The study of wound healing activity of Thespesia populnea L. bark, an approach for accelerating healing through nanoparticles and isolation of main active constituents.

The present study provides an evaluation for the wound healing activity of the ethanolic extract of Thespesia populnea L. bark (EBE) and its successive fractions in two doses level (1&2%), designed for determining the most bioactive fraction and the suitable dose. Furthermore, development of the most convenient formulation for these bioactive fractions through either their direct incorporation into hydrogel formulations or incorporation of chitosan-loaded nanoparticles with these bioactive fractions into hydrogel formulations. The highest excision wound healing activity was observed in petroleum ether (Pet-B) followed by ethyl acetate (Etac-B) fractions at the high dose (2%). The most suitable formulation designed for the Etac-B fraction was found to be the chitosan-loaded nanoparticles incorporated in the hydrogel formulation, while the conventional hydrogel formulation was observed to be the highly acceptable formulation for Pet-B fraction. Further phytochemical studies of the bioactive fractions led to the isolation of many compounds of different chemical classes viz; beta-sitosterol and lupeol acetate isolated from the Pet-B, in addition to cyanidin and delphinidin from the Etac-B. Our results revealed that EBE and its bioactive fractions (Pet-B & Etac-B) could be considered as strong wound healers through their anti-oxidant and anti-inflammatory activities, in addition to stimulating collagen synthesis.

A Comparative GC/MS Analysis of Citrus Essential Oils: Unveiling the Potential Benefits of Herb-Drug Interactions in Preventing Paracetamol-Induced Hepatotoxicity.

Our study aimed to test the potential of Citrus oils in protecting against paracetamol (PAR)-induced hepatotoxicity. The essential oils of Pineapple sweet orange (OO), Murcott mandarin (MO), Red grapefruit (GO), and Oval kumquat (KO) were investigated using gas chromatography coupled with mass spectrometry (GC/MS). Twenty-seven compounds were identified, with monoterpene hydrocarbons being abundant class. d-Limonene had the highest percentage (92.98 %, 92.82 %, 89.75 %, and 94.46 % in OO, MO, GO, and KO, respectively). Hierarchical cluster analysis (HCA) and principal components analysis (PCA) revealed that octanal, linalool, germacrene D, and d-limonene were the principal discriminatory metabolites that segregated the samples into three distinct clusters. In vitro antioxidant capacities were ranged from 1.2-12.27, 1.79-5.91, and 235.05-585.28 µM Trolox eq/mg oil for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic (ABTS), ferric-reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC), respectively. In vivo, citrus oils exhibited a significant reduction in alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and nitric oxide (NO). Additionally, there was an increase in glutathione reductase (GSH), and the liver architecture was nearly normal. Molecular docking revealed that d-limonene exhibited a good inhibitory interaction with cytochrome P450 (CYP450) isoforms 1A2, 3A4, and 2E1, with binding energies of -6.17, -4.51, and -5.61 kcal/mol, respectively.

Taming Food-Drug Interaction Risk: Potential Inhibitory Effects of Citrus Juices on Cytochrome Liver Enzymes Can Safeguard the Liver from Overdose Paracetamol-Induced Hepatotoxicity.

Paracetamol overdose is the leading cause of drug-induced hepatotoxicity worldwide. Because of N-acetyl cysteine's limited therapeutic efficacy and safety, searching for alternative therapeutic substitutes is necessary. This study investigated four citrus juices: Citrus sinensis L. Osbeck var. Pineapple (pineapple sweet orange), Citrus reticulata Blanco × Citrus sinensis L. Osbeck (Murcott mandarin), Citrus paradisi Macfadyen var. Ruby Red (red grapefruit), and Fortunella margarita Swingle (oval kumquat) to improve the herbal therapy against paracetamol-induced liver toxicity. UHPLC-QTOF-MS/MS profiling of the investigated samples resulted in the identification of about 40 metabolites belonging to different phytochemical classes. Phenolic compounds were the most abundant, with the total content ranked from 609.18 to 1093.26 µg gallic acid equivalent (GAE)/mL juice. The multivariate data analysis revealed that phloretin 3',5'-di-C-glucoside, narirutin, naringin, hesperidin, 2-O-rhamnosyl-swertisin, fortunellin (acacetin-7-O-neohesperidoside), sinensetin, nobiletin, and tangeretin represented the crucial discriminatory metabolites that segregated the analyzed samples. Nevertheless, the antioxidant activity of the samples was 1135.91-2913.92 µM Trolox eq/mL juice, 718.95-3749.47 µM Trolox eq/mL juice, and 2304.74-4390.32 µM Trolox eq/mL juice, as revealed from 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid, ferric-reducing antioxidant power, and oxygen radical absorbance capacity, respectively. The in vivo paracetamol-induced hepatotoxicity model in rats was established and assessed by measuring the levels of hepatic enzymes and antioxidant biomarkers. Interestingly, the concomitant administration of citrus juices with a toxic dose of paracetamol effectively recovered the liver injury, as confirmed by normal sections of hepatocytes. This action could be due to the interactions between the major identified metabolites (hesperidin, hesperetin, phloretin 3',5'-di-C-glucoside, fortunellin, poncirin, nobiletin, apigenin-6,8-digalactoside, 6',7'-dihydroxybergamottin, naringenin, and naringin) and cytochrome P450 isoforms (CYP3A4, CYP2E1, and CYP1A2), as revealed from the molecular docking study. The most promising compounds in the three docking processes were hesperidin, fortunellin, poncirin, and naringin. Finally, a desirable food-drug interaction was achieved in our research to overcome paracetamol overdose-induced hepatotoxicity.

