German scientists detail a method that uses methanol and ethanol to extract a series of lupulone types, which are known activators of the gene TRPC6, which mediates antidepressant activity.
In addition, the team from Friedrich-Alexander University discuss the use of Ultra High Performance Liquid Chromatography coupled to Diode Array Detection (UHPLC-DAD) as a new method to quantify these lupulones.
“For the first time, this method applied isolated standards of co- and n-lupulone, which allowed accurate absolute quantification of all three congeners in dietary supplements and phytopharmaceuticals,” the study team said.
Whilst the team found some supplements and phytopharmaceuticals may not provide effective blood plasma levels of co- and n-lupulone, the improved quantification method and the use of organic solvents could eventually produce β-acid enriched products with effective lupulone concentrations.
Hops in medicinal use
Besides predominant use in the brewing industry, dried hop strobiles can be used for health purposes, especially because of their sedative and sleep-enhancing properties.
The World Health Organization (WHO) has suggested hops for the treatment of indigestion and lack of appetite.
Dried hop cones contain 3–10% β-acids (lupulones), which are made up of co, n-, and ad-lupulones amongst others.
It is these three compounds that activate the same antidepressant cellular mechanism in vitro as hyperforin, the main active constituent of the medicinal plant St. John’s wort (Hypericum perforatum), which is widely used to treat mild to moderate depression.
The team began by identifying nine hop-based dietary supplements and phytopharmaceuticals from the global market.
These dietary supplements came in liquid or capsule form and had a hop extract of 200-400 milligrams per millilitre (mg/mL) per maximum recommended daily dose.
Methanol was then added to 100 mg of the dietary capsules in capsule form. The dilution steps were adapted depending on product composition to 1:50 for dietary supplements in capsule form, which contained hop extract only.
Liquid food supplements were diluted with methanol 1:200 or 1:5, filtered and directly used for UHPLC‒DAD analysis.
The team found highly variable lupulone concentrations observed in the herbal products. In some samples (Sample 2 (S2), S3, S4, S9), lupulones were not even detectable.
Ad-lupulone was not detectable (S2–4, S9) or below Limit of Quantitation (LOQ) (S5, S7, S8) in most of the samples.
The liquid food supplement S1 contained the highest amount of lupulones (around 2.1–2.7 mg/mL of co-lupulone, 1.3–2.2 mg/mL of n-lupulone, and 0.4‒0.7 mg/mL of ad-lupulone), resulting in a maximum daily intake of up to 9.3 mg of co-lupulone, 7.9 mg of n-lupulone, and 2.3 mg of ad-lupulone.
The research team thought this hop solution contained sufficient lupulone to possibly exert potential antidepressant effects.
Interestingly, phytopharmaceuticals (S7‒S9) did not contain considerably higher lupulone levels than capsules labelled as dietary supplement (S5, S6).
The team also found complete extraction of lupulones from raw hops achieved by organic solvents, whereas aqueous mixtures resulted in low recovery.
“Dried hop strobiles are commonly administered as herbal medicine,” the team concluded.
“Doses of up to 2.0 grams (g) per day of pure dried hops of those investigated would lead to an intake of less than 100 mg of lupulones.
Taking other hop varieties into consideration, the team thought the daily uptake might even increase to 200 mg of lupulones.
“Literature data indicated that these compounds exhibit relatively low toxicity. Daily administration of lupulone capsules (5 g/day) for a period of up to three months, for example, did not cause any toxic effects to internal organs in humans.”
Source: Journal of Pharmaceutical and Biomedical Analysis
Published online: doi.org/10.1016/j.jpba.2019.02.022
“Quantification of co-, n-, and ad-lupulone in hop-based dietary supplements and phytopharmaceuticals and modulation of their contents by the extraction method.”
Authors: Carolin Schulz, Chafia Chiheb, Monika Pischetsrieder