Metabolic responses of sea anemone and jellyfish to temperature and UV bleaching: Insights into stress adaptation using LCMS-based metabolomics, molecular networking and chemometrics.

INTRODUCTION: Climate change poses various threats to marine life, particularly in shallow tropical waters. OBJECTIVE: The impact of increased temperature and ultraviolet (UV) exposure on two photosymbiotic cnidarians, a common bubble-tip anemone and an upside-down jellyfish, was investigated. METHODS: To illustrate the response of aquatic organisms, the metabolomes of unstressed Entacmaea quadricolor and Cassiopea andromeda were compared for detailed metabolite profiling. UHPLC-MS coupled with chemometrics and GNPS molecular networking was employed for sample classification and identification of markers unique to stress responses in each organism. RESULTS: Several compounds with bioactive functions, including peptides and terpenoids, were reported for the first time in both organisms, viz. cyclic tetraglutamate, campestriene, and ceramide aminoethyl phosphonate (CEAP d18:2/16:0). Both anemone and jellyfish were subjected to either elevated UV-B light intensity up to 6.6 KJ m-2 or increased temperatures (28 °C, 30 °C, 32 °C, and 34 °C) over 4 days. Phospholipids, steroids, and ceramides emerged as chief markers of both types of stress, as revealed by the multivariate data analysis. Lysophosphatidylcholine (LPC 16:0), LPC (18:0/0:0), and echinoclasterol sulfate appeared as markers in both UV and thermal stress models of the anemone, whereas methyl/propyl cholestane-hexa-ol were discriminatory in the UV stress model only. In the case of jellyfish, nonpolar glycosyl ceramide GlcCer (d14:1/28:6) served as a marker for UV stress, whereas polar peptides were elevated in the thermal stress model. Interestingly, both models of jellyfish share a phospholipid, lysophosphatidylethanolamine (LPE 20:4), as a distinctive marker for stress, reported to be associated indirectly with the activity of innate immune response within other photosymbiotic Cnidaria such as corals and appears to be a fundamental stress response in marine organisms. CONCLUSION: This study presents several bioinformatic tools for the first time in two cnidarian organisms to provide not only a broader coverage of their metabolome but also broader insights into cnidarian bleaching in response to different stressors, i.e., heat and UV light, by comparing their effects in anemone versus jellyfish.

Cilostazol Combats Lipopolysaccharide-Induced Hippocampal Injury in Rats: Role of AKT/GSK3ß/CREB Curbing Neuroinflammation.

Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3ß/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aß1-42) and p-tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-κB levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3ß/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.

Myricetin-loaded SBA-15 silica nanoparticles for enhanced management of pyrexia, pain, and inflammation through modulation of MAPK/NF-κB and COX-2/PGE-2 pathways: Evidence from the biochemical, histological, and metabolomic analysis.

Myricetin (MYR) is a natural flavonoid that has several biological functions. However, some of its beneficial effects are diminished due to low water solubility, stability, and bioavailability. Herein, several kinds of silica nanoparticles (MCM-41 and SBA-15) were loaded with MYR to improve its biological activity as an analgesic, antipyretic, and anti-inflammatory component, thereby overcoming its drawbacks. The nanoparticles (MYR@SBA-15) were formulated optimally, transforming MYR into an amorphous state. This transformation was confirmed via several strategies, including differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder x-ray diffraction. As a result, there was a significant enhancement in the solubility and rate of dissolution in water. The anti-inflammatory benefits as an innovative strategy and the underlying mechanism of action of MYR and its SBA-15 silica nanoparticles (MYR@SBA-15) were investigated based on the biochemical, histological, immunohistochemical, and metabolomic assays alongside their antipyretic and analgesic characteristics. Compared to the usage of raw MYR, the administration of MYR@SBA-15 at doses of 25, 50, and 100 mg/kg significantly decreases pain perception by inhibiting the body's writhing motions induced by acetic acid. Furthermore, it helps regulate increased body temperature caused by baking yeast and effectively stabilizes it. It reduces the release of NO and PGE-2 in a concentration-dependent manner by down-regulating iNOS and COX-2 expression in the inflammatory model. MYR and MYR@SBA-15 also inhibit the nuclear translocation of NF-κB, downregulate the expression of mitogen-activated protein kinases (MAPKs), such as p38, ERK1/2, and JNK protein, and reduce the generation of proinflammatory cytokines, such as TNF-α. In addition, inflammatory cardinal signs like paw edema caused by carrageenan in rats are greatly suppressed by MYR and MYR@SBA-15 treatment when compared to the untreated group. More noteworthy outcomes are shown in the MYR@SBA-15, particularly at a dose of 100 mg/kg. These results of biochemical and immuno-histochemistry suggest that MYR@SBA-15 may be a useful analgesic antipyretic and may also help reduce inflammation by altering MAPKs/NF-κB and COX-2/PGE-2 signaling cascades. Serum metabolomics study demonstrated modifications in various low molecular weight metabolites with arthritis development. These metabolite levels were restored to normal when MYR@SBA-15 was administered via modulating several metabolic pathways, i.e., pyrimidine, energy metabolism, and proteins. Overall, MYR-loaded SBA-15 silica nanoparticles have demonstrated significant promise in enhancing the disturbed metaboloic pathways and providing a substantial capacity to regulate several oxidative stress and inflammatory mediators.

