• computational biology and bioinformatics
• nanomedicine
• diabetes

• Tumor Suppressor Protein p53/metabolism
• Poly (ADP-Ribose) Polymerase-1/metabolism
• HSP90 Heat-Shock Proteins/metabolism
• Animals
• Piperidines/pharmacology
• Piperidines/chemistry
• Benzodioxoles/pharmacology
• Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
• Molecular Docking Simulation
• Hyperglycemia/drug therapy
• Hyperglycemia/metabolism
• Alkaloids/pharmacology
• Alkaloids/chemistry
• Alkaloids/administration & dosage
• Polyunsaturated Alkamides/pharmacology
• Polyunsaturated Alkamides/chemistry
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Experimental/metabolism
• Alloxan
• Rats
• Humans
• Male
• Reactive Oxygen Species/metabolism
• Mice
• Nanoparticles/chemistry
• DNA Damage/drug effects

• ECR/2017/000355/LS Science and Engineering Research Board
• F.30-488/2019(BSR) University Grants Commission

• Biological activity
• ambient degradation
• bioactive compounds
• isolated compounds
• nanoparticles
• nanotechnology.

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are pro-inflammatory cytokines involved in acute and chronic inflammatory diseases. Indeed, immunotherapy blocking these 2 cytokines has been developed. Micro-immunotherapy (MI) also uses ultra-low doses (ULD) of pro-inflammatory cytokines, impregnated on lactose-sucrose pillules, to counteract their overexpression. The study has been conducted with 2 objectives: examine the anti-inflammatory effect in vitro and the capacity of 2 unitary medicines, TNF-α (27 CH) and IL-1β (27 CH), to reduce the secretion of TNF-α in human primary monocytes and THP-1 cells differentiated with phorbol-12-myristate-13-acetate, after lipopolysaccharide (LPS) exposure; then, investigate the presence of particles possibly containing starting materials using tunable resistive pulse sensing technique. The results show that the unitary medicines, tested at 3 pillules concentrations (5.5, 11 and 22 mM), have reduced the secretion of TNF-α in both models by about 10−20% vs. vehicle control, depending on concentration. In this exploratory study, particles (150−1000 nm) have been detected in MI ULD-impregnated pillules and a hypothesis for MI medicines mode of action has been proposed. Conscious that more evaluations are necessary, authors are cautious in the conclusions because the findings described in the study are still limited, and future investigations may lead to different hypothesis.

• anti-inflammatory unitary medicines
• micro-immunotherapy
• sub-micron particles
• ultra-low doses

• Aromatic
• Biological activity
• Medicinal
• Nanoparticles
• Plants

Gelsemium sempervirens L. (Gelsemium) is traditionally used for its anxiolytic-like properties and its action mechanism in laboratory models are under scrutiny. Evidence from rodent models was reported suggesting the existence of a high sensitivity of central nervous system to anxiolytic power of Gelsemium extracts and Homeopathic dilutions. In vitro investigation of extremely low doses of this plant extract showed a modulation of gene expression of human neurocytes. These studies were criticized in a few commentaries, generated a debate in literature and were followed by further experimental studies from various laboratories. Toxic doses of Gelsemium cause neurological signs characterized by marked weakness and convulsions, while ultra-low doses or high Homeopathic dilutions counteract seizures induced by lithium and pilocarpine, decrease anxiety after stress and increases the anti-stress allopregnanolone hormone, through glycine receptors. Low (non-Homeopathic) doses of this plant or its alkaloids decrease neuropathic pain and c-Fos expression in mice brain and oxidative stress. Due to the complexity of the matter, several aspects deserve interpretation and the main controversial topics, with a focus on the issues of high dilution pharmacology, are discussed and clarified.

• Animal models
• Anxiety
• Behavior
• Gelsemium sempervirens
• Gene expression
• Homeopathic medicine
• Neurocytes

• ATR-FTIR
• Antioxidant activity
• Leishmanicidal activity
• PCL-pluronic nanoparticles
• Red propolis extract
• SEM analysis
• Thermal analysis
• UPLC-DAD

• Polymeric nanoparticles
• biological activity
• drug delivery
• encapsulation techniques
• plant extracts

• Anti-Bacterial Agents/chemistry
• Anti-Bacterial Agents/pharmacology
• Caffeic Acids/chemistry
• Caffeic Acids/pharmacology
• Capsules
• Chemistry, Pharmaceutical/methods
• Drug Delivery Systems
• Escherichia coli/drug effects
• Lactic Acid/chemistry
• Methicillin-Resistant Staphylococcus aureus/drug effects
• Microbial Sensitivity Tests
• Nanoparticles/chemistry
• Particle Size
• Phenylethyl Alcohol/analogs & derivatives
• Phenylethyl Alcohol/chemistry
• Phenylethyl Alcohol/pharmacology
• Polyglycolic Acid/chemistry
• Polylactic Acid-Polyglycolic Acid Copolymer
• Staphylococcus aureus/drug effects

