Construction, characterization and application of locust bean gum/Phyllanthus reticulatus anthocyanin - based plasmonic silver nanocomposite for sensitive detection of ferrous ions.

Iron is a transition metal of tremendous eco-physiological significance. This work aimed at constructing a simple plasmonic Ag-nanocomposite (LBG/PRAg-NC) based on locust bean gum and Phyllanthus reticulatus anthocyanin in a sustainable manner for the optical detection of ferrous ions (Fe2+) in aqueous solution. LBG/PRAg-NC was prepared via a green chemistry route and thoroughly characterized for its physico-chemical and plasmonic attributes. Successful synthesis of LBG/PRAg-NC under room temperature with Phyllanthus reticulatus anthocyanin as reductant and locust bean gum as stabilizer was accomplished within 15 min. LBG/PRAg-NC exhibited small size (∼8.04 nm), spherically shaped nanosilver, with good colloidal dispersion, stability and prominent SPR absorption peak at 420 nm. XPS analysis revealed the existence of both Ag0 and Ag + species embedded in the biopolymer support. Furthermore, LBG/PRAg-NC was highly selective for Fe2+ as opposed to other interferents including Fe3+. The presence of Fe2+ engendered a redox oxidation of the analyte by the Ag+ species, prompting a rapid, concentration dependent increase in color and SPR absorption band intensity of LBG/PRAg-NC colloidal solution. In aqueous solution, the probe displayed a good linear range for Fe2+ (0.1-100 µM), and a low detection limit (LOD of 0.38 µM). The obtained detection limit is much lower than the guideline limit of Fe2+ content in drinking water, ∼5 µM. Additionally, the probe was successfully applied in determination of Fe2+ in aqueous solutions of apple juice, iron supplement tablet, and tap water, with commendable analytical performances. Therefore, our research findings demonstrate a facile, efficacious, cost-effective, and eco-friendly approach for the sustainable synthesis of plasmonic Ag-nanocomposites based solely on locust bean gum and Phyllanthus reticulatus anthocyanin. Importantly, these results validate the capacity of plasmonic Ag-nanocomposite constructed via green chemistry route as a simple, rapid, and selective probe for effective monitoring of trace amounts of Fe2+ in aqueous environment.

Development of pH-Responsive N-benzyl-N-O-succinyl Chitosan Micelles Loaded with a Curcumin Analog (Cyqualone) for Treatment of Colon Cancer.

This work aimed at preparing nanomicelles from N-benzyl-N,O-succinyl chitosan (NBSCh) loaded with a curcumin analog, 2,6-bis((3-methoxy-4-hydroxyphenyl) methylene) cyclohexanone, a.k.a. cyqualone (CL), for antineoplastic colon cancer chemotherapy. The CL-loaded NBSCh micelles were spherical and less than 100 nm in size. The entrapment efficiency of CL in the micelles ranged from 13 to 39%. Drug release from pristine CL was less than 20% in PBS at pH 7.4, whereas the release from CL-NBSCh micelles was significantly higher. The release study of CL-NBSCh revealed that around 40% of CL content was released in simulated gastric fluid at pH 1.2; 79 and 85% in simulated intestinal fluids at pH 5.5 and 6.8, respectively; and 75% in simulated colonic fluid at pH 7.4. CL-NBSCh showed considerably high selective cytotoxicity towards mucosal epithelial human colon cancer (HT-29) cells and lower levels of toxicity towards mouse connective tissue fibroblasts (L929). CL-NBSCh was also more cytotoxic than the free CL. Furthermore, compared to free CL, CL-NBSCh micelles were found to be more efficient at arresting cell growth at the G2/M phase, and induced apoptosis earlier in HT-29 cells. Collectively, these results indicate the high prospective potential of CL-loaded NBSCh micelles as an oral therapeutic intervention for colon cancer.

Synthesis of biocompatible Konjac glucomannan stabilized silver nanoparticles, with Asystasia gangetica phenolic extract for colorimetric detection of mercury (II) ion.

