Mitigation of intrahepatic cholestasis induced by 17α-ethinylestradiol via nanoformulation of Silybum marianum L.

BACKGROUND: Cholestasis is an important predisposing factor for hepatocyte damage, liver fibrosis, primary biliary cirrhosis, and even liver failure. Silybum marianum L. (SM) plant is used in teas or eaten in some countries due to its antioxidant and hepatoprotective properties. Because of its low and poor oral bioavailability, so we improve the therapeutic activity of Silybum marianum L. extract (SM) by studying the potential effects of nanoformulation of Silybum marianium L. extract (nano-SM) on 17α-ethinylestradiol (EE)-induced intrahepatic cholestasis. METHODS: Thirty female Sprague-Dawley rats were divided into 5 groups (6 rats/group). Group I: Rats were received the treatment vehicle and served as normal group. Group II:Rats were injected daily with EE (10 mg/kg) for five successive days. Group III-V: Rats were injected daily with EE (10 mg/kg) and treated with either Ursodeoxycholic acid (UDCA) (40 mg/kg), SM (100 mg/kg) and nano-SM (100 mg/kg) orally once/day throughout the trialfor five successive days, respectively. RESULTS: Nano-SM greatly dampened the increase in serum levels of total and direct bilirubin, alanine aminotransaminase, aspartate aminotransaminase, and alkaline phosphatase caused by EE. Furthermore, nano-SM increased the hepatic contents of reduced glutathione (GSH) and catalase (CAT) and also upregulated the relative hepatic gene expressions of Rho-kinase (ROCK-1), myosin light chain kinase (MLCK), and myosin phosphatase target subunit (MYPT1) compared to the EE-induced group. Administration of nano-SM reduced hepatic lipid peroxidation and downregulated the relative hepatic expressions of the nuclear factor-kappa B (NF-Ò¡B) and interleukin-1ß (IL-1ß). In addition, nano-SM improved the histopathological changes induced by EE. CONCLUSION: Nano-SM possessed a superior effect over SM, which can be considered an effective protective modality against EE-induced cholestatic liver injury through its antioxidant, anti-inflammatory activities, and enhancing bile acid (BA) efflux.

Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives.

Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.

Impact of Some Natural and Artificial Sweeteners Consumption on Different Hormonal Levels and Inflammatory Cytokines in Male Rats: In Vivo and In Silico Studies.

Substituting sugar with noncaloric sweeteners prevents overweight and diabetes development. They come in two types: artificial, like aspartame and sucralose, and natural, such as sorbitol. This research aimed to assess the effects of sucrose and these sweeteners on nutritional parameters, hematological parameters, hormones, and anti- and pro-inflammatory cytokines in male rats. Thirty rats had been separated into five groups. The results showed the highest significant increase in body weight gain, total food intake, and feed efficiency noticed in the aspartame group followed by sucralose, sucrose, and sorbitol, respectively. In contrast to RBCs and platelets, all sweeteners significantly reduced the hemoglobin level, Hct %, and WBC count. The aspartame group showed the highest decline in glycoproteins, steroids, and T3, and T4 hormones and a dramatic elevation in thyroid stimulating hormone, eicosanoid, and amine hormones compared with the control group. A vigorous elevation in anti- and proinflammatory cytokine levels was observed in the aspartame group, followed by sucralose, sucrose, and sorbitol groups. Aspartame has the highest docking scores when studying the interactions of sweeteners and a target protein associated with hormones or cytokines using in silico molecular docking, with the best absorption, distribution, metabolism, elimination, and toxicity properties compared to the remaining sweeteners.

Validating the protective role of orange and tangerine peel extracts foramending food safety against microorganisms' contamination using molecular docking.