• Condurango 6C and 30C
• apoptosis
• caspase-3
• homeopathy
• non-small-cell lung cancer (H460)
• reactive oxygen species

Whether the ultra-highly-diluted remedies used in homeopathy can effectively bring about modulations of gene expressions through acetylation/deacetylation of histones has not been explored. Therefore, in this study, we pointedly checked if the homeopathically-diluted anti-cancer remedy Condurango 30C (ethanolic extract of Gonolobus condurango diluted 10^-60 times) was capable of arresting the cell cycles in cervical cancer cells HeLa by triggering an epigenetic modification through modulation of the activity of the key enzyme histone deacetylase 2 vis-a-vis the succussed alcohol (placebo) control.

We checked the activity of different signal proteins (like p21^WAF, p53, Akt, STAT3) related to deacetylation, cell growth and differentiation by western blotting and analyzed cell-cycle arrest, if any, by fluorescence activated cell sorting. After viability assays had been performed with Condurango 30C and with a placebo, the activities of histone de-acetylase (HDAC) enzymes 1 and 2 were measured colorimetrically.

While Condurango 30C induced cytotoxicity in HeLa cells in vitro and reduced HDAC2 activity quite strikingly, it apparently did not alter the HDAC1 enzyme; the placebo had no or negligible cytotoxicity against HeLa cells and could not alter either the HDAC 1 or 2 activity. Data on p21^WAF, p53, Akt, and STAT3 activities and a cell-cycle analysis revealed a reduction in DNA synthesis and G1-phase cell-cycle arrest when Condurango 30C was used at a 2% dose.

Condurango 30C appeared to trigger key epigenetic events of gene modulation in effectively combating cancer cells, which the placebo was unable to do.

• Condurango 30C
• HDAC2
• cell cycle
• histone deacetylase activity
• ultra-highly-diluted remedy

• Abutilon indicum silver nanoparticles
• Antibacterial
• Apoptosis
• DNA fragmentation
• ROS generation

Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Treatment of diabetics often poses a problem in selection of the proper drug, its dose and unwanted side effects. Therefore, newer drugs with the least side effects but with highest efficiency are being relentlessly searched for. In recent years, nanotechnology has given new hope for the formulation of various drugs against a myriad of diseases, including diabetes. This review tries to give an overview of the advantages of various new drugs being used, including a wide range of nanoformulations of orthodox as well complementary and alternative medicines. Several studies and research reports based on nanotechnological approaches in the formulation of anti-diabetic drugs have pointed out the fact that research in the formulation of nanodrugs improved strategies for combating diabetes based on the plausible molecular mechanism of action of the drugs. Furthermore, attempts have also been made to delineate the optimum drug concentration and time of exposure in order to recommend a scientifically validated drug dose response in developing different therapeutic strategies. Thus, to a considerable extent, recent studies have contributed towards improving the life expectancy and quality of life of diabetics, through both targeted orthodox medicine and complementary medicine, particularly those obtained from natural resources.

• Diabetes
• Complementary and orthodox medicine(s)
• Orthodox anti-diabetic medicines
• Nanotechnology and nanomedicine
• Nanoformulation

This paper provides evidence that the leaves and stem of Passiflora serratodigitata L. dry crude extract (DCE), ethylacetate fraction (EAF), and residual water fraction show potential antiulcerogenic activity. Interestingly, the polymeric nanocapsule loaded with EAF had 10-fold more activity than the free EAF. Furthermore, the polymer nanoparticles provided homogeneous colloidal drug delivery systems and allowed overcoming challenges such as poor aqueous solubility as well as the physical-chemical instability of the organic extract, which presented 90% (w/w) of the flavonoid content. The entrapment efficiency of the total flavonoid was 90.6 ± 2.5% (w/v) for the DCE and 79.9 ± 2.7% (w/v) for the EAF. This study shows that nanoencapsulation improves both the physicochemical properties and the efficacy of the herbal formulations. Therefore, free and encapsulated extracts have the potential to be suitable drug design candidates for the therapeutic management of ulcer.

• Banerji Protocols
• Cancer treatment protocols
• complementary and alternative medicine
• exosomes
• homeopathy
• hormesis
• integrative medicine
• nanomedicine
• nanoparticles
• nosodes
• pulsed drug dosing

Gelsemium sempervirens L. (Gelsemium s.) is a traditional medicinal plant, employed as an anxiolytic at ultra-low doses and animal models recently confirmed this activity. However the mechanisms by which it might operate on the nervous system are largely unknown. This work investigates the gene expression of a human neurocyte cell line treated with increasing dilutions of Gelsemium s. extract.

