Protective potential of frankincense essential oil and its loaded solid lipid nanoparticles against UVB-induced photodamage in rats via MAPK and PI3K/AKT signaling pathways; A promising anti-aging therapy.

Frankincense oil has gained increased popularity in skin care, yet its anti-aging effect remains unclear. The current study aimed to investigate the anti-photoaging effect of frankincense (Boswellia papyrifera (Del.) Hochst., Family Burseraceae) essential oil in an in vivo model. The oil was initially extracted by two methods: hydro-distillation (HD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis revealed the dominance of n-octyl acetate, along with other marker compounds of B. papyrifera including octanol and diterpene components (verticilla 4(20) 7, 11-triene and incensole acetate). Thereafter, preliminary investigation of the anti-collagenase and anti-elastase activities of the extracted oils revealed the superior anti-aging effect of HD-extracted oil (FO), comparable to epigallocatechin gallate. FO was subsequently formulated into solid lipid nanoparticles (FO-SLNs) via high shear homogenization to improve its solubility and skin penetration characteristics prior to in vivo testing. The optimimal formulation prepared with 0.5% FO, and 4% Tween® 80, demonstrated nanosized spherical particles with high entrapment efficiency percentage and sustained release for 8 hours. The anti-photoaging effect of FO and FO-SLNs was then evaluated in UVB-irradiated hairless rats, compared to Vitamin A palmitate as a positive standard. FO and FO-SLNs restored the antioxidant capacity (SOD and CAT) and prohibited inflammatory markers (IL6, NFκB p65) in UVB-irradiated rats via downregulation of MAPK (pERK, pJNK, and pp38) and PI3K/AKT signaling pathways, alongside upregulating TGF-ß expression. Subsequently, our treatments induced Procollagen I synthesis and downregulation of MMPs (MMP1, MMP9), where FO-SLNs exhibited superior anti-photoaging effect, compared to FO and Vitamin A, highlighting the use of SLNs as a promising nanocarrier for FO. In particular, FO-SLNs revealed normal epidermal and dermal histological structures, protected against UVß-induced epidermal thickness and dermal collagen degradation. Our results indicated the potential use of FO-SLNs as a promising topical anti-aging therapy.

6-Paradol alleviates Diclofenac-induced acute kidney injury via autophagy enhancement-mediated by AMPK/AKT/mTOR and NLRP3 inflammasome pathways.

Diclofenac (DIC)-induced acute kidney injury (AKI) causes high morbidity and mortality. With the absence of satisfactory treatment, we investigated the protective effects of 6-Paradol (PDL) against DIC-induced AKI, with focus on renal autophagy and NLRP3 inflammasome pathways . PDL has anti-inflammatory, antioxidant and AMPK-activation properties. PDL was administered to DIC-challenged rats. Nephrotoxicity, oxidative stress, inflammatory, and autophagy markers and histopathological examinations were evaluated. Compared to DIC, PDL restored serum nephrotoxicity, renal oxidative stress and pro-inflammatory markers. PDL almost restored renal architecture, upregulated renal Nrf2 pathway via enhancing Nrf2 mRNA expression and HO-1 levels. PDL suppressed renal NF-κB mRNA expression, and NLRP3 inflammasome pathway expression. Moreover, PDL enhanced renal autophagy through upregulating LC3B, AMPK and SIRT-1, and suppressed mTOR, p-AKT mRNA expressions and phosphorylated-p62 levels. Our study confirmed that autophagy suppression mediates DIC-induced AKI via AMPK/mTOR/AKT and NLRP3-inflammasome pathways. Also, PDL's nephroprotective effects could provide a promising therapeutic approach against DIC-induced AKI.

Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study.

