Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats

The current study was undertaken to evaluate the protective activity of olive and rosemary leaves extracts on experimental liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. Highly significant decline in the values of body weight gain and highly statistically increase of liver/body weight ratio were noted in rats treated with TAA. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase and total bilirubin were statistically increased. Additionally, light microscopic examination of liver sections from rats treated with TAA showed a marked increase in the extracellular matrix collagen content and bridging fibrosis was prominent. There were bundles of collagen surrounding the lobules that resulted in large fibrous septa and distorted tissue architecture. Interestingly, the findings of this experimental study indicated that the extracts of olive and rosemary leaves and their combination possess hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, these results suggest that the hepatoprotective effects of these extracts may be attributed to their antioxidant activities.     

Indigofera oblongifolia as a fight against hepatic injury caused by murine trypanosomiasis

Trypanosoma evansi is a hazardous pathogenic parasite infecting a broad variety of livestock and affects wildlife worldwide. Trypanosoma evansi has gained resistance to most drugs used; therefore, it requires alternative medicines. The objective of this research was to investigate the impact of Indigofera oblongifolia leaf extract (IE) on T. evansi-induced hepatic injury.Mice were once infected with 1000 T. evansi. The treated group was gavaged with 100 mg/Kg IE after infection. Histological and biochemical changes in mice hepatic tissue were studied. Also, the oxidative damage in the liver was evaluated through determining the level of glutathione (GSH), Malondialdehyde (MDA), nitric oxide (NO) and catalase (CAT) markers. IE was able to suppress the induced parasitemia due to infection. Also, IE improved the histological liver architecture. Furthermore, the liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activity were improved after IE mice were treated. IE protects against hepatic damage caused by trypanosomiasis in mice. Further studies are needed to isolate the active compounds in IE and to monitor these compunds’ ameliorative function.     

Hematological and biochemical investigations on the effect of curcumin and Thymoquinone in male mice exposed to Thioacetamide

Currently, living organisms are increasingly exposed to many toxic chemicals in the environment. These substances pose a threat to human life, other living organisms and ecosystem. In fact, there is an increasing requirement to search for safe therapeutic sources today. Medicinal plants and natural products have become of great importance globally because of their therapeutic potential and medicinal properties, as well as their availability and the absence of harmful side effects for most of them. The present study was designed to explore the potential protective effect of curcumin (CUR) and thymoquinone (TQ) in male rats exposed to thioacetamide (TAA). The experimental mice were divided into eight groups. Group 1 was served as control. Group 2 was exposed to 50 mg/ kg body weight of TAA. Group 3 was exposed to CUR and TAA. Mice of group 4 were treated with TQ and TAA. Mice of group 5 were exposed to CUR plus TQ and TAA. Group 6 was supplemented with CUR. Group 7 was subjected to TQ. Mice of group 8 were treated with CUR and TQ. Hematological and biochemical alterations were evaluated after one month. Significant increases of white blood corpuscles (WBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) values were observed in group 2, while the values of red blood corpuscles (RBC), hemoglobin (Hb(, hematocrit (Hct), glutathione (GSH) and superoxide dismutase (SOD) were statistically decreased. Treatment with CUR, TQ and their combination inhibited the hematological and biochemical alterations induced by TAA toxicity. Moreover, the most protective effect was observed in mice treated with CUR plus TQ. These new results suggested that the protective effect of CUR and TQ attributed to their antioxidant properties.     

