A Chicago Medical School review explored the scientific evidence behind three natural compounds — genistein, curcumin, and resveratrol — often proposed for the treatment of cystic fibrosis (CF). The review concluded that while the mechanisms by which these substances function should be further investigated as potential drug treatments, there is little evidence today that — in their orally available form — these compounds can lessen CF symptoms in patients.
The study, “Natural Compounds as Therapeutic Agents in the Treatment Cystic Fibrosis,” was published in the Journal of Genetic Syndromes & Gene Therapy.
Many patients and their families seek alternatives in natural remedies, available over the counter at a fraction of that cost. But studies investigating the mechanisms and efficiency of the three most popular natural compounds — genistein, curcumin, and resveratrol — present a picture that is far from clear.
All three compounds are shown to target one of the most common CF mutations, ΔF508 CFTR, and genistein is also impacts the G551D mutation.
Genistein, found in many plants, has been shown to act as a ‘potentiator’ of CFTR — a drug that improves the function of the mutant protein in the cell membrane. The compound is associated with low toxicity, and studies have shown that genistein can modulate the ion channel at concentrations achievable when the substance is taken orally.
Curcumin, a constituent of turmeric, has shown anti-inflammatory, anti-tumor, and antioxidant effects in studies. Importantly for CF, it has also been shown to block a calcium pump known as SERCA. Other SERCA blockers can make mutant protein appear in the cell membrane, working as so-called ‘correctors.’ If a treatment can improve the rate at which mutant protein reaches the cell membrane, other treatments might be available to improve its function.
Some animal models testing curcumin have demonstrated the same effect on SERCA, where the compound also improved both gut and airway deficiencies. These studies are not in agreement, however, since other studies could not repeat the findings.
Curcumin is also poorly absorbed and rapidly metabolized, giving rise to very low plasma concentrations, not nearly in the range needed to impact SERCA. The observed effects might, in other words, be attributable to mechanisms not yet explored.
Resveratrol is a compound abundant in grapes and peanuts. Like the other substances, it has been shown to increase the availability, as well as the function, of ΔF508 mutant CFTR. As with curcumin, however, findings vary. Resveratrol also shares another characteristic with curcumin — the inability to reach therapeutic plasma concentrations by oral intake.
A study tested the maximal concentrations in people that can be achieved on human CF tissue, and saw no beneficial effects on chloride transport. Findings from in vitro experiments, and even animal models, clearly cannot be directly applied to humans.
While the price of these natural compounds is attractive, preparations of natural remedies are not standardized and manufacturers are not obliged to display the correct level of active ingredients, the researchers noted. Natural compounds could also interact with other drugs or natural compounds, producing adverse effects.
Since achievable plasma concentrations for curcumin and resveratrol are far lower than needed for a therapeutic effect, the compounds have to be chemically modified to increase absorption and bioavailability. It is, at this time, not possible to say if such a task is possible.
The review concluded that the exact mechanism by which such natural compounds might alter the availability or function of mutant CFTR is important to explore more fully. Such knowledge could instruct a rational design of synthetic drugs, at a reasonable cost, for CF.
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