[Tibetan formulas as pleiotropic signatures--application of network medicines in multimorbidity]

In the context of the network model of the organism, multimorbid states (≥ 2 chronic diseases at the same time) can be considered as a complex disease pattern which can be mapped as characteristic signatures. From the perspective of system theory, living systems such as the human body are viewed as networks of interacting parts. These in turn can themselves be subnetworks assigned to different complexity levels. They range, e.g., from the gene to the transcriptome, proteome, metabolome, and epigenome up to the network of the entire molecular interactions, the so-called interactome. In multimorbidity, the disease signature affects different networks at all levels, e.g., cell systems, organs, and functional systems. Based on this semiotics, certain signatures of effectiveness and profiles of action can be assigned to each drug. A drug signature represents the physicochemical stimuli that cause a reaction by the system, as well as the cross-links by which the entire connected system is affected at all levels. Phytotherapeutics, which chemically represent multi-component mixtures, have especially complex signatures. As multi-target medicines with a pleiotropic effect profile, they therapeutically affect different levels of the network, which is why they are also referred to as network medicines. Herbal formulas from traditional medicine systems such as Tibetan Medicine are an example for phytotherapeutics with a particularly complex pleiotropic signature. Also from the traditional point of view, a disease signature is set in relation with a corresponding drug signature. However, in this case, it is based on the traditional energetic understanding of diseases. Modern research results clearly indicate a widely diversified signature range of Tibetan Medicines and thus provide a rationale for their use in integrative treatment approaches for diseases with complex signatures, e.g. in multimorbidity. The system-theoretical approach discussed here represents a method to enable a connectivity of traditional methods from complementary and alternative medicine to the other disciplines of modern medicine.