Cymbopogon schoenanthus (Ethkher) ameliorates cadmium induced toxicity in swiss albino mice

Cadmium is among the toxic and hazardous metal widely dispersed in the environment in high levels. Current studies have provided new insights into antioxidant properties of bioflavonoid which have emerged as probable therapeutic and nutraceutical agents. The present study is geared to investigate the possible role of Cymbopogon schoenanthus (L.) Spreng. (or Ethkher) on heavy metal cadmium (Cd) induced oxidative stress in mice. Mice were randomly divided into four groups and treated for 15 days as follows: group 1: normal control-treated (saline); group 2: Ethkher leaves extract-treated (100 mg/kg); group 3: cadmium chloride (CdCl₂) treated; group 4: CdCl₂ plus Ethkher leaves extract. The results showed a significant reduction in hemoglobin, RBC and hematocrit in cadmium-treated mice as compared to control. Exposure to Cd caused a significant increase in the number of white blood cells (P < 0.05) indicating the occurrence of systemic inflammation. The results of this study also revealed that the mice intoxicated with Cd showed a significant increase in bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) activities. Cd intoxication leads to suppression in humoral immunity. However, pretreatment with Ethkher extract reversed almost all the abnormalities in the blood parameters showing noteworthy protection against cadmium induced toxicity in mice. The outcome of the present study revealed that the Ethkher possessed significant immunomodulatory activity and had a preventive effect on the hematological alterations in Cd intoxicated mice.     

Physiological investigations on the effect of olive and rosemary leaves extracts in male rats exposed to thioacetamide

Physiologically, it is known that thioacetamide (TAA) toxicity is generally associated with hepatic fibrosis induction, complicated metabolic disorders and health problems. The capability of extracts of olive and rosemary leaves to attenuate the severe physiological disturbances induced by thioacetamide (TAA) intoxication in male rats has been evaluated. Healthy male Wistar rats were used in the present study and were divided randomly into eight groups. Rats of the first group were served as normal control. Rats of the second group were administrated with TAA. Rats of the third, fourth and fifth groups were exposed to TAA plus olive leaves extract, TAA plus rosemary leaves extract and TAA plus olive and rosemary leaves extracts respectively. The sixth, seventh and eighth groups were supplemented with olive leaves extract, rosemary leaves extract, and olive and rosemary leaves extracts respectively. After 12 weeks of experimental treatments, the levels of serum glucose, total protein, albumin and high density lipoprotein cholesterol were significantly decreased, while the levels of triglycerides, cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, creatine kinase and lactate dehydrogenase were statistically increased in rats exposed to TAA. Administration of the studied extracts inhibited the hematobiochemical parameters and improved the physiological disturbances induced by TAA intoxication. Additionally, most improvements were noted in rats administrated with rosemary leaves extract followed by olive and rosemary leaves extracts and olive leaves extract. These results suggested that the effect of these extracts might be due to their antioxidant activities against TAA toxicity.     

Protective effect of olive and juniper leaves extracts on nephrotoxicity induced by thioacetamide in male mice

This study, for the first time, evaluates the effect of olive and juniper leaves extracts and their combination on thioacetamide (TAA)-induced nephrotoxicity in male mice. The experimental mice were divided into eight groups. Group 1 was served as control. Group 2 was exposed to TAA. Group 3 was treated with TAA and olive leaves extract. Group 4 was subjected to TAA and juniper leaves extract. Group 5 was exposed to TAA and olive and juniper leaves extracts. Groups 6, 7 and 8 were treated with olive, juniper, and olive and juniper leaves extracts respectively. In mice treated with only TAA, significant increases of blood urea nitrogen and uric acid were observed after six weeks. Moreover, levels of serum creatinine, blood urea nitrogen and uric acid were statistically increased in mice administrated with only TAA for twelve weeks. Insignificant alterations in levels of these haematobiochemical parameters were noted in other treated groups after six and twelve weeks. Histopathological evaluations of renal sections from mice treated with only TAA for twelve weeks showed severe damage of the renal corpuscles. Furthermore, the renal sections from mice treated with TAA and olive leaves extract, TAA and juniper leaves extract, TAA and olive and juniper leaves extracts, olive leaves extract, juniper leaves extract, and olive and juniper leaves extracts showed normal structures. In addition, it is conceivable therefore, that these extracts exhibit protective influences against TAA-induced nephrotoxicity, probably mediated through the antioxidative pathway roles.     

