A comprehensive tool in recycling plant-waste of Gossypium barbadense L agricultural and industrial waste extracts containing gossypin and gossypol: hepatoprotective, anti-inflammatory and antioxidant effects.

Improper management of agricultural and industrial cotton wastes causes environmental pollution and worsens the climate change challenge. Green recycling of cotton could contribute to a circular economy. One of the economic values of cotton wastes lies in their bioactive components. Two types of cotton wastes-agricultural and industrial-of the species Gossypium barbadense L. Giza 95 were targeted in the current study, aiming to maximize their medicinal value and investigate the anti-inflammatory, hepatoprotective, and antioxidant activities of their phytochemical extracts. Phytochemical extraction was performed using different solvents extraction. An anti-inflammatory effect was tested in carrageenan-induced acute edema in a rat paw model. A carbon tetrachloride chronic model of liver injury was used for the assessment of hepatoprotective potential. Liver enzymes (AST and ALT), oxidative stress markers (MDA and GSH), inflammatory biomarkers (C-reactive protein), and histopathological features were investigated. As a result, ethyl acetate proved to be the solvent of best choice to extract the gossypin polyphenolics, where the extracted amount reached 14,826.2 µg/g, followed by butanol (8751.4 µg/g extract). The chloroform (CHCL3) fraction showed the highest amounts of gossypol (190.7 µg/g extract), followed by petroleum ether. Cotton waste's composition analysis showed a wide range of components, including 33 metabolites such as gossypetin, polyphenolics, and other metabolites that possess therapeutic effects. Both chloroform extract and industrial waste extracts showed superior anti-inflammatory and hepatoprotective effects in comparison to other extracts. All tested extracts (ethyl acetate, chloroform, and industrial waste) showed proper antioxidant activities.

Novel thiazolidin-4-one benzenesulfonamide hybrids as PPARγ agonists: Design, synthesis and in vivo anti-diabetic evaluation.

In the current study, two series of novel thiazolidin-4-one benzenesulfonamide arylidene hybrids 9a-l and 10a-f were designed, synthesized and tested in vitro for their PPARÉ£ agonistic activity. The phenethyl thiazolidin-4-one sulphonamide 9l showed the highest PPARÉ£ activation % by 41.7%. Whereas, the 3-methoxy- and 4-methyl-4-benzyloxy thiazolidin-4-one sulphonamides 9i, and 9k revealed moderate PPARÉ£ activation % of 31.7, and 32.8%, respectively, in addition, the 3-methoxy-3-benzyloxy thiazolidin-4-one sulphonamide 10d showed PPARÉ£ activation % of 33.7% compared to pioglitazone. Compounds 9b, 9i, 9k, 9l, and 10d revealed higher selectivity to PPARÉ£ over the PPARδ, and PPARα isoforms. An immunohistochemical study was performed in HepG-2 cells to confirm the PPARÉ£ protein expression for the most active compounds. Compounds 9i, 9k, and 10d showed higher PPARÉ£ expression than that of pioglitazone. Pharmacological studies were also performed to determine the anti-diabetic activity in rats at a dose of 36 mg/kg, and it was revealed that compounds 9i and 10d improved insulin secretion as well as anti-diabetic effects. The 3-methoxy-4-benzyloxy thiazolidin-4-one sulphonamide 9i showed a better anti-diabetic activity than pioglitazone. Moreover, it showed a rise in blood insulin by 4-folds and C-peptide levels by 48.8%, as well as improved insulin sensitivity. Moreover, compound 9i improved diabetic complications as evidenced by decreasing liver serum enzymes, restoration of total protein and kidney functions. Besides, it combated oxidative stress status and exerted anti-hyperlipidemic effect. Compound 9i showed a superior activity by normalizing some parameters and amelioration of pancreatic, hepatic, and renal histopathological alterations caused by STZ-induction of diabetes. Molecular docking studies, molecular dynamic simulations, and protein ligand interaction analysis were also performed for the newly synthesized compounds to investigate their predicted binding pattern and energies in PPARÉ£ binding site.

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 [...].

Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.

Antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of "dimethyl dimethoxy biphenyl dicarboxylate" in male Wistar rats.

