Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles

Background: Cisplatin is a widely-used potent anti-cancer drug having severe side-effects precluding itssustained use.Objectives: Poly (lactide-co-glycolide) (PLGA)-nanoparticles loaded Boldine, an antioxidant ingredient ofethanolic extract of Boldo plant (Peumus boldus) was tested in cancer mice model, Mus musculus toexamine if it could reduce unwanted Cisplatin-induced toxicity in normal tissue.Material and methods: Nano-encapsulation of Boldine was done by following the standardized solventdisplacement method. Physico-chemical characterization of PLGA-encapsulated nano-Boldine (NBol) wasaccomplished through analyses of various spectroscopic techniques. Status of major antioxidant enzymes, functional markers, and lipid peroxidation (LPO) was also determined in certain tissue and serumsamples. Percentage of cells undergoing cytotoxic death, Reactive oxygen species (ROS) accumulationand mitochondrial functioning were analyzed in both normal and cancer mice. Nanoscale changes inchromatin organization were assessed by Transmission electron microscopy (TEM). mRNA and proteinexpressions of Top II, Bax, Bcl-2, Cyt c, caspase 3 were studied by RT-PCR, immunoblot andimmunofluorescence.Results: NBol had faster mobility, site-specific action and ability of sustained particle release. NBol readilyentered cells, prevented Cisplatin to intercalate with dsDNA resulting in reduction of chromatincondensation, with corresponding changes in ROS levels, mitochondrial functioning and antioxidantenzyme activities, leading to reduction in Deoxyribose nucleic acid (DNA) damage and cytotoxic celldeath. Expression pattern of apoptotic genes like Top II, p53, Bax, Bcl-2, cytochrome c and caspase-3suggested greater cytoprotective potentials of NBol in normal tissues.Conclusions: Compared to Boldine (Bol), NBol had better ability of drug carriage and protective potentials(29.00% approximately) against Cisplatin-induced toxicity. Combinational therapeutic use of PLGA-NBolcan reduce unwanted Cisplatin-induced cellular toxicity facilitating use of Cisplatin.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Evaluation of chemopreventive potentials of ethanolic extract of Ruta graveolens against A375 skin melanoma cells in vitro and induced skin cancer in mice in vivo / 中西医结合学报

Chemopreventive approach with natural products, particularly plants and plant-derived ones, is receiving increasing attention for their effective role against cancer without any palpable side effects. In this study, efficacy of ethanolic extract of Ruta graveolens (RG) on skin melanoma cells (A375) in vitro and on 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer in vivo has been tested in Swiss albino mice.

Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro / 中西医结合学报

Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo (Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin's cytotoxicity without affecting its anticancer potential.

Oleanolic acid isolated from ethanolic extract of Phytolacca decandra induces apoptosis in A375 skin melanoma cells: drug-DNA interaction and signaling cascade / 中西医结合学报

Oleanolic acid (OA) has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation.

Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anticancer effects on HeLa and PC3 cell lines: signalling pathway and drug-DNA interaction / 中西医结合学报

To test if myricanone (C21H24O5), a cyclic diarylheptanoid, has anticancer effects on two different cancer cell lines HeLa and PC3. The present study was conducted with a note on the drug-DNA interaction and apoptotic signalling pathway.

Homeopathic Thuja 30C ameliorates benzo(a)pyrene-induced DNA damage, stress and viability of perfused lung cells of mice in vitro / 中西医结合学报

To examine if the ultra-highly diluted homeopathic remedy Thuja 30C can ameliorate benzo(a)pyrene (BaP)-induced DNA damage, stress and viability of perfused lung cells of Swiss albino mice in vitro.

Homeopathic mother tincture of Phytolacca decandra induces apoptosis in skin melanoma cells by activating caspase-mediated signaling via reactive oxygen species elevation / 中西医结合学报

Preventive measures against skin melanoma like chemotherapy are useful but suffer from chronic side effects and drug resistance. Ethanolic extract of Phytolacca decandra (PD), used in homeopathy for the treatment of various ailments like chronic rheumatism, regular conjunctivitis, psoriasis, and in some skin diseases was tested for its possible anticancer potential.

