Journal of Experimental Pharmacology and Toxicology

Cardiovascular diseases remain a leading cause of global mortality, with thrombotic complications representing a major clinical challenge. This study aimed to evaluate the preclinical safety and pharmacological activity of Cardin, a multicomponent peptide complex derived from neonatal lamb heart tissue. Cardin was obtained through saline extraction, thermal treatment, ammonium sulfate precipitation, and purification using gel filtration and ion-exchange chromatography. The preparation was partially characterized by high-performance liquid chromatography (HPLC) and mass spectrometry, confirming the presence of multiple peptide fractions with distinct molecular masses; however, the complete amino acid sequences of individual components were not fully elucidated, and Cardin should therefore be regarded as a heterogeneous peptide mixture. In silico toxicity prediction indicated potential risks, including neurotoxicity, hepatotoxicity, and immunotoxicity. In contrast, in vivo experimental studies demonstrated no significant acute or cumulative toxicity at the tested doses. The median lethal dose (LD₅₀) was estimated to exceed 1000 mg/kg. Subacute and chronic administration did not result in observable adverse effects on behavior, body weight, or histological structure of major organs. Hematological and biochemical parameters remained within physiological ranges across all experimental groups, and no organ-specific toxicity was detected. Overall, Cardin exhibited a favorable safety profile in preclinical models despite discrepancies between computational predictions and experimental findings. These differences may reflect the limitations of in silico models when applied to complex multicomponent peptide systems. Further studies are required to clarify the contribution of individual peptide fractions and to better understand their mechanisms of action. Full article

Background: Psoriasis is an immune-mediated skin disorder marked by abnormal keratinocyte proliferation and immune cell infiltration, with dysregulated cytokines such as TNF-α, IL-6, and IL-17. Methotrexate (MTX) is an established systemic therapy for moderate to severe psoriasis; however, the efficacy of topical MTX remains uncertain and requires further evaluation in controlled studies. Purpose: This study evaluated a 1% topical MTX formulation in an imiquimod-induced mouse model of psoriasis and compared its effects with topical clobetasol propionate (0.05%) and tacrolimus (0.1%). In addition, in silico molecular docking was performed as an exploratory complement to the clinical and histological assessments; docking results are hypothesis-generating and do not demonstrate direct in vivo mechanisms. The study did not include a systemic MTX arm. Methods: Male C57BL/6 mice were randomized into five groups (negative control, IMQ positive control, clobetasol, tacrolimus, and MTX 1%). Psoriasis-like dermatitis was induced with topical 5% imiquimod for 7 days, followed by twice-daily topical treatment for 14 days. Clinical severity was scored using a murine PASI scale; skin samples were collected for histopathology and for measurement of TNF-α and IL-6 by ELISA. In silico docking against TNF-α and IL-6 was performed using AutoDock Vina; docking is reported as exploratory. Results: Topical MTX produced marked reductions in PASI scores and improved histological architecture compared with IMQ controls, with effects comparable to clobetasol and greater than tacrolimus in this model. MTX-treated skin showed lower TNF-α and IL-6 levels (expressed as pg/mg protein, Docking simulations confirmed moderate predicted binding affinities of MTX, clobetasol, and tacrolimus to TNF-α and IL-6; these findings are presented as exploratory and hypothesis-generating, and do not constitute proof of direct cytokine binding in vivo. Conclusion: In this imiquimod mouse model, a 1% topical MTX formulation demonstrated significant anti-inflammatory and antiproliferative effects, comparable to topical clobetasol and superior to tacrolimus under the conditions tested. These results support further pharmacokinetic, skin penetration, and safety studies to confirm local bioavailability and to evaluate systemic exposure before clinical translation. Full article

