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This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 µm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki-67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure.
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Neoplasias Cutáneas , Ácidos Sulfúricos , Animales , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Ratones , Ácidos Sulfúricos/efectos adversos , Ácidos Sulfúricos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Femenino , Malondialdehído/metabolismo , Inmunocompetencia , Catalasa/metabolismo , Piel/patología , Piel/metabolismo , Piel/efectos de los fármacos , Antígeno Ki-67/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.
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Artemisia , Enfermedades Inflamatorias del Intestino , Simulación del Acoplamiento Molecular , Extractos Vegetales , Artemisia/química , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Artritis/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/químicaRESUMEN
Skin cancer is the most widespread type of malignant tumor representing a major public health concern. Considering the numerous side effects associated with conventional treatments, phytotherapy may be regarded as a viable medicinal alternative. This study aimed to investigate the therapeutic potential of Orbea variegata (L.) Haw, an ornamental plant, in treating skin cancer using an animal model induced by a combination of ultraviolet (UV) irradiation and sulfuric acid treatment. The hydroethanolic extract of Orbea variegata underwent phytochemical characterization, identifying the presence of reducing sugars, coumarins, alkaloids, flavonoids, tannins, and saponins through qualitative screening. Quantitative analysis demonstrated significant amounts of phenolic compounds (29.435 ± 0.571 mg GAE/g of dry extract), flavonoids (6.711 ± 0.272 mg QE/g of dry extract), and tannins (274.037 ± 11.3 mg CE/g of dry extract). The administration the hydroethanolic extract in two concentrations (1 or 2 g/kg) to male Swiss mice exhibited no marked adverse effects, as evidenced by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activity levels. In addition, the extract significantly reduced skin hyperplasia and inflammation induced by UV/sulfuric acid treatment as noted in tissue analyses and decreased protein expression of nuclear proliferation marker (Ki-67). This improvement was associated with a marked decrease in oxidative stress, as indicated by diminished lipid peroxidation levels, and restoration of the activity of endogenous antioxidant enzyme catalase (CAT) to control levels. Our findings demonstrated the potential of Orbea variegata hydroethanolic extract to be considered as a treatment for skin cancer, exhibiting its apparent safety and efficacy in reducing inflammation and carcinogenesis in a UV/sulfuric acid-induced Swiss mouse model, attributed to its phytochemical content and associated antioxidant activities.
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Extractos Vegetales , Neoplasias Cutáneas , Animales , Masculino , Ratones , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Extractos Vegetales/farmacología , Carcinogénesis/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Modelos Animales de EnfermedadRESUMEN
Arthritis is a debilitating condition impacting the quality of life for millions worldwide, characterized by pain and inflammation. Understanding the mechanisms of arthritis and developing effective treatments are crucial. This study investigated the hydroethanolic extract of Artemisia herba-alba for its protective potential against arthritis hallmarks, oxidative stress, and lipid peroxidation in vitro. It also assessed its in vivo anti-arthritic activity. The phytochemical analysis identified various compounds within the extract, with high concentrations of polyphenols and flavonoids. These compounds are associated with numerous health benefits, making A. herba-alba a potential source of valuable phytochemicals. A. herba-alba demonstrated a notable effect in body weight loss, paw edema, and arthritic severity. Histopathological examination revealed structural improvements in bone and muscle tissues, emphasizing its therapeutic potential in managing chronic arthritis. Furthermore, while these findings are promising, further studies are necessary to delve deeper into the mechanisms underlying the observed hematological changes and to gain a more comprehensive understanding of the in vivo results. This research sets the stage for continued exploration, ultimately aiming to unlock the full potential of A. herba-alba in addressing chronic arthritis and enhancing the lives of those affected by this condition.
