cyclophosphamide (cp) is a chemotherapeutic agent that induces oxidative stress causing multiple organ damage. Sacubitril/valsartan, is a combined formulation of neprilysin inhibitor (sacubitril) and angiotensin II receptor blocker (valsartan), that induces the protective effect of brain natriuretic peptide. the aim of the current study is to investigate the prophylactic impacts of sacubitril/valsartan versus valsartan against CP-induced lung toxicity in rats. Rats were assigned randomly into 6 groups; control; received corn oil (2 ml/kg/day; p.o. for 6 days), sacubitril/valsartan (30 mg/kg; p.o. for 6 days), valsartan (15 mg/kg; p.o. for 6 days), CP (200 mg/kg; i.p. on day 5), sacubitril/valsartan + CP (30 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively), valsartan + CP (15 mg/ kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively). Both sacubitril/valsartan and valsartan produced a significant decrease in the inflammation and fibrosis markers in the BALF, in comparison with the CP group. Both sacubitril/valsartan and valsartan produced an apparent decrease in the relative genes expression of miR-150-3p and NF-κB, as well as a significant decrease in the relative expression of P38 and ERK1/2 MAPKs and an increase in the relative gene expression of Nrf-2, compared to CP group. Intriguingly, sacubitril/valsartan , showed subtle superiority in almost all investigated parameters, compared to valsartan. In conclusion, sacubitril/valsartan effectively abrogated the CP induced lung inflammation and fibrosis, providing a potential promising protection that could be linked to their ability to inhibit miR-150-3p via inhibition of NF-κB and MAPK signaling pathways. Cyclophosphamide (CP) is a chemotherapy that is broadly prescribed for the treatment of different types of cancer such as lymphomas, leukemia and multiple myeloma 1. CP may be also used in treatment of several autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus 2. CP causes serious adverse effects that can result in multiple organs damage. Among these adverse effects are cardiotoxicity, hepatotoxicity, nephrotoxicity and lung toxicity 3,4. CP is primarily metabolized to the active metabolite 4-hydroxycyclophosphamide which is equilibrates with its tautomer; aldophosphamide. The freely diffusible proportion of aldophosphamide into cells is minor, which it is subject to decomposition into two phosphoramide

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Alcoholic liver disease (ALD) refers to hepatic ailments induced by excessive alcohol intake. The pathogenesis of ALD comprises a complex interplay between various mechanistic pathways, among which inflammation and oxidative stress are key players. Boswellic acids (BAs), found in Boswellia serrata, have shown hepatoprotective effects owing to their antioxidant and anti-inflammatory activities, nevertheless, their therapeutic potential against ALD has not been previously investigated. Hence, this study was performed to depict the possible protective effect of BAs and detect their underlying mechanism of action in an experimentally-induced ALD mouse model. Male BALB/c mice were equally categorized into six groups: control, BAs-treated, ALD, and ALD that received BAs at three-dose levels (125, 250, and 500 mg/kg) by oral gavage for 14 days. Results showed that the high dose of BAs had the most protective impact against ALD according to histopathology examination, blood alcohol concentration (BAC), and liver function enzymes. Mechanistic investigations revealed that BAs (500 mg/kg) caused a significant decrease in cytochrome P450 2E1(CYP2E1), nicotine adenine dinucleotide phosphate oxidase (NOX) 1/2/4, p38 mitogen-activated protein kinase (MAPK), and sterol regulatory element-binding protein-1c (SREBP-1c) levels, and the expression of miR-155, yet increased peroxisome proliferator-activated receptor alpha (PPARα) levels. This led to an improvement in lipid profile and reduced hepatic inflammation, oxidative stress, and apoptosis indices. In summary, our study concludes that BAs can protect against ethanol-induced hepatic injury, via modulating NOX/p38 MAPK/PPARα pathways and miR-155 expression.

