Pemetrexed loaded gold nanoparticles as cytotoxic and apoptosis inducers in lung cancer cells through ROS generation and mitochondrial dysfunction pathway.

Supramolecular nanoparticles containing peptides and drugs have recently gained recognition as an effective tumor treatment drug delivery system. A multitarget drug termed pemetrexed is effective against various cancers, including nonsmall cell lung cancer. The work aims to establish the capability of pemetrexed gold nanoparticles (PEM-AuNPs) to induce apoptosis and explore molecular changes. X-ray diffraction, Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscope, and transmission electron microscope were used to investigate the synthesized nanoparticles. The MTT assay was utilized to investigate the anticancer properties of PEM-AuNPs at varying concentrations (50, 100, and 200 µM). PEM-AuNPs demonstrated a decrease in cell viability with 55.87%, 43.04%, and 25.59% for A549 cells and 54.31%, 37.40%, and 25.84% for H1299 cells at the respective concentrations. To assess apoptosis and perform morphological analysis, diverse biochemical staining techniques, including acridine orange-ethidium bromide and 4',6-diamidino-2-phenylindole nuclear staining assays, were employed. Additionally, 2',7'-dichlorofluorescein diacetate staining confirmed the induction of reactive oxygen species generation, while JC-1 staining validated the impact on the mitochondrial membrane at the IC50 concentration of PEM-AuNPs. Thus, the study demonstrated that the synthesized  PEM-AuNPs exhibited enhanced anticancer activity against both A549 and H1299 cells.

Facile construction of gefitinib-loaded zeolitic imidazolate framework nanocomposites for the treatment of different lung cancer cells.

Gefitinib (GET) is a revolutionary targeted treatment inhibiting the epidermal growth factor receptor's tyrosine kinase action by competitively inhibiting the ATP binding site. In preclinical trials, several lung cancer cell lines and xenografts have demonstrated potential activity with GET. Response rates neared 25% in preclinical trials for non-small cell lung cancer. Here, we describe the one-pot synthesis of GET@ZIF-8 nanocomposites (NCs) in pure water, encapsulating zeolitic imidazolate framework 8 (ZIF-8). This method developed NCs with consistent morphology and a loading efficiency of 9%, resulting in a loading capacity of 20 wt%. Cell proliferation assay assessed the anticancer effect of GET@ZIF-8 NCs on A549 and H1299 cells. The different biochemical staining (Calcein-AM and PI and 4',6-Diamidino-2-phenylindole nuclear staining) assays assessed the cell death and morphological examination. Additionally, the mode of apoptosis was evaluated by mitochondrial membrane potential (∆ψm) and reactive oxygen species. Therefore, the study concludes that GET@ZIF-8 NCs are pledged to treat lung cancer cells.

Inhibitory effects of Gracilaria edulis and Gracilaria salicornia against the MGMT and VEGFA biomarkers involved in the onset and advancement of glioblastoma using in silico and in vitro approaches.

Glioblastoma (GBM), an aggressive primary brain tumor originating from glial cells, poses significant treatment challenges due to its rapid growth and invasiveness. The exact mechanisms of GBM's brain damage remain unclear. This study examines primary molecular markers commonly assessed in GBM patients, including brain-derived neurotrophic factor (BDNF), platelet-derived growth factor receptor A (PDGFRA), O6-methylguanine DNA methyltransferase (MGMT), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA) using computational approaches. The study revealed significant differences (p ≤ 0.05) in PDGFRA, EGFR, and VEGFA expression rates, which are particularly interesting. Additionally, MGMT and VEGFA showed higher hazard ratios. Expression levels of MGMT and VEGFA were visualized in immune and malignant cells using single-cell RNA datasets GSE103224 and GSE148842. From a total of 48 compounds in Gracilaria edulis and 86 in Gracilaria salicornia, we identified 15 compounds capable of crossing the blood-brain barrier. Notably, 2-tridecanone (binding affinity [BA] = -4.2 kcal/mol; root mean square deviation [RMSD] = 1.479 Å) and decanoic acid, ethyl ester (BA = -4.2 kcal/mol; RMSD = 1.702 Å) from G. edulis interacted with MGMT via hydrogen bonds. The compound alpha-terpineol interacted with MGMT (BA = -5.7 kcal/mol; RMSD = 0.501 Å) and VEGFA (BA = -4.7 kcal/mol; RMSD = 2.483 Å). Ethanolic and methanolic extracts from G. edulis and G. salicornia demonstrated mild anti-cell proliferation properties in the GBM LN-229 cell line, suggesting potential therapeutic benefits. This study highlights the significance of molecular markers and natural compounds in understanding and potentially treating GBM.