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Antioxidantes , Artemisia , Artritis Experimental , Estrés Oxidativo , Extractos Vegetales , Artemisia/química , Animales , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Artritis Experimental/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Ratas , Masculino , Ratones , Enfermedad Crónica , Fitoquímicos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Flavonoides/farmacología , Edema/tratamiento farmacológico , Artritis/tratamiento farmacológicoRESUMEN
Aframomum melegueta K Schum (A. melegueta), an herbaceous plant renowned for its medicinal seeds, was investigated for its potential immunomodulatory effects in vitro and in vivo using ethanolic and methanolic extracts. The immunomodulatory effect was evaluated by measuring antibody titers using the agglutination technique, while anti-inflammatory activity was assessed in a carrageenan-induced mouse paw edema model. In vitro immunomodulatory activity was measured by lysozyme release from neutrophils. Additionally, white blood cell counts were analyzed post-extracts treatment. The MTT assay was employed to determine cytotoxicity, and the biochemical parameters of liver toxicity were evaluated. Remarkably, both extracts exhibited a dose-dependent reduction in paw edema (p < 0.001), with the most significant reduction observed at 1 g/kg (78.13 and 74.27% for ethanolic and methanolic extracts, respectively). Neutrophil degranulation was significantly inhibited in a dose-dependent manner (p < 0.003), reaching maximal inhibition at 100 µg/mg (60.78 and 39.7% for ethanolic and methanolic extracts, respectively). In comparison to the control group, both antibody production and white blood cell counts were reduced. Neither of the extracts showcased any cytotoxicity or toxicity. These findings suggest that A. melegueta extracts exhibit immunosuppressive and anti-inflammatory activities due to the presence of various biomolecules.
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Extractos Vegetales , Zingiberaceae , Ratones , Animales , Extractos Vegetales/química , Semillas/química , Antiinflamatorios/farmacología , Metanol , Etanol , Zingiberaceae/química , EdemaRESUMEN
Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.
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Ammi , Khellin , Ratas , Femenino , Ratones , Animales , Extractos Vegetales/química , Ammi/química , Khellin/química , Khellin/farmacología , Antioxidantes/farmacología , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Ratas Wistar , Flavonoides/farmacología , Antiinflamatorios/farmacologíaRESUMEN
Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/ß-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA's low bioavailability, emphasizing the need for enhanced therapeutic strategies.
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Neoplasias , Triterpenos , Masculino , Humanos , Fosfatidilinositol 3-Quinasas , Triterpenos/farmacología , Triterpenos/uso terapéutico , Transducción de Señal , Neoplasias/tratamiento farmacológico , Apoptosis , Proliferación Celular , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Colon cancer poses a complex and substantial global health challenge, necessitating innovative therapeutic approaches. Chalcones, a versatile class of compounds with diverse pharmacological properties, have emerged as promising candidates for addressing colon cancer. Their ability to modulate pivotal signaling pathways in the development and progression of colon cancer makes them invaluable as targeted therapeutics. Nevertheless, it is crucial to recognize that although chalcones exhibit promise, further pre-clinical studies are required to validate their efficacy and safety. The journey toward effective colon cancer treatment is multifaceted, involving considerations such as optimizing the sequencing of therapeutic agents, comprehending the resistance mechanisms, and exploring combination therapies incorporating chalcones. Furthermore, the integration of nanoparticle-based drug delivery systems presents a novel avenue for enhancing the effectiveness of chalcones in colon cancer treatment. This review delves into the mechanisms of action of natural chalcones and some derivatives. It highlights the challenges associated with their use in pre-clinical studies, while also underscoring the advantages of employing chalcone-based nanoparticles for the treatment of colon cancer.
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Cancer, characterized by the unregulated growth and dissemination of malignantly transformed cells, presents a significant global health challenge. The multistage process of cancer development involves intricate biochemical and genetic alterations within target cells. Cancer chemoprevention has emerged as a vital strategy to address this complex issue to mitigate cancer's impact on healthcare systems. This approach leverages pharmacologically active agents to block, suppress, prevent, or reverse invasive cancer development. Among these agents, piperine, an active alkaloid with a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and immunomodulatory effects, has garnered attention for its potential in cancer prevention and treatment. This comprehensive review explores piperine's multifaceted role in inhibiting the molecular events and signaling pathways associated with various stages of cancer development, shedding light on its promising prospects as a versatile tool in cancer chemoprevention. Furthermore, the review will also delve into how piperine enhances the effectiveness of conventional treatments such as UV-phototherapy and TRAIL-based therapy, potentially synergizing with existing therapeutic modalities to provide more robust cancer management strategies. Finally, a crucial perspective of the long-term safety and potential side effects of piperine-based therapies and the need for clinical trials is also discussed.
