Nanotoxic Effects of Silver Nanoparticles on Normal HEK-293 Cells in Comparison to Cancerous HeLa Cell Line.

PURPOSE: Biomimetic approaches for the synthesis of silver nanoparticles (AgNPs) had created a substantial impression among the research community that focuses on nano-bio interactions. In this study, an eco-friendly method using Rhizophora apiculata aqueous leaf extract as a reductant-rich hydrosol was followed to synthesize AgNPs and test its cytotoxicity. METHODS: To optimise the parameters for the synthesis of AgNPs, central composite design based on response surface methodology was used. The particles synthesized at a nano-scale were characterized in our previously published report. The present report further characterizes the nanoparticles by X-ray diffraction, SEM and TEM at varying sites and magnifications. The characterized AgNPs were tested for their cytotoxic effects on HEK-293 and HeLa cells. RESULTS: The cytotoxicity on the cell lines was dose-dependent. At a concentration of 2.5 µL/mL of the AgNPs-containing hydrosol, 100% inhibition of HEK-293 cells and 75% inhibition of the HeLa cells were observed. The IC50 value for AgNPs on HEK-293 was 0.622 µL/mL (12.135 ng), whereas, for HeLa cells, it was 1.98 µL/mL (38.629 ng). CONCLUSION: The nanoparticles were three-fold toxic towards the HEK-293 cells in comparison to the HeLa cells. Therefore, the therapeutic index is low for R. apiculata derived AgNPs on HeLa cells when tested in comparison with the HEK-293 cells. The nanotoxicity profile of the synthesized AgNPs seems more prominent than the nanotherapeutic index. According to our knowledge, this is the first-ever report on the optimization of synthesis of AgNPs using response surface methodology and identifying the therapeutic index of mangrove leaf-derived AgNPs.

Synthesis, optimization and characterization of silver nanoparticles using the catkin extract of Piper longum for bactericidal effect against food-borne pathogens via conventional and mathematical approaches.

Inspired with an increasing environmental awareness, we performed an eco-friendly amenable process for the synthesis of silver nanoparticles (AgNPs) using the catkins of Piper longum as an alternative approach with the existing methods of using plant extracts. The fabrication of nanoparticles occurred within 10 min. This was initially observed by colour change of the solution. UV-visible spectroscopic studies (UV-Vis) were performed for further confirmation. The analysis elucidated that the surface plasmon resonance (SPR) was specifically corresponding to AgNPs. Fourier transform infrared spectrophotometry (FTIR) studies indicated that polyphenols could possibly be the encapsulating agents. The size and shape of the nanoparticles was analysed using Transmission electron microscopy (TEM). The nanoparticles were predominant spheres ranging between 10 and 42 nm at two different scales. The formation of elemental silver was confirmed further by X-ray photoelectron spectroscopy (XPS) and X-ray powder diffraction (XRD). GC-MS analysis was used to identify the possible encapsulates on the nanoparticles. The antibacterial effect of the biosynthesized AgNPs was tested against two gram-positive (Bacillus cereus and Staphylococcus aureus), and five gram-negative (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhi) bacteria. Outcomes of the study suggest that these pathogens were susceptible to the AgNPs. This is the first ever international report on correlating the antibacterial effect of silver nanoparticles using mathematical modelling with a conventional antimicrobial assay. The results indicate that nanoparticles of silver synthesized using catkin extract of P. longum can be exploited towards the development of potential antibacterial agents.

Identification of possible reductants in the aqueous leaf extract of mangrove plant Rhizophora apiculata for the fabrication and cytotoxicity of silver nanoparticles against human osteosarcoma MG-63 cells.

Rhizophora apiculata is a less studied tannin-rich plant of the mangrove ecosystem with potent biomedical applications. Tannins have been known to reduce silver ions into silver nanoparticles which in particular are known to possess cytotoxic effects against a variety of cancer cells. The aqueous leaf extract was prepared and quantitatively analyzed for its phytochemical content. According to the quantitative phytochemical analysis, the extract was rich in tannins and other reducing sugars. The reducing sugar-rich extract was further used for the synthesis of silver nanoparticles. Taking these facts into consideration, in this study, an eco-friendly approach was followed to biosynthesize silver nanoparticles using a tannin-rich Rhizophora apiculata aqueous leaf extract. The synthesized nanoparticles were partially characterized by our previous reports. This report further characterizes the particles by determining its average size, polydispersity index and zeta potential using dynamic light scattering. After characterization, the nanoparticles were tested for cytotoxic effects against human osteosarcoma MG-63 cells. The effects were analyzed by microscopic observation and MTT assay. The results indicate that the tannin-rich extract reduced the precursor silver nitrate into silver nanoparticles of favorable size for tumor infiltration. The nanoparticles possessed significant cytotoxic effects against MG-63 cells which could be possibly attributed to the antioxidant activity of silver nanoparticles. Further studies at the molecular level can indicate its potential in nanomedicine for the treatment of bone cancer at the clinical level.

