Eman Al-Sayed

Hepatoprotective and Antioxidant Effect of Bauhinia hookeri Extract against Carbon Tetrachloride-Induced Hepatotoxicity in Mice and Characterization of Its Bioactive Compounds by HPLC-PDA-ESI-MS/MS

The hepatoprotective and antioxidant activity of Bauhinia hookeri ethanol extract (BHE) against CCl4-induced liver injury was investigated in mice. BHE was administered (500 and 1000 mg/kg/day) along with CCl4 for 6 weeks. The hepatic marker enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. The antioxidant parameters: glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. BHE treatment significantly inhibited the CCl4-induced increase in ALT (44 and 64%), AST (36 and 46%), ALP (28 and 42%), and MDA (39 and 51%) levels at the tested doses, respectively. Moreover, BHE treatment markedly increased the activity of antioxidant parameters GSH, GPx, GR, GST, and SOD. Histological observations confirmed the strong hepatoprotective activity. These results suggest that a dietary supplement of BHE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes of the liver. The hepatoprotective activity of BHE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of BHE were identified by HPLC-PDA-ESI/MS/MS.

Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: impact on oxidative stress, inflammation and calcitonin-gene related peptide.

The gastroprotective activity of an ellagitannin-rich fraction obtained from Eucalyptus citriodora (ECF) was investigated against ethanol-induced gastric ulceration in rats. The rats were pretreated with ECF (25, 50 and 100mg/kg) 1h before the administration of absolute ethanol to induce acute gastric ulceration. The gastric lesions were significantly reduced by all doses of ECF. Notably, pre-treatment with ECF (100mg/kg) conferred 99.6% gastroprotection, which is significantly higher than that produced by omeprazole. Moreover, ECF administration markedly increased the mucin content in a dose-dependent manner. The potent gastroprotective effect of ECF could be partly mediated by attenuating ethanol-induced oxidative stress. ECF-pre-treatment markedly increased the depleted GSH and SOD levels in a dose-dependent manner. Moreover, ECF significantly decreased the elevated MDA tissue levels induced by ethanol administration. The results demonstrated that ECF administration exerted a powerful anti-inflammatory activity as evidenced by the reduction in the pro-inflammatory markers; IL-1β, TNF-α, 5-LO and COX-2. Additionally, the caspase-3 tissue levels were significantly reduced in the groups pre-treated with ECF. These results suggest that ECF could exert a beneficial gastroprotective effect through their antioxidant, anti-inflammatory and anti-apoptotic properties. Furthermore, ECF pre-treatment significantly attenuated the ethanol-induced decrease in CGRP expression, which has a protective role against gastric ulceration. Histopathological examination revealed intact mucosal layer, absence of hemorrhage and necrosis in groups treated with ECF. Ellagitannins were identified as the major active constituents responsible for the marked antioxidant and gastroprotective properties of ECF. The HPLC-PDA-ESI/MS/MS technique was employed to identify the ellagitannins of E. citriodora.

Protective role of Cupressuflavone from Cupressus macrocarpa against carbon tetrachloride-induced hepato- and nephrotoxicity in mice.

The hepatoprotective and nephroprotective activity of cupressuflavone isolated from Cupressus macrocarpa was investigated against CCl4-induced toxicity in mice. Cupressuflavone was administered (40, 80, and 160 mg/kg/day) for five days. CCl4 was administered (0.5 mL/kg intraperitoneally) at the end of the experiment. A substantial increase (p < 0.001) in the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, total bilirubin, cholesterol, creatinine, uric acid, urea, and malondialdehyde was observed in the CCl4-treated group compared to the normal control group. In contrast, a significant reduction (p < 0.001) in glutathione and superoxide dismutase contents as well as the total protein level was evident in the CCl4-intoxicated mice. Cupressuflavone pretreatment markedly inhibited the CCl4-induced increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, cholesterol, creatinine, uric acid, urea, and malondialdehyde levels in a dose-dependent manner (p < 0.001 at all the tested doses). In addition, a significant (p < 0.001) and dose-dependent decrease in the total bilirubin levels was evident by cupressuflavone pretreatment (80 and 160 mg/kg/day) when compared to the CCl4-intoxicated group. Furthermore, cupressuflavone administration significantly increased the activity of antioxidant parameters glutathione and superoxide dismutase as well as the serum protein levels (p < 0.001 at all the tested doses) in a dose-dependent manner. Histological observations confirmed the strong hepato- and nephroprotective activity. These findings suggest that cupressuflavone could exert a beneficial effect against oxidative stress by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes induced by CCl4 in the liver and kidney tissues. The structure of cupressuflavone was identified by NMR, UV, and HRESI-MS/MS spectral data.

