Corrigendum to "Biochemical and pharmacological prospects of citrus sinensis peel" [Heliyon 8, (8), (August 2022), e09979].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09979.].

Biochemical and pharmacological prospects of Citrus sinensis peel.

Gastric ulcer and hepatotoxicity due to irrational drug overuse are two of the most serious conditions associated with inflammation and oxidative stress that affect the digestive system. This study aimed to experimentally evaluate the hepatoprotective/gastroprotective effects of aqueous and butanol citrus peel extracts and hesperidin in rat models of ulcer and hepatotoxicity. Acute toxicity study was performed for determining the safe dose of citrus extracts to analyze efficacy. In the experiments on hepatoprotective and gastroprotective effects, rats were classified into nine groups in each experiment: (1) negative control, (2) positive control hepatotoxic model with paracetamol (640 mg/kg)/gastric ulcer model:ethanol 70% (1 ml), (3)reference hepatoprotective:silymarin (25 mg/kg)/gastroprotective:ranitidine (50 mg/kg), and (4-9) groups treated for 2 weeks before induction of each disease with either citrus aqueous or butanol extracts or hesperidin (125-250 mg/kg). Drugs, ethanol, or tested compounds were administered orally. The levels of biochemical parameters, such as AST, ALT, NO, MDA, CRP, and ILß6, were significantly reduced, but CAT level was increased. Postmortem examination of liver and stomach tissues of treated animals revealed marked improvement compared with positive control animals. Hesperidin exerted the best hepatoprotective, antioxidant, anti-inflammatory, and gastroprotective effects, followed by butanol and then aqueous citrus peel extracts.

Pharmacological and metabolomic profiles of Musa acuminata wastes as a new potential source of anti-ulcerative colitis agents.

Musa acuminata (MA) is a popular fruit peels in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic approaches were found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS2 fragmentation and NMR spectroscopy. These include: cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside; gallic acid and flavonoids; quercetin, quercetin-3-O-ß-D-glucoside, luteolin-7-O-ß-D-glucopyranoside. GC/MS analysis of MA peels essential oil led to identification of 37 compounds. The leaves, pseudostem and fruit peels extracts were tested for their safety and their anti-ulcerative colitis efficacy in rats. Rats were classified into: normal, positive, prednisolone reference group, MA extracts pretreated groups (250-500 mg/kg) for 2 weeks followed by induction of ulcerative colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examinations were done. Inflammatory markers (ANCA, CRP and Ilß6) were measured in sera. The butanol extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of ulcerative colitis and lowered the inflammatory markers compared to untreated group. MA wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-ulcerative colitis food supplements.

Preclinical activity of fluvastatin-loaded self-nanoemulsifying delivery system against breast cancer models: Emphasis on apoptosis.

Statins trigger apoptotic cell death in some types of growing tumor cells in a cholesterol-lowering-independent manner. Self-nanoemulsifying delivery systems (SNEDs) are potentially effective for the suppression of breast cancer development. This study aims to investigate the potential anticancer activity of fluvastatin (FLV)-SNEDs in breast cancer while comparing it with FLV in vitro as well as in vivo exploiting/using MDA-MB-231 and Erhlich ascites carcinoma (EAC)-bearing mice, respectively. Biochemical analysis of liver and kidney functions, oxidative stress markers, and histopathological examinations of such tumor tissues were performed showing the potentiality of SNEDs as a nanocarrier for antitumor agents. FLV-SNEDs demonstrated more potent anticancer activity compared to FLV on MDA-MB-231 and hepatocellular carcinoma (HepG2) cells. In vivo experiments on the EAC-bearing mice model indicated that FLV and-to a greater extent-FLV-SNEDs ameliorated EAC-induced hepatotoxicity and nephrotoxicity. FLV or FLV-SNEDs evidently reduced the percent of Ki-67 +ve EAC cells by 57.5% and 86.5% in comparison to the vehicle-treated EAC group. In addition, FLV or FLV-SNEDs decreased Bcl-2 levels in serum and liver specimens. In contrast, FLV or FLV-SNEDs significantly activated the executioner caspase-3. Simultaneously, both FLV and FLV-SNEDs stimulated p53 signaling and modulated Bcl-2 protein levels in treated cells. Collectively, these results support the contribution of apoptotic cell death in mediating the anticancer activities of FLV and FLV-SNEDs against murine EAC model in vivo. This study provides new understandings of how FLV and FLV-SNEDs regulate EAC cell viability via upregulation of p53 signaling, and through modulation of cleaved caspase-3 as well as antiapoptotic Bcl-2 marker.

Prophylactic effect of probiotics fortified with Aloe vera pulp nanoemulsion against ethanol-induced gastric ulcer.

The purpose of this study was designed to evaluate the protective effect of probiotics fortified with Aloe vera pulp nanoemulsion on ethanol-induced gastric ulcer (GU). Freshly harvested Aloe vera pulp nanoemulsion was prepared and subsequently inoculated with 2% of the activated yogurt starter culture of Streptococcus thermophilus and Lactobacillus delbreukii subsp. bulgaricus (1:1). Chemical composition and physicochemical characterization of yogurt and the Aloe vera pulp nanoemulsion were assessed. GU was induced by ethanol. Rats were randomly assigned into control, GU, and four prophylactic groups including probiotics fortified with Aloe vera pulp nanoemulsion in the percentage of 0%, 10%, 20%, and 30% respectively. Serum levels of paraoxynase (POX) and tissue levels of malondialdehyde (MDA), nitric oxide (NO), and catalase (CAT) activity were assessed. Serum levels of nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1ß), matrix metalloproteinase-9 (MMP-9), ceramide, and homocysteine (Hcy) were evaluated. Results indicated that the Aloe vera pulp nanoemulsion was appeared in spherical nano form with droplets diameter around 330 nm. Ethanol induces GU to cause a significant increase in the levels of MDA, NO, NF-κB, IL-1ß, MMP-9, Hcy, and ceramide along with a significant decrease in POX and CAT activities compared to the control group (p < 0.05). Pretreatment with different concentrations of probiotics fortified with Aloe vera pulp nanoemulsion with, especially the 30% concentration, significantly reduce the oxidative stress and ameliorate the release of different inflammatory mediators suggesting it as a promising approach in the protection against GU via scavenging superoxide radicals and inhibiting the activation of the inflammatory signaling cascades.