Dimethyl dimethoxy biphenyl (DDB) dicarboxylate has been applied as a therapeutic modality for curing liver diseases, particularly hepatitis virus. The objective of this study was to assess the protective potential against Triton X-100 induced abnormal fat metabolism in addition to anti-inflammatory, analgesic, and antipyretic effects of DDB. The anti-inflammatory, antinociceptive, and antipyretic of DDB were investigated through induction of paw edema, pain, and fever in experimental rats. DDB decreased cholesterol and triglyceride contents. DDB resulted in inhibition of inflammation, nociception, and fever in the experimental models. DDB improved lipid profile, as evidence of hypolipidemic potential. It also showed anti-inflammatory, analgesic, and antipyretic properties.

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.

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC-MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin's potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity.

1,8 Cineole and Ellagic acid inhibit hepatocarcinogenesis via upregulation of MiR-122 and suppression of TGF-ß1, FSCN1, Vimentin, VEGF, and MMP-9.

Hepatocellular carcinoma (HCC) is one of the most burdened tumors worldwide, with a complex and multifactorial pathogenesis. Current treatment approaches involve different molecular targets. Phytochemicals have shown considerable promise in the prevention and treatment of HCC. We investigated the efficacy of two natural components, 1,8 cineole (Cin) and ellagic acid (EA), against diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) induced HCC in rats. DEN/2-AAF showed deterioration of hepatic cells with an impaired functional capacity of the liver. In addition, the levels of tumor markers including alpha-fetoprotein, arginase-1, alpha-L-fucosidase, and ferritin were significantly increased, whereas the hepatic miR-122 level was significantly decreased in induced-HCC rats. Interestingly, treatment with Cin (100mg/kg) and EA (60mg/kg) powerfully restored these biochemical alterations. Moreover, Cin and EA treatment exhibited significant downregulation in transforming growth factor beta-1 (TGF-ß1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and epithelial-mesenchymal transition (EMT) key marker, vimentin, along with a restoration of histopathological findings compared to HCC group. Such effects were comparable to Doxorubicin (DOX) (2mg/kg); however, a little additive effect was evident through combining these phytochemicals with DOX. Altogether, this study highlighted 1,8 cineole and ellagic acid for the first time as promising phytochemicals for the treatment of hepatocarcinogenesis via regulating multiple targets.

Design and synthesis of novel quinazolinone-based fibrates as PPARα agonists with antihyperlipidemic activity.

Aiming to discover new antihyperlipidemic agents, a new set of quinazolinone-fibrate hybrids 9a-r bearing the essential features for peroxisome proliferator-activated receptor-α (PPARα) agonistic activity was synthesized and the structures were confirmed by different spectral data. All the target compounds were screened for their PPARα agonistic activity. Compounds 9o and 9q exhibited potent activity, with EC50 values better than that of fenofibrate by 8.7- and 27-fold, respectively. Molecular docking investigations were performed for all the newly synthesized compounds in the active site of the PPARα receptor to study their interactions and energies in the receptor. Moreover, the antihyperlipidemic and antioxidant activities of compounds 9o and 9q were determined using Triton WR-1339-induced hyperlipidemic rats. Compound 9q exhibited effective hypolipidemic activity in a dose-dependent manner, where it significantly reduced the serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol. Furthermore, it possesses a powerful antioxidant profile where it significantly elevated the levels of reduced glutathione as well as the total antioxidant capacity and significantly decreased the malondialdehyde level. The histopathological studies revealed that compound 9q improved the aortic architecture and hepatic steatosis. These findings support that compound 9q could be a promising lead compound for the development of new antihyperlipidemic agents.

Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression.

The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, ß-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, ß-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and ß-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression).

Protective Mechanism of Acacia saligna Butanol Extract and Its Nano-Formulations against Ulcerative Colitis in Rats as Revealed via Biochemical and Metabolomic Assays.