Latest studies indicated that agro-food wastes are considered renewable sources of bioactive compounds. This investigation aimed to utilize natural extracts of citrus peels as antimicrobial and anti-aflatoxigenic agents for food safety. The bioactivity of two citrus peels was assessed by total phenolic, flavonoids, and antioxidant activity. Nanoemulsions were manufactured using high-speed homogenization. The mean particle size of the nanoemulsions ranged from 29.41 to 66.41 nm with a polydispersity index of 0.11-0.16. The zeta potential values ranged from -14.27 to -26.74 mV, indicating stability between 81.44% and 99.26%. The orange peel extract showed the highest contents of total phenolic and flavonoids compared to the other extracts and nanoemulsions (39.54 mg GAE/g and 79.54 mg CE/100 g, respectively), which agreed with its potential antioxidant activity performed by DPPH free radical-scavenging and ABTS assays. Chlorogenic, caffeic, ferulic, and catechin were the dominant phenolic acids in the extracts and nanoemulsions, while quercitrin, rutin, and hesperidin were the most abundant flavonoids. Limonene was the major volatile component in both oils; however, it was reduced dramatically from 92.52% to 76.62% in orange peel oil and from 91.79 to 79.12% in tangerine peel oil. Consistent with the differences in phenolics, flavonoids, and volatiles between orange and tangerine peel extracts, the antibacterial properties of orange extracts had more potential than tangerine ones. Gram-positive bacteria were more affected by all the examined extracts than Gram-negative ones. The antifungal activity of orange extract and nanoemulsion on seven fungal strains from Aspergillus spp had more potential than tangerine extracts. Additionally, using a simulated media, the orange peel extract and its nanoemulsion had a more anti-aflatoxigenic influence. Molecular docking confirmed the high inhibitory action of flavonoids, especially hesperidin, on the polyketide synthase (-9.3 kcal/mol) and cytochrome P450 monooxygenase (-10.1 kcal/mol) key enzymes of the aflatoxin biosynthetic mechanism.

The protective effects of some herbs on mitigating HFD-induced obesity via enhancing biochemical indicators and fertility in female rats.

The potential of plant-based diets and drugs to prevent and control obesity has been attributed to the presence of several biologically active phytochemicals. The study aimed to assess herb consumption's impact on alleviating the risks and hazards associated with obesity induced by a high-fat diet (HFD) and the promotion of fertility. Eighty rats were allocated into four distinct groups. Group 1 (G1) was provided with a basal diet and acted as the control group. Group 2 (G2) was provided with an HFD. Group 3 (G3) was provided with HFD supplemented with chia seeds and Hibiscus sabdariffa L. The fourth group of subjects was provided with HFD supplemented with Foeniculum vulgare (fennel) and Coriandrum sativum L. (coriander). The feeding session was sustained for 10 weeks, and the biochemical parameters were evaluated. The administration of Foeniculum vulgare (fennel) and Coriandrum sativum L. (coriander) (G4) resulted in a more significant reduction in all biochemical parameters compared to G3, which received a diet consisting of chia seeds and Hibiscus sabdariffa L. Additionally, the average number of embryonic lobes and the average number of offspring after birth were found to be considerably more significant in the normal control group (G1) and group (G4) compared to the HFD group (G2) and group (G3) (P < 0.01). Group 4 (G4) was administered a diet enriched with Foeniculum vulgare (fennel) and Coriandrum sativum L. (coriander), which demonstrated superior outcomes in many biochemical indicators and the promotion of fertility in obese female rats.

Polyphenols: Chemistry, bioavailability, bioactivity, nutritional aspects and human health benefits: A review.

Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed.

Evaluation of the cytotoxicity and genotoxicity potential of synthetic diacetyl food flavoring in silico, in vivo, and in vitro.

Diacetyl is a common ingredient that creates a buttery flavor in baked goods and other food products. The cytotoxic impact of diacetyl on a normal human liver cell line (THLE2) indicated an IC50 value of 41.29 mg/ml through MTT assay and a cell cycle arrest in the G0/G1 phase relative to the control. Administration of diacetyl at two-time points (acute-chronic) led to a significant increase in DNA damage indicated by the increase in tail length, tail DNA%, and tail moment. The mRNA and protein expression levels of genes in the rats' livers were then measured using real-time PCR and western blotting. The results showed an activation of the apoptotic and necrosis mechanism, with an upregulation of p53, Caspase 3, and RIP1 and a downregulation of Bcl-2 at the mRNA level. The ingestion of diacetyl disrupted the liver's oxidant/antioxidant balance, as evidenced by alterations in levels of GSH, SOD, CAT, GPx, GR, MDA, NO, and peroxynitrite. Additionally, heightened levels of inflammatory cytokines were shown. Histopathological examinations revealed necrotic foci and congested portal areas in the rats' liver cells after treatment with diacetyl. Diacetyl may interact moderately with Caspase, RIP1, and p53 core domain through In-silico, possibly resulting in upregulated gene expression.