Hepatoprotective effect of silver nanoparticles synthesized using aqueous leaf extract of Rhizophora apiculata.

Background: Liver plays a vital role in the elimination of xenobiotics that can induce hepatotoxicity in living organisms.Silver nanoparticles have evolved recently as an alternative in various industries and are used for their biomedical applications.Rhizophora apiculata is a least studied mangrove-based plant that has been used in the traditional medicine of Southeast Asia for its healing properties. It is a well-known fact that the generation of free radicals has been associated with oxidative stress.  Methods: Hence, in this study we used carbon tetrachloride as a hepatotoxin to induce liver damage. The protective effects of silver nanoparticles synthesized using Rhizophora apiculata on hepatotoxin-induced liver damage in experimental mice were assessed.  Results: The results of the assessment indicate that silver nanoparticles were effective in protecting the liver from damages induced by carbon tetrachloride.  Conclusion: Among existing literature, this is the first ever approach for hepatoprotective effect of nanoparticles derived using plant extract from mangrove ecosystem.

Toxic effects of magnetic nanoparticles on normal cells and organs.

Magnetic nanoparticles (MNPs) are promising candidates for drug delivery and treatment of various disorders. Toxicity evaluation is a critical point in the development of nanoformulations and therefore, draws considerable attention. Formulations involving individual or combinatorial nanoparticle suspensions might be used for targeted delivery and treatment. This might be a evaluated further for safety related issues considering future medications based on MNPs. Nanoparticle distribution in the body is dependent on its surface characteristics. Size, dose and routes of nanoparticle entry have to be taken into consideration for future assays.

Influence of diet and dietary nanoparticles on gut dysbiosis.

Human gut comprises of a huge mixture of microorganisms as they had co-existed for millions of years. The change in co-existence of microbial genera leads to dysbiosis, which creates several disorders in humans. Diet and diet associated agents can have a considerable influence on host health by regulating the gut microbiome, which can thereby maintain the homeostasis of the gut. Analysis of the gut microbiome and the agents that can have an influence on the gut need a profound understanding, which is the need of the hour. The current review therefore focuses on the influence of diet and dietary nanoparticles on the gut microbiota and their positive or adverse effect.

Toxicity of Doxorubicin (Dox) to different experimental organ systems.

Doxorubicin (Dox) is a valuable anticancer drug for hematologic and solid tumors. Yet, it can cause multi-organ toxicities in various patients. Since toxicity evaluation is a major criterion to discuss for every experiment, the current mini-review focuses on the toxicity of Dox to multiple organs and suggests the most probable mechanism. Though several mechanisms have been suggested, the role of oxidative stress remains elusive among other mechanisms and remains the most probable mechanism for cardiotoxic effect of Dox.

Development of a new HPLC method for wogonin in rat plasma: Compatibility of standard and test samples.

In the current paper, an HPLC/UV method was developed and validated for determination of wogonin in plasma. Considerable attention was paid to the preparation of standard samples and factors affecting drug distribution. A preparation procedure was devised to simulate the conditions the drug is expected to experience in vivo while pointing to the shortcomings of previously published methods. The method was validated according to the FDA regulations and showed to be highly efficient and capable of extracting the drug and IS from the plasma accurately and precisely within the specified range of 50-500 ng mL-1. Further, the standard sample preparation of this method can be used as a guideline for other methods, particularly when highly hydrophobic drugs with considerable protein binding are involved and could be valuable in the field of bioanalysis to improve the reliability of methods.

Capture of anti-coagulant active ingredients from Moutan Cortex by platelet immobilized chromatography and evaluation of anticoagulant activity in rats.