Herein, the synthesis of a biocompatible silver nanoparticles (AgNPs), for colorimetric detection of toxic mercury (II) ion (Hg2+), is reported. Phenolic-rich fraction of Asystasia gangetica leaf was extracted and used as a reductant of silver salt, all within the hydrophilic konjac glucomannan (KgM) solution as stabilizer, at room temperature (RT). The bioactive components of Asystasia gangetica phenolic extract (AGPE), as elucidated with a (UHPLC-MS-QTOF-MS), revealed plethora of phenolic compounds, which can facilitate the reduction of silver salt at ambient conditions. Sparkling yellow colloidal solution of KgM-AgNPs was realized within 1 h, at RT, having a UV-vis maximum at 420 nm. KgM-AgNPs was characterized using UV-vis, Raman and (FTIR), TEM, SEM, EDS, XRD, TGA/DTG. TEM and FESEM images showed that KgM-AgNPs were spherical, with particle size distribution around 10-15 nm from TEM. The KgM-AgNPs biocompatibility was investigated on mouse L929 fibrobroblast and rat erythrocytes, without any harmful damages on the tested cells. In aqueous environment, KgM-AgNPs demonstrated good detection capacity toward Hg2+, in a Hg2+ concentration dependent fashion, within 3 min. Absorbance ratios (A360/A408) was linear with Hg2+ concentrations from 0.010-10.0 to 10.0-60.0 µM, with an estimated (LOD) of 3.25 nM. The probe was applied in lake water sample, with satisfactory accuracy.

One-pot biofabrication and characterization of Tara gum/Riceberry phenolics-silver nanogel: A cytocompatible and green nanoplatform with multifaceted biological applications.

This work proposed a one-pot green route for the development of a biocompatible Tara gum-Riceberry phenolics­silver nanosphere hybrid nanocomposite (TG/RiPE-SNG) with manifold biological potentialities. The reaction system comprised of AgNO3 as nanosilver precursor, Riceberry phenolic extract as the green in situ reductant, and Tara gum as stabilizing and anchoring agent. TG/RiPE-SNG was extensively characterized using UV-vis spectroscopy, FTIR, RAMAN, TEM, FESEM, EDX, DLS/zeta potential, XRD, and TGA analyses. Small, stable, spherical, well-dispersed SNP with an average particle size of 13.01 nm and λmax of 421 nm were synthesized in situ, and uniformly distributed within the gel-like TG/RiPE composite. The prepared nanocomposite demonstrated superior antibacterial properties (MIC of 12.5 µg/mL) against S. aureus and S. epidermidis compared to the gum or extract. Additionally, TG/RiPE-SNG exhibited strong light barrier, tyrosinase inhibitory and antioxidant functionalities. TG/RiPE-SNG also exhibited high stability at different pH and was more thermally stable relative to the plain TG/RiPE composite. Furthermore, TG/RiPE-SNG showed good biocompatibility towards mouse L929 fibroblasts and rat erythrocytes. The obtained findings revealed a simple, benign, and inexpensive approach using only natural ingredients for the preparation of gum-based biopolymer-nanosilver hybrid nanocomposite and underscored the strong attributes of TG/RiPE-SNP as a nanomaterial with desirable biomedical potentials.

Fabrication of intelligent pH-sensing films with antioxidant potential for monitoring shrimp freshness via the fortification of chitosan matrix with broken Riceberry phenolic extract.

There is growing interest in chitosan-based intelligent packaging films for monitoring food quality. However, practical application of these biopolymeric films has been limited by their poor physical and mechanical attributes. Herein, a versatile colorimetric indicator film was developed based on chitosan (CHI) and broken Riceberry phenolic extract (RPE). The effects of RPE fortification on the microstructure, physical, and functional attributes of the CHI films were comprehensively evaluated. The results revealed that CHI-RPE films exhibited increased hydrophobicity, mechanical resistance, thermal stability, barrier properties, and antioxidant activity compared to plain CHI film. The CHI-RPE films were cytocompatible. Notably, CHI-RPE film also produced intense naked-eye detectable colorimetric response to pH (2-12) variation and volatile ammonia. When enclosed with fresh shrimp, CHI-RPE film changed from orange-red to yellow in response to shrimp spoilage. Thus, CHI-RPE film has high potential for fabricating pragmatic, smart packaging labels for on-site visual detection of freshness in seafood products.

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways.

Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.

Multifarious Biological Applications and Toxic Hg2+ Sensing Potentiality of Biogenic Silver Nanoparticles Based on Securidaca inappendiculata Hassk Stem Extract.