Protective effect of Terminalia muelleri against carbon tetrachloride-induced hepato and nephro-toxicity in mice and characterization of its bioactive constituents

Abstract Context: Terminalia is used in folk medicine for the treatment of various diseases. Objective: The objective of this study is to investigate the hepatonephro protective activity of a polyphenol-rich fraction (TMEF) obtained from Terminalia muelleri Benth. (Combretaceae) against CCl4-induced toxicity in mice. Materials and methods: TMEF was administered (100, 200, and 400 mg/kg/d) for 5 d. CCl4 was administered at the end of the experiment. Hepatic and renal biomarkers were measured in the serum. Glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were estimated in the liver and kidney tissues. The active constituents of TMEF were identified by HPLC–PDA–ESI/MS/MS. Results: TMEF is rich in ellagitannins, galloyl esters, phenolic acids, and flavone-C-glucosides. TMEF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT (17, 43, and 53%), AST (20, 46, and 58%), ALP (20, 48, and 56%), LDH (21, 47, and 58%), hepatic MDA (23, 49, and 54%), renal MDA (22, 35, and 52%), creatinine (48, 66, and 91%), uric acid (16, 34, and 59%), urea (22, 39, and 59%), and cholesterol (20, 27, and 46%). Furthermore, TMEF administration significantly (p < 0.001) increased hepatic GSH (15, 51, and 79%), renal GSH (23, 45, and 73%), hepatic SOD (9, 52, and 95%), renal SOD (39, 66, and 85%) and protein levels (17, 24, and 29%) at the tested doses of TMEF, respectively. Pretreatment with TMEF preserved the hepatic architecture and protected from ballooning degeneration, liver necrosis, renal inflammation, and degeneration of the kidney tubules. Conclusion: TMEF has a marked hepato-nephro protective effect.

Protective role of polyphenols from Bauhinia hookeri against carbon tetrachloride-induced hepato- and nephrotoxicity in mice

Abstract The hepatoprotective and nephroprotective activity of a polyphenol-rich fraction (BHPF) obtained from Bauhinia hookeri was investigated against CCl4-induced acute hepatorenal toxicity in mice. BHPF was administered (100, 200 and 400 mg/kg/day) for 5 days, then CCl4 was administered. BHPF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT, AST, ALP, LDH, total bilirubin, cholesterol, creatinine, uric acid, urea and malondialdehyde in a dose-dependent manner. In contrast, BHPF pretreatment markedly increased the contents of glutathione and superoxide dismutase in the liver and kidney tissues, indicating the strong in vivo antioxidant activity of BHPF. Pretreatment with BHPF preserved the hepatic architecture and conferred marked protection against necrosis and ballooning degeneration. Pretreatment with BHPF reduced the inflammatory cell aggregation and degenerative changes in the lining epithelium of the kidney tubules. It can be concluded that BHPF has a remarkable hepato- and nephroprotective activity by enhancing the antioxidant defense status, reducing lipid peroxidation and protecting against the histopathological changes induced by CCl4 in the liver and kidney tissues.