Ulcerative colitis (UC) is a relapsing inflammatory disease of unknown etiology. The increased risk of cancer in UC patients warrants for the development of novel drug treatments. Herein, this work concerns with the investigation of the protective effects of Acacia saligna butanol extract (ASBE) and its nanoformulations on UC in a rat model and its underlying mechanism. Colitis was induced by slow intrarectal infusion of 2 mL of 4% (v/v in 0.9% saline) acetic acid. Colon samples were evaluated macroscopically, microscopically, and assayed for pro-inflammatory cytokine levels. To monitor associated metabolic changes in acetic acid-induced UC model, serum samples were analyzed for primary metabolites using GC-MS followed by multivariate data analyses. Treatment with ASBE attenuated acetic acid-induced UC as revealed by reduction of colon weight, ulcer area, and ulcer index. ASBE treatment also reduced Cyclooxygenase-2 (COX-2), Prostaglandin E2 (PGE2) & Interleukin-1ß (IL-1ß) levels in the inflamed colon. The nano-formulation of ASBE showed better protection than the crude extract against ulcer indices, increased PGE2 production, and histopathological alterations such as intestinal mucosal lesions and inflammatory infiltration. Distinct metabolite changes were recorded in colitis rats including a decrease in oleamide and arachidonic acid along with increased levels of lactic acid, fructose, and pyroglutamic acid. Treatment with nano extract restored metabolite levels to normal and suggests that cytokine levels were regulated by nano extract in UC. Conclusion: ASBE nano extract mitigated against acetic acid-induced colitis in rats, and the underlying mechanism could be attributed to the modulatory effects of ASBE on the inflammatory cascades. The applicability of metabolomics developed in this rat model seems to be crucial for evaluating the anti-inflammatory mechanisms of new therapeutics for acute colitis.

Cardioprotective effect of thymol against adrenaline-induced myocardial injury in rats.

Cardiovascular disease represents a vital global disease burden. This study aims to assess the possible cardioprotective effect of thymol against adrenaline-induced myocardial injury (MI) in rats. Furthermore the effect of thymol on cardiac function biomarkers, electrocardiogram (ECG) alterations, oxidative stress, inflammation, apoptosis and histopathological changes was assessed. MI was induced by adrenaline (2 mg/kg, s.c.) injected as a single dose for 2 consecutive days (24 h apart). Normal and control groups received the vehicle for 21 consecutive days. The other 3 groups were orally administered thymol (15, 30, 60 mg/kg) for 21 consecutive days and on day 22, adrenaline was injected as a single dose for 2 consecutive days. Then ECG examination, biochemical, histopathological, immunohistochemical analyses were carried out. Thymol reversed adrenaline-induced reduction of heart rate, prolongation of RR interval and elevation of ST interval. Thymol pretreatment significantly reduced serum aspartate dehydrogenase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) levels in MI rats. Oral pretreatment with thymol increased reduced glutathione (GSH), reduced malondialdehyde (MDA), nuclear factor-kappa B (NF-κB), and interleukin-1ß (IL-1ß) cardiac contents in MI rats. Additionally, thymol administration significantly decreased protein expression of caspase-3, increased Bcl-2 protein expression in cardiac tissue and ameliorated histopathological changes. This study reveals that thymol exerted cardioprotective effect against adrenaline-induced MI in rats evidenced by improving cardiac function, attenuating ECG and histopathological changes which may be partly mediated through its anti-oxidant, anti-inflammatory and anti-apoptotic effect.

The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract.

Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of various organs. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENA in different organs namely, liver, stomach and colon and the potential protective effect of GE against these mechanisms. Methods: Adult male albino rats were assigned into four groups. A normal control group received the vehicle, another group was injected with a single necrogenic dose of DENA (200 mg/kg, i.p) on day 21. Two groups received oral GE (108 or 216 mg/kg) daily for 28 days. Sera, liver, stomach and colon were obtained 7 days after DENA injection. Serum aspartate transaminase and alanine transaminase were detected as well as reduced glutathione (GSH), malondialdehyde, nitric oxide metabolites, interleukin 1ß, tumor necrosis factor (TNF-α), alpha-fetoprotein (AFP) and nuclear factorerythroid 2-related factor2 (Nrf2) in liver, stomach and colon. Histopathological studies and immunohistochemical examination of cyclooxygenase-2 (COX2) were conducted. Results: DENA induced elevation in liver function enzymes with significant increase in oxidation and inflammation biomarkers and AFP while decreased levels of Nrf2 in liver, stomach and colon were detected. Histologically, DENA showed degenerative changes in hepatocytes and inflammatory foci. Inflammatory foci displayed increased expression of COX2 in immunohistochemical staining. GE-pretreatment improved liver function and restored normal GSH with significant mitigation of oxidative stress and inflammatory biomarkers compared to DENA-treated group. AFP was reduced by GE in both doses, while Nrf2 increased significantly. Histology and immunostaining of hepatic COX-2 were remarkably improved in GE-treated groups in a dose dependent manner. Conclusion: GE exerted a potential anti-proliferative activity against DENA in liver, stomach and colon via Nrf2 activation, whilst suppression of oxidation and inflammation.