Evidence in support of gene regulatory hypothesis: Gene expression profiling manifests homeopathy effect as more than placebo

Background: Use of ultra-high diluted remedies in homeopathy and their claimed efficacy in curing diseases has been challenged time and again by non-believers despite many evidence-based positive results published in favor of their efficacy in curing/ameliorating disease symptoms. Aims: To test the ability of ultra-high diluted homeopathic remedies beyond Avogadro’s limit, if any, in manifesting gene modulating effects in controlled in vitro experimental model. Methods: Since cancer cells manifest aberrant epigenetic gene expressions, we conducted global microarray gene expression profiling of HeLa cells (an established epigenetic model of HPV18 positive cell line) treated with two different potentized homeopathic remedies, namely, Condurango 30c and Hydrastis canadensis 30C (used in the treatment of cancer), as compared to that of placebo (succussed alcohol 30c). Results: Data revealed distinctly different expression patterns of over 100 genes as a consequence of treatment with both homeopathc remedies compared to placebo. Conclusion: Results indicate that action of the potentized drugs was “more than placebo” and these ultra-highly diluted drugs acted primarily through modulation of gene expression.

Introdução: O uso de medicamentos homeopáticos ultra-diluídos e a sua presumível eficácia na cura de doenças têm sido reiteradamente contestados por céticos, apesar dos muitos resultados positivos, baseados em evidências, demonstrando a sua eficácia na cura/melhora de sintomas patológicos. Objetivos: Testar a possível capacidade de medicamentos homeopáticos diluídos além do limite de Avogadro para apresentar efeitos de modulação genética em modelo experimental in vitro. Métodos: Sendo que as células neoplásicas manifestam expressões epigenéticas aberrantes, investigamos através de micro-arranjo o perfil global de expressão genética de células HeLa (modelo epigenético já estabelecido de linhas celulares HPV18 positivas) tratadas com 2 medicamentos homeopáticos dinamizados, a saber, Condurango 30c e Hydrastis canadensis 30c (utilizados no tratamento de neoplasias) comparados com um placebo (álcool sucussionado 30c). Resultados: Os dados indicaram diferentes perfis de expressão em mais de 100 genes nas células tratadas com os medicamentos homeopáticos por comparação ao placebo. Conclusão: Os resultados indicam que o efeito dos medicamentos dinamizados foi “mais do que placebo” e que essa ação foi principalmente mediada por modulação da expressão genética.

Ethanolic extract of Thuja occidentalis blocks proliferation of A549 cells and induces apoptosis in vitro / 中西医结合学报

To study the possible anticancer and antiproliferative activities of ethanolic leaf extract of Thuja occidentalis (TO) on A549 non-small lung carcinoma cells in vitro.

Dihydroxy-isosteviol methyl ester of Pulsatilla nigricans extract reduces arsenic-induced DNA damage in testis cells of male mice: its toxicity, drug-DNA interaction and signaling cascades / 中西医结合学报

To evaluate the ameliorative efficacy of dihydroxy-isosteviol methyl ester (DIME) of Pulsatilla nigricans extract in arsenic-induced DNA damage in testis cells of mice.

Ameliorative potentials of Syzygium jambolanum extract against arsenic-induced stress in L6 cells in vitro / 中西医结合学报

To determine the ameliorative potentials of Syzygium jambolanum (SJ) extract in L6 skeletal muscle cells in regard to arsenic-induced impairment of optimum glucose homeostasis and improper functioning of mitochondria.

Potential of the homeopathic remedy, Arnica Montana 30C, to reduce DNA damage in Escherichia coli exposed to ultraviolet irradiation through up-regulation of nucleotide excision repair genes / 中西医结合学报

To examine to what degree an ultra-highly diluted homeopathic remedy, Arnica Montana 30C (AM-30C), used in the treatment of shock and injury, can modulate the expression of nucleotide excision repair genes in Escherichia coli exposed to ultraviolet (UV) irradiation.

Potentized homeopathic drug Arsenicum Album 30C inhibits intracellular reactive oxygen species generation and up-regulates expression of arsenic resistance gene in arsenine-exposed bacteria Escherichia coli / 中西医结合学报

To examine if potentized homeopathic drug Arsenicum Album 30C (Ars Alb 30C) can reduce sodium arsenite-induced toxicity in Escherichia coli.