Starting from the crude extract, six 100 × (centesimal, c) dilutions of Gelsemium s. (2c, 3c, 4c, 5c, 9c and 30c) were prepared according to the French homeopathic pharmacopoeia. Human SH-SY5Y neuroblastoma cells were exposed for 24 h to test dilutions, and their transcriptome compared by microarray to that of cells treated with control vehicle solutions.

Exposure to the Gelsemium s. 2c dilution (the highest dose employed, corresponding to a gelsemine concentration of 6.5 × 10^-9 M) significantly changed the expression of 56 genes, of which 49 were down-regulated and 7 were overexpressed. Several of the down-regulated genes belonged to G-protein coupled receptor signaling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Fisher exact test, applied to the group of 49 genes down-regulated by Gelsemium s. 2c, showed that the direction of effects was significantly maintained across the treatment with high homeopathic dilutions, even though the size of the differences was distributed in a small range.

The study shows that Gelsemium s., a medicinal plant used in traditional remedies and homeopathy, modulates a series of genes involved in neuronal function. A small, but statistically significant, response was detected even to very low doses/high dilutions (up to 30c), indicating that the human neurocyte genome is extremely sensitive to this regulation.

• Blood brain barrier
• Drug delivery
• Lung cancer
• STAT3 siRNA nanoparticle
• mice

The public health and individual risks of inappropriate antibiotic prescribing and conventional over-the-counter symptomatic drugs in pediatric treatment of acute otitis media (AOM) and upper respiratory infections (URIs) are significant. Clinical research suggests that over-the-counter homeopathic medicines offer pragmatic treatment alternatives to conventional drugs for symptom relief in children with uncomplicated AOM or URIs. Homeopathy is a controversial but demonstrably safe and effective 200-year-old whole system of complementary and alternative medicine used worldwide. Numerous clinical studies demonstrate that homeopathy accelerates early symptom relief in acute illnesses at much lower risk than conventional drug approaches. Evidence-based advantages for homeopathy include lower antibiotic fill rates during watchful waiting in otitis media, fewer and less serious side effects, absence of drug-drug interactions, and reduced parental sick leave from work. Emerging evidence from basic and preclinical science research counter the skeptics' claims that homeopathic remedies are biologically inert placebos. Consumers already accept and use homeopathic medicines for self care, as evidenced by annual US consumer expenditures of $2.9 billion on homeopathic remedies. Homeopathy appears equivalent to and safer than conventional standard care in comparative effectiveness trials, but additional well-designed efficacy trials are indicated. Nonetheless, the existing research evidence on safety supports pragmatic use of homeopathy in order to “first do no harm” in the early symptom management of otherwise uncomplicated AOM and URIs in children.

• Homeopathy
• acute care
• adverse drug reactions
• benefit risk assessment
• comparative effectiveness
• cost effectiveness
• otitis media
• pediatric
• upper respiratory infections

• biodegradable polymers
• biomedical applications
• cellular uptake
• drug delivery
• nanoparticles

• A549 lung adenoma cells
• PLGA nanoparticles
• Phytolacca decandra
• apoptosis
• betulinic acid
• intracellular calcium content

• Adaptation
• Antioxidants
• Drug delivery systems
• Herbal medicine
• Homeopathy
• Infectious disease treatment
• Medicinal plants
• Nanomedicine
• Nanoparticles
• Network medicine
• Silica

• T32 AT001287 NCCIH NIH HHS

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.

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.

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.

Ethanolic extract of Polygala senega (EEPS) had little or no cytotoxic effects on normal lung cells, but caused cell death and apoptosis to lung cancer cell line A549. In the present paper, ethanolic root extract of P. senega (EEPS) was nanoencapsulated (size: 147.7 nm) by deploying a biodegradable poly-(lactic-co-glycolic) acid (PLGA). The small size of the NEEPS resulted in an enhanced cellular entry and greater bioavailability. The growth of cancer cells was inhibited better by NEEPS than EEPS. Both EEPS and NEEPS induced apoptosis of A549 cells, which was associated with decreased expression of survivin, PCNA mRNA, and increased expression of caspase-3, p53 mRNAs of A549 cells. The results show that the anticancer potential of the formulation of EEPS-loaded PLGA nanoparticles was more effective than EEPS per se, probably due to more aqueous dispersion after nanoencapsulation. Therefore, nanoencapsulated ethanolic root extract of P. senega may serve as a potential chemopreventive agent against lung cancer.