Facile engineering of aptamer-coupled silk fibroin encapsulated myogenic gold nanocomposites: investigation of antiproliferative activity and apoptosis induction.

Nanocomposites selectively induce cancer cell death, holding potential for precise liver cancer treatment breakthroughs. This study assessed the cytotoxicity of gold nanocomposites (Au NCs) enclosed within silk fibroin (SF), aptamer (Ap), and the myogenic Talaromyces purpureogenus (TP) against a human liver cancer cell (HepG2). The ultimate product, Ap-SF-TP@Au NCs, results from a three-step process. This process involves the myogenic synthesis of TP@Au NCs derived from TP mycelial extract, encapsulation of SF on TP@Au NCs (SF-TP@Au NCs), and the conjugation of Ap within SF-TP@Au NCs. The synthesized NCs are analyzed by various characteristic techniques. Ap-SF-TP@Au NCs induced potential cell death in HepG2 cells but exhibited no cytotoxicity in non-cancerous cells (NIH3T3). The morphological changes in cells were examined through various biochemical staining methods. Thus, Ap-SF-TP@Au NCs emerge as a promising nanocomposite for treating diverse cancer cells.

Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.

Improvement of diabetic wound healing by topical application of Vicenin-2 hydrocolloid film on Sprague Dawley rats.

BACKGROUND: Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. The risk of developing diabetic foot ulcers for diabetic patients is 15% over their lifetime and approximately 85% of limb amputations is caused by non-healing ulcers. Unhealed, gangrenous wounds destroy the structural integrity of the skin, which acts as a protective barrier that prevents the invasion of external noxious agents into the body. Vicenin-2 (VCN-2) has been reported to contain prospective anti-oxidant and anti-inflammatory properties that enhance cell proliferation and migration. Sodium Alginate (SA) is a natural polysaccharide that possesses gel forming properties and has biodegradable and biocompatible characteristics. Therefore, the objective of this study is to evaluate the effect of SA wound dressings containing VCN-2 on diabetic wounds. METHODS: Wounds were inflicted in type-1 diabetic-streptozotocin (STZ) induced male Sprague Dawley rats. Subsequently, relevant groups were topically treated with the indicated concentrations (12.5, 25 and 50 µM) of VCN-2 hydrocolloid film over the study duration (14 days). The control group was treated with vehicle dressing (blank or allantoin). Wounded tissues and blood serum were collected on 0, 7 and 14 days prior to sacrifice. Appropriate wound assessments such as histological tests, nitric oxide assays, enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were conducted to confirm wound healing efficacy in the in vivo model. One-way Analysis of Variance (ANOVA) was used for statistical analysis. RESULTS: Results showed that hydrocolloid film was recapitulated with VCN-2 enhanced diabetic wound healing in a dose-dependent manner. VCN-2 reduced pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), mediators (iNOS and COX-2), and nitric oxide (NO) via the NF-κB pathway. Data suggests that the VCN-2 film facilitated healing in hyperglycemic conditions by releasing growth factors such as (VEGF and TGF-ß) to enhance cell proliferation, migration, and wound contraction via the VEGF and TGF-ß mechanism pathways. CONCLUSIONS: This study's findings suggest that VCN-2 may possess wound healing potential since topical treatment with VCN-2 hydrocolloid films effectively enhanced wound healing in hyperglycemic conditions.

Mini Review: Wound healing potential of edible plants.

Wound healing is a natural intricate cascade process involving cellular, biochemical and molecular mechanism to restore the injured or wounded tissue. Malaysia's multi-ethnic social fabric is reflected in its different traditional folk cuisines with different nutritional important ingredients. Despite these differences, there are some commonly used pantry ingredients among Malaysians and these ingredients may possess some healing power for acute and chronic wounds. These essential nutritional ingredients are included Amla (Ribes uva-crispa), Cinnamon (Cinnamomun venum), Curry Leaves (Murraya koenigii), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), Garlic (Allium indica), Onion (Allium cepa) and Tamarind (Tamarindus indica). This article provides a review of the remedies with confirmed wound healing activities from previous experiments conducted by various researchers. Most of the researchers have focused only on the preliminary studies through appropriate model; hence detailed investigations which including pharmacological and pre-clinical studies are needed to discover its molecular mechanisms. In this review article, we have discussed about the wound healing potential of few commonly used edible plants and their known mechanism.

