Empagliflozin Exhibits Hepatoprotective Effects Against Bile Duct Ligation-induced Liver Injury in Rats: A Combined Molecular Docking Approach to In Vivo Studies.

BACKGROUND: Cholestatic liver damage is a chronic disease caused by dysfunction of the hepaticbiliary system. Oxidative stress and inflammation are essential factors in the pathogenesis of cholestasis. Thus, the current study was designed to examine the effect of empagliflozin on bile duct ligation-induced liver damage in rats. METHODS: This study was done on male Wistar rats, which were randomly assigned to the four experimental groups: sham control (SC), bile duct ligation (BDL), SC plus empagliflozin (SC+EMPA) (receiving 10 mg of EMPA orally for 7 days), BDL plus empagliflozin 10 mg/kg (BDL+ EMPA). At the end of the study, the rats were sacrificed, and serum and tissue samples were collected to analyze biochemical parameters, biomarkers of oxidative stress, inflammatory markers, and histopathological changes. The molecular docking technique was performed to elucidate the interaction of EMPA and Cu/Zn-superoxide dismutase (SOD1). RESULTS: The results showed that BDL elevated the serum activity of ALT, AST, ALP, and levels of TBIL and TPro. BDL also intensifies the oxidative stress state in rats, which was confirmed by augmenting lipid peroxidation (MDA), protein oxidation (PCO), and altering antioxidant defense parameters through decreased SOD, catalase (CAT), and glutathione peroxidase (GPX) levels. Furthermore, the histopathological changes in the liver demonstrated the aggravation of inflammation and oxidative stress. In contrast, treatment with EMPA has shown anti-inflammatory and anti-oxidant effects by reducing TNF-α and IL-6 pro-inflammatory marker proteins, restoring the antioxidant status (increased SOD and GPX), reducing ALT, AST, ALP, TBIL levels, and protein oxidation, and improving the histopathological alterations through reducing bile duct proliferation, fibrosis, focal and portal inflammation. According to the attained findings, the SOD1 activity can be regulated by the EMPA. Our documentation presents direct evidence at the molecular level related to the ability of EMPA to exert its antioxidant performance through certain measures in a particular molecular route. CONCLUSION: The results showed EMPA to have hepatic protective effects in rats against cholestatic liver injury, an effect mediated by its antioxidant and anti-inflammatory properties.

The Hydroalcoholic Extract of Nasturtium officinale Reduces Lung Inflammation and Oxidative Stress in an Ovalbumin-Induced Rat Model of Asthma.

Background: Asthma is known as a disease that causes breathing problems in children and adults and is also associated with chronic inflammation and oxidative stress of the airways. Nasturtium officinale (NO) possesses a wide range of pharmacological properties, particularly anti-inflammation and antioxidant potentials. Thus, this study for the first time was aimed to investigate anti-inflammatory and antioxidative activities of NO extract (NOE) in an ovalbumin-induced rat model of asthma. Materials and Methods: Forty-four male Wistar rats were sensitized with ovalbumin (OVA) to induce asthma symptoms. The animals were allocated into five groups: control (C), asthmatic (A), A + NOE (500 mg/kg), NOE (500 mg/kg), and A + dexamethasone (DX, 2.5 mg/kg). After 7 days, blood and tissue samples were taken from the rats. Then, the level of inflammatory markers, oxidative stress parameters, and antioxidant enzymes activity were measured. Results: The obtained results showed that OVA-sensitive rats significantly increased the levels of pro-inflammatory cytokines IL-1B, TGF-ß, and SMA-α compared to the control group (p < 0.05), while treatment with NOE remarkably reduced the SMA-α gene expression compared to the asthma group (p < 0.05). Furthermore, it decreased the expression of IL-1B and TNF-α genes, although it was not statistically significant. The level of glutathione peroxidase (GPX) significantly reduced in A group compared to the C group (p < 0.05), whereas NOE administration significantly increased this marker (p < 0.05). Moreover, NOE attenuated inflammation and alveolar injury in the lungs of OVA-sensitive rat compared to the nontreated A group. Conclusions: Overall, our findings demonstrated that NOE somewhat is able to reduce airway inflammation by reducing inflammatory and increasing GPX activity. Indeed, further experiments investigating the impact of different extract doses are needed to confirm the antioxidant and anti-inflammatory effects of NOE.

