Medicine in motion: Opportunities, challenges and data analytics-based solutions for traditional medicine integration into western medical practice.

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.

Myrcene and terpene regulation of TRPV1.

Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced calcium flux responses. Terpenes contribute differentially to calcium fluxes via TRPV1 induced by Cannabis-mimetic cannabinoid/terpenoid mixtures. Myrcene dominates the TRPV1-mediated calcium responses seen with terpenoid mixtures. Myrcene-induced calcium influx is inhibited by the TRPV1 inhibitor capsazepine and Myrcene elicits TRPV1 currents in the whole-cell patch-clamp configuration. TRPV1 currents are highly sensitive to internal calcium. When Myrcene currents are evoked, they are distinct from capsaicin responses on the basis of Imax and their lack of shift to a pore-dilated state. Myrcene pre-application and residency at TRPV1 appears to negatively impact subsequent responses to TRPV1 ligands such as Cannabidiol, indicating allosteric modulation and possible competition by Myrcene. Molecular docking studies suggest a non-covalent interaction site for Myrcene in TRPV1 and identifies key residues that form partially overlapping Myrcene and Cannabidiol binding sites. We identify several non-Cannabis plant-derived sources of Myrcene and other compounds targeting nociceptive TRPs using a data mining approach focused on analgesics suggested by non-Western Traditional Medical Systems. These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.