Anti-Inflammatory Potential of Ethyl Acetate Fraction of Moringa oleifera in Downregulating the NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated Macrophages.

In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.

Moringa oleifera Flower Extract Suppresses the Activation of Inflammatory Mediators in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages via NF-κB Pathway.

Aim of Study. Moringa oleifera Lam. (M. oleifera) possess highest concentration of antioxidant bioactive compounds and is anticipated to be used as an alternative medicine for inflammation. In the present study, we investigated the anti-inflammatory activity of 80% hydroethanolic extract of M. oleifera flower on proinflammatory mediators and cytokines produced in lipopolysaccharide- (LPS-) induced RAW 264.7 macrophages. Materials and Methods. Cell cytotoxicity was conducted by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nitric oxide (NO) production was quantified through Griess reaction while proinflammatory cytokines and other key inflammatory markers were assessed through enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Results. Hydroethanolic extract of M. oleifera flower significantly suppressed the secretion and expression of NO, prostaglandin E2 (PGE2), interleukin- (IL-) 6, IL-1ß, tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2). However, it significantly increased the production of IL-10 and IκB-α (inhibitor of κB) in a concentration dependent manner (100 µg/mL and 200 µg/mL). Conclusion. These results suggest that 80% hydroethanolic extract of M. oleifera flower has anti-inflammatory action related to its inhibition of NO, PGE2, proinflammatory cytokines, and inflammatory mediator's production in LPS-stimulated macrophages through preventing degradation of IκB-α in NF-κB signaling pathway.

Development of a highly biocompatible antituberculosis nanodelivery formulation based on para-aminosalicylic acid-zinc layered hydroxide nanocomposites.

Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 µg/mL compared to the free drug PAS with a MIC of 5.0 µg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies.

Beneficial effects of mangiferin isolated from Salacia chinensis on biochemical and hematological parameters in rats with streptozotocin-induced diabetes.

Salacia chinensis L. is a traditional Southeast Asian herbal medicine and used in the treatment of diabetes. To investigate the antidiabetic properties of mangiferin from Salacia chinensis and its beneficial effect on toxicological and hematological parameters in streptozotocin induced diabetic rats. Mangiferin was orally treated with the dose of 40 mg/kg body weight/day for 30 days to diabetic rats. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in diabetic treated groups with mangiferin and glibenclamide. Mangiferin treated diabetic rats significantly (p<0.05) lowered the level of blood glucose, in addition, altered the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters including AST, ALT and ALP were also significantly reduced after treatment with mangiferin in diabetic rats. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved through the administration of mangiferin. Thus, our results indicate that mangiferin present in S. chinensis possesses antidiabetic properties and nontoxic nature against chemically induced diabetic rats. Further experimental investigations are warrant to make use of its relevant therapeutic effect to substantiate its ethno-medicinal usage.

Investigation of antiproliferative efficacy and apoptosis induction in leukemia cancer cells using irinotecan-loaded liposome-embedded nanofibers constructed from chitosan.

Liposomes and nanofibers have been implemented as efficacious vehicles for delivering anticancer drugs. With this view, this study explores the antiproliferative efficacy and apoptosis induction in leukemia cancer cells utilizing irinotecan-loaded liposome-embedded nanofibers fabricated from chitosan, a biological source. Specifically, we investigate the effectiveness of poly(ε-caprolactone) (PCL)/chitosan (CS) (core)/irinotecan (CPT)nanofibers (termed PCL-CS10 CPT), PCL/chitosan/irinotecan (core)/PCL/chitosan (shell) nanofibers (termed CS/CPT/PCL/CS), and irinotecan-coloaded liposome-incorporated PCL/chitosan-chitosan nanofibers (termed CPT@Lipo/CS/PCL/CS) in releasing irinotecan in a controlled manner and treating leukemia cancer. The fabricated formulations were characterized utilizing Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, dynamic light scattering, zeta potential, and polydispersity index. Irinotecan was released in a controlled manner from nanofibers filled with liposomes over 30 days. The cell viability of the fabricated nanofibrous materials toward Human umbilical vein endothelial cells (HUVECs) non-cancerous cells after 168 h was >98 % ± 1 %. The CPT@Lipo/CS/PCL/CS nanofibers achieved maximal cytotoxicity of 85 % ± 2.5 % against K562 leukemia cancer cells. The CPT@Lipo/CS/PCL/CS NFs exhibit a three-stage drug release pattern and demonstrate significant in vitro cytotoxicity. These findings indicate the potential of these liposome-incorporated core-shell nanofibers for future cancer therapy.

