Dose-Dependent Effects of Different Humic Substances in Preclinical Test Systems

With the aim of developing humic preparations for medical use, we investigated two naturally occurring and three synthetic humic substances (HS) for their effects on inflammation, spontaneous contractile activity (SCA) of smooth muscles, and the reaction time of blood coagulation. The results indicate that low concentrations (1–10 μg/mL) of HS enhanced the SCA of smooth muscle strips from guinea pigs by stimulating alpha(2)-adrenoceptors and dopamine D2 receptors, intermediate HS concentrations (10–250 μg/mL) reduced the release of tumor necrosis factor-alpha (TNF-α), and high HS concentrations (250–1,000 μg/mL) acted as anticoagulants. A few humic samples were found to exhibit bimodal dose–response curves that will have to be further investigated.