INTRODUCTION: The use of environmentally benign resources for nanoparticles synthesis is consistently pushed to the front burner in a bid to ensure and enhance environmental protection and beneficiation. In this light, application of different plant parts for the reduction and stabilization of nanoparticles is gaining popularity. MATERIALS AND METHODS: In this contribution, we have exploited Securidaca inappendiculata stem extract (SISE), as the reducing and stabilizing agent for room temperature synthesis of highly stable and dispersed AgNPs. The major bioactive compounds in SISE were profiled using an ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-MS-QTOF-MS). RESULTS AND DISCUSSION: SISE could reduce silver salts to its nanoparticles almost instantaneously with a maximum absorption spectrum at 423 nm, under the optimal conditions. The fabricated SISE AgNPs was extensively characterized using FTIR, TEM, SEM, XRD, EDS, Zeta analysis/DLS and TGA/DTG analysis. SISE AgNPs with average particles size between 10-15 nm and a zeta potential value of -19.5 ± 1.8 mV was obtained. It was investigated for in-vitro biological applications by carrying out, antimicrobial, antioxidant, hemolytic, cytotoxicity and antidiabetic assays. It was found that SISE AgNPs exhibited potent antimicrobial capacity against some food borne microbes, good antioxidant property, while also demonstrating high biocompatibility. Moreover, with a view to extending further the applications SISE AgNPs, it was tested as a colorimetric nanoprobe for Hg2+ detection in aqueous environment, where good linearity between 0.10 and 10.0 µM, with a detection limit of 26.5 nM, were obtained. The practicality of the probe was investigated by carrying out Hg2+ detection in water sample, with good accuracy and precision. DISCUSSION: Overall, this work introduced a new stabilizer for biocompatible AgNPs with far-reaching applications.

Chromolaena odorata (Siam weed): A natural reservoir of bioactive compounds with potent anti-fibrillogenic, antioxidative, and cytocompatible properties.

Protein fibrillation and oxidative damage are closely associated with the development of many chronic diseases such as Alzheimer's disease, Parkinson's disease and transthyretin amyloidoses. This work aimed at evaluating the fibrillogenic, antioxidant, anti-oxidative, hemolytic and cytotoxic activities of phenolic-rich extract from Chromolaena odorata (L) R.M. King & H. Rob aerial parts (COPE). As revealed by Thioflavin-T fluorescence, transmission electron microscopy, NBT redox cycling and ANS fluorescence analyses, COPE suppressed the fibril formation of hen egg-white lysozyme by directly binding to the protein and preventing surface exposure its of hydrophobic clusters. In addition, COPE demonstrated potent radical scavenging activities against DPPH˙ and ABTS˙+, chelated ferrous ions, and inhibited metal-catalyzed oxidation of bovine serum albumin. The observed effects could be explained by the high content of flavonoids (22.82 QE/g) and phenolics (190 mg GAE/g) present in COPE. UHPLC-ESI-QTOF-MS/MS analysis of COPE in negative ionization mode revealed that the predominant compounds were phenolics and terpenoids. Furthermore, COPE was found to exert very minimal cytotoxic effects against human red blood cells (≤ 5% hemolysis) and human embryonic kidney (HEK-293) cells (≥ 80% viability). These findings suggested that with further investigations, phenolic-rich extract from C odorata could be effectively valorized for pharmacological applications against protein fibrillogenic and oxidative damage related conditions.

Fabrication of label-free and eco-friendly ROS optical sensor with potent antioxidant properties for sensitive hydrogen peroxide detection in human plasma.

Herein, biogenic silver nanoparticles, Cafi-AgNPs was produced based on Cassia fistula-phenolic-rich extract (Cafi) only, without any toxic chemical reagent or organic solvent. Cafi bioactives were characterized using UHPLC-ESI-QTOF-MS/MS analysis. The as-synthesized nanoparticles were characterized using physico-chemical techniques including UV-vis, TEM, SEM, EDX, FTIR, DLS, Zeta potential, XRD, TGA and DGA. In addition, their antioxidant properties and cytocompatibility on erythrocytes and HEK-293 cells were examined. Results show that Cafi mediated the successful synthesis of stable well-dispersed AgNPs. Cafi-AgNPs demonstrated potent reducing and radical scavenging activities against ABTS˙+, DPPH˙ and NO˙. Furthermore, Cafi-AgNPs was compatible with human erythrocytes and HEK-293 cells. Based on the superior surface plasmonic and biological attributes of Cafi-AgNPs, its potential in H2O2 sensing was evaluated. The proposed sensor demonstrated satisfactory analytical performances with linearity of 10-200 µM, detection limit of 3.0 µM for H2O2, and was successfully applied in the detection of H2O2 in human plasma.