Pimenta dioica and Pimenta racemosa: GC-based metabolomics for the assessment of seasonal and organ variation in their volatile components, in silico and in vitro cytotoxic activity estimation.

Volatile constituents isolated from the stems (S) and leaves (L) of Pimenta dioica (PD) and Pimenta racemosa (PR) during the four seasons were analyzed using GLC/FID (Gas liquid chromatography - flame ionization detector) and GLC/MS (Gas liquid chromatography - mass spectrometry). Eighty-nine compounds were identified in all samples, in which oxygenated monoterpene represented by eugenol was the major constituent in PDS-S3 (autumn) (88.71%) and PDS-S2 (summer) (88.41%). Discrimination between P. dioica and P. racemosa leaves and stems in different seasons was achieved by applying chemometrics analysis comprising Principal Component Analysis (PCA) and Hierarchal Cluster Analysis (HCA). For P. dioica, they were partially segregated where leaves collected from spring and autumn were superimposed, and similarly for P. dioica stems collected in summer and autumn. For P. racemosa leaves, the PCA score plot showed that all seasons were completely segregated from each other, with the winter and autumn samples being in very close distance to each other. P. racemosa stems collected in autumn and spring exhibited significant variation, as they were completely detached from each other. Moreover, summer and winter fell in a near distance to each other. An in vitro cell viability assay was done to evaluate the variation in the cytotoxicity of the isolated essential oils against breast (MCF-7), hepatic (HepG-2), and cervical (HeLa-2) cancer cell lines using the MTT assay. The maximum cytotoxic effect was observed by PDL against HeLa, HepG-2 and MCF-7 cells with IC50 values equal to 122.1, 139.6, and 178.7 µg mL-1, respectively. An in silico study was done to assess the cytotoxic effect of the major compounds detected in the oils by determining their inhibitory effect on human DNA topoisomerase II (TOP-2), human cyclin-dependent kinase 2 (CDK-2) and matrix metalloproteinase 13 (MMP-13). o-Cymene followed by eugenol showed the highest fitting with all of the examined proteins approaching doxorubicin. It can be concluded that GC coupled with chemometrics provide a strong tool for the discrimination of samples, while Pimenta could afford a natural drug that could alleviate cancer.

Bioassay-guided fractionation and identification of antidiabetic compounds from the rind of Punica Granatum Var. nana.

This study aimed to evaluate the antidiabetic potential of the rind of Punica granatum var. nana. Acute oral toxicity test revealed the safety profile of its ethanolic extract. The extract was administered at 200 mg/kg b.wt to streptozotocin-induced diabetic rats. Serum diagnostic markers of diabetes (insulin, glucose and glycated hemoglobin), inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide), and oxidative stress (total antioxidant capacity and reduced glutathione and malondialdehyde) were assayed. The ethanolic extract was further fractionated and assessed for the aforementioned bioactivities at two different doses (100 and 200 mg/kg b.wt). The results revealed that the ethyl acetate fraction of rind exhibited the highest activities. Using different chromatographic techniques, four compounds were isolated and identified as rutin, gallic acid, nictoflorin, and tulipanin. In conclusion: The ethyl acetate fraction of the rind of Punica granatum var. nana may provide a potential therapeutic approach for hyperglycemia.

Efficient wound healing composite hydrogel using Egyptian Avena sativa L. polysaccharide containing ß-glucan.

The purpose of this study was to develop an efficient wound healing PVA-biopolymer composite hydrogel using the polysaccharide derived from Egyptian Avena sativa L. The prepared polysaccharide showed high ß-glucan content which accelerates wound healing. The ß-glucan content was 13.28% and GC analysis revealed that glucose was the major sugar component (71.19%). Different PVA-polysaccharide hydrogels combined with different polymers and loaded with 0.3% bacitracin zinc were developed using the freezing-thawing method. The used polymers were; polyvinylpyrrolidone (PVP), Carbopol 940 (CP), hydroxyethylcellulose (HEC), hydroxypropyl methylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC). The prepared hydrogels were characterized by determination of gel fraction, swelling ratio, mechanical and bioadhesive properties. The results revealed that hydrogels prepared using anionic (NaCMC and CP) and more hydrophilic (HEC) polymers showed better swelling ratio, bioadhesive and mechanical characters compared with hydrogels prepared using cationic (PVP) or less hydrophilic (HPMC) polymers. For two selected formulations containing HEC (F7) and NaCMC (F9), disk diffusion method and In vitro microbial penetration were performed for microbiological assessment. In addition, In vivo evaluation of the anti-inflammatory and wound healing activity compared with conventional products were performed on rats. The results showed higher anti-inflammatory activity of F7 (21.4% edema reduction) compared with F9 (19.8% edema reduction). Similarly, F7 showed better healing (99% relative wound size reduction) than F9 (75%). The current study revealed the potential of using the prepared Egyptian Avena sativa L. polysaccharide and HEC for development of an efficient wound healing dressing with antimicrobial and anti-inflammatory activities.