Chemoprotective effect of omega-3 fatty acids on thioacetamide induced hepatic fibrosis in male rats

The current study was designed to investigate the possible protective effect of omega-3 fatty acids from fish oil on hepatic fibrosis induced by thioacetamide (TAA) in male rats. The experimental animals were divided into four groups. The first group was received saline solution and served as control. The second group was given 250 mg/kg body weight of TAA. The third group was treated with omega-3 fatty acids and TAA. The fourth group was given saline solution and supplemented with omega-3 fatty acids. Treatment of rats with TAA for three and six weeks resulted in a significant decrease in body weight gain, while the value of liver/body weight ratio was statistically increased. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and total bilirubin were significantly increased. After three weeks of exposure to only TAA, liver sections showed an abnormal morphology characterized by noticeable fibrosis with the extracellular matrix collagen contents and damage of liver cells’ structure. Liver sections from rats treated with only TAA for six weeks revealed an obvious increase in extracellular matrix collagen content and bridging fibrosis. Treating TAA-intoxicated rats with omega-3 fatty acids significantly attenuated the severe physiological and histopathological changes. Finally, the present investigation suggests that omega-3 fatty acids could act against hepatic fibrosis induced by TAA due to its antioxidant properties, thus supporting its use in hepatic fibrosis therapy.     

The induction of tyrosine aminotransferase activity and its use as an indirect assay for endotoxin in mice infected with Plasmodium vinckei petteri

Gauci R., Bennett D., Clark I. A. and Bryant C. 1982. The induction of tyrosine aminotransferase activity and its use as an indirect assay for endotoxin in mice infected with Plasmodium vinckei petteri. International Journal for Parasitology12: 279–284. It has been suggested that the malaria parasite contains an endotoxin-like substance which, by activating the reticuloendothelial system, causes much of the pathology of malaria when it is released into the host bloodstream during schizogony. In this study, an in vivo assay was developed, based on the determination of hepatic tyrosine aminotransferase activity in infected mice, to measure substances which act like endotoxin. Tyrosine aminotransferase is important in gluconeogenesis and is induced by endotoxin. Mice infected with Plasmodium vinckei petteri become sensitised to bacterial endotoxin as small amounts of endotoxin, without effect in uninfected mice, elevate tyrosine aminotransferase activity. The increase in sensitivity is gradual and progressive and is detectable by day 2 of the 9 day infection. Tyrosine aminotransferase activity is first lowered and then raised markedly during the course of the disease. A cell-free preparation of malaria parasites increased tyrosine aminotransferase activity when injected into mice sensitised with Coxiella antigen. These results are consistent with the hypothesis that parasitised red cells contain an endotoxin-like substance which directly or indirectly may be responsible for producing some of the symptoms of malaria in mice.     

Induced resistance against Alternaria brassicae blight of mustard through plant extracts

An experiment was conducted to study the effect of plant extracts on soluble sugar, soluble phenol and defence-related enzymes response against Alternaria blight in mustard crop. The efficacy of six selected plant extracts (5 and 10%) used as foliar sprays at 60 and 70 days after sowing and mustard leaves was used for investigation. The results indicate that soluble phenol and sugar content in mustard leaves significantly increases in response to spraying of Azadirachta indica seed kernel, Calotropis procera and A. indica leaf extracts. The soluble protein, viz. peroxidase, polyphenol oxidase and phenylalanine ammonia lyase content, was higher in mustard leaves sprayed with C. procera leaves extract, A. indica seed kernel and Allium sativum bulb extract.     

