Construction of carboxymethyl chitosan/PVA/chitin nanowhiskers multicomponent film activated with Cotylelobium lanceolatum phenolics and in situ SeNP for enhanced packaging application.

This work focused on the construction of bioactive packaging films based on carboxymethyl chitosan and poly(vinyl alcohol) (CMP) as polymeric matrix and fortified with chitin nanowhiskers, Cotylelobium lanceolatum phenolic extract (CL) and in situ synthesized nano selenium. Extensive morphological, microstructural, physical and mechanical analysis revealed that the nanofillers were well-dispersed and integrated into CMP matrix. Incorporation of the extract and nano selenium produced excellent UV blocking properties without seriously compromising the transparency of the composite (CMP/CNW/CLNS1) film. Moreover, blending of CMP with the filler materials significantly elevated (p < 0.05) the surface hydrophobicity (WCA by 35.4°), water barrier (by 53.86 %), tensile strength (from 29.35 to 33.09 MPa), elongation at break (from 64.28 to 96.48 %), and thermal properties of the resultant CMP/CNW/CLNS1 film, with concomitant reduction in water solubility and swellability. Furthermore, the CMP/CNW/CLNS films exhibited remarkable improvement in antioxidant properties. When used for packaging of peeled fresh garlic cloves, the CMP/CNW/CLNS1 film pouch, not the plain CMP or CMP/CNW film pouches, inhibited weight loss, oxidative browning, and the emergence of black mold on the packaged cloves. The developed CMP/CNW/CLNS1 film demonstrated enhanced capacity to safeguard the quality of packaged food and improved shelf life. Therefore, the present study suggests that incorporation of CNW/CLNS into carboxymethyl chitosan/PVA films is a suitable and facile strategy for the fabrication of films with improved mechanical, physico-chemical and functional properties with great potential for application as a sustainable active packaging material in the food industry.

Insights into the formulation properties, biocompatibility, and permeability of poorly water-soluble methoxyflavones with PEG400 and propylene glycol.

Herein, thermal and non-thermal techniques were used to elucidate the putative physical and chemical interactions between poorly water-soluble Kaempferia methoxyflavones and PEG400/propylene glycol. Additionally, the biocompatibility of methoxyflavone-glycol solutions was evaluated using Caco-2 cells whereas the absorptive transport was investigated by measuring the apparent permeability coefficient (P app) of the methoxyflavones and transepithelial electrical resistance (TEER) of the Caco-2 cell monolayer. Data from differential scanning calorimetry, Fourier-transform infrared (FTIR), and proton nuclear magnetic resonance (1H NMR) spectroscopic analysis revealed physico-chemical compatibility between the three methoxyflavones and PEG400/propylene glycol. Furthermore, PEG400 and propylene glycol solutions of the methoxyflavones were shown to be compatible with Caco-2 cells at pharmacologically effective concentrations. In vitro transport studies across the Caco-2 cell monolayer revealed high P app values of 24.07 × 10-6 to 19.63 × 10-6 cm s-1 for PEG400 solutions of the methoxyflavones. The TEER values of the Caco-2 cell monolayers indicated that the increased drug transport was partly due to increased tight junction openings, but without compromising the epithelial barrier integrity. The good pharmaceutical and biocompatibility profiles, as well as improved transport of the methoxyflavones in PEG400 and propylene glycol solutions, are suggestive of the worthiness of this approach for further consideration pertaining to the development of these drugs into oral liquid dosage forms.

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.

Insights into the remarkable attenuation of hen egg white lysozyme amyloid fibril formation mediated by biogenic gold nanoparticles stabilized by quercetin-functionalized tara gum.

Aberrant protein misfolding and/or aggregation and fibrillation has been linked to the pathogenesis of several debilitating chronic diseases including Alzheimer's and Parkinson's disease. Inhibiting protein amyloidogenesis has been proposed as a viable strategy to prevent or ameliorate associated disorders. Herein, we investigated the anti-amyloidogenic properties of biogenic gold nanoparticles (QTG-GNP) prepared via a simple green chemistry route and stabilized by quercetin-functionalized tara gum (QTG). The synthesized QTG-GNP was extensively characterized for its physicochemical attributes via UV-visible spectroscopy, TEM, FESEM, EDX, DLS/Zeta potential, FTIR, RAMAN, XRD, XPS, and TGA analyses, as well as for its biological properties. The results revealed that small-sized (5.01 ± 1.17 nm), well-dispersed, highly stable and round-shaped biogenic gold nanoparticles were successfully synthesized at room temperature with QTG as the sole reductant /stabilizer. Importantly, QTG-GNP demonstrated potent anti-aggregation and fibrillation inhibitory effects against amyloidogenic hen egg white lysozyme (HEWL). Also, QTG-GNP was able to dissociate pre-formed HEWL amyloid fibrils. Furthermore, the constructed nanoparticles exhibited potent anti-radical activities against DPPH and ABTS+ and were cytocompatible with mouse L929 fibroblast cells. On the basis of these findings, it was established that QTG-GNP holds strong prospects for further development as an agent for countering protein aggregation and associated disease conditions.

