Folic Acid-Conjugated Chitosan-Coated Solid Lipid Nanoparticles: Precision Targeting of Artemisia vulgaris Essential Oils for Anticancer Therapy.

In this study, we developed Solid Lipid Nanoparticles (SLN-NPs) loaded with Artemisia vulgaris essential oil and coated with folic acid-chitosan (AVEO-SCF-NPs) to enhance drug delivery in biotechnology and pharmaceutical sectors. AVEO-SCF-NPs were synthesized using homogenization and ultra-sonication methods and comprehensively characterized. These nanoparticles exhibited a particle size of 253.67 nm, Polydispersity Index (PDI) of 0.26, zeta potential (ζ-p) of +39.96 mV, encapsulation efficiency (%EE) of 99.0 %, and folic acid binding efficiency (% FB) of 46.25 %. They effectively inhibited MCF-7, HT-29, and PC-3 cancer cells with IC50 values of 48.87 µg/mL, 88.48 µg/mL, and 121.34 µg/mL, respectively, and demonstrated antibacterial properties against Gram-positive strains. AVEO-SCF-NPs also exhibited scavenging effects on ABTS (IC50 : 203.83 µg/mL) and DPPH (IC50: 680.86 µg/mL) free radicals and inhibited angiogenesis, as confirmed through CAM and qPCR assays. Furthermore, these nanoparticles induced apoptosis, evidenced by up-regulation of caspase 3 and 9, down-regulation of TNF-α genes, and an increase in SubG1 phase cells. The high loading capacity of SCF-NPs for AVEO, coupled with their multifaceted biological properties, highlights AVEO-SCF-NPs as promising candidates for cancer therapy in the biotechnology and pharmaceutical industries.

Enhancing Healthcare Outcomes and Modulating Apoptosis- and Antioxidant-Related Genes through the Nano-Phytosomal Delivery of Phenolics Extracted from Allium ampeloprasum.

The application of nano drug delivery systems, particularly those utilizing natural bioactive compounds with anticancer properties, has gained significant attention. In this study, a novel nano-phytosome-loaded phenolic rich fraction (PRF) derived from Allium ampeloprasum L. was developed. The antitumor activity of the formulation was evaluated in BALB/c mice with TUBO colon carcinoma. The PRF-loaded nano-phytosome (PRF-NPs) exhibited a sphere-shaped structure (226 nm) and contained a diverse range of phenolic compounds. Animal trials conducted on TUBO tumor-bearing mice demonstrated that treatment with PRF-NPs at a dosage of 50 mg TPC/Kg/BW resulted in significant improvements in body weight and food intake, while reducing liver enzymes and lipid peroxidation. The expression of apoptosis-related genes, such as Bax and caspase-3, was upregulated, whereas Bcl2 was significantly downregulated (p < 0.05). Furthermore, the expression of GPx and SOD genes in the liver was notably increased compared to the control group. The findings suggest that the phytosomal encapsulation of the phenolic rich fraction derived from Allium ampeloprasum L. can enhance the bioavailability of natural phytochemicals and improve their antitumor properties. The development of PRF-NPs as a nano drug delivery system holds promise for effective breast cancer treatment.

Betanin inhibits PI3K/AKT/mTOR/S6 signaling pathway, cell growth and death in osteosarcoma MG-63 cells.

