Quercetin Attenuates Non-Alcoholic Fatty Liver Disease in Association with the Inhibition of Hepatic IL-1β/iNOS and IL-1β/CD45 Axes of Inflammation and Fibrosis Accompanied by Reduced Endogenous Metabolites and Apoptosis Saif A. Alqahtani, Hanan H. Alshehri, Hend Ashour, Hend Abdallah, Laila Rashed, Rehab M. Badi, Muataz E. D. Mohammed, Bahjat Al-Ani, Norah M. Alzamil, Alia Albawardi, Basma E. Aboulhoda Metabolites, 2026 Background: Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), and tissue leukocyte infiltration (CD45 +ve) are connected with multiorgan injury and fibrosis. We investigated whether the induction of NAFLD can cause dysregulation in the hepatic IL-1β/iNOS and IL-1β/CD45 axes of inflammation and fibrosis, as well as in endogenous metabolites (lipids, glucose, and insulin) and apoptosis, in the presence and absence of the flavonoid quercetin. Methods: The model group of rats was fed with a high-fat and high-carbohydrate diet (HFCD) for 4 weeks. The protective group of rats was given both quercetin (50 mg/kg) and HFCD for 4 weeks. All rats were sacrificed on day 29. Results: NAFLD was induced in rats as demonstrated by dyslipidemia, hyperglycemia, insulin resistance, liver inflammation, and elevation of liver injury enzymes. NAFLD was also associated with the upregulation of hepatic IL-1β, iNOS, CD45, and apoptosis (p53). Biomarkers of fibrosis (TIMP-1 and α-SMA) were also elevated, and fibrosis was confirmed in the model group by increased collagen deposition and elevated stages of fibrosis score (Stage 1 to 2 of Brunt’s NASH classification). All these parameters were significantly (p < 0.01) modulated by quercetin treatment. Additionally, a significant (p < 0.001) correlation between IL-1β and hepatic injury parameters was observed. Conclusions: These findings suggest a potential association between NAFLD and the IL-1β/iNOS and IL-1β/CD45 axes of liver injury and fibrosis, as well as dyslipidemia, glycemia, and apoptosis, with quercetin exhibiting beneficial hepatic pleiotropic effects.
Suppression of non-alcoholic fatty liver disease by thymoquinone associated with inhibition of miRNA-155/ROS/p53/TIMP-1-mediated fibrosis and autophagy upregulation Mohammad Y. Alshahrani, Fahad S. Al Amri, Nervana M. Bayoumy, Muath Suliman, Basma E. Aboulhoda, Hend Abdallah, Walaa Ibrahim, Heba Elwi, Alia Albawardi, Bahjat Al-Ani, Hend Ashour, Norah M. Alzamil Turkish Journal of Biochemistry, 2026 Objective liver fibrosis is a hallmark of non-alcoholic fatty liver disease (NAFLD; complication, and dysregulation of microRNA-155 (miRNA-155) is connected with hepatic fibrosis. We sought to investigate the link between hepatic miRNA-155/oxidative stress (ROS)/apoptosis (p53)/profibrosis (TIMP-1) axis-mediated liver fibrosis in NAFLD-induced hepatic injury in association with the inhibition of the autophagosome marker, LC3 with and without the incorporation of the plant phytochemical compound thymoquinone (TQ). Methods NAFLD was induced by feeding rats with a high fat and carbohydrate diets (HFCD) until being culled at day 28 (model group). The protective group received both, thymoquinone 10 mg/kg, i.p and HFCD until day 28. Results We documented in the model group hepatic induction of injury and fibrosis associated with the increase of tissue and blood levels of miRNA-155, ROS, p53, TIMP-1, and dyslipidemia. Whereas, inhibition of LC3 and the antioxidant enzymes by HFCD was observed. All these parameters were protected (p<0.01) by TQ. In addition, we observed a significant (p<0.001) correlation between hepatic fibrosis and liver injury parameters. Conclusions NAFLD is associated with the modulation of hepatic miRNA-155/ROS/p53/TIMP-1 axis as well as LC3, liver fibrosis, and dyslipidemia while being protected by thymoquinone.
