The objective of the current study is to investigate the effect of rice bran oil (RBO) on hepatic fibrosis as a characteristic response to persistent liver injuries. Rats were randomly allocated into five groups: the negative control group, thioacetamide (TAA) group (thioacetamide 100 mg/kg thrice weekly for two successive weeks, ip), RBO 0.2 and 0.4 groups (RBO 0.2mL and 0.4 mL/rat/day, po) and standard group (silymarin 100 mg/kg/day, po) for two weeks after TAA injection. Blood and liver tissue samples were collected for biochemical, molecular, and histological analyses. Liver functions, oxidative stress, inflammation, liver fibrosis markers were assessed. The obtained results showed that RBO reduced TAA-induced liver fibrosis and suppressed the extracellular matrix formation. Compared to the positive control group, RBO dramatically reduced total bilirubin, AST, and ALT blood levels. Furthermore, RBO reduced MDA and increased GSH contents in the liver. Simultaneously RBO downregulated the NF-κβ signaling pathway, which in turn inhibited the expression of some inflammatory mediators, including Cox-2, IL-1β, and TNF-α. RBO attenuated liver fibrosis by suppressing the biological effects of TGF-β1, α-SMA, collagen I, hydroxyproline, CTGF, and focal adhesion kinase (FAK). RBO reduced liver fibrosis by inhibiting hepatic stellate cell activation and modulating the interplay among the TGF-β1 and FAK signal transduction. The greater dosage of 0.4 mL/kg has a more substantial impact. Hence, this investigation presents RBO as a promising antifibrotic agent in the TAA model through inhibition of TGF-β1 /FAK/α-SMA.
The activation of the Nrf2/HO-1 signaling pathway regulates cellular antioxidant stress and exerts anti-inflammatory and cytoprotective effects against acute lung injury (ALI). The present study aimed to evaluate the therapeutic role of L-carnitine (LC) against potassium dichromate (PD) - induced acute lung injury in adult male albino rats via modulation of Nrf2/HO-1 signaling pathway. For this purpose, forty rats were randomly allocated into 5 groups (8 rats each). The normal group received intranasal (i.n.) saline, while the ALI group received intranasal instillation of PD as a single dose of 2 mg/kg. The 3d – 5th groups received PD then after 24 h administered L-carnitine (25, 50 and 100 mg/kg; orally) for 3 consecutive days. The therapeutic effect of L-carnitine was evaluated by assessment of serum levels of glutathione (GSH) and malondialdehyde (MDA) along with measurement of lung contents of transforming growth factor β1 (TGFβ1), protein kinase B (AKT), Nuclear factor erythroid-2 related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) and glutathione cysteine ligase modifier subunit (GCLM) expression. Post-treatment with L-carnitine effectively increased the levels of GSH and AKT, elevated Nrf2 and its target genes and decreased the levels of MDA and TGFβ1 in comparison with PD control rats. Additionally, L-carnitine effectively reduced the number of goblet cell, inhibited the mucus formation in bronchioles and interstitial inflammatory infiltrate as well as alleviated the destruction of alveolar walls, and the congestion of blood vessels in lung tissue induced by PD. Our findings showed that L-carnitine may be a promising therapeutic agent against PD-induced acute lung injury.
Alzheimer’s disease (AD) is characterized by an active inflammatory response induced by the brain’s deposition and accumulation of amyloid-beta (Aβ). Cannabinoid receptor type 2 (CB2R) is expressed in specific brain areas, modulating functions, and pathophysiologies in CNS. Herein, we aimed to evaluate whether activation of CB2R can improve the cognitive impairment in the experimental AD-like model and determine the involved intracellular signaling pathway. Injection of D-galactose (150 mg/kg, i.p.) was performed to urge AD-like features in bilaterally ovariectomized female rats (OVC/D-gal rats) for 8-weeks. Then, AM1241, a CB2R-agonist (3 and 6 mg/kg), was injected intraperitoneally starting from the 6th week. Treatment with AM1241, significantly down-regulated; Toll-like receptor4 (TLR4), Myd88 (TLR4-adaptor protein) genes expression, and the pro-inflammatory cytokines (NFκB p65, TNF-α, IL-6, and IL-12). In contrast, it enhanced BDNF (the brain-derived neurotrophic factor) and CREB (the cyclic AMP response element-binding protein) as well as the immune-modulatory cytokines (IL-4 and IL-10) levels. Moreover, AM1241 lessened the immune-expression of GFAP, CD68, caspase-3, and NFκB p65 markers and mended the histopathological damage observed in OVC/D-gal rats by decreasing the deposition of amyloid plaques and degenerative neuronal lesions, as well as improving their recognition and learning memory in both novel object recognition and Morris water maze tests. In conclusion, activating CB2R by the selective agonist AM1241 can overrun cognitive deficits in OVC/D-gal rats through modulation of TLR4/ NFκB p65 signaling, mediated by modulating CREB/BDNF pathway, thereby can be applied as a potential therapeutic strategy in AD treatment.