Assessment of the effect of drying on Brassica greens via a multiplex approach based on LC-QTOF-MS/MS, molecular networking, and chemometrics along with their antioxidant and anticancer activities.

Turnip (Brassica rapa var rapa L.) leaves are a rich source of versatile bioactive phytochemicals with great potential in the food and herbal industries. However, the effect of drying on its constituents has never been studied before. Hereto, three drying techniques were compared, namely, lyophilization (LY), vacuum oven (VO), and shade drying (SD). Chemical profiling utilizing liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS) combined with chemometrics showed the different impacts of the drying methods on the phytochemical composition of the alcoholic leaf extracts. Unsupervised principal component analysis (PCA) and supervised partial least squares-discriminant analysis (PLS-DA) of the LC-QTOF-MS/MS data showed distinct distant clustering across the three drying techniques. Loading plots and VIP scores demonstrated that sinapic acid, isorhamnetin glycosides, and sinapoyl malate were key markers for LY samples. Meanwhile, oxygenated and polyunsaturated fatty acids were characteristic for SD samples and oxygenated polyunsaturated fatty acids and verbascoside were characteristic for VO samples. LY resulted in the highest total phenolics (TP) and total flavonoid (TF) contents followed by SD and VO. LY and SD samples had much higher antioxidant activity than VO measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC), and iron metal chelation assays. According to the anticancer activity, the drying methods were ranked in descending order as SD > LY â‰« VO when tested against colon, breast, liver, and lung cancer cell lines. Among the identified compounds, flavonoids and omega-3 fatty acids were key metabolites responsible for the anticancer activity as revealed by partial least squares (PLS) regression and correlation analyses. In conclusion, compared to LY, SD projected out as a cost-effective drying method without compromising the phytochemical and biological activities of Brassica greens. The current findings lay the foundation for further studies concerned with the valorization of Brassica greens.

Correction: Ammar et al. Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses. Nutrients 2022, 14, 841.

In the original publication [...].

Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats.

Liver fibrosis is a common chronic hepatic disease. This study aimed to investigate the effect of pitavastatin (Pit) against thioacetamide (TAA)-induced liver fibrosis. Rats were divided into four groups: (1) control group; (2) TAA group (100 mg/kg, i.p.) three times weekly for 2 weeks; (3 and 4) TAA/Pit-treated group, in which Pit was administered orally (0.4 and 0.8 mg/kg/day) for 2 weeks following TAA injections. TAA caused liver damage manifested by elevated serum transaminases, reduced albumin and histological alterations. Hepatic malondialdehyde (MDA) was increased, and glutathione (GSH) and superoxide dismutase (SOD) were decreased in TAA-administered rats. TAA upregulated the inflammatory markers NF-κB, NF-κB p65, TNF-α and IL-6. Treatment with Pit ameliorated serum transaminases, elevated serum albumin and prevented histopathological changes in TAA-intoxicated rats. Pit suppressed MDA, NF-κB, NF-κB p65, the inflammatory cytokines and PI3K mRNA in TAA-intoxicated rats. In addition, Pit enhanced hepatic antioxidants and boosted the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA. Moreover, immunohistological studies supported the ability of Pit to reduce liver fibrosis via suppressing p-AKT expression. In conclusion, Pit effectively prevents TAA-induced liver fibrosis by attenuating oxidative stress and the inflammatory response. The hepatoprotective efficacy of Pit was associated with the upregulation of Nrf2/HO-1 and downregulation of NF-κB and PI3K/Akt signalling pathways.

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.

Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer's disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC-ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC-ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aß aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1ß), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3ß and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management.

Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway.

