Nanogold morphologies with the same surface chemistry provoke a different innate immune response: An in-vitro and in-vivo study.

Gold nanomaterials (GNMs) have unique optical properties with less antigenicity, and their physicochemical properties have strong relation with an immunological response at bio-interface including antigenicity. An interpretation of this correlation would significantly impact on the clinical and theranostic applications of GNMs. Herein, we studied the effect of GNMs morphology on the cytotoxicity (in-vitro), innate immune responses, hepatotoxicity, and nephrotoxicity (in-vivo studies) using gold nano-cups (GNCs), porous gold nanospheres (PGNSs) and solid gold nano particles (SGNPs) coated with the same ligand to ensure similar surface chemistry. The cytotoxicity was assessed via sulfo-rhodamine B (SRB) assay, and the cytotoxicity data showed that morphological features at nanoscale dimensions like surface roughness and hollowness etc. have a significant impact on cellular viability. The biochemical and histopathological study of liver and kidney tissues also showed that all GNMs did not show any toxicity even at high concentration (100 µL). The relative quantification of cytokine gene expression of TNF-α, IFN-γ, IL-4, 1L-6, and 1L-17 (against each morphology) was checked after in-vivo activation in mice. Among the different nanogold morphologies, PVP stabilized GNCs (PVP-GNCs) showed the highest release of pro-inflammatory cytokines, which might be due to their high surface energy and large surface area for exposure as compared to other nanogold morphologies studied. The pro-inflammatory cytokine release could be suppressed by coating with some anti-inflammatory polymer, i.e., inulin. The in-vitro results of pro-inflammatory (TNF-α, IL-1) cytokines also suggested that all GNMs may induce activation of macrophages and Th1 immune response. The in-vivo activation results showed a decrease in mRNA expression of the cytokines (TNF-α, IFN-γ, IL-4, 1L-6 and 1L-17). Based on these findings, we proposed that the shape and morphology of GNMs control their immune response at nano-bio interface, and it must be considered while designing their role for different biomedical applications like immuno-stimulation and bio-imaging.

Supramolecular lipid nanoparticles as delivery carriers for non-invasive cancer theranostics.

Nanotheranostics is an emerging frontier of personalized medicine research particularly for cancer, which is the second leading cause of death. Supramolecular aspects in theranostics are quite allured to achieve more regulation and controlled features. Supramolecular nanotheranostics architecture is focused on engineering of modular supramolecular assemblies benefitting from their mutable and stimuli-responsive properties which confer an ultimate potential for the fabrication of unified innovative nanomedicines with controlled features. Amalgamation of supramolecular approaches to nano-based features further equip the potential of designing novel approaches to overcome limitations seen by the conventional theranostic strategies, for curing even the lethal diseases and endowing personalized therapeutics with optimistic prognosis, endorsing their clinical translation. Among many potential nanocarriers for theranostics, lipid nanoparticles (LNPs) have shown various promising advances in theranostics and their formulation can be tailored for several applications. Despite the great advancement in cancer nanotheranostics, there are still many challenges that need to be highlighted to fill the literature gap. For this purpose, herein, we have presented a systematic overview on the subject and proposed LNPs as the potential material to manage cancer via non-invasive approaches by highlighting the use of supramolecular approaches to make them robust for cancer theranostics. We have concluded the review by entailing the future perspectives of lipid nanotheranostics towards clinical translation.

Protective Effects of Ellagic Acid Against Alcoholic Liver Disease in Mice.

Ellagic acid, a natural polyphenolic compound commonly present in vegetables, fruits, nuts, and other edible plants, exerts many pharmacological activities. The present project was designed to explore the hepatoprotective effect of ellagic acid against alcohol-induced liver disease (ALD) and the correlation among alcohol, oxidative stress, inflammation, and gut microbiota. Fifty percent (v/v) alcohol (10 mL/kg bw daily) was orally administrated for 4 weeks in mice along with ellagic acid (50 and 100 mg/kg bw). Alcohol administration significantly (p < 0.05) increased the activities of alanine aminotransferase and serum aspartate aminotransferase, levels of triglyceride, low density lipoprotein, free fatty acid, and total cholesterol, and decreased contents of the high-density lipoprotein in model group compared with the control group, which were further improved by ellagic acid (50 or 100 mg/kg bw). Furthermore, daily supplementation of ellagic acid alleviated hepatic antioxidant activities (glutathione peroxidase, catalase, malondialdehyde, superoxide dismutase, and glutathione), proinflammatory cytokines levels (IL-6, IL-1ß, and TNF-α), genes expressions (Tlr4, Myd88, Cd14, Cox2, Nos2, and Nfκb1), and histopathological features in alcohol-induced liver injured mice. Additionally, results also revealed that ellagic acid supplementation improved alcohol-induced gut microbiota dysbiosis. In conclusion, ellagic acid mitigated oxidative stress, inflammatory response, steatosis, and gut microbiota dysbiosis in ALD mice. Our results suggested that ellagic acid could be applied as an ideal dietary therapy against ALD.

