Prenylflavonoid variation in Humulus lupulus: distribution and taxonomic significance of xanthogalenol and 4′- O-methylxanthohumol

Abstract

The resins produced by either lupulin or leaf glands of over 120 plants of Humulus lupulus and one plant of H. japonicus (Cannabinaceae) were analyzed for the presence of prenylated flavonoids. The H. lupulus taxa investigated were H. lupulus var. lupulus from Europe, H. lupulus var. cordifolius from Japan, and H. lupulus from North America. Fifty-two of the plants examined were cultivars of European, American, and Japanese origin. Twenty-two flavonoids were detected in the glandular exudates of H. lupulus by HPLC-MS–MS. Xanthohumol (3′-prenyl-6′- O-methylchalconaringenin) was the principal prenylflavonoid in all H. lupulus plants and was accompanied by 11 structurally similar chalcones. Ten flavonoids were identified as the flavanone isomers of these chalcones. Three other prenylchalcones were isolated from H. lupulus cv. ‘Galena’, one of which was identified as 3′-prenyl-4′- O-methylchalconaringenin (named ‘xanthogalenol’). The distribution of three 4′-O-methylchalcones, i.e. xanthogalenol, 4′- O-methylxanthohumol, and 4′,6′-di- O-methylchalconaringenin, was found to be limited to wild American plants from the Missouri–Mississippi river basin, H. lupulus var. cordifolius, and most of their descendents. These 4′- O-methylchalcones were absent from cultivars of European origin, and from wild hops from Europe and southwestern USA. The flavonoid dichotomy (presence versus absence of 4′- O-methylchalcones) indicates that there are at least two evolutionary lineages within H. lupulus (European and Japanese–American), which is in agreement with morphological, molecular, and phytogeographical evidence. Leaf glands of H. japonicus from eastern Asia did not produce the H. lupulus prenylflavonoids.