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Colorectal cancer (CRC) poses a significant challenge in healthcare, necessitating the exploration of novel therapeutic strategies. Natural compounds such as polyphenols with inherent anticancer properties have gained attention as potential therapeutic agents. This review highlights the need for novel therapeutic approaches in CRC, followed by a discussion on the synthesis of polyphenols-based nanoparticles. Various synthesis techniques, including dynamic covalent bonding, non-covalent bonding, polymerization, chemical conjugation, reduction, and metal-polyphenol networks, are explored. The mechanisms of action of these nanoparticles, encompassing passive and active targeting mechanisms, are also discussed. The review further examines the intrinsic anticancer activity of polyphenols and their enhancement through nano-based delivery systems. This section explores the natural anticancer properties of polyphenols and investigates different nano-based delivery systems, such as micelles, nanogels, liposomes, nanoemulsions, gold nanoparticles, mesoporous silica nanoparticles, and metal-organic frameworks. The review concludes by emphasizing the potential of nanoparticle-based strategies utilizing polyphenols for CRC treatment and highlights the need for future research to optimize their efficacy and safety. Overall, this review provides valuable insights into the synthesis, mechanisms of action, intrinsic anticancer activity, and enhancement of polyphenols-based nanoparticles for CRC treatment.
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Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therapy, and chemotherapy, are associated with significant side effects and limitations. Photodynamic therapy (PDT) is a promising alternative that has the potential to provide a minimally invasive and highly targeted approach to treating prostate cancer. PDT involves the use of photosensitizers (PSs) that are activated by light to produce reactive oxygen species (ROS), which can induce tumor cell death. There are two main types of PSs: synthetic and natural. Synthetic PSs are classified into four generations based on their structural and photophysical properties, while natural PSs are derived from plant and bacterial sources. Combining PDT with other therapies, such as photothermal therapy (PTT), photoimmunotherapy (PIT), and chemotherapy (CT), is also being explored as a way to improve its efficacy. This review provides an overview of conventional treatments for prostate cancer, the underlying principles of PDT, and the different types of PSs used in PDT as well as ongoing clinical studies. It also discusses the various forms of combination therapy being explored in the context of PDT for prostate cancer, as well as the challenges and opportunities associated with this approach. Overall, PDT has the potential to provide a more effective and less invasive treatment option for prostate cancer, and ongoing research is aimed at improving its selectivity and efficacy in clinical settings.
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Caralluma europaea is a medicinal plant used in Moroccan popular medicine, which has been employed as a remedy attributed to its anti-inflammatory, antipyretic, antinociceptive, antidiabetic, neuroprotective, and antiparasitic properties. The aim of the present study was to investigate the antitumor activity of both the methanolic and aqueous extract of C. europaea. The effects of increasing concentrations of aqueous and methanolic extracts on human colorectal cancer HT-29 and HCT116 cell lines and human prostate cancer PC3 and DU145 cell lines were examined on cell proliferation using MTT assay and cell cycle analysis. The induction of apoptosis was also assessed by determining protein expression of caspase-3 and poly-ADP-ribose polymerase (PARP) cleavage by western blot. The methanolic extract of C. europaea exerted significant antiproliferative effects on HT-29 (IC50 values 73 µg/ml), HCT116 (IC50 values 67 µg/ml), PC3 (IC50 values 63 µg/ml) and DU145 cells (IC50 values 65 µg/ml) after 48 hr treatment. Further, incubation with methanolic extract of C. europaea induced cell cycle arrest in G1 phase and an apoptotic process for all treated cell lines. In conclusion, the present results suggest that C. europaea, exhibited that these natural compounds are significant apoptosis inducers which may have considerable potential for development of effective natural product anticancer agents.
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Apocynaceae , Neoplasias Colorrectales , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Apoptosis , Células HCT116 , Metanol , Neoplasias Colorrectales/tratamiento farmacológicoAsunto(s)
COVID-19 , ChAdOx1 nCoV-19 , Vacunas contra la COVID-19 , Humanos , Agregación Plaquetaria , SARS-CoV-2RESUMEN
Inflammatory bowel disease (IBD) is a group of chronic disorders that includes two main disease forms, Crohn's disease, and ulcerative colitis. The understanding of the intestinal inflammation occurring in IBD has been immeasurably advanced by the development of the now numerous murine models of intestinal inflammation. The usefulness of this research tool in IBD arises from a convergence of underlying genetic susceptibility, immune system dysfunction, environmental factors, and shifts in gut microbiota. Due to the multifactorial feature of these diseases, different animal models have been used to investigate the underlying mechanisms and develop potential therapeutic strategies. The results of preclinical efficacy studies often inform the progression of therapeutic strategies. This review describes the distinct feature and limitations of each murine IBD model and discusses the previous and current lessons from the IBD models.