This research investigated if pitavastatin (Pita) might protect rats' kidneys against thioacetamide (TAA). By altering the PTEN/AKT/mTOR pathway, pitavastatin may boost kidney antioxidant capacity and minimize oxidative damage. Statins have several benefits, including antioxidant and anti-inflammatory characteristics. The principal hypothesis of this study was that Pita can regulate the miR-93/PTEN/AKT/mTOR pathways, which is thought to be responsible for its renoprotective effects. The experiment divided male rats into four groups. Group 1 included untreated rats as the control. Group 2 included rats which received TAA (100 mg/kg intraperitoneally thrice a week for two weeks) to destroy their kidneys. Groups 3 and 4 included rats which received Pita orally at 0.4 and 0.8 mg/kg for 14 days after TAA injections. Renal injury increased BUN, creatinine, and MDA levels and decreased glutathione (GSH) levels. Pitavastatin prevented these alterations. TAA decreased PTEN and increased miR-93, Akt, p-Akt, mTOR, and Stat3 in the kidneys. Pitavastatin also regulated the associated culprit pathway, miR-93/PTEN/Akt/mTOR. In addition, TAA induced adverse effects on the kidney tissue, which were significantly ameliorated by pitavastatin treatment. The findings suggest that pitavastatin can attenuate renal injury, likely by regulating the miR-93/PTEN/Akt/mTOR pathway. This modulation of the pathway appears to contribute to the protective effects of pitavastatin against TAA-induced renal injury, adding to the growing evidence of the pleiotropic benefits of statins in renal health.

Role of Goldenberry (Fruits with Husk) Extract in Ameliorating the Architecture and Osmotic Fragility of Red Blood Cells in Obese Rats.

Goldenberry (GB) is a promising fruit that can be a constituent in many possible nourishments. No notifications were obtained regarding the impact of exposure to goldenberry extract in the viewpoint of blood rheological properties as well as erythrocyte osmotic fragility of red blood cells (RBCs) in obese rats. A substantial reduction in plasma triglyceride, total cholesterol, and LDL, with a considerable increment in HDL levels relative to the obese group (p ≤ 0.05), was observed in rats receiving low and high doses of GB, accompanied by restoration of SOD activity and GSH levels. Rheological parameters of rats' blood have been studied over a wide range of shear rates (225-1875 s-1). A significant decrease in blood viscosity in rats who received low and high doses of GB extract was compatible with every shear rate compared to the control group. The shear stress values of the obese rats reduced appreciably (p ≤ 0.05) in all values of shear rate (from 75 to 500 s-1) proportional to the control group, while in the groups that received low and high doses of GB extract, shear stress was restored to the control values. Finally, administration of GB extract significantly decreased yield stress and indices of whole blood aggregation, with an extremely substantial increment in flow rate, in rats given low or high doses of GB compared to obese ones. The result also showed a decrease in both the average raised osmotic fragility and the hemolysis rate in rats after supplementation with low and high doses of GB extract.

Erythropoietin mitigated thioacetamide-induced renal injury via JAK2/STAT5 and AMPK pathway.

The kidney flushes out toxic substances and metabolic waste products, and homeostasis is maintained owing to the kidney efforts. Unfortunately, kidney disease is one of the illnesses with a poor prognosis and a high death rate. The current investigation was set out to assess erythropoietin (EPO) potential therapeutic benefits against thioacetamide (TAA)-induced kidney injury in rats. EPO treatment improved kidney functions, ameliorated serum urea, creatinine, and malondialdehyde, increased renal levels of reduced glutathione, and slowed the rise of JAK2, STAT5, AMPK, and their phosphorylated forms induced by TAA. EPO treatment also greatly suppressed JAK2, Phosphatidylinositol 3-kinases, and The Protein Kinase R-like ER Kinase gene expressions and mitigated the histopathological alterations brought on by TAA toxicity. EPO antioxidant and anti-inflammatory properties protected TAA-damaged kidneys. EPO regulates AMPK, JAK2/STAT5, and pro-inflammatory mediator synthesis.

Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways.

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1ß, transforming growth factor-ß1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.

Comparative flavonoid profile of orange (Citrus sinensis) flavedo and albedo extracted by conventional and emerging techniques using UPLC-IMS-MS, chemometrics and antioxidant effects.

