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The Antifungal Mechanism of Isoxanthohumol from Humulus lupulus Linn.
Authors:Yin-Fang Yan  Tian-Lin Wu  Sha-Sha Du  Zheng-Rong Wu  Yong-Mei Hu  Zhi-Jun Zhang  Wen-Bin Zhao  Cheng-Jie Yang  Ying-Qian Liu
Affiliation:1.School of Pharmacy, Lanzhou University, Lanzhou 730000, China; (Y.-F.Y.); (T.-L.W.); (S.-S.D.); (Z.-R.W.); (Y.-M.H.); (W.-B.Z.); (C.-J.Y.);2.State Key Laboratory of Grassland Agro-ecosystems, Lanzhou University, Lanzhou 730000, China
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.
Keywords:Humulus lupulus Linn.   isoxanthohumol   antifungal activity   Botrytis cinerea
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