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.

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC–MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), β-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1β and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κβ levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer’s yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Doxorubicin (DOX) is a standard anticancer agent exerting devastating effects as nephrotoxicity, hepatotoxicity and cardiotoxicity. The purpose of this study was to increase the clinical use of DOX through decreasing its detrimental effects via combination with ACE inhibitors to ameliorate the induced acute kidney injury (AKI). AKI was induced by a single injection of DOX (7.5 mg/kg; i.p.) as Group 1; control (vehicle), Group 2; DOX (7.5 mg/kg; i.p.) single dose, Group 3 and 4; Lisinopril (Lis, 20 mg/kg) and Enalapril (Enal, 40 mg/kg) orally administration for 15 consecutive days after DOX injection, respectively. Serum samples were used to measure creatinine and BUN, tissue samples were extracted to determine myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (TAC) and kidney injury molecule (KIM-1) using ELISA technique. Heme oxygenase (HO-1) RNA expression was quantified in tissue using real time polymerase chain reaction (PCR). Parts of the kidney tissue were kept in formalin for immunohistochemical demonstration of Cleaved Caspase-3 and NF-κβ immune staining and the other part was used for pathological examination. Oral treatment with Lis (20 mg/kg) and Enal (40 mg/kg) for 15 consecutive days reversed DOX effects as they reduced the serum creatinine and BUN, kidney levels of MPO and MDA, whereas the drugs increased tissue TAC. The administration of Lis and Enal with DOX also reduced KIM-1and HO-1 RNA expression. A significant decrease in cleaved caspase-3 and NF-κβ immunostainings in conjunction with pronounced amelioration in pathologies in the rat kidney were observed. We concluded that DOX adverse effects can be controlled by Lis and Enal.

Background and purpose: Growing evidence advocates that upregulation of toll-like receptor 4 (TLR4) has been suggested as a causative influence in the development and complications of diabetes mellitus. We aimed to study the antidiabetic activity of chrysin against streptozotocin (STZ)-induced diabetesviadown-regulation of TLR4/nuclear factor (NF-κβ)/heat shock protein 70 (HSP70) pathway as well as modulation of clusters of differentiation 4 (CD4+) in rats.Experimental approach: Fifty rats were divided into five groups (n = 10). Group I, normal rats received a single intraperitoneal injection of buffer citrate; group II, STZ-induced diabetic rats; groups III-V, diabetic rats received glimepiride (0.5 mg/kg; p.o.) or chrysin (40 and 80 mg/kg; p.o.) respectively, for 10 days. Serum samples were extracted to determine nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH), insulin, CD4+, TLR4, and NF-κβ. Pancreatic tissue samples were extracted to determine glucose transporter 2 (GLUT2). Part of the pancreas was kept in formalin for pathological studies.Findings/Results: An elevation in blood glucose, NO, and MDA serum levels and a reduction of pancreatic GLUT2 content, insulin, and GSH serum levels were observed in diabetic rats. STZ injection, also, showed an increase in serum TLR4, NF-κβ, and HSP70 levels and a reduction in serum CD4+ levels with pancreatic cells necrosis. These biochemical and histological changes were reversed in glimepiride and chrysin groups.Conclusion and implications: The present study proved that chrysin has a potent anti-diabetic effect through the elevation of insulin and GLUT2 levels, the reduction of oxidative stress, and the inflammatory pathways TLR4/NF-κβ/HSP70 with the regulation of CD4+.

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.