It is possible to develop new chemopreventive compounds so that cancer cells can be targeted in an exclusive manner. Bioactive natural compounds have demonstrated to be efficient chemotherapeutic agents, safe and cost-effective. Majority of anti-cancer medications are derived from natural sources, particularly of plant origins. Betanin (betanidin-5-O-ß-glucoside) is the most common betacyanin with antioxidant, anti inflammatory and anticancer properties. The present study therefore investigated the effect of betanin onosteosarcoma MG-63 cells. The mechanistic pathway of inflammatory responses, cell proliferation and apoptosis were investigated. The MG-63 cells were treated with betanin for 24 h. Betanin actions on the appearance of cell arrangements, morphological changes, ROS induced Δψm , cell migration, cell adhesion and proliferative mechanistic marker expression of PI3K/AKT/mTOR/S6were analyzed. Betanin inhibited MG-63 cells at IC50 concentrations between 9.08 and 54.49 µM and induced apoptosis by triggering the ROS mechanism. Betanin inhibited proliferation and migration of MG-63 cells and induced DNA fragmentation. Betanin also modified the key mediator expression levels of PI3K/AKT/mTOR/S6 signaling pathways. Betanin can potentially be utilized in bone carcinoma therapeutics to inhibit, reverse or delay osteosarcoma.

Cellular and subcellular interactions of graphene-based materials with cancerous and non-cancerous cells.

Despite significant advances in early detection and personalized treatment, cancer is still among the leading causes of death globally. One of the possible anticancer approaches that is presently receiving a lot of attention is the development of nanocarriers capable of specific and efficient delivery of anticancer drugs. Graphene-based materials are promising nanocarriers in this respect, due to their high drug loading capacity and biocompatibility. In this review, we present an overview on the interactions of graphene-based materials with normal mammalian cells at the molecular level as well as cellular and subcellular levels, including plasma membrane, cytoskeleton, and membrane-bound organelles such as lysosomes, mitochondria, nucleus, endoplasmic reticulum, and peroxisome. In parallel, we assemble the knowledge about the interactions of graphene-based materials with cancerous cells, that are considered as the potential applications of these materials for cancer therapy including metastasis treatment, targeted drug delivery, and differentiation to non-cancer stem cells. We highlight the influence of key parameters, such as the size and surface chemistry of graphene-based materials that govern the efficiency of internalization and biocompatibility of these particles in vitro and in vivo. Finally, this review aims to correlate the key parameters of graphene-based nanomaterials specially graphene oxide, such as size and surface modifications, to their interactions with the cancerous and non-cancerous cells for designing and engineering them for bio-applications and especially for therapeutic purposes.

Heracleum persicum Essential Oil Nanoemulsion: A Nanocarrier System for the Delivery of Promising Anticancer and Antioxidant Bioactive Agents.

Essential oils are important compounds for the prevention and/or treatment of various diseases in which solubility and bio-accessibility can be improved by nanoemulsion systems. Heracleum persicum oil nanoemulsion (HAE-NE) was prepared and biological properties were investigated against human breast cancer cells and normal human fibroblasts foreskin. Particle size, zeta potential and poly dispersity index were 153 nm, −47.9 mV and 0.35, respectively. (E)anethole (57.9%), terpinolene (13.8%), É£-terpinene (8.1%), myrcene (6.8%), hexyl butyrate (5.2%), octyl butanoate (4.5%) and octyl acetate (3.7%) was detected in nanoemulsion. Proliferation of cancer cells at IC50 = 2.32 µg/mL was significantly (p < 0.05) inhibited, and cell migration occurred at 1.5 µL/mL. The HAE-NE at 1.5, 2.5 and 3.5 µg/concentration up-regulated caspase 3 and enhanced sub-G1 peak of cell cycle with nil cytotoxic effects in the liver, kidney and jejunum of mice. Villus height, villus width, crypt depth and goblet cells in mice group fed with 10 and 20 mg/kg body weight of HAE-NE improved. Cellular redox state in the liver indicated 10 and 20 mg/kg body weight of nanoemulsion significantly up-regulated the expression of SOD, CAT and GPx genes. Heracleum persicum oil nanoemulsion could be an eco-friendly nanotherapeutic option for pharmaceutical, cosmetological and food applications.

Effects of Syringic Acid on Apoptosis, Inflammation, and AKT/mTOR Signaling Pathway in Gastric Cancer Cells.