A facile one-step jet-milling approach for the preparation of proliposomal dry powder for inhalation as effective delivery system for anti-TB therapeutics.

OBJECTIVE: Physicochemical characterization and assessment of aerosol dispersion performance of anti-TB proliposome dry powders for inhalation (DPIs) prepared using a single-step jet-milling (JM) approach. SIGNIFICANCE: Conventional tuberculosis (TB) treatment involves isoniazid and rifampicin as first-line agents in extended oral multi-drug regimes. Liposomal DPIs are emerging as promising alternatives for targeted delivery of anti-TB agents to alveolar macrophages harboring Mycobacterium tuberculosis. However, traditional approaches for liposomal DPI preparation are tedious, time consuming and require sophisticated/expensive equipment. The proposed JM technique for preparation of proliposome DPIs could obviate these limitations and facilitate use of these drugs for more effective and safer treatment. METHODS: Proliposome DPIs containing isoniazid and/or rifampicin, cholesterol and cholesterol sulfate were successfully prepared via JM (injection pressure, 7.4 bar; milling pressure, 3.68 bar). Their physicochemical, content uniformity, and in vitro aerosol dispersion performance were assessed using scanning electron microscopy/energy-dispersive X-ray spectroscopy, transmission electron microscopy, dynamic light scattering/Zeta potential, X-ray diffraction spectroscopy, thermogravimetric analysis, high-performance liquid chromatography, and the Next-Generation Impactor. RESULTS: The DPIs exhibited consistent, spherically shaped, smooth particles. Drug particles were evenly distributed with acceptable content uniformity. Drug crystallinity was not significantly affected by milling and the formulations had minimal (<2.0%) water content. After reconstitution of the DPIs, the hydrodynamic size was about 370.9-556.2 nm and charge was -12.3 to -47.3 mV. Furthermore, the proliposome DPIs presented emitted dose (69.04-89.03%), fine particle fraction, <4.4 µm (13.7 - 57.8%), and mass median aerodynamic diameter (<3.0 µm), which satisfied the requirements for deep lung delivery. CONCLUSION: The proposed approach was suitable for preparation of proliposome DPIs that could be deployed for local targeting of the lower respiratory tract for the treatment of TB.

Antiproliferative Activities of the Lipophilic Fraction of Eucalyptus camaldulensis against MCF-7 Breast Cancer Cells, UPLC-ESI-QTOF-MS Metabolite Profile, and Antioxidative Functions.

Although a number of pharmacological properties have been linked to Eucalyptus camaldulensis leaf essential oil and extracts, the biological attributes of the lipophilic fraction remain unknown. Moreover, only a limited number of active compounds have so far been identified. This work aimed to investigate the anti-oxidative, anti-aggregation, and cytotoxic properties as well as profile the secondary metabolites in the lipophilic fraction of E. camaldulensis leaf extract (Lipo-Eucam) using UHPLC-ESI-QTOF-MS and gas chromatography-mass spectrometry (GC-MS). It was found that Lipo-Eucam possessed potent antioxidant properties against DPPH, ABTS, and FRAP with IC50 values of 31.46, 32.78, and 10.12 µg/mL, respectively. The fraction was able to attenuate metal-catalyzed oxidation of bovine serum albumin (BSA) in a dose-dependent manner (p < 0.05) and abrogated the aggregation of amyloidogenic BSA as revealed by the Congo red assay and transmission electron microscopy. Furthermore, Lipo-Eucam demonstrated potent cytotoxic effects against MCF-7 (IC50 7.34 µg/mL) but was noncytotoxic at used concentrations against HEK-293 cells (IC50 > 80 µg/mL), suggestive of its selective anticancer properties. Spectrophotometric, UHPLC-MS, and GC-MS analysis revealed that Lipo-Eucam is rich in phenolics, flavonoids, terpenoids, volatile constituents, and a plethora of active metabolites, probably responsible for the observed activities. These findings indicate that Lipo-Eucam is endowed with pharmacologically relevant active principles with strong potential for use in the amelioration of disease conditions related to oxidative stress, protein aggregation, and breast cancer and therefore worthy of further investigations.

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.

Synthesis of gold nanoparticles/polyaniline boronic acid/sodium alginate aqueous nanocomposite based on chemical oxidative polymerization for biological applications.