Impacts of designed vanillic acid-polymer-magnetic iron oxide nanocomposite on breast cancer cells.

The engineered nano-vehicle was constructed using magnetic iron oxide nanoparticles (MIONs) and chitosan (CTS) to stabilize anticancer agent vanillic acid (VNA) which was loaded on CTS-coated MIONs nanocarrier, and more importantly, to achieve sustained VNA release and subsequent proper anticancer activity. The new thermally stable VNA-CTS- MIONs nanocomposite was spherical with a middle diameter of 6 nm and had a high drug loading of about 11.8 %. The MIONs and resulting nanocomposite were composed of pure magnetite and therefore, were superparamagnetic with saturation magnetizations of 53.3 and 45.7 emu.g-1, respectively. The release profiles of VNA from VNA-CTS-MIONs nanocomposite in different pH values were sustained and showed controlled pH-responsive delivery of the loaded VNA with 89 % and 74 % percentage release within 2354 and 4046 min at pH 5 and 7.4, respectively, as well as were in accordance with the pseudo-second-order model. The VNA-CTS-MIONs nanocomposite treatment at diverse concentrations remarkably decreased the viability and promoted ROS accumulation and apoptosis in the MDA-MB-231 breast cancer cells. Hence, it can be a propitious candidate for the management of breast cancer in the future.

Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells.

Background: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection. Objective: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells. Methodology: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits. Results: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells. Conclusion: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review.

High blood glucose levels are a hallmark of the metabolic syndrome known as diabetes mellitus. More than 600 million people will have diabetes by 2045 as the global prevalence of the disease continues to rise. Contemporary antidiabetic drugs reduce hyperglycemia and its consequences. However, these drugs come with undesirable side effects, so it's encouraging that research into plant extracts and bioactive substances with antidiabetic characteristics is on the rise. Natural remedies are preferable to conventional anti-diabetic drugs since they are safer for the body, more affordable and have fewer potential adverse effects. Biological macromolecules such as liposomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions and metallic nanoparticles are explored in this review. Current drug restrictions have been addressed, and the effectiveness of plant-based antidiabetic therapies has enhanced the merits of these methods. Plant extracts' loading capacity and the carriers' stability are the primary obstacles in developing plant-based nanocarriers. Hydrophilic, hydrophobic, and amphiphilic drugs are covered, and a brief overview of the amphipathic features of liposomes, phospholipids, and lipid nanocarriers is provided. Metallic nanoparticles' benefits and attendant risks are highlighted to emphasize their efficiency in treating hyperglycemia. Researchers interested in the potential of nanoparticles loaded with plant extracts as antidiabetic therapeutics may find the current helpful review.

Synthesis of bisindolylmethanes and their cytotoxicity properties.

Polymer supported dichlorophosphate (PEG-OPOCl(2)) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and their anti-cancer activity are evaluated.

The combination of mitragynine and morphine prevents the development of morphine tolerance in mice.

Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.

Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats.

