Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases

Abstract

Abstract:Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products, and their integration with self-care, music and mHealth, expands precision/personalized medicine strategies for chronic diseases via pharmacological-behavioral combination therapies.

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

“…Positive data from clinical studies of digital technologies for the treatment of pain suggest an emergence of "digital analgesics" (11,13,14). Using digital therapeutics to deliver non-pharmacological interventions such as music and/or physical exercise creates new opportunities for combining these modalities with pharmacotherapies and clinicallyvalidated natural products (4)(5)(6). While development of digital therapeutics does not require preclinical testing (in contrast to regulatory requirements for investigational new drug (IND) enabling studies), translational implications of our study include: (1) using EE as a preclinical surrogate for testing combinations of non-pharmacological modalities for the treatment of pain and other chronic diseases, and (2) preclinical testing and FIGURE 8 | Working model of mechanisms by which musical compositions can exert their analgesic and anticonvulsant activities.…”

“…To innovate treatments for neurological disorders, we have been studying diverse strategies to integrate digital health technologies with CNS drugs (4)(5)(6). Digital health is a branch of healthcare that employs internet, digital, and mobile technologies for improving health and/or treating diseases.…”

Shellmycin A–D, Novel Bioactive Tetrahydroanthra-γ-Pyrone Antibiotics from Marine Streptomyces sp. Shell-016

“…Microbial secondary metabolites with widely divergent chemical structures have been regarded not only as prolific drug candidates, but also an inspiration for the starting point of drug design [1]. For half a century, antibiotics derived from microorganisms have become the leading drugs in different clinical fields due to their distinct structures and excellent activities [2,3]. However, the emerging of drug-resistant bacteria and drug-resistant tumors has prompted people to search for new drugs and novel mechanisms of action [4,5].…”

“…shell-016 from the Binzhou shell dike island was studied. Four new polyketides, named shellmycin A-D (1)(2)(3)(4), containing the tetrahydroanthra-γ-pyrone skeleton, were isolated ( Figure 1). The structures and relative configurations of the compounds were elucidated by NMR and high-resolution mass spectrometry (HR-MS).…”

EP2311454 treatment for atopic dermatitis: therapeutic efficiency in patients and anti-inflammatory in vitro

“…Multiple studies correlate treatment with different antioxidants with inhibition of pro-inflammatory gene expression and increased expression of antiinflammatory genes (11). Concerning resveratrol, a natural non-flavonoid polyphenolic compound, its being related to healthy habits (12). Moreover, emerging evidence on its implication in a number of pathophysiological processes like cancer (13), cardiovascular diseases (14), or inflammatory diseases (15) are arising.…”