Effects of anthraquinone extract from Rheum officinale Bail on the physiological responses and HSP70 gene expression of Megalobrama amblycephala under Aeromonas hydrophila infection

We evaluated the effect of dietary supplementation with anthraquinone extract (from Rheum officinale Bail) on the resistance to Aeromonas hydrophila infection in Megalobrama amblycephala. The fish were randomly divided into two groups: a control group (fed a standard diet) and a treatment group (standard diet supplemented with 0.1% anthraquinone extract) and fed for 10 weeks. We then challenged the fish with A. hydrophila and recorded mortality and changes in serum cortisol, lysozyme, alkaline phosphatase (ALP), total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and the relative expression of heat shock protein 70 (HSP70) mRNA for a period of 5 d. Supplementation with 0.1% anthraquinone extract significantly increased serum lysozyme activity before infection, serum ALP activity at 24 h after infection, serum total protein concentration 12 h after infection, hepatic CAT activity 12 h after infection, hepatic SOD activity before infection, and the relative expression of hepatic HSP70 mRNA both before infection and 6 h after infection. In addition, the supplemented group had decreased levels of serum cortisol 6 h after infection, serum AST and ALT activities 12 h after infection, and hepatic MDA content 12 h after infection. Mortality was significantly lower in the treatment group (86.67%) than the control (100%). Our results suggest that ingestion of a basal diet supplemented with 0.1% anthraquinone extract from R. officinale Bail can enhance resistance against pathogenic infections in M. amblycephala.     

Diphenyl diselenide modulates nucleotidases,reducing inflammatory responses in the liver of <Emphasis Type="Italic">Toxoplasma gondii</Emphasis>-infected mice

The aim of this study was to verify the effect of diphenyl diselenide (PhSe)₂ on hepatic nucleotidases and on the concentration of purines in mice infected by Toxoplasma gondii. The animals were divided into four groups: Group A (uninfected), Group B (uninfected and treated with (PhSe)₂), Group C (infected), and Group D (infected and treated with (PhSe)₂). The inoculation (groups C and D) was performed with 50 cysts of T. gondii (ME-49 strain). Mice from groups B and D were treated with 5 μmol kg^?1 of (PhSe)₂. Liver tissue from infected mice showed less severe inflammation, elevated ATP/ADO ratio, elevated NTPDase, 5′nucleotidase, and ADA activities compared to the uninfected group (Group A; P < 0.05). However, infected and treated mice showed decreased ATP levels and elevated ADO levels, as well as higher NTPDase and 5′nucleotidase activities and decreased ADA activity in the hepatic tissue compared to the infected group (P < 0.05). Moreover, the (PhSe)₂ treatment of infected mice reduced the hepatic inflammation and showed an immunomodulatory effect on ectonucleotidases of hepatic lymphocytes, which it returned to basal levels. Therefore, chronic infection by T. gondii induces hepatic inflammation in mice, and it is possible that purine levels and nucleotidase activities in hepatic tissue are related to the pathogenesis of the infection in this tissue. The treatment with (PhSe)₂ was able to reverse the hepatic inflammation in mice chronically infected, possibly due to the modulation of purinergic enzymes that produce an anti-inflammatory profile through the purinergic system in the liver tissue.     

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma. Because the parasite’s eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg–induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.     

The Ras Antagonist,Farnesylthiosalicylic Acid (FTS), Decreases Fibrosis and Improves Muscle Strength in dy2J/dy2J Mouse Model of Muscular Dystrophy

The Ras superfamily of guanosine-triphosphate (GTP)-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS) is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy^2J/dy^2J mouse model of merosin deficient congenital muscular dystrophy. The dy^2J/dy^2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy^2J/dy^2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy^2J/dy^2J mouse model of congenital muscular dystrophy.     

Effects of Pentoxifylline on Liver and Thymus of Plasmodium berghei ANKA Infected Swiss Albino Mice

Infection of Swiss albino mice with Plasmodium berghei ANKA (PbA), a lethal strain, led to injury of the liver, thymic atrophy and high host mortality. Action of pentoxifylline (PTX), an inhibitor of TNF-α (tumor necrosis factor alpha), was investigated on hepatic necrosis, thymic atrophy, increased percentage of Sub G0/G1 hepatic and thymic populations, parasitemia and survivability of the infected mice host. Our data suggest the importance of PTX in mice survival and curing of liver cirrhosis, without affecting the parasitemic condition of the infected mice. Histomorphological changes were well evident from the appearance of hypertrophied hepatic cells with abundance of pigments. In the thymus no cortico-medullary demarcation was observed with presence of hypertrophied thymocytes. Hyperplasia of hepatic cells in the Sub-G0/G1 stage as revealed by flow cytometric analyses, was suppressed by PTX which is an indication of apoptotic effect of PTX in mice. Mice treated with PTX showed a significant decrease of necrotic areas in liver and thymus, suggesting that PTX treatment controls TNF-α effect, and thus PTX may be used as an adjuvant in the treatment of malaria.     