ETHNOPHARMACOLOGICAL RELEVANCE: In Africa, Aframomum species have been traditionally used to treat illnesses such as inflammation, hypertension, diarrhea, stomachache and fever. Moreover, Aframomum melegueta seed extracts (AMSE) are used in traditional medicine to relieve stomachaches and inflammatory diseases. AIM: Chronic administration of diclofenac (DIC) has been reported to cause acute kidney injury (AKI), which is a serious health condition. The nephroprotective effect of AMSE is yet to be elucidated. Accordingly, this study aims to investigate the phytoconstituents of standardized AMSE, evaluate its nephroprotective effects against DIC-induced AKI in rats, and elaborate its underlying molecular mechanisms. MATERIALS AND METHODS: The quantitative estimation of major AMSE constituents and profiling of its secondary metabolites were conducted via RP-HPLC and LC-ESI/Triple TOF/MS, respectively. Next, DIC (50 mg/kg)-induced AKI was achieved in Sprague-Dawley rats and DIC-challenged rats were administered AMSE (100 and 200 mg/kg) orally. All treatments were administered for five consecutive days. Blood samples were collected and the sera were used for estimating creatinine, urea and, kidney injury molecule (KIM)-1 levels. Kidney specimens were histopathologically assessed and immunohistochemically examined for c-Myc expression. A portion of the kidney tissue was homogenized and examined for levels of oxidative stress markers (MDA and GSH). Heme oxygenase (HO)-1, TNF-α, IL-6, Bax, Bcl2 and caspase-3 renal levels were quantified by ELISA. Moreover, the protein expression levels of NF-Ò¡B p65 was quantified using Western blot analysis, whereas mRNA expression levels of AMPK, SIRT-1, nuclear factor erythroid-2-related factor (Nrf2) and STAT3 were detected using qRT-PCR in the remaining kidney tissues. RESULTS: Standardized AMSE was shown to primarily contain 6-gingerol, 6-shogaol and 6-paradol among the 73 compounds that were detected via LC-ESI/Triple TOF/MS including phenolic acids, hydroxyphenylalkanes, diarylheptanoids and fatty acids. Relative to DIC-intoxicated rats, AMSE modulated serum creatinine, urea, KIM-1, renal MDA, TNF-α, IL-6, Bax, and caspase-3 levels. AMSE has also improved renal tissue architecture, enhanced GSH and HO-1 levels, and upregulated renal Nrf2, AMPK, and SIRT-1 mRNA expression levels. Furthermore, AMSE suppressed NF-Ò¡B p65 protein and STAT3 mRNA expression, and further reduced c-Myc immunohistochemical expression in renal tissues. Overall, our findings revealed that AMSE counteracted DIC-induced AKI via its antioxidant, anti-inflammatory, and antiapoptotic activities. Moreover, AMSE activated Nrf2/HO1 and AMPK/SIRT1, and inhibited NF-Ò¡B/STAT3 signaling pathways. Therefore, AMSE is a promising agent for inhibiting DIC-induced nephrotoxicity.

Application of a comprehensive metabolomics approach for the selection of flaxseed varieties with the highest nutritional and medicinal attributes.

Flaxseed is considered an indispensable generally recognized as safe (GRAS) source of polyphenolic lignans, polyunsaturated fatty acids (PUFA), fibers as well as minerals and vitamins. The metabolite content of flaxseed reflects its nutritional and medicinal value. Therefore, the selection of flaxseed variety for food industry is dependent on its metabolome. A metabolomics approach based on liquid or gas chromatography coupled to mass spectrometry has been applied to discriminate different flaxseed cultivars that are commercially available in Egypt. The available Sakha cultivars were subjected to a comprehensive metabolomics and lipidomics approach for investigation of their metabolomes. Our results showed that among the screened cultivars, Sakha 6, with its yellow-colored testa, showed marked metabolic discrimination. This yellow cultivar showed high accumulation of essential amino acids. Additionally, the oil of this cultivar accumulated the highest content of the two essential PUFA: alpha-linolenic acid (an ω-3 fatty acid) and linoleic acid (an ω-6 fatty acid). Interestingly, the content of the main antinutritional cyanogenic glycosides such as linustatin and neolinustatin was lower, while, the content of medicinally-important secondary metabolites was higher in Sakha 6 cultivar. These results support the use of this cultivar for human consumption owing to its high nutritional and medicinal value.

Comparative Metabolite Profiling of Four Citrus Peel Cultivars via Ultra-Performance Liquid Chromatography Coupled with Quadrupole-Time-of-Flight-Mass Spectrometry and Multivariate Data Analyses.

Citrus plants are one of the most economical fruit bearing trees grown worldwide for their medicinal use as well as for the flavor and food industry. This study attempts to characterize the metabolome difference in polyphenols of four Citrus species fruit peels; C. reticulata Blanco cv. Egyptian, C. sinensis (L.) Osbeck cv. Olinda Valencia, C. aurantiifolia Swingle cv. Mexican and C. paradisi Macfad. cv. Duncan via ultra-performance liquid chromatography coupled with quadrupole-time-of-flight-mass spectrometry platform. A total of 163 metabolites were characterized of which 28 were detected for the first time in Citrus cultivars including eight coumarin derivatives, three cinnamic acids conjugates, one polymethoxyflavone, 5 O-glycosides, 2 C-glycosides, three flavone-di-O-glucosides and six acetyl sugar derivatives of luteolin and kaempferol in addition to oxygenated and methylated fatty acids. Flavonoids amounted for the most abundant secondary metabolites class in the studied Citrus peels. The relative variability among these Citrus peels was estimated using clustering analysis with flavonoids accounting for cvs. segregation. Hierarchical clustering analysis revealed the chemical similarity of C. reticulata, C. sinensis and C. paradise peels and being distant them from that of C. aurantiifolia. To the best of our knowledge, this study provides the first report for metabolite compositional differences in these four Citrus peels.

Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars.

The objective of our study is to highlight the therapeutic effect and mechanism of action by which purified Flaxseed hydrolysate (PFH) which is a lignan rich fraction exerts its anticancer activity on a human breast cancer cell line (T47D) and in mice bearing tumor. HPLC analysis of PFH of six flaxseed cultivars had shown that PFH of the cultivar Giza 9 (PFH-G9) contains the highest concentration of SDG (81.64 mg/g). The in vitro cytotoxic potentiality of PFH's of six flaxseed cultivars was screened against a panel of human cancer cell lines. PFH -G9 showed the most significant cytotoxic activity against ER-receptor positive breast cell lines MCF7 and T47D with IC50 13.8 and 15.8 µg/ml, respectively. Moreover, PFH-G9 reduced the expression of the metastasis marker, 1-α, metalloproteinases and vascular endothelial growth factor (VEGF), one of the most potent stimulators of angiogenesis, while it increased the caspase-3 dependent apoptosis. Our study also showed that dietary intake of 10% of Giza 9 Flaxseeds (FS), fixed oil (FSO) or Flax meal (FSM) twice daily for 3 weeks in mice-bearing solid Ehrlich ascites carcinoma (EAC) resulted in reducing the tumor volume, the expression of estrogen, insulin growth factor, progesterone, VEGF and MMP-2, but enhanced expression of caspase-3.

Comparative study of the hypocholesterolemic, antidiabetic effects of four agro-waste Citrus peels cultivars and their HPLC standardization

ABSTRACT Citrus is an economically important fruit for Egypt, but its peel also is one of the major sources of agricultural waste. Due to its fermentation, this waste causes many economic and environmental problems. Therefore it is worthwhile to investigate ways to make use of this citrus waste generated by the juice industry. This study was aimed to explore the hypocholesterolemic, antidiabetic activities of four varieties of citrus peels agrowastes, to isolate the main flavonoids in the active fractions and to quantify them by HPLC method for nutraceutical purposes. All the tested samples of the agro-waste Citrus fruits peels showed significant decrease in cholesterol, triacylglyceride and glucose. The most decrease in cholesterol level was observed by mandarin peels aqueous homogenate and its hexane fraction (59.3% and 56.8%, respectively) reaching the same effect as the reference drug used (54.7%). Mostly, all samples decrease triacylglyceride (by 36%-80.6%) better than the reference drug used (by 35%), while, glucose was decreased (by 71.1%-82.8 and 68.6%-79.6%, respectively) mostly by the aqueous homogenates (except lime) and alcoholic extracts (except mandarin) of Citrus fruits peels better than the reference drug used (by 68.3%). All the isolated pectin, from the four cultivars, has significant effect on the three parameters. The comparative HPLC rapid quantification of nobiletin in the different by-product citrus varieties hexane fractions revealed that nobiletin is present in higher concentration in mandarin (10.14%) than the other species. Nobiletin and 4′,5,7,8-tetramethoxy flavone were isolated from mandarin peels hexane fraction by chromatographic fractionation. This is the first report of the comparative HPLC quantification of nobiletin and biological studies of different citrus peels species as agro-waste products. Based on these results, we suggest the possibility that Citrus fruits peels may be considered as an antidiabetic and hypocholesterolemic nutraceutical product.

Antidepressant-Like Effect of Selected Egyptian Cultivars of Flaxseed Oil on a Rodent Model of Postpartum Depression.

Flaxseed (Linum usitatissimum L.) is a multipurpose crop with health promoting potential. This study was undertaken to investigate the fatty acid profile and yield of fixed oil of six Egyptian flaxseed cultivars. The selected cultivars with the highest content of polyunsaturated fatty acids (PUFAs) (G9 and G10) were assessed for their antidepressant-like effect in rat model of postpartum depression (PPD) induced by hormone-simulated pregnancy followed by hormone withdrawal and compared to fluoxetine. As compared to control group, administration of G9 and G10 (270 mg/kg/day, p.o) for two weeks during the postpartum period can alleviate anxiety and depressive-like behaviors and biochemical changes in PPD-induced rats. This was confirmed by evaluation of anxiety-like behaviors (elevated plus maze, open field test, and forced swim test tests), in addition to biochemical analysis (brain monoamine oxidase-A, corticosterone level, proinflammatory cytokines, and hippocampal redox state). In conclusion, flaxseed oil of Egyptian cultivars G9 and G10 exhibited significant antidepressant-like effect in rat model of PPD without affecting locomotor activity. At the treatment doses, the antidepressant-like activity of Giza 9 oil is comparable to fluoxetine.

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.