Head of the Laboratory "Sciences and Engineering of Biomedicals, Biophysics and Health" Higher Institute of Health Sciences, Hassan First University of Settat, Morocco
Artemisia herba alba Outperforms Indomethacin with Multitarget Efficacy and Safety in CFA Arthritic Model Hicham Wahnou, Martin Ndayambaje, Imane Nait Irahal, Zaynab Ouadghiri, Wafaa Taha, et al. Antioxidants, 2026 Rheumatoid arthritis remains a major clinical challenge requiring safer and more effective alternatives to conventional non-steroidal anti-inflammatory drugs (NSAIDs). This pioneering study evaluated the anti-inflammatory, analgesic, antioxidant, and safety effects of Artemisia herba alba extract in complete Freund’s adjuvant (CFA)-induced arthritis in rats. Animals received oral Artemisia herba alba (250 or 500 mg/kg), indomethacin (3 mg/kg), or saline for 15 days. CFA induced marked joint inflammation, mechanical allodynia, locomotor impairment, and oxidative stress. Treatment with Artemisia herba alba 500 mg/kg significantly reduced paw swelling, improved mobility in the open-field test, and markedly attenuated pain hypersensitivity. In parallel, biochemical analyses showed restoration of total antioxidant capacity, prevention of lipid peroxidation, and normalization of creatinine levels. Unlike indomethacin, which induced hepatotoxicity (elevated ASAT (Aspartate Aminotransferase)/ALAT (Alanine Aminotransferase)) and pronounced oxidative stress, Artemisia herba alba preserved liver and kidney function and did not produce histopathological alterations. Histological findings further indicated reduced inflammatory infiltrate and cartilage protection, particularly at 500 mg/kg. Taken together, these results suggest that Artemisia herba alba displays a multitarget effect with anti-inflammatory, antioxidant and analgesic activity, along with a superior safety profile compared with indomethacin, consistent with reports from other phenolic-rich natural products. However, findings should be interpreted in light of the small sample size and preclinical study design, and further mechanistic and clinical investigations are warranted.
SARS-CoV-2: A Liver Brief Youness Limami, Hicham Wahnou, Martin Ndayambaje, Soufyane Hba, Oumaima Chgari, et al. Wires Mechanisms of Disease, 2025 The Coronavirus Disease 2019 (COVID‐19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), has revealed the virus's ability to induce multi‐organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID‐19 patients are explored, focusing on direct viral infection, immune‐mediated damage, and the gut–liver axis. SARS‐CoV‐2 enters liver cells through the Angiotensin‐Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell‐Specific Intercellular adhesion molecule‐3‐Grabbing Non‐integrin (DC‐SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre‐existing liver conditions, such as metabolic‐associated fatty liver disease (MAFLD), alcohol‐related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID‐19 patients. Post‐COVID‐19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug‐Induced Liver Injury (DILI) from COVID‐19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS‐CoV‐2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver‐related complications in both acute and Long COVID‐19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology
Protective Antioxidant Potential of Argan Oil Versus Other Edible Oils in LPS-Challenged Mouse Heart and Kidney Soufiane Rabbaa, Habiba Bouchab, Mounia Tahri-Joutey, Yassir Laaziouez, Youness Limami, et al. International Journal of Molecular Sciences, 2025 Oxidative stress plays a key role in tissue damage during inflammation, highlighting the need for effective antioxidant interventions. This study investigates the antioxidant potential of argan oil (AO)—obtained from Argania spinosa (L.) Skeels almonds—in comparison with olive oil (OO), cactus seed oil (CSO), and colza oil (CO). Quantitative analyses of total polyphenols and pigments—including chlorophylls, carotenoids, and xanthophylls—were conducted alongside antioxidant capacity assessments via DPPH, ABTS, and FRAP assays. The methanolic fraction consistently demonstrated the highest phenolic concentration and antioxidant efficacy across all oils. To establish in vivo relevance, a male C57BL/6J mouse model of acute oxidative stress was induced by lipopolysaccharide (LPS) administration. Pretreatment with oils significantly modulated key oxidative stress biomarkers—SOD, CAT, GPx activities, GSH levels, and lipid peroxidation (MDA)—in both heart and kidney. LPS challenge induced marked oxidative imbalance, notably increasing enzymatic activity and MDA levels, while depleting GSH in the heart and elevating it in the kidney. However, pretreatment with oils effectively restored redox homeostasis, with AO showing particularly potent effects and a stronger regulatory effect observed in the kidney. Hierarchical clustering of z-score-normalized heatmaps revealed distinct oxidative stress signatures, clearly separating LPS-treated heart and kidney tissues from other groups due to heightened oxidative markers. In contrast, oil-treated and oil-combined-with-LPS groups clustered closer to the control, underscoring the protective effect of oils against LPS-induced oxidative stress, with efficiency varying by oil type. Pearson correlation analysis, complemented by multivariate principal component analysis (PCA), further emphasized strong positive associations between antioxidant enzymes (SOD, CAT, GPx) and MDA levels, while GSH exhibited tissue-specific behavior—negatively correlated in the heart but positively in the kidney—highlighting divergent redox regulation between organs. Collectively, AO demonstrated robust cardioprotective and nephroprotective properties, supporting its potential as a natural dietary strategy against inflammation-induced oxidative stress.