Antiulcer activity of Cyperus alternifolius in relation to its UPLC-MS metabolite fingerprint: A mechanistic study.

BACKGROUND: Gastric ulcer is one of the main prevalent gastrointestinal multi-etiological disorders with many associated complications and adverse effects. Our aim was to develop safer antiulcer therapies based on methanol or ethyl acetate extracts of tubers and aerial parts from Cyperus alternifolius. METHODS: Gastric ulceration was experimentally generated by administration of single oral doses of indomethacin (30 mg/kg) to fasted rats. The animals received methanol or ethyl acetate extracts of C. alternifolius tuber and methanol or ethyl acetate extracts of aerial parts at two dose levels (50 or 100 mg/kg). Ranitidine (50 mg/kg) was used as standard anti-ulcer drug. After 4 h, the ulcer number and the total ulcer score were determined and TNF-α was assessed. Also, pathological and histochemical examination for gastric mucosa were performed. The metabolome heterogeneity of the different extracts was explored using (UPLC-MS) aided by supervised pattern recognition, i.e., orthogonal partial least squares discriminate analysis (OPLS-DA). A second OPLS-DA model was employed to link the UPLC-MS derived metabolome of the different extracts to their antiulcer activity to identify activity mediating metabolites. RESULTS: The extracts significantly reduced ulcer number, total ulcer score and TNF-α content in the stomach. Methanol or ethyl acetate extracts of tubers were most effective even more than ranitidine. In parallel, the histopathological examination showed an improvement of damaged mucosa. A high PAS reaction was observed in the treated groups indicating a relieve of the mucosal layer. A mechanistic clue of the C. alternifolius antiulcer potential was provided by the identification of its bioactive compounds using OPLS-DA. Both methanol extracts of tubers and aerial parts were more enriched in phenolic acids. The ethyl acetate extract of the aerial part was more abundant in two aldehydes. A mechanism of action was postulated based on their reported actions viz. α-carbonic anhydrase inhibition, anti-inflammatory and analgesic activity by its antioxidant activity and downregulation of several inflammatory mediators. CONCLUSION: This is the first study to report on the antiulcer activity of C. alternifolius tubers with identification of the key bioactive compounds and the mode of action. Future phytochemical and biological evaluation of the identified bioactive compounds are needed to confirm the plant tubers as safer alternative or adjunct therapy compared to conventional antiulcer drugs.

Protective effect of some natural products against chemotherapy-induced toxicity in rats.

AIM: There is a great interest in combining anticancer drugs with natural products aiming at maximizing their efficacy while minimizing systemic toxicity. Hence, the present study was constructed aiming to investigate the protective potential of three natural products, 1,8-cineole an essential oil from Artemisia herba alba, exopolysaccharide (EPS) from locally identified marine streptomycete, and ellagic acid (EA), against chemotherapy-induced organ toxicity. METHODS: Isolation, production and characterization of EPS from marine streptomycete was done. Animals were allocated into five groups, GP1: normal control, GP2: cyclophosphamide (CYC), GP3: 1,8-cineole + CYC, GP4: EPS + CYC, GP4: EA + CYC. All drugs were administered orally 1 week before and concomitantly with CYC. Electrocardiography (ECG) analysis, liver enzymes (ALT and AST), cardiac serum markers (LDH and CK), oxidative stress biomarkers in hepatic and cardiac tissues (GSH and MDA), TGF-ß1 and histopathological examination of hepatic and cardiac tissues were executed. RESULTS: The isolated stain produced EPS was identified as Streptomyces xiamenensis. EPS contains uronic, sulphate groups and different monosugars with Mw 4.65 × 104 g/mol and showed antioxidant activity against DPPH. Pretreatment of rats with 1,8-cineole, EPS and EA improved ECG abnormalities, decrease serum markers of hepato- and cardiotoxicity, prevent oxidative stress and decrease TGF-ß1 in liver and heart tissues. CONCLUSION: The present results demonstrate the hepatoprotective and cardioprotective effects of the above-mentioned natural products against CYC organ toxicity.

