The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.

Abstract

Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus, against Botrytis cinerea; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea. The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea, with an EC50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea. This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi.

The Antimicrobial Activity and Characterization of Bioactive Compounds in Peganum harmala L. Based on HPLC and HS-SPME-GC-MS

“…Petri dishes were incubated at 25°C, and the mycelial growth diameter was measured using the cross-bracketing method until the fungal growth of the blank control had completely covered the Petri dishes. The inhibitory rates were calculated according to the following formula (Yan et al, 2021 ):…”

Phytoestrogens and Health Effects

“…Their role in plants seems to be poorly documented, while their estrogenic activities, which are essentially provided by 8-prenylnaringenin, are often cited. However, Yan et al, [ 23 ] recently reported a significant anti-fungal activity of isoxanthohumol on Botritis cinerea . This means that the prenylflavanones can act as phytoalexins in hops.…”

Redox-Based Strategies against Infections by Eukaryotic Pathogens

“…Ethanolic extract of Humulus lupulus containing isoxanthohumol exhibited moderate antifungal activity against five tested phytopathogenic fungi in vitro but proved highly efficient in vivo against Botrytis cinerea , a broad range plant pathogen. Interestingly, the antifungal mechanism was connected to the carbohydrate metabolic process: The TCA cycle as well as respiration were inhibited upon exposure to isoxanthohumol, consequently preventing ATP production [ 72 ]. Consequently, membrane lipid peroxidation occurred together with an increased expression of redox enzymes, including SOD, catalase, APX, and GPX, and of H 2 O 2 concentration.…”