Protective Effects of Sodium Copper Chlorophyllin and/or Ascorbic Acid Against Barium Chloride-Induced Oxidative Stress in Mouse Brain and Liver Salma Benayad, Basma Es-Sai, Yassir Laaziouez, Soufiane Rabbaa, Hicham Wahnou, et al. Molecules, 2025 Barium chloride (BaCl2), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl2-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl2 exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl2 exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl2 exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl2-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl2-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination.
Argan Oil: A Natural Bioactive Lipid Modulating Oxidative Stress and Inflammation Soufiane Rabbaa, Habiba Bouchab, Yassir Laaziouez, Youness Limami, Boubker Nasser, et al. Antioxidants, 2025 Nutrition is a key determinant in modulating disease risk, with numerous studies highlighting the role of antioxidants and lipids, particularly the micronutrient and fatty acid composition of natural oils and their bioactive metabolites. In this context, argan oil—a vegetable oil extracted from the kernels of Argania spinosa—has gained significant attention due to its well-balanced fatty acid profile, rich in oleic and linoleic acids, and its high levels of antioxidant compounds, including tocopherols, polyphenols, and phytosterols, particularly schottenol and spinasterol. Thanks to its unique composition, argan oil exhibits protective properties against harmful biological processes, such as oxidative stress and inflammation, both of which play a significant role in various diseases. Preclinical studies, both in vitro and in vivo, have demonstrated that argan oil reduces oxidative stress by preventing DNA damage, protein carbonylation, and lipid peroxidation, while simultaneously increasing antioxidant defenses. Furthermore, it modulates inflammatory responses by decreasing pro-inflammatory biomarkers, increasing anti-inflammatory markers, and limiting immune cell infiltration across different tissues. These antioxidant and anti-inflammatory effects are thought to be linked to argan oil’s ability to regulate key signaling pathways, such as Nrf-2 and NF-κB. Although direct evidence remains limited, studies suggest that its main bioactive components—fatty acid, γ-tocopherol, ferulic acid, and campesterol—can influence these pathways, either by activating Nrf2 to boost antioxidant defenses or by inhibiting NF-κB to suppress inflammation. This review explores the antioxidant and anti-inflammatory properties of argan oil, drawing insights from a range of scientific studies to better understand its therapeutic potential.