Sansevieria species show various bioactivities. Nevertheless, its therapeutic prospect in liver fibrosis even now is uninvestigated. The present study was conducted to analyze the metabolomic profile of Sansevieria trifasciata hort ex. Prain leaves and roots via HPLC-PAD-ESI/MS and evaluation of its hepatoprotective effect. The identified phytoconstituents were mainly steroidal saponins, phenolics and terpenoids. Sixty-one compounds were tentatively identified in StLE and fifty-nine compounds in StRE. Thioacetamide-induced liver fibrosis rat model was used to evaluate the hepatoprotective effect of Sansevieria trifasciata extracts via activation of the NRF2/ARE signaling pathway. Measurements of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) were significantly decreased in treated groups with StLE and StRE (at doses of 200 and 100 mg/kg/day) compared with the TAA group. Also, the levels of reduced glutathione (GSH) content and hepatic mRNA levels of Nrf2, HO-1, NQO-1 and Keap-1 were markedly elevated. The prominent hepatoprotective effect was shown in StRE treated groups. Histological findings further confirmed the protective role of the plant against TAA-induced liver fibrosis. In conclusion, the abovementioned results indicated that the hepatoprotective mechanism of StLE and StRE could be achieved by activating Nrf2-ARE signaling pathways to alleviate oxidative stress and inflammation.
Introduction: Apricot (Prunus armeniaca L.) has been widely used for the treatment of several disorders such as liver diseases, but the hepatoprotective and anticancer activities of its seeds were not studied before. In this study, we evaluated the pharmacological effects of apricot seeds extracts and amygdalin on prevention of liver damage and treatment of hepatocellular carcinoma. Methods: Amygdalin contents of apricot seeds in ethanolic extracts were determined using high performance liquid chromatography (HPLC) then, the ethanolic apricot seeds extract and amygdalin were evaluated for its hepatoprotective activity against carbon tetrachlorideinduced hepatotoxicity and anticancer activity against N-nitrosodiethylamine (NDEA)- induced hepatocarcinogenesis. Results: The amount of amygdalin was 5.72 g and 10.22 g/100 g extract for 70% and 99.9% ethanolic apricot seeds extracts, respectively. Pretreatment of the rats with 70% and 99.9% ethanolic apricot seeds extracts (100 mg/kg), amygdalin and silymarin (50 mg/kg) prevented elevation in liver function parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) caused by carbon tetrachloride injection with significant increase in albumin, total proteins, and no effect on total direct bilirubin when compared to those in hepatotoxic group. Both extracts also showed anticancer activity against hepatocellular carcinoma via diminishing the elevated serum levels of AST, ALT, ALP, total, direct bilirubin, albumin, total proteins, alpha-fetoprotein, malondialdehyde (MDA) and nitric oxide (NO) and elevating the decreased hepatic reduced glutathione (GSH) level when compared with NDEA- intoxicated group. Conclusion: Apricot seeds possess hepatoprotective and anticancer activities that justify its traditional use, and its potential for the treatment of liver diseases including hepatocellular carcinoma
Introduction: Liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. The goal of this investigation was to look into the anti-fibrotic effect of apigenin (APG), an antioxidant found in various plants, versus thioacetamide (TAA)-triggered hepatic scarring in rats and the potential mechanisms behind it. Methods: TAA was administered thrice weekly (100 mg/kg, i.p.) for two weeks to produce hepatic scarring. APG was administered after TAA for 14 days (5 or 10 mg/kg, orally). Thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated. Results: TAA increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (FAK), hypoxia-inducible factor-1α (HIF-1α), and inflammatory cytokines, decreased interleukin-10 (IL-10), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and elevated serine-threonine protein kinase (AKT) expression. Furthermore, TAA increased hepatic contents of collagen I, connective tissue growth factor (CTGF), hydroxyproline, and alpha-smooth muscle actin. On the other hand, APG evaded these changes and mitigated the harmful effects of TAA in a dose-dependent way. Histopathological and immunohistochemical observations reinforced these biochemical outcomes. Conclusion: APG can potentially alleviate liver fibrosis mediated via FAK and HIF1 inhibiting signaling pathways.
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