Rapid green synthesis of silver nanoparticles from silver nitrate by a homeopathic mother tincture Phytolacca Decandra / 中西医结合学报

To examine if a homeopathic mother tincture (Phytolacca Decandra) is capable of precipitating silver nanoparticles from silver nitrate (AgNO(3)) and to characterize the biosynthesized nanoparticles for evaluating their biological activities.

Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways / 中西医结合学报

To evaluate the role of chelidonine isolated from ethanolic extract of Chelidonium majus in inducing apoptosis in HeLa cells and to assess the main signalling pathways involved.

Phenotypic evidence of ultra-highly diluted homeopathic remedies acting at gene expression level: a novel probe on experimental phage infectivity in bacteria / 中西医结合学报

To explore if some ultra-highly diluted homeopathic remedies claimed to have antiviral effects can demonstrate any discernible action in the bacteria Escherichia coli through modulating infectivity potentials of the bacteriophage φX174 DNA.

Anticancer potentials of root extract of Polygala senega against benzoapyrene-induced lung cancer in mice / 中西医结合学报

To evaluate anticancer potentials of Polygala senega on lung cancer induced by benzo[a]pyrene (B[a]P) in mice.

Analysis of the capability of ultra-highly diluted glucose to increase glucose uptake in arsenite-stressed bacteria Escherichia coli / 中西医结合学报

Whether ultra-highly diluted homeopathic remedies can affect living systems is questionable. Therefore, this study sees value in the analysis of whether homeopathically diluted glucose 30C has any effect on Escherichia coli exposed to arsenite stress.

Potentized homeopathic drug Arsenicum Album 30C positively modulates protein biomarkers and gene expressions in Saccharomyces cerevisae exposed to arsenate / 中西医结合学报

This study examines if homeopathic drug Arsenicum Album 30C (Ars Alb 30C) can elicit ameliorative responses in yeast (Saccharomyces cerevisiae) exposed to arsenate.

An initial report on the efficacy of a millesimal potency Arsenicum Album LM 0/3 in ameliorating arsenic toxicity in humans living in a high-risk arsenic village / 中西医结合学报

Background: Millions of people are at risk of groundwater arsenic contamination, and there is no known remedy that can effectively remove the symptoms of prolonged arsenic poisoning. A potentized homeopathic drug, Arsenicum Album LM 0/3 (Ars Alb LM 0/3), is claimed in homeopathic literature to have the ability to treat symptoms similar to that of arsenic poisoning. Objective: This study examines whether Ars Alb LM 0/3 could provide some degree of amelioration for the victims living in an arsenic-affected village where no arsenic-free drinking water is available. Design, setting, participants and interventions: This study was carried out on volunteers living in an arsenic-affected village where no arsenic-free drinking water is available. Twenty-eight volunteers from the village of Dasdiya, in Haringhata block under Nadia District, West Bengal, India, an arsenic-contaminated village where wells contain 55 to 95 μg/L arsenic, were selected to undertake a double-blind and placebo-controlled trial. The subjects provided samples of blood and urine before and after 2 months of taking either "verum" or "placebo". Another 18 subjects living in an arsenic-free village, served as the negative controls. Main outcome measures: Samples of blood and urine from the subjects were assayed for arsenic content, according to various toxicity biomarkers and pathophysiological parameters. Results: Out of the original 28 subjects, only 14 subjects provided samples while the other 14 dropped out. There were elevated levels of arsenic in the blood and urine, alkaline and acid phosphatases, lipid peroxidation, and glutathione activities and increased blood glucose, triacylglycerol, cholesterol, and low-density lipoprotein cholesterol contents, whereas there were decreased levels of aspartate and alanine aminotransferases, gamma glutamyl transferase, glucose-6-phosphate dehydrogenase contents, high-density lipoprotein cholesterol and packed cell volume in the subjects. After 2 months of homeopathic remedy administration, the verum-fed subjects showed positive modulations within these parameters with slight lowering of matrix metalloproteinase activity as compared with the placebo group. Conclusion: Ars Alb LM 0/3 shows potential for use in high-risk arsenic villages as an interim treatment for amelioration of arsenic toxicity until more extensive medical treatment and facilities can be provided to the numerous victims of arsenic poisoning.