Ferrostatin-1 Partially Suppressed the Anti-Fibrotic Actions of Thymoquinone in a Rat Model of Cholestasis-Induced Liver Injury Hend Ashour, Hind Zafrah, Muataz Elsiddig Dafaalla Mohammed, Laila Ahmed Rashed, Abbas Mohamed Abbas, Samaa Samir Kamar, Asmaa Mohammed ShamsEldeen International Journal of Morphology, 2025 Cholestasis is a leading cause of hepatic fibrosis.The herbal plant thymoquinone (TQ) has a well-known hepatoprotective effect against liver fibrosis.In this study, we investigated the role of ferroptosis in TQ-mediated antifibrotic action in a rat model of extrahepatic cholestasis developed secondary to bile duct ligation (BDL).Four groups (n=10) of adult male Wistar albino rats were included in the study; 1) control, 2) BDL model, 3) treated group with 50 mg.kg-1.day-1TQ, and group 4) rats in this group were treated with TQ and the ferroptosis inhibitor, ferrostatin-1 (Fer-1) at a dose of 1 mg.kg-1.day-1.TQ treatment effectively attenuated the inflammation and fibrosis detected in the BDL group by modulating (P<0.01),NF-B, TNF-, interleukins; IL-6, 10, TGF-1, collagen type I, III.TQ improved liver function which was confirmed by histological H&E and Sirius red stain.TQ augmented (p<0.001) the heme oxygenase (HO-1) protein levels about 4 fold compared to the BDL group suggesting its role in hepatic protection.TQ stimulated the ferroptosis process and increased glutathione peroxidase (GPX4), Iron content, and the transferrin receptor (TfR-1).Fer-1 addition to TQ did not affect the anti-inflammatory actions of TQ.However, it significantly (p<0.001)attenuated its antifibrotic property.In conclusion, The antifibrotic effect of Thymoquinone was partially inhibited secondary to Fer-1.Thus, documenting the mediating role of ferroptosis in the TQ protection against hepatic fibrosis.
Extracellular vesicles in renal therapeutics: involvement of microRNAs Hend Ashour, Hind Zafrah, Mohamed H. Elsayed Folia Morphologica Poland, 2025 Recently, intensive scientific efforts have been directed to investigate the role of small non-coding RNA (miRs) in different renal diseases. Extracellular vesicles (EVs) are small secretory vesicles released from almost all mammalian cells. EVs-miRs cargo plays a significant role in regulating various aspects of the biological machinery of the recipient cells. EVs-miRs may play an essential role in promoting cellular regenerative functions. miRs contained within the EVs fractions are capable of preserving their function throughout their journey from the cell of origin to the host cells. Our review discusses the role of EVs-miRs in different renal diseases as a novel approach to managing particular renal injuries. We have tried to simplify the possible modulatory impact of miRs at ultrastructural cellular pathological signalling, demonstrating both hazardous and beneficial subtypes based on published research. Further investigations are still needed in this regard, as miRs may have dual effects, as EVs-miR-23a could attenuate renal fibrosis through the activation of Akt and the inhibition of FoxO1 signalling. We have found that EVs-miR-23a was upregulated by hypoxia-inducible factor (HIF-1a) in hypoxic TECs and activated macrophages to accelerate the renal inflammatory cytokine storm and promote interstitial fibrosis.
Current perspectives on regenerative potential of mesenchymal stem cells in alleviating cardiac injuries: Molecular pathways and therapeutic enhancement Asmaa M ShamsEldeen, Sara A Hosny, Khaled Maghib, Hend Ashour World Journal of Stem Cells, 2025 Mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue have promising potential in regenerative medicine. The regenerative capacity of MSCs depends on their successful migration and engraftment at the injured site. Several preclinical and clinical studies have reported that MSCs effectively treat cardiac dysfunction. However, significant obstacles to MSC homing include peripheral sequestration and low survival rates. MSC-secreted extracellular vesicles exhibit effects similar to those of MSCs, contributing to cellular proliferation, differentiation, and various paracrine functions. This review explores the molecular pathways and mechanisms by which MSCs and extracellular vesicles modulate cardiac injuries. Additionally, we discuss the challenges associated with MSC homing and various strategies to enhance the process.
Thymoquinone and quercetin protect against hepatic steatosis in association with SIRT1/AMPK stimulation and regulation of autophagy, perilipin-2, and cytosolic lipases Hend Ashour, Laila A. Rashed, Radwa T. M. Hassanein, Basma E. Aboulhoda, Hasnaa A. Ebrahim, Mohamed H. Elsayed, Miran A. Elkordy, Omaima M. Abdelwahed Archives of Physiology and Biochemistry, 2023 BACKGROUND We sought to investigate thymoquinone (TQ)/quercetin combination in preventing hepatic steatosis (HS). MATERIALS AND METHODS The included rat groups; (1) Control, (2) HS model, (3) HS treated with TQ 10 mg.kg-1.d-1, (4) HS treated with quercetin 50 mg.kg-1.d-1, and (5) HS treated with both compounds for 4 weeks. RESULTS TQ/quercetin co-treatment augmented the anti-steatosis potential of each ingredient. The results revealed more (p < 0.001) sirtuin (SIRT1)/AMP-activated protein kinase (p-AMPK) upregulation compared to each treatment in line with autophagy protein Atg7 enhancement, and suppressed pro-inflammatory and oxidation markers. They diminished the hepatic lipogenic enzymes and perilipin-2 and activated the cytosolic lipases adipose triglyceride lipase (ATGL). Histological and Biochemical analysis revealed diminished lipid deposition and improved liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) compared to the data of separate treatments. CONCLUSION TQ and quercitin effectively upregulated SIRT1/p-AMPK and regulated hepatic perilipin-2/ATGL, inflammation and oxidative stress, preserved liver structure and function. TQ/quercetin combination additively prevents HS.
