Ethnopharmacological Relevance Traditional pharmacopeias have been developed by multiple cultures and evaluated for efficacy and safety through both historical/empirical iteration and more recently through controlled studies using Western scientific paradigms and an increasing emphasis on data science methodologies for network pharmacology. Traditional medicines represent likely sources of relatively inexpensive drugs for symptomatic management as well as potential libraries of new therapeutic approaches. Leveraging this potential requires hard evidence for efficacy that separates science from pseudoscience. Materials and Methods We performed a review of non-Western medical systems and developed case studies that illustrate the epistemological and practical translative barriers that hamper their transition to integration with Western approaches. We developed a new data analytics approach, in silico convergence analysis, to deconvolve modes of action, and potentially predict desirable components of TM-derived formulations based on computational consensus analysis across cultures and medical systems. Results Abstraction, simplification and altered dose and delivery modalities were identified as factors that influence actual and perceived efficacy once a medicine is moved from a non-Western to Western setting. Case studies on these factors highlighted issues with translation between non-Western and Western epistemologies, including those where epistemological and medicinal systems drive markets that can be epicenters for zoonoses such as the novel Coronavirus. The proposed novel data science approach demonstrated the ability to identify and predict desirable medicinal components for a test indication, pain. Conclusions Relegation of traditional therapies to the relatively unregulated nutraceutical industry may lead healthcare providers and patients to underestimate the therapeutic potential of these medicines. We suggest three areas of emphasis for this field: First, vertical integration and embedding of traditional medicines into healthcare systems would subject them to appropriate regulation and evidence-based practice, as viable integrative implementation mode. Second, we offer a new Bradford-Hill-like framework for setting research priorities and evaluating efficacy, with the goal of rescuing potentially valuable therapies from the nutraceutical market and discrediting those that are pseudoscience. Third, data analytics pipelines offer new capacity to generate new types of TMS-inspired medicines that are rationally-designed based on integrated knowledge across cultures, and also provide an evaluative framework against which to test claims of fidelity and efficacy to TMS made for nutraceuticals.

Mast cell lipid bodies are key to initiation, maintenance and resolution of inflammatory responses in tissue. Mast cell lines, primary bone marrow-derived mast cells and peripheral blood basophils present a 'steatotic' phenotype in response to chronic insulin exposure, where cells become loaded with lipid bodies. Here we show this state is associated with reduced histamine release, but increased capacity to release bioactive lipids. We describe the overall lipid phenotype of mast cells in this insulin-induced steatotic state and the consequences for critical cellular lipid classes involved in stages of inflammation. We show significant insulin-induced shifts in specific lipid classes, especially arachidonic acid derivatives, MUFA and PUFA, the EPA/DHA ratio, and in cardiolipins, especially those conjugated to certain DHA and EPAs. Functionally, insulin exposure markedly alters the FcεRI-induced release of Series 4 leukotriene LTC4, Series 2 prostaglandin PGD2, Resolvin-D1, Resolvin-D2 and Resolvin-1, reflecting the expanded precursor pools and impact on both the pro-inflammation and pro-resolution bioactive lipids that are released during mast cell activation. Chronic hyperinsulinemia is a feature of obesity and progression to Type 2 Diabetes, these data suggest that mast cell release of key lipid mediators is altered in patients with metabolic syndrome.

Cellular lipotoxicity manifests as the steatotic accumulation of lipid droplets or lipid bodies, and/or induction of phospholipidosis. Lipotoxicity can be induced by hyperinsulinemia/nutrient overload, cationic amphiphilic drugs (CAD), and innate immunological stimuli, all of which are stimuli relevant to mast cell physiology. Hyper-accumulation of mast cell lipid bodies in response to hyperinsulinemia has been documented but lipotoxicity in response to CAD or innate immunologic stimuli has not been analysed comparatively. Moreover, gaps in our understanding of this steatosis remain, specifically as to whether hyperinsulinemia-driven steatosis in these cells attains lipotoxic levels or is accompanied by phospholipidosis. To compare endocrine, pharmacological and innate immunological stimuli for their ability to induce steatosis and phospholipidosis in a rat basophilic leukemia mast cell model (RBL2H3), differential fluorescence microscopy staining and quantitation of phospholipidosis and steatosis in the RBL2H3 cell line was examined in response to applied endocrine, pharmacological and innate immunological stimuli. The three classes of stimuli differentially induced phospholipidosis and steatosis. PPARγ up-regulation was not uniformly associated with the expansion of the lipid body population. Fluorescence imaging of lipid-enriched structures generated in response to lipotoxic cationic amphiphilic drugs, chronic insulin exposure and TLR2/4 ligands revealed differential staining patterns when visualized using lipophilic dyes. It is concluded that lipotoxicity-inducing pathways in this model mast cell system are diverse, and include steatotic responses to an endocrine stimulus, as well as phospholipidosis responses to cationic lipophilic drugs not previously described in this cell type.