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Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino , Animales , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , RatonesRESUMEN
Despite the remarkable decrease in cervical cancer incidence due to the availability of the HPV vaccine and implementation of screening programs for early detection in developed countries, this cancer remains a major health problem globally, especially in developing countries where most of the cases and mortality occur. Therefore, more understanding of molecular mechanisms of cervical cancer development might lead to the discovery of more effective diagnosis and treatment options. Research on long noncoding RNAs (lncRNAs) demonstrates the important roles of these molecules in many physiological processes and diseases, especially cancer. In the present review, we discussed the significance of lncRNAs altered expression in cervical cancer, highlighting their roles in regulating highly conserved signaling pathways, such as mitogen-activated protein kinase (MAPK), Wnt/ß-catenin, Notch, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways and their association with the progression of cervical cancer in order to bring more insight and understanding of this disease and their potential implications in cancer diagnosis and therapy.
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Point-of-care (POC) testing for Toxoplasma infection has the potential to revolutionize diagnosis and management of toxoplasmosis, especially in high-risk populations in areas with significant environmental contamination and poor health infrastructure precluding appropriate follow-up and preventing access to medical care. Toxoplasmosis is a significant public health challenge in Morocco, with a relatively heavy burden of infection and, to this point, minimal investment nationally to address this infection. Herein, we analyse the performance of a novel, low-cost rapid test using fingerstick-derived whole blood from 632 women (82 of whom were pregnant) from slums, educational centres, and from nomad groups across different geographical regions (i.e. oceanic, mountainous) of Morocco. The POC test was highly sensitive and specific from all settings. In the first group of 283 women, sera were tested by Platelia ELISA IgG and IgM along with fingerstick whole blood test. Then a matrix study with 349 women was performed in which fingerstick - POC test results and serum obtained by venipuncture contemporaneously were compared. These results show high POC test performance (Sensitivity: 96.4% [IC95 90.6-98.9%]; Specificity: 99.6% [IC95 97.3-99.9%]) and high prevalence of Toxoplasma infection among women living in rural and mountainous areas, and in urban areas with lower educational levels. The high performance of POC test confirms that it can reduce the need for venipuncture and clinical infrastructure in a low-resource setting. It can be used to efficiently perform seroprevalence determinations in large group settings across a range of demographics, and potentially expands healthcare access, thereby preventing human suffering.
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Pruebas en el Punto de Atención/normas , Toxoplasma/inmunología , Toxoplasmosis/sangre , Toxoplasmosis/diagnóstico , Adolescente , Adulto , Anciano , Anticuerpos Antiprotozoarios/sangre , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Persona de Mediana Edad , Marruecos/epidemiología , Pruebas en el Punto de Atención/economía , Embarazo , Prevalencia , Factores de Riesgo , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , Toxoplasmosis/epidemiología , Toxoplasmosis/inmunología , Toxoplasmosis Congénita/sangre , Toxoplasmosis Congénita/diagnóstico , Adulto JovenRESUMEN
Ulcerative colitis (UC) and Crohn's disease (CD) are chronic and multifactorial diseases that affect the intestinal tract, both characterized by recurrent inflammation of the intestinal mucosa, resulting in abdominal pain, diarrhea, vomiting and, rectal bleeding. Inflammatory bowel diseases (IBD) regroup these two disorders. The exact pathological mechanism of IBD remains ambiguous and poorly known. In genetically predisposed patients, defects in intestinal mucosal barrier are due to an uncontrolled inflammatory response to normal flora. In addition to the genetic predisposition, these defects could be triggered by environmental factors or by a specific lifestyle which is widely accepted as etiological hypothesis. The involvement of the CD40/CD40L platelet complex in the development of IBD has been overwhelmingly demonstrated. CD40L is climacteric in cell signalling in innate and adaptive immunity, the CD40L expression on the platelet cell surface gives them an immunological competence. The IL-1, a major inflammation mediator could be involved in different ways in the development of IBD. Here, we provide a comprehensive review regarding the role of platelet CD40/CD40L in the pathophysiological effect of IL-1 in the development of Crohn's disease (CD). This review could potentially help future approaches aiming to target these two pathways for therapeutic purposes and elucidate the immunological mechanisms driving gut inflammation.