A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

The role of Toll-like receptors in the immune-adrenal crosstalk

Sepsis and septic shock remain major health concerns worldwide, and rapid activation of adrenal steroid release is a key event in the organism's first line of defense during this form of severe illness. Toll-like receptors (TLRs) are critical in the early immune response upon bacterial infection, and recent data from our lab demonstrate a novel link between the innate immune system and the adrenal stress response mediated by TLRs. Glucocorticoids and TLRs regulate each other in a bidirectional way. Bacterial toxins acting through TLRs directly activate adrenocortical steroid release. TLR-2 and TLR-4 are expressed in human and mice adrenals and TLR-2 deficiency is associated with an impaired glucocorticoid response. Furthermore, TLR-2 deficiency in mice is associated with marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have an impaired adrenal corticosterone release following inflammatory stress induced by bacterial cell wall compounds. This defect appears to be associated with a decrease in systemic and intraadrenal cytokine expression. In conclusion, TLRs play a crucial role in the immune–adrenal crosstalk. This close functional relationship needs to be considered in the treatment of inflammatory diseases requiring an intact adrenal stress response.Fil: Bornstein, S. R.. Heinrich Heine University; AlemaniaFil: Ziegler, C. G.. Heinrich Heine University; AlemaniaFil: Krug, A. W.. Heinrich Heine University; AlemaniaFil: Kanczkowski, W.. Heinrich Heine University; AlemaniaFil: Besuhli, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: McCann, S. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Wirth, M.. University of Dresden; AlemaniaFil: Zacharowski, K.. Heinrich Heine University; Alemani