Cordycepin Isolated from Cordyceps militaris: Its Newly Discovered Herbicidal Property and Potential Plant-Based Novel Alternative to Glyphosate

There is currently much interest in finding new phytochemicals among plants and fungi as nature-based alternatives to replace problematic herbicides such as glyphosate, which are preferentially used in agricultural production. We discovered striking herbicidal potency in Cordyceps militaris (L.) and identified cordycepin as its principal plant growth inhibitor. Cordycepin obtained as an ethyl acetate extract was subjected to column chromatography and evaluated for its bioassay-guided phytotoxic capacity against Raphanus sativus (radish), showing a maximum inhibition on germination and growth of radish (IC(50) = 0.052–0.078 mg/mL). Gas chromatography-mass spectrometry (GC-MS) (m/z: 251.2) and liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) ([M + Na](+) m/z: 274.1; [M + H](+) m/z: 252.1) analyses confirmed cordycepin as the major component of the tested column fraction (55.38%). At 0.04 mg/mL, cordycepin showed 3.8–5.9- and 3.3–3.7-fold greater inhibition of the germination and growth of radish than benzoic acid (BA) and glyphosate, respectively. Compared with BA, isolated cordycepin reduced plant chlorophyll and carotenoid contents (2.0–9.5 -fold), while proline, total phenolic and total flavonoid contents were increased 1.2–1.8-fold. Finally, cordycepin promoted electrolyte leakage and malondialdehyde accumulation in radish aerial parts. Thus, cordycepin successfully isolated from Cordyceps militaris is a highly potent plant growth inhibitor with pending worldwide patent and may become a potential plant-based novel alternative to the disputed glyphosate.