In vitro and in vivo evaluation of the wound healing properties and safety assessment of two seaweeds (Sargassum ilicifolium and Ulva lactuca)

Seaweeds have been regarded as a reservoir of biologically active molecules that are important in the pharmaceutical industry. The aim of the present study was to explore the wound healing properties and to assess the safety of the seaweed Sargassum ilicifolium and Ulva lactuca. Enhanced cell proliferation and cell migration activities were observed in L929 cells treated with S. ilicifolium extract compared to U. lactuca extract treated cells and the control group. In-vivo experiments were conducted using five groups (10 in each) of Albino mice (BALB/c). Mice in group I and group II were treated (Orally, 100 mg/kg BW/day) with aqueous extracts of S. ilicifolium and U. lactuca, respectively for 14 days. Treatment group III received a topical application of the aqueous extract of S. ilicifolium (25% w/w) and ointment base (75% w/w) (2 g/kg BW/day, for 14 days). Group IV (Control) received an equal amount of distilled water, orally and mice in group V kept without wounds. The extract from S. ilicifolium showed stronger wound healing properties than the one from Ulva lactuca. Histopathological findings also revealed that the healing process was significantly enhanced in the mice group treated orally with S. ilicifolium aqueous extract. These findings show that S. ilicifolium species possess promising wound healing properties in-vitro and in-vivo.     

Hepatic production of apolar aldehydes in rats with carbon tetrachloride-induced cirrhosis

The aim of this study was to identify apolar aldehydes in liver homogenates from rats with CCl₄-induced cirrhosis and, as a corollary, the antioxidant effect of zinc administration. The study was performed in five control rats and in ten cirrhotic rats which were further sub-divided into two groups to receive either a standard diet or one supplemented with zinc. The percentage of hepatic fibrosis, plasma malondialdehyde concentration and alanine aminotransferase activity were measured as well as the following aldehydes: hexanal, octanal, decanal, 2-hexenal, 2-octenal, 2-nonenal, 2,4-heptadienal and 2,4-decadienal. Of the 10 cirrhotic rats, 4 had elevated concentrations of the highly toxic 2,4-dialkenals which coincided with a higher percentage of fibrosis and plasma alanine aminotransferase activity. These aldehydes were not observed in the control group. Zinc administration was associated with a reduction of the hepatic malondialdehyde concentration and an amelioration on the degree of hepatic injury. In conclusion, this study demonstrates the presence of the highly toxic 2,4-dialkenals in hepatic tissue of rats whith CCl₄-induced cirrhosis. Results obtained would suggest that these particular aldehydes may be related to the severity of the hepatic injury.     

Dietary fish oil reduces systemic inflammation and ameliorates sepsis-induced liver injury by up-regulating the peroxisome proliferator-activated receptor gamma-mediated pathway in septic mice

This study investigated the effect of dietary fish oil on systemic inflammation and hepatic injury in mice with polymicrobial sepsis. Male ICR mice were assigned to a control group (C, n=30) and a fish oil group (FO, n=30). Mice in the C group were fed a semi-purified diet with 10% soybean oil, and those in the FO group were fed a fish oil diet (2.5% fish oil+7.5% soybean oil; w/w). Three weeks later, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed at 0, 6 and 24 h after CLP, respectively. Results showed that compared with C group, the FO group had lower plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nitrite at 6 and 24 h after CLP. Also, peritoneal lavage fluid concentrations of TNF-α and prostaglandin (PG) E2 were significantly lower at 24 h in the FO than in the C group. The FO group had lower myeloperoxidase activities at 6 h after CLP in various organs. Plasma aminotransferase and alanine aminotransferase activities revealed significantly decreased in the FO group. The DNA-binding activity of peroxisome proliferators-activated receptor gamma (PPARγ) and mRNA expression of I kappaB alpha (IκBα) were up-regulated while nuclear factor (NF)-κB p65 DNA-binding activity, inducible nitric oxide synthase protein expression and the concentration of nitrotyrosine were significantly decreased in the FO group in liver after CLP. These results indicate that dietary fish oil administration may attenuate systemic inflammation and up-regulate hepatic PPARγ DNA-binding activity, which may consequently have ameliorated liver injury in these septic mice.     