Hibiscus attenuates renovascular hypertension–induced aortic remodeling dose dependently: the oxidative stress role and Ang II/cyclophilin A/ERK1/2 signaling Asmaa Mohammed ShamsEldeen, Ahmed Fawzy, Hend Ashour, Marwa Abdel-Rahman, Hend Elsayed Nasr, Lina Abdelhady Mohammed, Noha Samir Abdel Latif, Amr M. Mahrous, Shereen Abdelfattah Frontiers in Physiology, 2023 Introduction: The high levels of angiotensin II (Ang II) can modify the vascular tone, enhance vascular smooth muscle cells (VSMCs) proliferation and hypertrophy and increase the inflammatory cellular infiltration into the vessel wall. The old herbal nonpharmacological agent, Hibiscus (HS) sabdariffa L has multiple cardioprotective impacts; thus, we investigated the role of HS extract in amelioration of renovascular hypertension (RVH)-induced aortic remodeling.Materials and methods: Thirty-five rats (7/group) were randomly allocated into 5 groups; group: I: Control-sham group, and RVH groups; II, III, IV, and V. The rats in RVH groups were subjected to the modified Goldblatt two-kidneys, one clip (2K1C) for induction of hypertension. In group: II, the rats were left untreated whereas in group III, IV, and V: RVH-rats were treated for 6 weeks with low dose hibiscus (LDH), medium dose hibiscus (MDH), and high dose hibiscus (HDH) respectively.Results: We found that the augmented pro-contractile response of the aortic rings was ameliorated secondary to the in-vivo treatment with HS dose dependently. The cyclophilin A (CyPA) protein levels positively correlated with the vascular adhesion molecule-1 (VCAM-1) and ERK1/2, which, in turn, contribute to the reactive oxygen species (ROS) production. Daily HS intake modified aortic renovation by enhancing the antioxidant capacity, restraining hypertrophy and fibrosis, downregulation of the metastasis associated lung adenocarcinoma transcript (MALAT1), and cyclophilin A (CyPA)/ERK1/2 levels.Discussion: Adding to the multiple beneficial effects, HS aqueous extract was able to inhibit vascular smooth muscle cell proliferation induced by 2K1C model. Thus, adding more privilege for the utilization of the traditional herbal extracts to attenuate RVH-induced aortopathy.
Nicorandil mitigates amiodarone-induced pulmonary toxicity and fibrosis in association with the inhibition of lung TGF-β1/PI3K/Akt1-p/mTOR axis in rats Inas Harb, Hend Ashour, Laila A. Rashed, Abeer Mostafa, Mai Samir, Basma Emad Aboulhoda, Hala El‐hanbuli, Eman Rashwan, Heba Mahmoud Clinical and Experimental Pharmacology and Physiology, 2023 The long-term side effect of the antiarrhythmic drug, amiodarone (AMIO), such as lung toxicity, remains a critical clinical issue. The previous knowledge denotes diverse antioxidant, anti-inflammatory, and antifibrotic properties of the antianginal drug, nicorandil (NI). Therefore, we aimed to investigate the possible protective effect of NI on pulmonary tissue remodeling following AMIO-induced lung toxicity. The included rats were assigned into four equal groups (n = 8): 1) control, 2) control group that received NI 10 mg.kg-1 .day-1 , 3) model group that received AMIO in a dose of 60 mg.kg-1 .day-1 , and 4) treated group (AMIO-NI) that were treated with AMIO plus NI as shown above. Drug administration continued for 10 weeks. AMIO resulted in deteriorated (P < 0.001) pulmonary functions accompanied by respiratory acidosis. AMIO showed an obvious histological injury score with intense collagen deposition, disturbed nitric oxide synthase enzymes (NOS/iNOS), and increased alpha smooth muscle actin expression. Furthermore, AMIO upregulated the transforming growth factor (TGF-β1)/phosphoinositide-3 kinase (PI3K)-Akt1-p/mammalian target of rapamycin (mTOR) axis, which determined the possible mechanism of AMIO on pulmonary remodeling. NI treatment significantly (P < 0.001) prevented the AMIO-induced lung toxicity, as well as inhibited the TGF-β1/PI3K/Akt1-p/mTOR axis in the lung tissue of rats. The results were confirmed by an in-vitro study. CONCLUSION: The current results revealed that NI was effective in preserving the lung structure and functions. Amelioration of the oxidative stress and modulation of TGF-β1/PI3K/Akt1-p/mTOR have been achieved. This study suggests NI administration as a preventive therapy from the serious pulmonary fibrosis side effect of AMIO. This article is protected by copyright. All rights reserved.