Protein glycation and oxidation inhibitory activity of Centella asiatica phenolics (CAP) in glucose-mediated bovine serum albumin glycoxidation.

The study aimed to evaluate the inhibitory effects of Centella asiatica phenolics (CAP) on bovine serum albumin glycoxidation in a BSA-glucose model in vitro. The impact of the phenolic extract on the formation of total fluorescent advanced glycation end products (AGEs) and Amadori adducts were determined. Dityrosine, N-formylkynurenine, kynurenine and protein-carbonyls were quantified as markers of protein oxidation. Protein structural perturbations were determined by Congo red binding and FTIR analysis. Chemical characterization and CAP phytoconstituent profile was obtained by colorimetric and UHPLC-ESI-qTOF-MS analysis, respectively. Our data show that CAP attenuated the formation of fluorescent AGEs (38.5%), Dityrosine (44.6%), N-formylkynurenine (42.9%), Amadori products, and resisted structural alterations of BSA subjected to glycation. These effects could be due to the antioxidant and radical scavenging activities of CAP mediated by the presence of phenolics and triterpenoids. The results collectively suggest that CAP possesses antiglycative properties with potentials for nutraceutical applications.

Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of Bacopa monnieri (L.) Wettst (Brahmi) Extract.

The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative. The objective of this study was to determine the effectiveness of Bacopa monnieri extract (BME) in the modulation of TTR amyloidogenesis and disruption of preformed fibrils. Using aggregation assays and transmission electron microscopy, it was found that BME abrogated the formation of human TTR aggregates and mature fibrils but did not dis-aggregate pre-formed fibrils. Through acid-mediated and urea-mediated denaturation assays, it was revealed that BME mitigated the dissociation of folded human TTR and L55P TTR into monomers. ANS binding and glutaraldehyde cross-linking assays showed that BME binds at the thyroxine-binding site and possibly enhanced the quaternary structural stability of native TTR. Together, our results suggest that BME bioactives prevented the formation of TTR fibrils by attenuating the disassembly of tetramers into monomers. These findings open up the possibility of further exploration of BME as a potential resource of valuable anti-TTR amyloidosis therapeutic ingredients.

Structural Stabilization of Human Transthyretin by Centella asiatica (L.) Urban Extract: Implications for TTR Amyloidosis.

Transthyretin is responsible for a series of highly progressive, degenerative, debilitating, and incurable protein misfolding disorders known as transthyretin (TTR) amyloidosis. Since dissociation of the homotetrameric protein to its monomers is crucial in its amyloidogenesis, stabilizing the native tetramer from dissociating using small-molecule ligands has proven a viable therapeutic strategy. The objective of this study was to determine the potential role of the medicinal herb Centella asiatica on human transthyretin (huTTR) amyloidogenesis. Thus, we investigated the stability of huTTR with or without a hydrophilic fraction of C. asiatica (CAB) against acid/urea-mediated denaturation. We also determined the influence of CAB on huTTR fibrillation using transmission electron microscopy. The potential binding interactions between CAB and huTTR was ascertained by nitroblue tetrazolium redox-cycling and 8-anilino-1-naphthalene sulfonic acid displacement assays. Additionally, the chemical profile of CAB was determined by liquid chromatography quadruple time-of-flight mass spectrometry (HPLC-QTOF-MS). Our results strongly suggest that CAB bound to and preserved the quaternary structure of huTTR in vitro. CAB also prevented transthyretin fibrillation, although aggregate formation was unmitigated. These effects could be attributable to the presence of phenolics and terpenoids in CAB. Our findings suggest that C. asiatica contains pharmaceutically relevant bioactive compounds which could be exploited for therapeutic development against TTR amyloidosis.