Protective effect of berberine chloride on Plasmodium chabaudi-induced hepatic tissue injury in mice

The present study aimed to investigate the protective role of berberine (BER) against Plasmodium chabaudi-induced infection in mice. Animals were divided into three groups. Group I served as a vehicle control. Group II and group III were infected with 1000 P. chabaudi infected erythrocytes. Group III was gavaged with 100 μl of 10 mg/kg berberine chloride for 10 days. All mice were sacrificed at day 10 post-infection. The percentage of parasitemia was significantly reduced more than 30%, after treatment of mice with BER. Infection caused marked hepatic injuries as indicated by histopathological alterations as evidenced by the presence of hepatic lobular inflammatory cellular infiltrations, dilated sinusoids, vacuolated hepatocytes, increased number of Kupffer cells and the malaria pigment, hemozoin. These changes in livers led to the increased histological score. Also, infection induced a significant increase in liver alanine aminotransferase and aspartate aminotransferase and a significant increase in the total leucocytic count. Moreover, mice became anemic as proved by the significant decrease in erythrocyte number and haemoglobin content. BER showed a significant protective potential by improving the above mentioned parameters. Based on these results, it is concluded that berberine could offer protection against hepatic tissue damage.     

Celecoxib Ameliorates Portal Hypertension of the Cirrhotic Rats through the Dual Inhibitory Effects on the Intrahepatic Fibrosis and Angiogenesis

Background

Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension.

Objective

To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it.

Methods

Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated.

Results

Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1α (HIF-1α), and c-fos were also down-regulated after celecoxib treatment.

Conclusions

Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its modulation on VEGF/VEGFR-2 through the down-regulation of integrated signal pathways involving PGE2- HIF-1α- VEGF and p-ERK- c-fos- VEGFR-2.     

In vitro alpha-amylase and alpha-glucosidase inhibitory activity and in vivo antidiabetic activity of Quercus coccifera (Oak tree) leaves extracts

Quercus species are group of plants known as oak which represent important genus of Fagaceae family. These species are widely distributed in Mediterranean countries. Many of those species used in traditional medicine to treat and prevent various human disorders such as diabetes. Exhausted extraction for Quercus coccifera leaves were carried out using n-hexane, chloroform, methanol, boiled water and microwaved water. Extracts were subjected to phytochemical screening, acute toxicity study, and in vitro and in vivo animal model to evaluate antidiabetic activity of the produced extracts. The highest in vitro activity against α-amylase and α-glucosidase activity was obtained from methanolic extract with an IC₅₀ of 0.17 and 0.38 µg/ml respectively and better than the positive control acarbose. While the rest of the extract was either with moderate or low activity. Similarly, in the in vivo study, methanolic extract with a concentration of 200 mg/kg/day was able to reduce the blood glucose level for the diabetic mice to 146.8 mg/dL with normal bodyweight and biochemical signs when compared to the normal mice group. While the rest of the extracts were either with moderate or low ability to maintain blood glucose level for diabetic mice with few signs of hepatic and renal toxicity and weight loss. All data were statistically significantly different with p-value of less than 0.001 at confidence interval of 95% with high variance homogeneity. In conclusion, methanolic plant leaves extract of Q. coccifera can possibly be used alone to control the elevation of blood glucose level with a renal and hepatic protective property.