Neutrophils and Neutrophil-Based Drug Delivery Systems in Anti-Cancer Therapy Hicham Wahnou, Riad El Kebbaj, Soufyane Hba, Zaynab Ouadghiri, Othman El Faqer, et al. Cancers, 2025 Neutrophils, the most abundant white blood cells, play a dual role in cancer progression. While they can promote tumor growth, metastasis, and immune suppression, they also exhibit anti-tumorigenic properties by attacking cancer cells and enhancing immune responses. This review explores the complex interplay between neutrophils and the tumor microenvironment (TME), highlighting their ability to switch between pro- and anti-tumor phenotypes based on external stimuli. Pro-tumorigenic neutrophils facilitate tumor growth through mechanisms such as neutrophil extracellular traps (NETs), secretion of pro-inflammatory cytokines, and immune evasion strategies. They contribute to angiogenesis, tumor invasion, and metastasis by releasing vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Conversely, anti-tumor neutrophils enhance cytotoxicity by generating reactive oxygen species (ROS), promoting antibody-dependent cell-mediated cytotoxicity (ADCC), and activating other immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Recent advances in neutrophil-based drug delivery systems have harnessed their tumor-homing capabilities to improve targeted therapy. Neutrophil-mimicking nanoparticles and membrane-coated drug carriers offer enhanced drug accumulation in tumors, reduced systemic toxicity, and improved therapeutic outcomes. Additionally, strategies to modulate neutrophil activity, such as inhibiting their immunosuppressive functions or reprogramming them towards an anti-tumor phenotype, are emerging as promising approaches in cancer immunotherapy. Understanding neutrophil plasticity and their interactions with the TME provides new avenues for therapeutic interventions. Targeting neutrophil-mediated mechanisms could enhance existing cancer treatments and lead to the development of novel immunotherapies, ultimately improving patient survival and clinical outcomes.
Gamma-Tocopherol: A Comprehensive Review of Its Antioxidant, Anti-Inflammatory, and Anticancer Properties Basma Es-Sai, Hicham Wahnou, Salma Benayad, Soufiane Rabbaa, Yassir Laaziouez, et al. Molecules, 2025 Gamma-tocopherol (γ-tocopherol), a major isoform of vitamin E, exhibits potent antioxidant, anti-inflammatory, and anticancer properties, making it a promising therapeutic candidate for treating oxidative stress-related diseases. Unlike other tocopherol isoforms, γ-tocopherol effectively neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), providing robust cellular protection against oxidative damage and lipid peroxidation. Its anti-inflammatory effects are mediated through the modulation of pathways involving cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α), reducing chronic inflammation and its associated risks. In cancer therapy, γ-tocopherol demonstrates multifaceted activity, including the inhibition of tumor growth, induction of apoptosis, and suppression of angiogenesis, with significant efficacy observed in cancers such as prostate, lung, and colon. Preclinical and clinical studies support its efficacy in mitigating oxidative stress, inflammation, and cancer progression, with excellent tolerance at physiological levels. However, high doses necessitate careful evaluation to minimize adverse effects. This review consolidates current knowledge on γ-tocopherol’s biological activities and clinical implications, underscoring its importance as a natural compound for managing inflammation, oxidative stress, and cancer. As a perspective, advancements in nanoformulation technology could enhance γ-tocopherol’s bioavailability, stability, and targeted delivery, offering the potential to optimize its therapeutic application in the future.
Curcumin-Based Nanoparticles: Advancements and Challenges in Tumor Therapy Hicham Wahnou, Riad El Kebbaj, Bertrand Liagre, Vincent Sol, Youness Limami, et al. Pharmaceutics, 2025 Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin’s clinical application. Nanotechnology offers a viable solution to these challenges by enabling the development of curcumin-based nanoparticles (CNPs) that enhance its bioavailability and therapeutic efficacy. This review provides a comprehensive overview of the recent advancements in the design and synthesis of CNPs for cancer therapy. We discuss various NP formulations, including polymeric, lipid-based, and inorganic nanoparticles, highlighting their role in improving curcumin’s pharmacokinetic and pharmacodynamic profiles. The mechanisms by which CNPs exert anticancer effects, such as inducing apoptosis, inhibiting cell proliferation, and modulating signaling pathways, are explored in details. Furthermore, we examine the preclinical and clinical studies that have demonstrated the efficacy of CNPs in treating different types of tumors, including breast, colorectal, and pancreatic cancers. Finally, the review addresses the current challenges and future perspectives in the clinical translation of CNPs, emphasizing the need for further research to optimize their design for targeted delivery and to enhance their therapeutic outcomes. By synthesizing the latest research, this review underscores the potential of CNPs as a promising avenue for advancing cancer therapy.