Promising role of Lawsonia inermis L. leaves extract and its nano-formulation as double treatment against aflatoxin toxicity in ulcerated-rats: Application in milk beverage.

Aflatoxins are an unavoidable contaminant of foods. The current work aimed to study the ameliorating effect of Lawsonia inermis L. extract and its nano-formulation versus aflatoxin ingestion in ulcerative rats. Lawsonia inermis L. bioactivity was evaluated by both antioxidant & antimicrobial assays. The nanoparticles characterization measurements were evaluated. Different parameters in the fortified milk beverage were assessed. Seventy two Sprague-Dawley male rats were randomized into 12 groups (6 rats/group) where peptic ulcer was induced with a single aspirin dose (500 mg/kg BW) orally. The nutritional and biochemical parameters were evaluated. The results showed that antioxidant activity and total phenolic content increased with increasing nano-formulation ratio. A remarkable improvements in all the treated groups, either for ulcer alone or for aflatoxin exposed ulcerative groups in normal and nano-formulation. Conclusively, Lawsonia inermis L. & its nano-formulation could act as dual therapy for ulcer treatment and the hazardous effects of aflatoxin exposure.

Effect of nano-encapsulated food flavorings on streptozotocin-induced diabetic rats.

Flavors and aromas are widely used in food and pharmaceutical industries to enhance food palatability. However, it is worth noting that they may also have bioactivity. This study aims to examine the potential impact of key flavors and their nanocapsules on health and diseases, such as type 2 diabetes mellitus (T2DM). The 36 nanocapsules of key flavorings were prepared by high shear homogenization (HSH). Seventy-two male Sprague-Dawley rats received a single dosage of streptozotocin (35 mg kg-1 body weight) intraperitoneally. All of the nutritional and biochemical parameters were statistically analyzed. A virtual docking study was conducted. Linalool nanoemulsion results showed the highest encapsulation efficiency (86.76%), while isoamyl acetate nanoparticles showed the lowest (69.99%). According to GC-MS analysis, encapsulation did not affect the flavoring structure with particle size distributions ranging from 277.3 to 628.8 nm. Using TEM, nanoemulsion particles appeared spherical with a desired nanometric diameter size. In the oral glucose tolerance test, flavorings in oil and nanoforms had no discernible hypoglycemia effects in normal rats. The nutritional and biochemical parameters confirmed that both normal and nanoencapsulation forms demonstrated a potential anti-hyperglycemic effect, and enhanced the rat health compared to the raw flavorings. The studied flavorings and their nanocapsules seem to have the potential double effect of a flavor compound as a food palatability enhancer with a potential beneficial effect on type 2 diabetes mellitus without any health drawbacks.

Cornu aspersum mucin attenuates indomethacins-induced gastric ulcers in mice via alleviating oxidative stress and inflammation.

In the past three decades, a significant progress has been made in the prevention and treatment of gastric ulcers. The incidence of the disease has decreased, but gastric ulcer is still a medical problem. Currently, the available drugs for gastric ulcer treatment have many side effects; therefore, searching for new and safe therapeutic agents is mandatory. The present study aims to investigate the gastroprotective potential of Cornu aspersum (C. aspersum) mucin against gastric ulcers, and the mechanisms related to oxidative stress and inflammation. C. aspersum mucin was collected from 50 snails. The characteristics of C. aspersum mucin (chemical and microbiological) were evaluated. Mice were pretreated with famotidine and C. aspersum mucin (7.5 and 15 ml/kg b.w.) for 5 days, and then gastric ulcers were induced by indomethacin. Macroscopic examination, biochemical estimations, and Quantitative real-time PCR were carried out. Also, histopathological and immunohistopathological examinations were evaluated. We found that the high dose of the mucin significantly decreased the gastric mucosal malondialdehyde (MDA) and nitric oxide (NO) contents as well as interleukin 1ß (IL-1ß) and nuclear factor kappa ß (NF-Ò¡B) expression, and inducible nitric oxide synthase (iNOS) immunostaining. It also increased the gastric mucosal GSH and catalase contents as well as hemoxygenase-1 (HO-1) and nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions with regressions in gastric mucosal lesions. In conclusion, C. aspersum mucin could be a potential therapeutic candidate to protect against gastric ulceration.

