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Persistent inflammation contributes to various inflammatory conditions. Inflammation-related diseases may be treated by inhibiting pro-inflammatory mediators and cytokines. Curcumin and coumarin derivatives can target signalling pathways and cellular factors to address immune-related and inflammatory ailments. This study involved designing and synthesising three series of coumarin-based analogs that incorporated curcumin and other heterocycles. These analogs were evaluated for their potential as anti-inflammatory agents in LPS-induced macrophages. Among the fourteen synthesised coumarin derivatives, compound , which contained 3,4-dimethoxybenzylidene hydrazinyl, demonstrated the highest anti-inflammatory activity with an EC value of 5.32 μM. The anti-inflammatory effects of were achieved by modulating signalling pathways like AKT/mTOR and Nrf2/HO-1, and downregulating NF-kβ, resulting in reduced production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α. The modelling studies revealed that and dexamethasone bind to the same TNF-α pocket, suggesting that has potential as a therapeutic agent superior to dexamethasone for TNF-α.

Objectives: The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC). Methods: Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX. Results: The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs. Conclusions: The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman’s correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.

Diabetic retinopathy causes loss of vision in adults at working-age. Few therapeutic options are available for treatment of diabetic retinopathy. Carbamazepine (CARB), a widely used antiepileptic drug, was recently accounted for its neuroprotective effect. Nerve growth factor (NGF) activates various cascades among which, PI3K/Akt/mTOR pathway has a vital action in NGF-mediated neuronal differentiation and survival. This study evaluated the effect of CARB in the treatment of diabetic retina and unveiled some of the underlying molecular mechanisms. Alloxan diabetes model was induced in 36 albino well-acclimatized mice. After establishment of the diabetic model in 9 weeks, mice were assigned to treatment groups: (1) saline, (2) alloxan-diabetic, (3 and 4) alloxan+CARB (25 or 50 mg per kg p.o) for 4 weeks. After completion of the therapeutic period, mice were sacrificed and eyeballs were enucleated. Retinal levels of NGF and PI3K/Akt were assessed using real-time polymerase chain reaction. Further, total and phosphorylated TrKA, PI3K, Akt, mTOR as well as Caspase-3 were measured by Western blot analysis. Histopathological examination demonstrated that CARB attenuated vacuolization and restored normal thickness and organization of retinal cell layers. In addition, CARB increased pTrKA/TrKA ratio and ameliorated diabetes-induced reduction of NGF mRNA and immunostaining in retina. Additionally, it augmented the mRNA expression of PI3K and Akt, as well as the protein level of the phosphorylated PI3/Akt/mTOR. Results highlighted, for the first time, the neuronal protective effect for CARB in diabetic retina, which is mediated, at least in part, by activation of the NGF/PI3K/Akt/mTOR pathway.

Vicia faba L. is a legume from the family Fabaceae. Ancient Egyptians consumed fava beans thousands of years ago and they are still one of the most popular foods in Egypt. The current study examined the anti-Parkinson effect of 80% methanolic extracts of seeds or sprouts of the fava ‘Sakha 3 ‘cultivar which has been selected based on the total phenol content among three cultivars tested. In addition, the extracts were characterized by reversed-phase high-performance liquid chromatography coupled with diode array detection and quadrupole-time-of-flight-mass spectrometry (RP-HPLC–DAD-QTOF-MS). Three doses (200, 400, and 600 mg/kg) of 80% methanol extracts of seeds or sprouts of the Sakha 3 cultivar were evaluated in rotenone–Parkinsonian mice from behavioral, biochemical, and histopathological aspects. The extract of fava sprouts (600 mg/kg dose) showed the most beneficial effect. It improved motor activity, enhanced striatal dopamine level, and decreased the striatal malondialdehyde, as well as the expression of the inflammatory markers, compared with the rotenone control group and groups receiving lower therapeutic doses of the extracts or l -Dopa. In addition, these findings were supported by a histopathological investigation which indicated that mice treated with the 600-mg/kg dose of the sprout extract showed a low number of degenerated neurons. The application of RP-HPLC–DAD-QTOF-MS and mass/mass spectroscopy enabled the metabolic profiling of the sprouts and seeds of the ‘Sakha 3′ cultivar. It is obvious that germination increased the amounts of phenolic acids, saponins, and aromatic amino acids, together with a dramatic increase in flavonoids. In conclusion, the 80% methanolic extract of sprouts of the fava “Sakha 3” cultivar may be a promising candidate for treating Parkinsonism if appropriate safety data are available.

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In search of novel antiviral and anticancer agents with promising pharmacotoxicological profile, a study was initiated to synthesize new 2-thioxo-4-thiazolidinones as well as 2-phenylimino-4-thiazolidinones substituted with benzimidazole ring system. The compounds were screened primarily for their antiviral as well as anticancer activities. The synthesis of some novel 5-substituted thiazolidinones was also described. None of the tested compounds showed inhibitory activity against Hepatitis C virus replication. Two 2-phenylimino-4-thiazolidinone derivatives ( 9a and 10 ) exhibited significant antiproliferative activity against human colon carcinoma cell line HCT 116 and human hepatocellular carcinoma HEPG2 cell line, respectively. Results also indicated that six thiazolidinone derivatives ( 5a , 5d , 5e , 5f , 5h , and 9d ) showed moderate antiproliferative activity against human breast adenocarcinoma cell line MCF7 in comparison to the standard drug Doxorubicin. Moreover, a docked pose of the most potent three cytotoxic compounds 5a , 5h , and 9d against MCF7 was obtained bound to Human N -acetyl transferase1 NAT1 binding pocket by molecular operating environment module.