Moutan Cortex (MC) is a well-known Chinese medicine for promoting blood circulation and relieving blood stasis. The intent of this study was to evaluate the anticoagulant activity of MC and capture the bioactive compounds by platelet immobilized chromatography. Sprague Dawley (SD) rats were randomly divided into the control group, aspirin group and MC group (1.25, 2.5, 5g/kg/d). Coagulation system and platelet activity were investigated to evaluate the anti-coagulation effect of MC. The effective components of MC were captured by platelet immobilized chromatography. High performance liquid chromatography-diode array detection (HPLC-DAD) and liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) analysis were used to identify the binding ingredients. Meanwhile, the efficacy of active ingredients was assessed through inhibiting platelet adhesion and regulating the expression of platelet related proteins. Principal findings showed that 2.5g/kg/d MC significantly prolonged thrombin time (TT) and 5g/kg/d MC significantly prolonged TT and prothrombin time (PT). MC exhibited an inhibitory potency on adenosine diphosphate-induced platelet aggregation. Four active compounds were found by platelet immobilized chromatography including oxypaeoniflorin, tetragalloylglucose, pentagalloyl glucose and benzoylpaeoniflorin; these active ingredients significantly up-regulated the expression of hsp-70 and coronin-1B, reduced the ratio of adhesion platelets. These results suggest that MC markedly promoted blood circulation and relieved blood stasis by inhibiting platelet activation, as an anti-coagulant, elucidating its potential capacity to treat cardiovascular diseases.

Apigenin's anticancer properties and molecular mechanisms of action: Recent advances and future prospectives.

Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytochemical compounds from natural resources such as fruits and vegetables are responsible for decreasing the risk of certain cancers among the consuming populations. Apigenin, a flavonoid phytochemical found in many kinds of fruits and vegetables, has been shown to exert significant biological effects, such as anti-oxidant, anti-inflammatory and most particularly anti-neoplastic properties. This review is intended to summarize the most recent advances in the anti-proliferative and chemo-preventive effects of apigenin in different cancer models. Analysis of the data from the studied cancer models has revealed that apigenin exerts its anti-proliferative effects through multiple and complex pathways. This guided us to discover some controversial results about the exact role of certain molecular pathways such as autophagy in the anticancer effects of apigenin. Further, there were cumulative positive evidences supporting the involvement of certain pathways such as apoptosis, ROS and DNA damage and repair. Apigenin possesses a high potential to be used as a chemosensitizing agent through the up-regulation of DR5 pathway. According to these preclinical findings we recommend that further robust unbiased studies should consider the possible interactions between different molecular pathways.

Autophagy: An overview and its roles in cancer and obesity.

Autophagy is a normal physiological process necessary for cellular homeostasis to maintain adequate levels of cellular components. It is essential to stabilize the source of energy during development and nutritional stress and plays the dual role of survival or cell killing in various diseases including cancer. The selectivity of the response to removal of selected organelles may vary according to the each type. Macroautophagy forms a double-membraned autophagosome around the organelle destined for processing. Microautophagy involves direct engulfment of the cellular components by lysosomal invagination. Chaperone mediated autophagy (CMA) is highly selective and is dependent on the chaperone hsc70 for its activity. The effects of all these types are implemented by autophagy related genes. In this review, the markers, activators, inhibitors biological effects and roles of the three classes of autophagy in cancer and obesity are discussed.

Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia.

Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia.

Silver nanoparticles provoke apoptosis of Dalton's ascites lymphoma in vivo by mitochondria dependent and independent pathways.

The aim of this report was to investigate the antitumor and apoptotic effects of silver nanoparticles (AgNPs) on the Dalton's ascites lymphoma cells in vivo. Thirty Swiss albino male mice were assigned into five groups of six each. Group I were intact animals. Group II animals served as tumor control injected with DAL cells intraperitonially. Group III induced animals received plant extract (17 mg/kg BW) and Group IV induced animals received AgNPs (35 µg/kg BW). Group V induced animals received standard anticancer drug 5-Fluorouracil (5-FU, 20 µg/kg BW). The treatment period was 10 days excluding the day of tumor injection. Tumor cells were collected after euthanizing the animals and real-time PCR was used to analyze p53, caspase-3, 8, 9, 12 and cytochrome C expressions. Results indicate that the AgNPs were efficient in prolongation of life span, reduction of tumor volume and body weight in tumor animals. All the apoptotic genes were upregulated by treatment with AgNPs. To conclude, the present study elicits that AgNPs are potent in antitumor activity and the molecular mechanism is by the induction of apoptosis through the mitochondrial dependent and independent pathways.