Comparative assessment of functional properties, free and bound phenolic profile, antioxidant activity, and in vitro bioaccessibility of rye bran and its insoluble dietary fiber.

In cereals, 95% of dietary fiber is associated with phenolic compounds. The present study examined the functional properties, phenolic composition, antioxidant activity, and in vitro bioaccessibility of phenolics and flavonoids present in rye bran (RB) and its insoluble dietary fiber (IDF). Compared to RB, higher functional properties (WHC, WRC, and OHC) were represented by IDF due to its porous structure. The IDF contained lower free but higher bound phenolics and flavonoids content as compared to RB, whereas highest total phenolics (556.6 mg GAE/100 g) and flavonoids (378.3 mg RE/100 g) content were observed in IDF. Results had identified significant differences (p < .05) in phenolic acids composition between RB and IDF determined by HPLC-MS and the total phenolic acids were higher in IDF. The antioxidant capacity of IDF was higher than RB in DPPH, FRAP, ABTS, and reducing power assay. However, the in vitro phenolics and flavonoids bioaccessibility of IDF was much lower because of its high content of bound phenolics and flavonoids. PRACTICAL APPLICATIONS: A successful comparative study between RB and its IDF has been conducted in this research work that edifies the health benefits associated with the phytochemicals linked with RB and IDF. The present study also carries rich information regarding the cereal chemistry of RB that truly facilitates the food developers to specifically focus on the bioaccessibility of phenolic compounds present in IDF and RB. The findings about the functional properties and antioxidant capacities of RB and its IDF can also open new research horizons when dealing with food product development tasks, specifically related to therapeutic and medically tailored meals for the targeted customers.

Transport, metabolism and remedial potential of functional food extracts (FFEs) in Caco-2 cells monolayer: A review.

Caco-2, a human intestinal carcinoma cell line, has been used to test the absorption and transport mechanism of functional foods and drugs across the intestinal epithelium in order to study their antioxidant, anticancer and anti-inflammatory activities. Caco-2 cells represent the morphological and functional characteristics of small intestinal cells and capable of expressing brush borders, tight junctions, intestinal efflux and uptake transporters which regulate permeation of drugs and functional food extracts from intestinal lumen to systemic circulation. The integrity of the Caco-2 monolayer is controlled by establishing the TEER between 200 and 1000 O per cm2. FFEs affect intestinal permeability by adjusting the tight junction proteins between the cells in order to maintain the epithelial barrier function. Because of the side effects of medicines, there is an increased interest in functional food extracts (FFEs) as drug substitutes. Functional foods undergo intricate transport processes and biotransformation after oral administration. Metabolism and transport studies of FFEs in Caco-2 cells are very important for determining their bioavailability. Functional foods and their constituents produce anti-proliferative and anti-cancer effects through apoptosis, cell cycle arrest and inhibition of various signal transduction pathways across Caco-2 cell lines. The current review has summarized the anti-inflammation, anticancer, antioxidant and cholesterol lowering potential of FFEs using Caco-2 cells through reducing local inflammatory signals, production of ROS and lipid accumulation. The transport, bioavailability, metabolism, mechanisms of actions, cellular pathways adopted by FFEs across Caco-2 cell lines are predominantly affected by their molecular weight, structures and physicochemical properties. These studies are beneficial for investigating the different mechanisms of action of FFEs in the human body.

Effect of Caesalpinia bonduc Polyphenol Extract on Alloxan-Induced Diabetic Rats in Attenuating Hyperglycemia by Upregulating Insulin Secretion and Inhibiting JNK Signaling Pathway.

Caesalpinia bonduc has been used in herbal medicines for the treatment of a wide range of diseases from decades. The present study has explored the remedial potential and underlying mechanism of polyphenol extract of Caesalpinia bonduc in alloxanized diabetic rats. HPLC/MS analysis confirmed the presence of phenolics in considerable concentrations in Caesalpinia bonduc extract. Administration of different doses (250 and 500 mg/kg) of CPP extract to hyperglycemic rats for 8 weeks restored blood and serum glucose, insulin, glycosylated hemoglobin, leptin, amylin, and carbohydrate metabolizing enzymes level towards normal compared to alloxanized diabetic group. The effect of CPP extract on various genes such as Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 in insulin signaling pathway and Traf-4, Traf-6, and Mapk-8 in MAPK downstream JNK cascade was examined through qRT-PCR to access the core molecular mechanism involved in CPP-induced recovery of diabetes. Results have revealed that CPP extract reduced oxidative stress in pancreatic ß cells by restoring free radical scavenging potential, reducing the mRNA expression of Mapk-8, Traf-4, and Traf-6, and increasing the Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 expression ensuing regeneration of ß cells and subsequent insulin release from pancreas. The results obtained in this study recommend that CPP extract may be a promising therapeutic restorative agent in the treatment of diabetes mellitus.