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats.

BACKGROUND: The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury. AIM: In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury. METHODS: Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed. RESULTS: Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers. CONCLUSION: In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.

Soft coral Cespitularia stolonifera: New cytotoxic ceramides and gastroprotective activity.

In the present study, a new ceramide, namely 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diol (1), along with four known steroids, including 24-methylcholesta-5, 24(28)-diene-3ß-ol (2), 24-methylcholesta-5, 24(28)-diene-3ß-acetate (3), 4-methyl-24-methylcholesta-22-ene-3-ol (4), and cholesterol, was isolated and characterized from CH2Cl2/MeOH extract of Cespitularia stolonifera. A new acetate derivative of compound 1, termed 2S, 3R-4E, 8E-2-(heptadecanoylamino)-heptadeca-4, 8-diene-1, 3-diacetate (1a), was also prepared in the present study. All the structures were established on the basis of modern spectroscopic techniques, including FT-IR, 1D, 2D-NMR, HRESI-MS, and GC-MS, in addition of chemical methods. (-)-Alloaromadendren, ledane, (1)-alloaromadendren oxide, isoaromadendrene epoxide and (-)-caryophellen oxide were identified from the n-hexane fraction using GC-MS. The extract and the two ceramides (1) and (1a) exhibited significant cytotoxic activity against lung cancer A549 cells, while the extract and the two steroids (2) and (3) exhibited significant cytotoxic activity against breast cancer MCF-7 cells. The CH2Cl2/MeOH extract exhibited significant antiulcer activity in both ethanol and acetic acid induced ulcer models in rats, as evidenced by histopathological, histochemical, and biochemical examinations.

Anti-depressant effect of hesperidin in diabetic rats.

This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.

Inhibition of the renin-angiotensin system attenuates the development of liver fibrosis and oxidative stress in rats.

1. The present study was designed to investigate the potential antifibrotic and anti-oxidant effects of lisinopril, fosinopril and losartan in an experimental rat model of liver injury using carbon tetrachloride (CCl(4)). 2. First, the potential hepatoprotective dose of each drug was screened against CCl(4)-induced acute hepatotoxicity. Then, we chose the minimum hepatoprotective dose of each drug to further investigate the mechanisms involved in the hepatoprotection using a chronic model of hepatotoxicity induced by CCl(4). 3. Liver function was assessed in addition to histopathological examination. Furthermore, oxidative stress markers (reduced glutathione (GSH) and lipid peroxides levels) and markers of fibrosis (hydroxyproline content and liver fibrosis area) were assessed. 4. It was found that treatment of animals with different drugs concomitantly with CCl(4) significantly counteracted the changes in liver function induced by CCl(4) (except fosinopril). In addition, the drugs ameliorated the histopathological changes induced by CCl(4). All drugs significantly counteracted lipid peroxidation and GSH depletion (except fosinopril) compared with the CCl(4)-intoxicated group. Moreover, the drugs studied significantly reduced liver hydroxyproline levels and the area of fibrosis compared with the CCl(4)-intoxicated group. 5. In conclusion, the present study provides evidence for the hepatoprotective effect of lisinopril, fosinopril and losartan. Both lisinopril and losartan was found to have better hepatoprotective potential than fosinopril against CCl(4)-induced hepatotoxicity. These hepatoprotective effects can be explained on the basis of anti-oxidant and antifibrotic mechanisms, mainly enhancement of GSH and reduction of lipid peroxidation and fibrosis.