Gastric cancer is one of the most common cancer and deadly disease worldwide. Despite substantial advances made in the treatment of gastric cancer, existing therapies still encounter bottlenecks. Chemotherapy, for instance, could lead to serious side effects, high drug resistance and treatment failure. Phytochemical-derived compounds from plants offer novel strategies as potent drug molecules in cancer therapy. Given the low toxicity and higher tolerance rate of naturally occurring compounds, the present study evaluated the effects of syringic acid on cytotoxicity, oxidative stress, mitochondrial membrane potential, apoptosis, and inflammatory responses in gastric cancer cell line (AGS). AGS cells were treated with various concentrations (5-40 µg/mL) of syringic acid for 24 h, after which cytotoxicity was analyzed. Reactive Oxygen Species (ROS), antioxidant enzyme activities, mitochondrial membrane potential (MMP, Δψ m), cell morphologies, the expression of apoptotic markers and protein expression patterns were also investigated. Results indicated that syringic acid-treated cells developed anti-cancer activities by losing MMP, cell viability, and enhancing intracellular ROS. Syringic acid selectively developed apoptosis in a dose-dependent manner via enhanced regulation of caspase-3, caspase-9 and Poly ADP-ribose Polymerase (PARP) whereas decreasing the expression levels of p53 and BCL-2. Syringic acid also lowered activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) whereas Thio Barbituric Acid Reactive Substances (TBARS) increased. Syringic acid suppressed gastric cancer cell proliferation, inflammation, and induced apoptosis by upregulating mTOR via AKT signaling pathway. The study suggests syringic acid may constitute a promising chemotherapeutic candidate for gastric cancer treatment. Our study is the first report on the anti-cancer effects of syringic acid against gastric cancer cells via apoptosis, inhibition of inflammation, and the suppression of the mTOR/AKT signaling pathway.

Production of GABA-enriched idli with ACE inhibitory and antioxidant properties using Aspergillus oryzae: the antihypertensive effects in spontaneously hypertensive rats.

The present study aimed to develop a fermented food (idli) with enhanced γ-aminobutyric acid (GABA) and angiotensin I-converting enzyme (ACE) inhibitory properties using a GABA-producing fungus. Aspergillus oryzae NSK fermented idli batter and GABA was maximized (451.7 mg kg-1) in 120 h. The ACE inhibitory, 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging and nitric oxide radical scavenging activities increased to 41.8%, 1.9 and 0.6 µmol trolox equivalent antioxidant capacity (TEAC) per gram in 120 h, respectively. In contrast, phytic acid and trypsin inhibitor activities decreased to 3.01 g kg-1 and 30.8 mg kg-1, respectively. The systolic blood pressure of spontaneously hypertensive rats in the fermented idli diet group was lower than those fed a plain idli diet. Lipid peroxidation in the plain idli diet group was significantly higher, whereas superoxide dismutase and glutathione reductase activities were significantly lower. The expression of genes ET-1, HSP70, NF-κB and iNOS in the aorta of SHRs that received GABA-containing diets was down-regulated between 2.2 and 3.8 fold. The production of GABA-enriched foods can be a promising approach to lower the blood pressure of spontaneously hypertensive rats.

Modeling of glutamic acid production by Lactobacillus plantarum MNZ

Background: L-glutamic acid, the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism acts as a precursor of γ-amino butyric acid (GABA). In the present study, culture condition for enhanced glutamic acid production by Lactobacillus plantarum MNZ was optimized and the influence of such conditions on GABA production was evaluated. Results: Results indicated that glutamic acid increased up to 3-fold (3.35) under the following condition: pH 4.5, temperature 37ºC, 12% (w/v) glucose and 0.7% (w/v) ammonium nitrate; whilst GABA production was enhanced up to 10-fold under the following condition: pH 4.5, temperature 37ºC, 6% (w/v) glucose and 0.7% (w/v) ammonium nitrate. Conclusions: This is the first report for dual biosynthesizing activities of a lactic acid bacterium for the production of glutamic acid and GABA. The results of this study can be further used for developing functional foods rich inglutamic acid and subsequently GABA as a bioactive compound.