Portulaca oleracea methanolic extract attenuate bile duct ligation-induced acute liver injury through hepatoprotective and anti-inflammatory effects.

INTRODUCTION: Cholestasis is a liver disease caused by a malfunction of the hepato-biliary system. Oxidative stress as a systemic complication is the main characteristic of cholestasis. The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of Portulaca oleracea (PO) methanolic extract on liver dysfunction and tissue damage induced by bile duct ligation (BDL) in rats. MATERIALS AND METHODS: Twenty-eight male Wistar rats were randomly divided into four groups: sham control (SC), BDL alone, SC plus 500 mg/kg methanolic extract of PO orally for 1 week, and BDL plus 500 mg/kg methanolic extract of PO orally for 1 week. After 1 week, the animals were anesthetized, and the liver and blood samples were taken from each animal. Biochemical parameters, oxidative stress biomarkers, histopathological changes, as well as the gene expression of IL-1, TNF-α, TGF-ß, and α-SMA have been evaluated. RESULTS: The methanolic extract of PO at a dose of 500 mg/kg significantly decreased the plasma levels of aminotransferases, alkaline phosphatase as compared to BDL group (P < 0.05), while it had no significant effect on the levels of oxidative stress markers in the hepatic tissue. The plasma level of malondialdehyde and ferric-reducing antioxidant power were markedly elevated in the BDL group in comparison to SC group (P < 0.05), while treatment with PO significantly reduced these markers (P < 0.05). The administration of PO attenuated hydroxyproline content, bile duct proliferation, and inflammation score in the cholestatic liver in contrast to non-treated BDL rats (P < 0.05). Moreover, the methanolic extract of PO markedly declined the expression of TNF-α and TGF-ß pro inflammatory genes in contrast to BDL rats. CONCLUSIONS: Taken together, our findings showed that PO attenuated liver injury by decreasing liver function tests, inflammation, and hydroxyproline content. As a result, it is suggested that PO can be applied in cholestatic liver damage as a therapeutic or adjuvant agent.

Antioxidant and Anti-Inflammatory Effects of Origanum majorana L. Methanolic Extract on Bile Duct Ligation in Male Rats.

INTRODUCTION: Cholestasis is caused by malfunction of the hepatobiliary system. This disorder is the result of the accumulation of bile fatty acids and other toxins in the liver. The aim of the current study was to investigate the antioxidative and hepatoprotective effects of methanolic extract of Origanum majorana L. (OM) on hepatic disorder and tissue damage induced by bile duct ligation (BDL) in rats. Materials and methods. Twenty-eight male Wistar rats were randomly divided into 4 groups including sham control group received vehicle (SC-V), bile duct ligation received vehicle (BDL-V), bile duct ligation group received OM extract (BDL + OM), and sham control group received OM extract (SC + OM). One day after surgery, the animals received vehicle or methanolic extract of OM 300 mg/kg/day for 7 consecutive days by oral gavage. Finally, the animals were anesthetized and the blood samples were collected from each animal. After sacrificing of animals, liver tissue from each rat was removed and divided into three parts: one part was used for preparing of homogenized tissue, one part was fixed in 10% neutral formalin for histopathology examination, and the third part was kept in liquid nitrogen for gene expression analysis. Biomarkers of oxidative stress in the liver tissue and serum, as well as histopathological changes of the liver, were assessed. Also, the gene expression of IL-1, TNF-α, TGF-ß, and α-SMA has been measured. RESULTS: The results showed that BDL-V significantly increased the activity of ALT, AST, ALP, and total bilirubin compared to the SC-V group. The oxidative stress markers such as MDA and FRAP significantly increased due to BDL, while the CAT activity reduced in the BDL-V group compared to SC-V group. Oral treatment with OM reduced ALT and AST activity, although it was not statistically significant. OM treatment considerably increased the activity of CAT compared to BDL group. BDL-V induced a significant histological change in the liver, while treatment with OM at a dose of 300 mg/kg showed a minor effect on histopathological changes. In addition, the mRNA of IL-1, TNF-α, TGF-ß, and α-SMA significantly increased in the BDL-V group, while treatment with OM only significantly reduced TGF-ß in comparison with BDL-V rats. CONCLUSIONS: The results of the present study showed that oral administration of OM extract had a moderate protective effect on cholestasis due to BDL. Indeed, more studies with different doses of extract are needed to confirm this finding.