Hepatoprotective and antioxidant activity of Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in mice

Abstract Context: Liver disease is a serious problem. Polyphenolic compounds have marked antioxidant effect and can prevent the liver damage caused by free radicals. In vitro studies have revealed the strong antioxidant activity of an ellagitannin-rich plant, namely, Melaleuca styphelioides Sm. (Myrtaceae). Objective: In view of the limited therapeutic options available for the treatment of liver diseases, the hepatoprotective potential of the methanol extract of M. styphelioides leaves (MSE) was investigated against CCl4-induced liver injury in mice. Materials and methods: MSE was administered (500 and 1000 mg/kg/d p.o.) along with CCl4 for 6 weeks. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. Glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. The bioactive components of MSE were identified by NMR, UV and HRESI-MS/MS data. Results: MSE treatment (500 and 1000 mg/kg/d) markedly inhibited the CCl4-induced increase in the levels of AST (31 and 38%), ALT (29 and 32%), ALP (13 and 19%), and MDA (22 and 37%) at the tested doses, respectively. MSE treatment markedly increased the levels of GSH (29 and 57%) and antioxidant enzymes compared with the CCl4-treated group. MSE was more effective than silymarin in restoring the liver architecture and reducing the fatty changes, central vein congestion, Kupffer cell hyperplasia, inflammatory infiltration, and necrosis induced by CCl4. The LD50 of MSE was more than 5000 mg/kg. Conclusion: MSE confers potent antioxidant and hepatoprotective effects against CCl4-induced toxicity.

Molluscicidal and antischistosomal activities of methanol extracts and isolated compounds from Eucalyptus globulus and Melaleuca styphelioides

Abstract Context: Schistosomiasis is a parasitic disease that results in severe organ damage. Snail control is the best measure to control schistosomiasis. Plant-derived molluscicides have gained increasing attention for the control of schistosomiasis because they have low toxicity towards non-target organisms. Tannins are particularly suitable for snail control because they are less toxic than saponins to non-target organisms. Objective: To identify the most toxic components of two plants belonging to the family Myrtaceae, namely Eucalyptus globulus Labill. and Melaleuca styphelioides Sm against the different developmental stages of Schistosoma mansoni and its snail host. Materials and methods: The 80% MeOH leaf extracts of the tested plants and their isolated compounds were screened for their molluscicidal activity (expressed as LC50 and LC90 after 24 h exposure) against the snail Biomphalaria alexandrina. The anti-schistosomal activity of the tested samples was determined at 20 ppm (after 1 or 2 h exposure) against the different developmental stages of S. mansoni, including the miracidia, cercariae and worms. Biochemical parameters were measured to determine the toxicity mechanisms of the treated snails. The structures of the isolated compounds were elucidated based on NMR, UV and HRESI-MS/MS data. Results: Potent molluscicidal activity was observed for the ellagitannin dimer eucalbanin B (12), with an LC50 value of 55 ppm. Treatment of the snails with the LC25 of eucalbanin B (30.8 ppm) resulted in a significant decrease in the protein level by 22.7% and 25.8% in the snail tissues and hemolymph, respectively. The decreased protein content was attributed to destruction of the snail tissue and impairment in protein synthesis under stress conditions of intoxication with eucalbanin B. Alterations in the activities of the transaminases and phosphatases in the treated snails indicated destruction and intoxication of the snail tissues. A significant increase in the levels of the transaminases alanine aminotransferase (ALT) (57.8%) and aspartate aminotransferase (AST) (113.2%) in the snail hemolymph and a significant decrease in their tissue levels to 7.4 and 48.6%, respectively, were attributed to their release from the damaged tissue into the hemolymph. Alkaline phosphatase (ALP) was significantly increased by 38.5 and 181.4% in the hemolymph and tissues, respectively. Acid phosphatase (ACP) was also significantly increased by 48.4 and 21.2% in the hemolymph and tissues, respectively. The 80% MeOH extract of E. globulus together with mallophenol B (3), 2,2,8-trimethyl-6-formyl-chrom-3-ene-7-O-β-d-glucopyranoside (5) and benzyl alcohol 7-O-(3′,4′,6′-tri-O-galloyl)-β-d-glucopyranoside (10) exhibited miracidicidal activity with almost 100% toxicity at 20 ppm for the three compounds and 80% toxicity for the extract. Moreover, E. globulus extract showed cercaricidal and schistosomicidal activity with 100 and 40% mortality, respectively. Conclusion: E. globulus is a potential source for biocidal compounds against S. mansoni and its snail host. This is the first study to test the biocidal activity of the isolated compounds.