Enhancing date seed phenolic bioaccessibility in soft cheese through a dehydrated liposome delivery system and its effect on testosterone-induced benign prostatic hyperplasia in rats.

Introduction: The consumption of dairy products, including soft cheese, has been associated with numerous health benefits due to their high nutritional value. However, the phenolic compounds bioaccessibility present in soft cheese is limited due to their poor solubility and stability during digestion. So, this study aimed to develop an innovative soft cheese enriched with date seed phenolic compounds (DSP) extracted ultrasonically and incorporated into homogeneous liposomes and study its attenuation effect on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Methods: Date seed phenolic compounds were extracted using 98 and 50% ethanol along with water as solvents, employing ultrasonication at 10, 20, and 30-min intervals. The primary and secondary DSP-liposomes were prepared and dehydrated. The particle size, zeta potential, encapsulation efficiency, and morphology were measured. Incorporating dehydrated liposomes (1-3% w/w) into soft cheese and their impact on BPH using male Sprague-Dawley rats was assessed. After inducing BPH, rats were fed a cheese diet with dehydrated DSP-liposomes. Over 8 weeks, parameters including nutrition parameters, prostate enlargement analysis, biochemical parameters, hormones level, oxidative stress, and cytokines were analyzed. Results and Discussion: The results showed that ultrasound-assisted extraction effectively reduced the extraction time and 30 min extraction EtOH 50% was enough to extract high yield of phenolic compounds (558 mg GA/g) and flavonoids (55 mg qu/g) with high antioxidant activity (74%). The biological results indicate that prostate weight and prostate index% were diminished in the treatment groups (1 and 2) compared to the BPH control group. The high antioxidant content present in the DSP-liposomes acted as the catalyst for suppressing the responses of the inflammatory cytokines, inhibiting the anti-inflammatory IL-10 production, and suppressing the elevated levels of lipid peroxidation products compared to the BPH group. Conclusion: The treatment group (2) supplemented with dehydrated secondary DSP-liposomes exhibited the most significant variance (p < 0.05) as opposed to the BPH group. Liposomal encapsulation was proved to be a feasible approach for administering DSP in soft cheese, thereby establishing new functional food category possessing prophylactic properties against the advancement of BPH in rats.

Assessment of the antiulcer properties of Lawsonia inermis L. leaves and its nano-formulation against prolonged effect of acute ulcer in rats.

Peptic ulcer syndrome (PUD) has been acknowledged as one of the most frequent causes of morbidity and mortality worldwide throughout the 20th and 21st centuries. Several reports indicated the ability of plant derived dosages as antiulcer agents. Many prior investigations have implied some biological activities of Lawsonia inermis L. The aim of this current investigation was to estimate the antiulcer capability of Lawsonia inermis L. leaves and its nano formulation against hazardous biochemical and histological changes in aspirin-induced ulcer rats. Methods divided into 6 groups (6 rats/group), Normal control (negative), Group (1) receiving dose of (200 g/kg) Lawsonia inermis L. for 8 weeks, Group (2) receiving (200 g/kg) nano Lawsonia inermis L. leaves for 8 weeks, Group (3) ulcer control group receiving a single dose (500 mg aspirin/kg rat body weight),groups 4& 5 receiving aspirin and either Lawsonia inermis L. leaves or nano Lawsonia inermis L. leaves for 8 weeks. Results: improvements in all the tested parameters as well as hepatic enzymes activities and some blood biochemical parameters. Conclusion Lawsonia inermis L.at the tested dose could prevent ulcer formation in the tested animals that may offer safe and low cost effective treatment for gastric ulcer.

Bioactivity and antidiabetic properties of Malva parviflora L. leaves extract and its nano-formulation in streptozotocin-induced diabetic rats.