This study was conducted to evaluate the effects of thyme, ginger, and their nano-particles, as alternatives to antibiotic growth promotors (AGP), on productive performance, carcass traits, meat quality and gut health of broiler chickens. A total of 270 one-day-old broiler chicks were randomly distributed into 6 groups, each consisting of 3 replicates ( n  = 15 chicks/replicate). The birds in group 1 were fed the control diet which contained neither antibiotic growth promotors nor phytogenic feed additives (PFA). Birds in group 2 were fed diets containing 0.05% of AGP (Bacitracin methylene disalicylate). Chicks in group 3 and 4 were fed diets supplemented with 1.0% of thyme and ginger, respectively, whereas birds in group 5 and 6 were offered diets including 0.10% of nano-thyme and nano-ginger, respectively. The experiment lasted for 35 days. It was found that thyme and ginger with their nano-products, like the antibiotic, improved the body weight, weight gain and feed conversion rate of birds. The effect of ginger and nano-ginger on body weight and weight gain was greater than other treatments. During the overall feeding period, the feed cost of production was the highest in antibiotic group, but was the lowest in ginger and nano-ginger treatments. There was no effect of dietary treatments on carcass yield or organs weight except bursa of Fabricius and abdominal fat. Thyme, ginger and their nano-composites increased the weight of bursa and reduced the abdominal fat amount. The phytogenic additives and their nano-particles improved the colour, water holding capacity, and flavor of meat. Moreover, these additives reduced the total intestinal bacterial count as well as the total aerobic mesophilic count of meat. The effect of PFA and their nano-particles on the bacterial count was similar to that of antibiotic. In conclusion, thyme and ginger with their nano- particles can be considered as promising agents in feeding of broilers to improve the growth performance, gut health and meat quality. Moreover, these additives can be used as alternatives to AGP to overcome its health hazards and the high cost. The nanotechnology of herbal plants enables them to be added in smaller amounts in poultry diets with producing the same effect of raw ingredients, and this could be due to the higher bioavailability.

White mustard ( Sinapis alba L.) seeds are the most commonly used mustard species in herbal medicine to treat a wide range of inflammatory disorders. Due to its increased bioavailability and lower toxicity, the green biosynthesis of metal nanoparticles (M-NPs) utilizing plant extract as a capping agent has been demonstrated over a number of years. Thus, the current study sought to examine the in vitro biological activity of copper oxide nanoparticles  (CuO-NPs) and selenium nanoparticles (Se-NPs) that were biosynthesized using aqueous, methanolic, and petroleum ether extracts from S. alba seeds. Phytochemical and in vitro biological activities (antioxidant, scavenging, anti-diabetic, anti-acetylcholinesterase, anti-arthritic, anti-inflammatory, and cytotoxic activities) were assayed in all prepared extracts before and after being used for the biosynthesis of the M-NPs. It was found that the total methanolic extract possessed the highest biological activities compared to other native extracts. The LC-ESI-MS/MS analysis of secondary metabolites showed that the total methanolic extract contained 7 phenolic acids and 9 flavonoid aglycones. This helped find the active ingredients. We characterized 8 phenolic acid derivatives, 7 flavonoid glycosides, 4 aliphatic glucosinolates, and 3 aromatic aryl glucosinolates in the aqueous extract. Furthermore, the methanolic extract contains the highest concentrations of total polyphenols, condensed tannins, and total flavonoid compounds. The biosynthesized Se-NPs using methanolic extract showed higher in vitro biological activities compared to those of the biosynthesized CuO-NPs. The median lethal dose (LD 50 ) showed that the biosynthesized Se-NPs using the studied extracts appeared safer compared to those of the biosynthesized CuO-NPs. The findings of this study concluded that the total methanolic extract is the most suitable bioresource for biosynthesizing Se-NPs through green nanotechnology, with higher biological efficiency in relation to its metabolite fingerprint.

Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.

Background/Objectives: Endophytic fungi represent an alternative source for resveratrol (RES) production. The present study aims to utilize mycoendophytic-derived resveratrol as a reducing agent for the synthesis of silver nanoparticles (AgNPs), in addition to further assay the cytotoxic activity of a RES-conjugated nanocarrier system toward human epidermoid carcinoma A-431 cells. Methods: Alternaria alternata AUMC 16209 was isolated from the stem of grapevine Vitis vinifera L. cultivar prime. Strain identification was achieved through morphological and molecular characterization using ITS sequencing. A. alternata AUMC 16209 exhibited RES production capability upon cultivation on PDB medium for seven days with a total of 8.25 mg/L as determined by HPLC. The crude RES was purified using flash chromatography followed by structure elucidation through 1H and 13C NMR analyses. The purified RES was used for green synthesis of nanoparticles, acting as a reducing agent for silver ions. Results: Stable RES-AgNPs were fabricated at particle sizes ranging from 25 to 47 nm. RES-AgNPs observed a plasmon resonance absorption band at 415 nm with a negative zeta potential value of −38.5 mV. The crystalline structure of RES-AgNPs was addressed through X-ray diffraction analysis. FT-IR spectroscopy confirms the involvement of the functional –OH group and the aromatic C=C bond in the reduction and stabilization process. RES-AgNPs was more efficient to inhibit the cellular proliferation of human epidermoid carcinoma A-431 cells compared to RES alone. Conclusions: This report introduces for the first time an endophytic A. alternata as a sustainable source for RES production and emphasizes its potential for green synthesis of stable AgNPs with promising cytotoxic activity.