Phytochemical and biological study of callus cultures of Tulbaghia violacea Harv. Cultivated in Egypt.

As in vitro plant cultures are used extensively to produce bioactive metabolites, our goal was to establish calli from Tulbaghia violacea Harv. flowers and assess the tissue phytochemically and biologically. Murashige & Skoog medium(MS) + 22.6 µM 2,4-dichlorophenoxyacetic acid +2.2 µM benzylaminopurine induced callus from flowers. Gas chromatography/mass spectrometry(GC/MS) analyses of n-hexane extracts of calli(HC) and flowers(HF) revealed 33 and 32 components(92.6 and 98.5%, respectively). Hydrocarbons were predominant in HC (55.0%), whereas a higher percentage of oxygenated compounds was found in HF(74.6%). Trans(E)-anethole(39.1%) and 16-hentriacontanone (30.3%) dominated in HF and HC, respectively. However, sulphur compounds were only detected in HF. Quantitative estimation of thiosulphinates, phenolics, flavonoids and saponins in ethanolic extracts of calli(EC) and flowers(EF) showed much higher contents in EF. Antioxidant, antimicrobial and cytotoxic screening of extracts demonstrated that EF was the most potent, followed by HF and EC; conversely, HC was inactive. Although HC and EC were less biologically active, these calli could be an alternative source of bioactive metabolites.

Bioassay-guided fractionation of a hepatoprotective and antioxidant extract of pea by-product.

The hepatoprotective and antioxidant activities of the hydroalcoholic extract (PE) of pea (Pisum sativum L.) by-product were evaluated, using CCl4-induced oxidative stress and hepatic damage in rats. These activities were assessed via measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin, malondialdehyde (MDA), reduced glutathione (GSH), protein thiols (PSH), nitrite/nitrate levels, glutathione-peroxidase (GSH-Px), glutathione-S-transferase (GST) activities, as well as, histopathological evaluation. PE revealed significant hepatoprotective and antioxidant activities mostly found in n-butanol fraction. Chromatographic fractionation of this active fraction led to the isolation of five flavonoid glycosides namely, quercetin-3-O-sophorotrioside (1), quercetin-3-O-rutinoside (2), quercetin-3-O-(6″″-O-E sinapoyl)-sophorotrioside (3), quercetin-3-O-(6″″-O-E feruloyl)-sophorotrioside (4) and quercetin-3-O-ß-D-glucopyranoside (5). The isolated compounds were quantified in PE, using a validated HPLC method and the nutritional composition of pea by-product was also investigated. Our results suggest that pea by-product contained biologically active constituents which can be utilised to obtain high value added products for nutraceutical use.

Variations of the chemical composition and bioactivity of essential oils from leaves and stems of Liquidambar styraciflua (Altingiaceae).

OBJECTIVES: This study aimed to evaluate the variations of the chemical composition and bioactivity of essential oils of Liquidambar styraciflua L. (Altingiaceae) collected in different seasons. METHODS: The oils were analysed by GLC/FID and GLC/MS. The antioxidant activity was investigated by diphenylpicrylhydrazyl (DPPH) and superoxide anion radical scavenging assays and the deoxyribose degradation assay. Inhibition of both 5-lipoxygenase (5-LOX) and prostaglandin E2 (PGE2) production in hepatic cancer (HepG-2) cells were used to assess the anti-inflammatory activity. The cytotoxic activity was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. KEY FINDINGS: Altogether, 64 volatile secondary metabolites were identified. The major components of the leaf oil were d-limonene, α-pinene and ß-pinene, and of the stem oil were germacrine D, α-cadinol, d-limonene, α-pinene, and ß-pinene. Leaf and stem oils collected in spring could reduce DPPH● (IC50 = 3.17 and 2.19 mg/ml) and prevent the degradation of the deoxyribose sugar (IC50 = 17.55 and 14.29 µg/ml). The stem oil exhibited a higher inhibition of both 5-LOX and PGE2 than the leaf oil. The cytotoxic activity of leaf and stem oils was low in cancer cell lines (IC50 = 136.27 and 119.78 µg/ml in cervical cancer (HeLa) cells). CONCLUSIONS: Essential oils of L. styraciflua exhibited an interesting anti-inflammatory activity with low cytotoxicity, supporting its traditional use to treat inflammation.