Gold nanoparticles/polyaniline boronic acid/sodium alginate aqueous nanocomposite ((PABA-SAL)@AuNPs) was fabricated. Aniline boronic acid (ABA) served as reductant of gold salt, all within the SAL solution. While ABA reduced gold salt to its nanoparticles, the ABA monomer was also oxidized to its conducting polymeric form (PABA). The presence of PABA in the reaction mixture exerted solubility and stability challenge, thus SAL was used as stabilizer and solubilizer for PABA. The numerous cis-diol groups of SAL could bind to boronic acid groups of PABA to furnish PABA-SAL repeating polymer structure for AuNPs anchoring. Sparkling ruby red (PABA-SAL)@AuNPs have absorption peaks at 529 and 718 nm. Average particle sizes of nanocomposite were within 15-20 nm, with hydrodynamic diameter of 48.6 ± 0.9 nm, zeta potential of -32.5 ± 1.6 mV and conductivity value of 2015.3 ± 3.2 µS/cm. (PABA-SAL)@AuNPs possessed antibacterial activities against seafood associated bacterial isolates, with MIC and MBC ranging from 4 to 8 µg/mL. The moderate antioxidant capacity of (PABA-SAL)@AuNPs was observed, without any deleterious damages on human red blood cells. It also has good biocompatibility on Caco-2 and RAW 264.7, with cell viability not less than 70%. These results confirm the high prospect of (PABA-SAL)@AuNPs for possible biomedical applications.

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.

Valorization of Pichia spent medium via one-pot synthesis of biocompatible silver nanoparticles with potent antioxidant, antimicrobial, tyrosinase inhibitory and reusable catalytic activities.

The purpose of this study was to determine the feasibility of a novel biogenic synthesis of silver nanoparticles using Pichia pastoris spent medium - a major waste product from heterologous protein expression as the sole reducing and capping agent, with potential biological, antimicrobial and wastewater remediation applications. Using UV-vis spectroscopy, TEM, XRD, EDX, FTIR, SEM we demonstrated the successful bio-fabrication of Pichia spent medium encapsulated silver nanoparticles (PSM-AgNPs). PSM-AgNPs displayed substantial antiradical activity against DPPH and ABTS. The antiradical activity against ABTS was similar to that of the control, ascorbic acid. PSM-AgNPs also revealed potent anti-tyrosinase and antibacterial activity against some common foodborne pathogenic microbes. Human erythrocyte hemolytic and embryonic colon Caco-2 cell viability assays suggest that PSM-AgNPs was biocompatible. In addition, PSM-AgNPs, was also effective in the catalytic degradation of methyl orange and Congo red dyes with pseudo first order rate constants of 0.2301 min-1 and 4.7 × 10-3 s-1, respectively. These results present a clean, convenient, and inexpensive approach for the biosynthesis of silver nanoparticles with potential implications in the eco-friendly, safe and effective utilization of waste culture media, mitigation of pathogenic bacteria and management of industrial effluents.

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.

Centella asiatica phenolic extract-mediated bio-fabrication of silver nanoparticles: characterization, reduction of industrially relevant dyes in water and antimicrobial activities against foodborne pathogens.

In this article, we have reported an environmentally benign and cost-effective method for the synthesis of monodispersed silver nanoparticles (AgNPs), based on Centella asiatica phenolic extracts (CAPE). The presence of phenolics was confirmed by ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time of flight mass spectrometry (UHPLC-ESI-qTOF-MS). Colloidal AgNPs synthesized under different concentrations of silver nitrate were monitored with a UV-vis spectrophotometer. Maximum absorption spectra intensity was found to range between 430-440 nm, during a synthesis time of 90 minutes at room temperature. The as-synthesized CAPE-AgNPs, was subjected to various instrumental characterizations such as, transmission electron microscopy (TEM), X-ray powder diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS) and zeta potential. At the optimized synthesis conditions, spherical and monodispersed CAPE-AgNPs were obtained, with an absorption maximum at 430 nm. The crystalline CAPE-AgNPs had a face-centered-cubic (fcc) crystallographic structure, possessing average sizes estimated from TEM, to be between 20-25 nm diameter, a hydrodynamic diameter from DLS of about 90 nm and a zeta potential value of -28.7 mV. FTIR results validated the presence of phenolics on the surfaces of CAPE-AgNPs. The anti-microbial capacity of CAPE-AgNPs was further demonstrated on different pathogenic bacterial strains with satisfactory performances. As a result of the high surface area to volume ratio of CAPE-AgNPs, it was investigated as a catalyst towards the reduction of prominent environmental pollutants, 4 nitrophenol (4 NP), Congo red (CR) and methylene blue (MB). Pseudo first order kinetics were obtained with rate constants of 3.9 × 10-3 s-1 for 4 NP, 54.7 × 10-3 min-1 for MB and 5.6 × 10-3 s-1 for CR. The catalytic performance and antimicrobial activities of CAPE-AgNPs suggest its potential application in wastewater treatment and control of pathogenic microbes.