Hepatoprotective and antioxidant effect of ellagitannins and galloyl esters isolated from Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in HepG2 cells.

Abstract Context In a previous study, the total extract of Melaleuca styphelioides Sm. (Myrtaceae) showed a significant hepatoprotective effect in a CCl4-induced toxicity model in mice. However, the active components responsible for the activity of the extract were not identified. Objective To determine the in vitro hepatoprotective activity of the isolated pure compounds from M. styphelioides leaves using the CCl4-challenged HepG2 cell model. Materials and methods The hepatoprotective activity of the compounds (at concentrations of 100, 50 and 25 μm), the total extract and silymarin (Sil) (100, 50 and 25 μg/ml) was determined by measuring the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after pretreatment with the tested samples for one hour. Glutathione (GSH) and superoxide dismutase activity (SOD) were estimated to determine the mechanisms of the hepatoprotective activity. Results Some compounds showed marked hepatoprotection, including tellimagrandin I, which produced 42, 36 and 31% decrease in ALT and 47, 43 and 37% decrease in AST, at the tested concentrations, respectively, pedunculagin (32, 32 and 30% decrease for ALT and 48, 48 and 45% for AST), tellimagrandin II (38, 32 and 26% decrease for ALT and 45, 40 and 34% for AST) and pentagalloyl glucose (30, 28 and 26% decrease for ALT and 45, 38 and 36% for AST). Tellimagrandin I and II showed the highest increase in GSH (113, 105 and 81% and 110, 103 and 79%, respectively), which was comparable to Sil. Pedunculagin produced the highest increase in SOD (497, 350 and 258%). Conclusion This study highlights promising natural hepatoprotective candidates derived from M. styphelioides.

Analgesic and anti-inflammatory activities of epicatechin gallate from Bauhinia hookeri

Hit, Lead & Candidate Discovery

Cytotoxic Oleanane-Type Saponins from the Leaves of Albizia anthelmintica Brongn.

Two new oleanane‐type saponins: β‐d‐xylopyranosyl‐(1 → 4)‐6‐deoxy‐α‐l‐mannopyranosyl‐(1 → 2)‐1‐O‐{(3β)‐28‐oxo‐3‐[(2‐O‐β‐d‐xylopyranosyl‐β‐d‐glucopyranosyl)oxy]olean‐12‐en‐28‐yl}‐β‐d‐glucopyranose (1) and 1‐O‐[(3β)‐28‐oxo‐3‐{[β‐d‐xylopyranosyl‐(1 → 2)‐α‐l‐arabinopyranosyl‐(1 → 6)‐2‐acetamido‐2‐deoxy‐β‐d‐glucopyranosyl]oxy}olean‐12‐en‐28‐yl]β‐d‐glucopyranose (2), along with two known saponins: (3β)‐3‐[(β‐d‐Glucopyranosyl‐(1 → 2)‐β‐d‐glucopyranosyl)oxy]olean‐12‐en‐28‐oic acid (3) and (3β)‐3‐{[α‐l‐arabinopyranosyl‐(1 → 6)‐[β‐d‐glucopyranosyl‐(1 → 2)]‐β‐d‐glucopyranosyl]oxy}olean‐12‐en‐28‐oic acid (4) were isolated from the acetone‐insoluble fraction obtained from the 80% aqueous MeOH extract of Albizia anthelmintica Brongn. leaves. Their structures were identified using different NMR experiments including: 1H‐ and 13C‐NMR, HSQC, HMBC and 1H,1H‐COSY, together with HR‐ESI‐MS/MS, as well as by acid hydrolysis. The four isolated saponins and the fractions of the extract exhibited cytotoxic activity against HepG‐2 and HCT‐116 cell lines. Compound 2 showed the most potent cytotoxic activity among the other tested compounds against the HepG2 cell line with an IC50 value of 3.60μm. Whereas, compound 1 showed the most potent cytotoxic effect with an IC50 value of 4.75μm on HCT‐116 cells.