Compositions with synergistic anti-inflammatory effect in inflammatory diseases resulting from activation and consequent degranulation of mast cell and followed by secretion of inflammatory biomolecules from the activated mast cells, composed of a heavily sulfated, non-bovine proteoglycan such as chondroitin sulfate C and one or more of a hexosamine sulfate such as D-glucosamine sulfate, a flavone such as quercetin, a special organic extra virgin kernel seed olive oil, S-adenosylmethionine and diphenhydramine.