CONTEXT: Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance. OBJECTIVE: The present study was to investigate the therapeutic effects of the hydroethanolic extract of Moringa oleifera (MO) leaves and flowers against hepatotoxicity induced by acetaminophen (APAP) in rats. MATERIALS AND METHODS: In the hepatoprotective study, either flowers or leaves of hydroethanolic extract (200 or 400 mg/kg bw through IP injection) were administered an hour after APAP administration. N-Acetylcysteine (NAC) was used as the positive control for this study. Liver and kidney function tests including lipid peroxidation levels were analyzed and histopathological changes of liver and kidney were also observed. RESULTS: Acetaminophen-induced hepatotoxicity increased the activities of liver marker enzymes. Histologically, the liver was observed to have inflammation and bridging necrosis. Liver marker enzymes were significantly reduced when treated with flower and leaf extracts of MO in animals with APAP induced toxicity. In addition, there were no significant changes observed in clinical markers of kidney function. Histological observation on liver tissue from the rats treated with MO flower and leaf extract showed reduction in the severity of the liver damage. DISCUSSION AND CONCLUSION: These results indicated the possible therapeutic action of flower and leaf extract from MO in protecting liver damage in rats given an over dosage of APAP.

Chitosan-encapsulated nickel oxide, tin dioxide, and farnesol nanoparticles: Antimicrobial and anticancer properties in breast cancer cells.

Breast cancer is the most frequent cancer in women; however, it is curable in most cases (up to 80 %) when detected and treated at an early non-metastatic stage. Nanotechnology has led to the development of potential chemotherapeutic techniques, particularly for tumor treatment. Nanotechnology has therapeutic and pharmaceutical applications. Chitosan, a natural polymer derived from chitin, has been extensively studied for its potential applications in a wide range of fields. This includes medicine for its anticancer properties. In the present study, Chitosan-encapsulated-NiO-TiO2-Farnesol hybrid nanomaterials (CNTF HNMs) were synthesized and characterized using several techniques, including electron microscopy (TEM, FE-SEM), spectroscopy (UV-visible [UV-Vis], Fourier Transform Infrared [FT-IR] spectroscopy, and photoluminescence [PL]), energy-dispersive X-ray spectroscopy (EDX) composition analysis, X-ray diffraction, and dynamic light scattering (DLS) analyses. With an estimated average crystallite size of 34.8 nm, the face-cantered cubic crystalline structure of the CNTF HNMs is identified. Cell viability assay by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), DAPI (4',6-diamidino-2-phenylindole) staining, dual AO/EtBr (Acridine Orange/ Ethidium bromide), JC-1 (5,5,6,6'-tetrachloro-1,1',3,3' tetraethylbenzimi-dazoylcarbocyanine iodide), DCFH-DA (Dichloro-dihydro-fluorescein diacetate), Annexin V-FITC (Fluorescein isothiocyanate) /PI (Propidium Iodide), and cell cycle study was used to assess the ability of nanoparticles (NPs) to kill MDA-MB-231 cells. The CNTF HNMs had high antibacterial effectiveness against multi-drug resistant extended-spectrum beta-lactamases (ESBL)-producing gram-negative bacterial pathogens and reference strains. The findings suggest that NPs increased the number of reactive oxygen species (ROS), changed the Δψm, and initiated apoptosis. There is enormous potential for CNTF HNMs as both antibacterial and anticancer agents.

Chitosan biopolymer functionalized with graphene oxide and titanium dioxide with Escin metallic nanocomposites for anticancer potential against colon cancer.

Our study produced GO-TiO2-chitosan-escin nanocomposites (GTCEnc), characterized them using physical and biological methods, and evaluated their potential as cancer treatment candidates. Standard protocols were used to produce GTCEnc. Nanocomposites are created using XRD, FTIR, UV-Vis, and PL spectroscopy analysis. The morphology and ultrastructure of nanocomposites were investigated using SEM and TEM. Nanocomposites containing TiO2, GO, chitosan, and escin nanostructures were characterized using diffraction, microscopy, and spectroscopy; the antimicrobial activity of GTCEnc was investigated. Various methods were used to test the anticancer activity of GTCEnc against COLO 205 cell lines, including MTT, EtBr/AO, DAPI, JC-1, Annexin-V/FITC, cell cycle analysis, and activation of pro-apoptotic markers, such as caspase-3, -8, and -9. The nanocomposites were cytotoxic to COLO 205 cells, with an IC50 of 22.68 µg/mL, but not to 293T cells. In cells treated with nanomaterials, cytotoxicity, nuclear damage, apoptosis induction, and free radical production were significantly increased. Our finding suggests that GTCEnc has potent anticancer and antibacterial activity in vitro because of its unique nanocomposite properties and antibacterial and anticancer activity in vitro. Additional research is required to understand the clinical efficacy of these nanocomposites.