Diabetes is a drastic health problem resulting from an endocrine disorder. M. parviflora L. might represent an antioxidant-rich food source and thus applies to pharmaceutical and therapeutic applications in oxidative stress-related degenerative diseases. In the current work, we assessed the antidiabetic activity of M. parviflora L. leaves extract and its nano-formulation in rats. M. parviflora L. bioactivity was evaluated by both antioxidant and antimicrobial assays. The nano-formulation characteristics (Mass, TEM, and Zeta potential) were evaluated. Twenty-four male Sprague-Dawley rats were administered streptozotocin (STZ) intraperitoneally for only one dose (35 mg/kg body weight). All of the nutritional and biochemical parameters were statistically analyzed. The results showed that M. parviflora L. is rich in phenolics and flavonoids with high antioxidant action. The antifungal activity of the extract was evident, especially with Fusarium culmorum and aspergillus flavus. The extract and its nano-formulation have shown antidiabetic properties when tested on diabetic rats as they improved all the biochemical parameters; decreased glucose level in serum, increased insulin production, marked improvement in lipid profile, liver and kidney functions, and that was more proved with the histopathological examinations. Conclusively, M. parviflora L. extract and its nano-formulation could attenuate or effectively help in controlling diabetes through its therapeutic properties exhibited by the action of the plant antioxidant components.

Microencapsulation of Plant Phenolic Extracts Using Complex Coacervation Incorporated in Ultrafiltered Cheese Against AlCl3-Induced Neuroinflammation in Rats.

Plant-derived phenolic compounds have numerous biological effects, including antioxidant, anti-inflammatory, and neuroprotective effects. However, their application is limited because they are degraded under environmental conditions. The aim of this study was to microencapsulate plant phenolic extracts using a complex coacervation method to mitigate this problem. Red beet (RB), broccoli (BR), and spinach leaf (SL) phenolic extracts were encapsulated by complex coacervation. The characteristics of complex coacervates [zeta potential, encapsulation efficiency (EE), FTIR, and morphology] were evaluated. The RB, BR, and SL complex coacervates were incorporated into an ultrafiltered (UF) cheese system. The chemical properties, pH, texture profile, microstructure, and sensory properties of UF cheese with coacervates were determined. In total, 54 male Sprague-Dawley rats were used, among which 48 rats were administered an oral dose of AlCl3 (100 mg/kg body weight/d). Nutritional and biochemical parameters, including malondialdehyde, superoxide dismutase, catalase, reduced glutathione, nitric oxide, acetylcholinesterase, butyrylcholinesterase, dopamine, 5-hydroxytryptamine, brain-derived neurotrophic factor, and glial fibrillary acidic protein, were assessed. The RB, BR, and SL phenolic extracts were successfully encapsulated. The RB, BR, and SL complex coacervates had no impact on the chemical composition of UF cheese. The structure of the RB, BR, and SL complex coacervates in UF cheese was the most stable. The hardness of UF cheese was progressively enhanced by using the RB, BR, and SL complex coacervates. The sensory characteristics of the UF cheese samples achieved good scores and were viable for inclusion in food systems. Additionally, these microcapsules improved metabolic strategies and neurobehavioral systems and enhanced the protein biosynthesis of rat brains. Both forms failed to induce any severe side effects in any experimental group. It can be concluded that the microencapsulation of plant phenolic extracts using a complex coacervation technique protected rats against AlCl3-induced neuroinflammation. This finding might be of interest to food producers and researchers aiming to deliver natural bioactive compounds in the most acceptable manner (i.e., food).

The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer.

The effect of nano tamoxifen and some bioactive components such as yeast, isoflavone, and silymarin on the level of resistance and prevention of breast cancer progression in experimental animals is the target of this study. Thirty female Sprague-Dawley rats received a single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) intragastrically. After fourteen days of DMBA admission, the procedure protocol started out. Finally, all the experimental results evaluated, tabulated and statistically analyzed. The results demonstrated a highly significant elevation in the 8-OHdG level in group 1 (nano yeast) and 3 (nano silymarin) while the results demonstrated a highly significant reduction in group 2 (nano tamoxifen). The apoptosis results demonstrated a significant elevation in group 3 (nano silymarin) where appeared significant reduction in group 4 (nano isoflavone). ErbB-2 results demonstrated a significant elevation in group 2 (nano tamoxifen) and a significant reduction in each of group 3 (nano silymarin) and 4 (nano isoflavone). The lipid peroxide level demonstrated an extremely significant reduction in group 4 (nano isoflavone). And a significant reduction of total antioxidant was observed in group 3 (nano silymarin) in comparison to injected animals control. This may be considered a new vision and strategy to resist breast cancer disease or prevent progression.