Introduction: Citrus fruits are one of the most frequently counterfeited processed products in the world. In the juice production alone, the peels, divided into flavedo and albedo, are the main waste product. The extracts of this by-product are enriched with many bioactive substances. Newer extraction techniques generally have milder extraction conditions with simultaneous improvement of the extraction process. Methods: This study presents a combinatorial approach utilizing data-independent acquisition-based ion mobility spectrometry coupled to tandem mass spectrometry. Integrating orthogonal collision cross section (CCS) data matching simultaneously improves the confidence in metabolite identification in flavedo and albedo tissues from Citrus sinensis. Furthermore, four different extraction approaches [conventional, ultrasonic, High Hydrostatic Pressure (HHP) and Pulsed Electric Field (PEF)] with various optimized processing conditions were compared in terms of antioxidant effects and flavonoid profile particularly polymethoxy flavones (PMFs). Results: A total number of 57 metabolites were identified, 15 of which were present in both flavedo and albedo, forming a good qualitative overlapping of distributed flavonoids. For flavedo samples, the antioxidant activity was higher for PEF and HHP treated samples compared to other extraction methods. However, ethyl acetate extract exhibited the highest antioxidant effects in albedo samples attributed to different qualitative composition content rather than various quantities of same metabolites. The optimum processing conditions for albedo extraction using HHP and PEF were 200 MPa and 15 kJ/kg at 10 kV, respectively. While, HHP at medium pressure (400 MPa) and PEF at 15 kJ/kg/3 kV were the optimum conditions for flavedo extraction. Conclusion: Chemometric analysis of the dataset indicated that orange flavedo can be a valid source of soluble phenolic compounds especially PMFs. In order to achieve cross-application of production, future study should concentrate on how citrus PMFs correlate with biological engineering techniques such as breeding, genetic engineering, and fermentation engineering.

How do cultivar origin and stepwise industrial processing impact Sesamum indicum seeds' metabolome and its paste and in relation to their antioxidant effects? A case study from the sesame industry.

Sesame is a valuable crop recognized for its rich composition and myriad of health benefits. The current study attempts to characterize sesame seeds' metabolome in relation to geographical origins i.e., Egypt, Sudan, Nigeria, in addition to samples from paste production lines along its different steps. UPLC-PDA-ESI-qTOF-MS was employed for untargeted profiling and in correlation to antioxidant capacity using DPPH, FRAP and ß-carotene-lineolate assays. 139 Peaks were identified, including novel phospholipids and catechol lignan in sesame. Furthermore, discriminatory markers belonging to coumarins, lignans, phenolic and organic acids were revealed among raw accessions, whereas roasted and unroasted seeds were distinguished by sugar, peptide/amino acid, and organic acid contents. Negative processing impact was observed in the loss of lignans during dehulling and decreased antioxidant capacity in sesame paste. However, malic acid in roasted seeds and verbascoside in Nigerian sesame could account for their improved antioxidant effects as revealed using chemometrics.

Comparative Untargeted Metabolic Profiling of Different Parts of Citrus sinensis Fruits via Liquid Chromatography-Mass Spectrometry Coupled with Multivariate Data Analyses to Unravel Authenticity.

Differences between seven authentic samples of Citrus sinensis var. Valencia peel (albedo and flavedo) and juices from Spain and Uruguay, in addition to a concentrate obtained from Brazil, were investigated by untargeted metabolic profiling. Sixty-six metabolites were detected by nano-liquid chromatography coupled to a high-resolution electrospray-ionization quadrupole time-of-flight mass spectrometer (nLC-ESI-qTOF-MS) belonging to phenolic acids, coumarins, flavonoid glycosides, limonoids, terpenes, and fatty acids. Eleven metabolites were detected for the first time in Citrus sinensis and identified as citroside A, sinapic acid pentoside, apigenin-C-hexosyl-O-pentoside, chrysoeriol-C-hexoside, di-hexosyl-diosmetin, perilloside A, gingerol, ionone epoxide hydroxy-sphingenine, xanthomicrol, and coumaryl alcohol-O-hexoside. Some flavonoids were completely absent from the juice, while present most prominently in the Citrus peel, conveying more industrial and economic prospects to the latter. Multivariate data analyses clarified that the differences among orange parts overweighed the geographical source. PCA analysis of ESI-(-)-mode data revealed for hydroxylinoleic acid abundance in flavedo peel from Uruguay the most distant cluster from all others. The PCA analysis of ESI-(+)-mode data provided a clear segregation of the different Citrus sinensis parts primarily due to the large diversity of flavonoids and coumarins among the studied samples.

Metabolomics approach of Symphyotrichum squamatum ethanol extract and its nano-Ag formulation protective effect on gastric ulcer via bio-chemical and pathological analyses.

ContextGastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.Materials and MethodsChemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.ResultsUPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.ConclusionPresent results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.

Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis.

Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin's (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis.