Tumor necrosis factor receptor (TNFR) activation and nuclear factor kappa B (NFκB) expression play a significant role in the activation of nod-like receptor pyrin domain-1 containing 3 (NLRP3) inflammasome inflammatory pathway, which is involved in the pathogenesis of ulcerative colitis (UC). Furthermore, miRNA-223 expression was shown to exert counter-regulatory effect on NLRP3 expression. Interestingly, polyphenols are attaining increased importance for their potential effectiveness in ameliorating certain diseases owing to their antioxidant and anti-inflammatory activity. In accord, our study attempted to investigate the effect of mulberry tree (Morus macroura) fruit extract (MFE) against acetic acid (AA)- induced UC in rats, which is not previously investigated, based on previous promising results for MFE in alleviating gastric ulcer in rats. First, total phenolic (TPC), total flavonoid (TFC), and total anthocyanin content (TAC) were determined in MFE. Then, MFE (300 mg/kg) and sulfasalazine (Sulfa), as a standard treatment (100 mg/kg), were given orally for seven days before intra-rectal induction of UC by AA (2 ml, 4% v/v) on day eight. The extent of UC was evaluated macroscopically and microscopically. Biochemically, the colonic TNFR1, NLRP3, p- NFκB p65, TNFα, interleukin-1 beta (IL-1β), IL-18 levels, miRNA-223 expression and caspase-1 activity were assayed. MFE significantly reduced macroscopic and microscopic scores, colonic levels of TNFR1, NLRP3, p-NFκB p65, TNFα, IL-1β, IL-18, and caspase-1 activity, and showed increased miRNA-223 expression, almost similarly to Sulfa effects. In conclusion, our study provided a novel impact for MFE against AA-induced UC in rats through affecting miRNA-223 expression and halting TNFα/NFκB/NLRP3 inflammatory pathway.

Background: As a result of the increased consumption of sugar-rich and fatty-products, and the increase in the preference for such products, metabolic disorders are becoming more common at a younger age. Hyperlipidemia, insulin resistance [IR] and inflammatory status induced by high fat high fructose diet [HFHFD] increase the risk of developing cardiovascular diseases [CVDs] which are the leading cause of death worldwide. Objective: This study is aiming to determine the effects of HFHFD on cardiovascular disease [CVD]-related parameters. Also, the possible protective and curative effects of cinnamon extract on cardiac diseases. Methodology: Fifty adult male Sprague Dawley rats were divided into five groups: Group I: [control]. Group II rats were fed a diet with 45 kcal% fat and drink fructose 60% [HFHFD] for 8w. Group III: fed on HFHFD and pioglitazone [PGZ 20 mg/kg/b.wt]. Group IV: fed on HFHFD and cinnamon extract200mg/kg.b.w. Group V: fed on HFHFD and treated with combination of PGZ drug and cinnamon extract. At the end of the experiment, blood glucose, serum insulin, lipid profile, and oxidative stress markers were done. Heart tissues were used for Inflammatory cytokines [tumor necrosis factor-α [TNF-α] and interleukin 6 [IL-6], nuclear factor kappa [NF-κB], and cardiac enzymes beside histopathological examination. Results: HFHFD administration resulted signs of cardiomyopathy revealed by significant increase in blood glucose, serum insulin, homeostasis model assessment of IR [HOMA-IR] index with disturbed lipid profile. Also, significant increase in serum cardiac enzymes, inflammatory cytokines and oxidative stress markers were also noticed. PGZ and cinnamon extract treatment resulted in a significant decrease in glucose, insulin, and HOMA-IR index, amelioration of lipid profile, cardiac enzymes, inflammatory cytokines and oxidative stress markers. Conclusion: The current study revealed that cinnamon extract improves cardiomyopathy resulted from HFHFD administration possibly via hypolipidemic, anti-inflammatory and anti-oxidative ways. It can be used as food supplement has cardioprotective role in patients with metabolic disorders

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