Stimulatory effect of docosahexaenoic acid alone or loaded in zinc oxide or silver nanoparticles on the expression of glucose transport pathway.

The role of glucose transporters (GLUTs) in diabetes mellitus has become more prominent as a possible therapeutic target. In the present study, we aimed to compare the effect of zinc oxide nanoparticles (ZnONPs), silver nanoparticles (AgNPs), and docosahexaenoic acid (DHA) alone or loaded in ZnONPs or AgNPs on insulin signaling pathway and GLUTs expression in diabetic rats. In the experimental part, rats were divided into seven groups; control, diabetic, and the other five groups were diabetic received different treatments. Fasting blood sugar (FBS), serum level of insulin, insulin resistance (IR), and serum level of phosphatidylinositol 3-kinase (PI3K) were evaluated. In addition, insulin expression in pancreatic islets was assessed by immunohistochemical analysis, and the expression of liver GLUTs 1, 2, and 4 and liver insulin receptor substrate-1 (IRS-1) was evaluated by real-time polymerase chain reactions (RT-PCR). The results of the current study showed that ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs attenuated levels of FBS, insulin and decreased IR in diabetic rats through enhancing the expression of GLUTs as well as IRS-1 and PI3K. Furthermore, AgNPs loaded with DHA showed the most significance with high comparability to the control group. In conclusion, this study elucidated the role of GLUTs and IRS-1 in diabetes and introduced novel characteristics of ZnONPs, AgNPs, and DHA alone or loaded in ZnONPs or AgNPs as a therapeutic modality to activate GLUTs and IRS1, which may be beneficial for diabetic patients with IR.

Homocysteine and Asymmetrical Dimethylarginine in Diabetic Rats Treated with Docosahexaenoic Acid-Loaded Zinc Oxide Nanoparticles.

Hyperglycemia, the hallmark of diabetes mellitus, is considered one of the endothelial dysfunction risk factors, the main reason of vascular complication. In this study, we aimed to evaluate homocysteine (Hcy) and asymmetrical dimethylarginine (ADMA) levels in diabetic rats and the possibility to attenuate the elevation of these two parameters by supplementation of docosahexaenoic acid (DHA) alone or loaded zinc oxide nanoparticles (ZnONPs) to improve endothelial dysfunction in streptozotocin (STZ)-induced diabetic rats. Forty male albino rats weighing 180-200 g were classified as control, diabetic, diabetic treated with DHA, and diabetic treated with DHA-loaded zinc oxide nanoparticles (DHA/ZnONPs) groups. Fasting blood glucose, insulin, ADMA, Hcy, and nitric oxide (NO) were estimated. Fatty acids (linoleic acid (LA), arachidonic acid (AA), DHA, α-linolenic acid (ALA), and oleic acid (OA)) were also evaluated by reversed phase HPLC using a UV detector. The results showed that fasting blood sugar, insulin resistance, LA, AA, OA, ADMA, and Hcy increased significantly in diabetic rats compared with control while fasting insulin, DHA, ALA, and NO decreased significantly in diabetic rats. In both treated groups, fasting blood sugar, insulin resistance, LA, AA, OA, ADMA, and Hcy significantly decreased as compared with the diabetic group while fasting insulin, DHA, ALA, and NO were significantly increased. In conclusion, DHA and DHA/ZnONP supplementation protect against diabetic complications and improve endothelial dysfunction as well as hyperhomocysteinemia in diabetes. DHA/ZnONP-treated group appeared more efficient than DHA alone.

Hypoxia-induced oxidative stress in high altitude population: impact of coenzyme Q10 supplementation.

OBJECTIVE: The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10) supplementation on oxidative stress engendered from hypoxia in population live at high altitude. METHODS: This is an intervention study in which 50 females of volunteers population-36 of them who live at high altitude compared with the placebo group (14 from the total population that live at sea level). Blood samples were collected in -anticoagulant tubes from control and high altitude before and after CoQ10 supplementation (150 mg/day for 2, 4 and 8 weeks). Plasma was separated and used for the determination of malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), paraoxonase (PON1) by spectrophotometer, CoQ10 and vitamin E by high performance liquid chromatography (HPLC). RESULTS: Our results appeared that TAC, PON1, vitamin E and CoQ10 concentrations were significantly decreased in population at high altitude at base line compared to placebo group population at sea level. Whereas, administration of CoQ10 attenuated all measured parameters especially after eight weeks of administration. CONCLUSION: We concluded that coenzyme Q10 supplement at a dose of 150 mg/day has a powerful effect in oxidative stress parameters and increased antioxidant parameters included vitamin E in population with hypoxia after 4 and 8 weeks. So that supplementation positively affects oxidative stress and is recommended CoQ10 supplementation in population who live at high altitude.

The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis.

OBJECTIVE: The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. METHODS: To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. RESULTS: Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. CONCLUSION: Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect carvacrol structure and increase its efficiency and stability. Moreover, nano-encapsulation of carvacrol is more efficient than nano-emulsion.