Discovery of plant-lipid mixtures that synergistically stimulate innate immune system

Juzen-taiho-to (JTT) is an herbal medicine known to exhibit safe and effective immunostimulatory activity. It is clinically used to improve the immune functions of cancer patients undergoing chemotherapy and radiation therapy in Japan. The chemical constituents responsible for its therapeutic effects are poorly characterized due to the chemical complexity of this formulation and possible synergism. In the course of the study to identify immunostimulants in JTT, we discovered plant-lipid mixtures that exhibit immunostimulatory activity. One such example is a mixture of glucocerebroside-ceramide, two lipid components identified from JTT. Glucocerebroside and ceramide synergistically stimulate THP-1, a human leukemia monocytic cell line. Our finding suggests that lipid constituents in JTT exhibit immunostimulatory activity as a mixture, but not as a single entity. Further mechanistic studies on those plant lipids would enable us to better understand the molecular basis of safe and effective immunostimulation exhibited by JTT.