The role of angiotensin-converting enzyme 2 (ACE2) genetic variations in COVID-19 infection: a literature review Manal S. Fawzy, Hend Ashour, Aya Allah Ashraf Shafie, Nesrine Ben Hadj Dahman, Abdelhamid M. Fares, Sarah Antar, Ahmed S. Elnoby, Fatma Mohamed Fouad Egyptian Journal of Medical Human Genetics, 2022 Background The angiotensin-converting enzyme-2 (ACE2) is recognized to be the fundamental receptor of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), responsible for the worldwide Coronavirus Disease-2019 (COVID-19) epidemic. However, genetic differences between people besides racial considerations and their relation to disease susceptibility are still not fully elucidated. Main body To uncover the role of ACE2 in COVID-19 infection, we reviewed the published studies that explore the association of COVID-19 with the functional characteristics of ACE2 and its genetic variations. Notably, emerging studies tried to determine whether the ACE2 variants and/or expression could be associated with SARS-CoV/SARS-CoV2 have conflicting results. Some researchers investigated the potential of “population-specific” ACE2 genetic variations to impact the SARS-CoV2 vulnerability and suggested no ethnicity enrichment for ACE2 polymorphisms that could influence SARS-CoV2 S-protein binding. At the same time, some studies use data mining to predict several ACE2 variants that could enhance or decline susceptibility to SARS-CoV. On the other hand, fewer studies revealed an association of ACE2 expression with COVID-19 outcome reporting higher expression levels of ACE2 in East Asians. Conclusions ACE2 gene variants and expression may modify the deleterious consequences of SARS-CoV2 to the host cells. It is worth noting that apart from the differences in gene expression and the genetic variations of ACE2, many other environmental and/or genetic factors could modify the disease outcome, including the genes for the innate and the adaptive immune response.
Modulation of miR-192/NF-κB/ TGF-β/ E-cadherin by thymoquinone protects against diethylnitrosamine /carbon tetrachloride hepatotoxicity Hend Ashour, Maha Eid Farghaly, Akef Abdelhalim Khowailed, Basma Emad Aboulhoda, Laila Ahmed Rashed, Mohamed Mahmoud Elsebaie, Safy Salah Gaber Physiology International, 2022 Scientific efforts have been made for a better understanding of the pathogenesis of hepatocellular carcinoma (HCC). We investigated the possible role of miR-192/nuclear factor-κB (NF-κB)/transforming growth factor-β (TGF-β)/E-cadherin in hepatic tumorigenesis. We expected a modulatory impact of thymoquinone. Thirty adult male rats were assigned into 3 groups (n = 10); (1) Control group. Group (2): Experimental HCC induced by intraperitoneal injection of diethylnitrosamine (DENA) followed by carbon tetrachloride (CCl4). Group (3): Thymoquinone 20 mg kg−1/oral supplementation starting from the model induction to the end of the 8th week. The HCC (DENA-CCL4) model was confirmed by elevated serum levels of alpha-fetoprotein and transaminases (ALT, AST) and by histopathological examination which denoted marked cellular atypia and features of neoplasia. Suppressed hepatic miR-192 and E-cadherin expression were detected in the HCC (DENA-CCL4) group accompanied by elevated tumor necrosis factor (TNF-α), interleukin (IL6)/NF-κB & TGF-β1. Thymoquinone treatment protected the rat livers from hepatic tumorigenesis. Thymoquinone diminished (P < 0.001) alpha-fetoprotein and improved ALT, AST. It preserved hepatic miR-192 and normal E-cadherin expression. Thymoquinone-treated rats showed abrogated TNF-α, IL6/NF-κB/TGF-β. Thymoquinone increased cell apoptosis markers Bax/Bcl2 and diminished cellular atypia. Pearson's correlations revealed positive association between miR-192 expression and E-cadherin and Bax/Bcl2 as well, and it was negatively correlated to alpha-fetoprotein, NF-κB and TGF-β and the cellular atypia score. In conclusion, thymoquinone protected the liver tissues through preserving miR-192 and E-cadherin and aborting NF-κB & TGF-β signaling. The current results highlight a new role for thymoquinone in preventing hepatic tumorigenesis.
