suggest that Silymarin interacts with heme.

Graphical Abstract

Keywords:

• Silymarin
• β-haematin
• hemozoin
• P. falciparum
• heme
• chloroquine

Acknowledgments

Authors are thankful to the Director, CSIR-CIMAP for R&D facilities. Two of us (PRM and YK) are grateful to DBT and UGC for providing Senior Research Fellowship. The help of Ms. Shalini Trivedi during preparation of manuscript is gratefully acknowledged. This study was a part of in-house project OLP-17 of CSIR-CIMAP, Lucknow, India with funding from CSIR Network Program BSC02.

Disclosure statement

None to declare.