Background: The ethnomedicinal use of Ficus exasperata Vahl (Moraceae) in the management of various diseases is popular in most Sub-Saharan African regions. Different parts of the plant have been exploited and used for various local remedies. In this study, the hypoglycemic effect of the aqueous leaf and root bark of Ficus exasperata Vahl (Moraceae) was evaluated using an experimental rat model. Aim: The aim of this study is to evaluate the hypoglycemic effect of the aqueous extract of the leaf and root bark of Ficus exasperata Vahl (Moraceae). Objectives: The chief objective was to determine the hypoglycemic activity of the aqueous extract of the root bark of Ficus exasperata in Wistar albino rats and to determine if there exists a synergy in the hypoglycemic effect between the aqueous extract of the leaf and root bark of the plant, thus justifying its local use. Method: Wistar rats, 100—180g, used for the experiment, were diabetically induced with Alloxan monohydrate. The 40 Wistar rats used for the experiment were divided into six groups (A, B, C, D, E, and F) with 7 animals in each group, except group F, which had only 5. Diabetes was experimentally induced in groups A, B, C, D, and E with a single intraperitoneal administration of Alloxan (150 mg/kg), while group F was administered an equivalent 1ml of distilled water. Group A was treated with aqueous leaf extract (FL) (400 mg/kg/day), group B was treated with aqueous root bark extract (FR) (400 mg/kg/day), group C was treated with a combination of leaf and root bark aqueous extract at a ratio of 1:1 (200 mg: 200 mg/kg/day), and group D was treated with Metformin (150 mg/kg/day), while groups E and F were treated as controls (given only regular food and water). The extracts were administered orally by intragastric intubation, and treatment lasted for three weeks, with the fasting blood sugar measured weekly. Result: At the end of the experimental period, the consecutive treatment of the animals with the leaf and root bark extracts of Ficus exasperata resulted in a significant reduction (p < 0.05) in the blood sugar of the test animal groups A (73.4 ± 2.64 mg/dL), B (66 ± 3.29 mg/dL), and C (80 ± 4.29 mg/dL) compared to the control group E (610 ± 15.5 mg/dL) (diabetically induced but not treated). These results also compare favourably with those of animals treated with the standard drug Metformin (150mg/kg/day), group D (57 ± 7.02 mg/dL), and the control group F (74.4 ± 2.54 mg/dL) (not diabetically induced and not treated). Conclusion: The results suggest that the aqueous root extract of Ficus exasperata may have a slightly higher hypoglycemic effect than the aqueous leaf extract of the plant (p < 0.05). More importantly, the result indicates that the combination of the leaf and root extract of Ficus exasperata, as demonstrated in group C (80 ± 4.29 mg/dL) and as commonly used locally, may not hold any advantage over the use of either the leaf, as in group A (73.4 ± 2.64 mg/dL), or root bark extract, as in group B (66 ± 3.29 mg/dL), of the plant. Full article

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is one of the most common cancers globally, occurring in all types of populations, but current therapy faces multiple barriers, urgently requiring new alternatives for improvement. Hesperidin (HSP) is a bioflavonoid with pleiotropic properties that has been mentioned in studies for enhancing response to chemotherapy, including in the case of cisplatin (CIS). Methods: Using Detroit 562 cells, HSP, CIS, and the combinatorial treatment of the two were examined by MTT assay, morphological analysis, and mitochondrial and nuclear assessment for 24 h. Results: The results showed that the combination of HSP+CIS produces superior effects, reducing cell viability by up to 16%and producing cell rounding and shrinkage and significant alterations in nuclei and mitochondria compared to individual treatments. Conclusions: HSP may be an important candidate in improving CIS cytotoxicity in Detroit 562 cells and could be considered a promising natural adjuvant. The combined treatment of the phytocompound and CIS led to superior outcomes, enhancing the effects of CIS. Full article

Cardiovascular diseases (CVDs) and the coronavirus disease 2019 (COVID-19) pandemic represent major, interrelated global health challenges, largely mediated by dysregulation of the renin–angiotensin–aldosterone system (RAAS). Traditionally, therapeutic strategies have focused on inhibiting the classical ACE/angiotensin II (Ang II)/AT₁ receptor axis, which drives vasoconstriction, inflammation, fibrosis, and cardiovascular remodeling. However, the discovery of angiotensin-converting enzyme 2 (ACE2) has revealed an alternative, counter-regulatory RAAS pathway with significant physiological and therapeutic relevance, particularly in the context of COVID-19. ACE2 catalyzes the conversion of Ang II to angiotensin-(1–7), thereby activating the Mas receptor axis, which exerts vasodilatory, anti-inflammatory, antifibrotic, and antioxidative effects. SARS-CoV-2-induced downregulation of ACE2 disrupts this protective pathway, contributing to cardiovascular injury and post-COVID-19 complications. This review examines classical and alternative RAAS signaling, elucidates the molecular basis of ACE2-mediated cardioprotection, and critically evaluates emerging therapeutic strategies, including natural products targeting the ACE2/angiotensin-(1–7)/Mas receptor axis in cardiovascular disease and post-COVID-19 complications. Full article