Evaluation of Safety of Stewart's Wood Fern (Dryopteris stewartii) and Its Anti-Hyperglycemic Potential in Alloxan-Induced Diabetic Mice.

Diabetes has become a critical challenge to the global health concerns. Cytotoxicity and development of resistance against available drugs for management of diabetes have shifted the focus of global scientific researchers from synthetic to herbal medications. Therefore, the current study was conducted to investigate the possible anti-hyperglycemic potential of Dryopteris stewartii using Swiss albino mice. To evaluate any possible toxic effect of the plant, acute oral toxicity test was performed while the anti-diabetic effects of aqueous and ethanol extracts at 500 mg/kg, positive, negative and normal control were assessed simultaneously. The anti-diabetic study revealed that aqueous extract has higher anti-diabetic potential than ethanol extract while lowered blood glucose level at second week reaching 150 mg/dL, exerting stronger anti-diabetic effects, compared to ethanol extract (190 mg/dL). Oral glucose tolerance findings revealed that aqueous extract decreased blood glucose level by -0.41-fold, compared to ethanol extract showing a decrease by only -0.29-folds. The histopathological evaluation of liver and pancreas of all groups revealed normal cell architecture with no morphological abnormalities. These results suggested the possible use of D. stewartii as anti-diabetic herbal drug in near future. However, these recommendations are conditioned by deep mechanistic studies.

Nanolipogel Loaded with Tea Tree Oil for the Management of Burn: GC-MS Analysis, In Vitro and In Vivo Evaluation.

The GC-MS analysis of tea tree oil (TTO) revealed 38 volatile components with sesquiterpene hydrocarbons (43.56%) and alcohols (41.03%) as major detected classes. TTO efficacy is masked by its hydrophobicity; nanoencapsulation can address this drawback. The results showed that TTO-loaded solid lipid nanoparticles (SLN1), composed of glyceryl monostearate (2% w/w) and Poloxamer188 (5% w/w), was spherical in shape with a core-shell microstructure. TTO-SLN1 showed a high entrapment efficiency (96.26 ± 2.3%), small particle size (235.0 ± 20.4 nm), low polydispersity index (0.31 ± 0.01), and high negative Zeta potential (-32 mV). Moreover, it exhibited a faster active agent release (almost complete within 4 h) compared to other formulated TTO-SLNs as well as the plain oil. TTO-SLN1 was then incorporated into cellulose nanofibers gel, isolated from sugarcane bagasse, to form the 'TTO-loaded nanolipogel' which had a shear-thinning behavior. Second-degree thermal injuries were induced in Wistar rats, then the burned skin areas were treated daily for 7 days with the TTO-loaded nanolipogel compared to the unmedicated nanolipogel, the TTO-loaded conventional gel, and the normal saline (control). The measurement of burn contraction proved that TTO-loaded nanolipogel exhibited a significantly accelerated skin healing, this was confirmed by histopathological examination as well as quantitative assessment of inflammatory infiltrate. This study highlighted the success of the proposed nanotechnology approach in improving the efficacy of TTO used for the repair of skin damage induced by burns.

Unveiling Antimicrobial and Antioxidant Compositional Differences between Dukkah and Za'atar via SPME-GCMS and HPLC-DAD.

Interest in plant-based diets has been on the rise in recent years owing to the potential health benefits of their individual components and the notion that plant-based diets might reduce the incidence of several diseases. Egyptian dukkah and Syrian za'atar are two of the most historic and famous Middle Eastern herbal blends used for their anti-inflammatory, hypolipidemic, and antidiabetic effects. Headspace SPME-GCMS and HPLC-DAD were adopted for characterizing the aroma profile and phenolic compounds of both herbal blends, respectively. Further, vapor-phase minimum inhibitory concentration was employed for assessing each blend's antibacterial potential, while their antioxidant potential was estimated via in vitro antioxidant assays. SPME headspace analysis indicated the abundance of ethers and monoterpene hydrocarbons, while HPLC revealed the presence of several phenolics including rosmarinic acid, ferulic acid, and rutin. Biological investigations affirmed that vapor-phase of the tested blends exhibited antibacterial activities against Gram-positive and Gram-negative pathogens, while the antioxidant potential of the blends was investigated and expressed as Trolox (125.15 ± 5.92 to 337.26 ± 13.84 µM T eq/mg) and EDTA (18.08 ± 1.62 to 51.69 41 ± 5.33 µM EDTA eq/mg) equivalent. The presented study offers the first insight into the chemical profile and biological activities of both dukkah and za'atar.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.