Journal of Experimental Pharmacology最新文献

Purpose: The worldwide threat of herpes virus infections and their resistance against the existing drugs creates an urgent need for the development of novel drug candidates. An RNase H like domain is present in the protein encoded by the highly conserved ul15 gene (UL15) of Herpes Simplex Virus, ul89 gene encoded protein (UL89) of Human Cytomegalo Virus and Human Immunodeficiency Virus (HIV) integrase proteins. This provided a way repurpose HIV integrase inhibitors as HSV UL15 and HCMV UL89 inhibitors.

Materials and methods: The protein sequences were aligned using the Clustal Omega software to determine the conserved amino acid positions. Schrodinger software was used for docking studies, protein-ligand interaction and simulation studies. The selected drugs were screened to analyse their anti- HSV-1 and HSV-2 activities by Cytopathic effect (CPE) inhibition assay and RT-PCR using Vero cells as host. The experiments were further analyzed by the two-way ANOVA test using Bonferroni's post-HOC using GraphPad Prism software version 8.0.2. The RT-PCR experimental results were analyzed using the 2^-∆∆Ct Livak method to determine the fold reduction in viral gene expression.

Results: The in-silico studies showed the binding abilities of anti-HIV drugs to the active site of UL15 and UL89 by blocking their metal ions, similar to HIV integrase. Among the anti-HIV drugs tested, Elvitegravir and raltegravir were most effective in controlling the HSV-1 and HSV-2 infections at concentrations as low as 1.6 µg/mL when tested with 10TCID₅₀ viral challenge dose. Elvitegravir was most effective in reducing the viral gene expression as tested by RT-PCR.

Conclusion: The tested FDA approved drug molecules showed the potential to be repurposed as an antiHSV and antiHCMV agent. The in silico and in vitro results warrant further investigation in preclinical and clinical studies to validate its therapeutic potential and safety for HSV-related infections.

Background: Acridones are heterocyclic alkaloids characterized by a tricyclic ring structure, featuring nitrogen at the 10th position and a carbonyl group at the 9th position. These compounds exhibit notable antibacterial and antifungal activities, positioning them as possible candidates for medicinal uses.

Objective: This research focused on the synthesis of N10-acetyl-3,4-dimethylacridone (Compound 3), a new acridone derivative, and the evaluation of its antifungal and antibacterial qualities against Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli.

Methods: Compound 3 was synthesised using anthranilic acid and 2,3-dimethyl aniline, followed by acetylation with acetic anhydride and cyclisation with sulphuric acid. The compound underwent characterisation using IR, NMR, and elemental analysis techniques. The antimicrobial and antifungal activities were evaluated using the agar well diffusion method, with inhibition zones recorded at concentrations of 50, 100, 300, and 400 mg/mL.

Results: Compound 3 exhibited significant antibacterial efficacy at a concentration of 400 mg/mL. The inhibitory zones measured 35 mm for Pseudomonas aeruginosa and 26 mm for Escherichia coli, notably exceeding the conventional antibiotic gentamicin, which recorded 25 mm and 28 mm, respectively. Moderate action was noted against Staphylococcus aureus (19 mm) and Candida albicans (20 mm), but gentamicin and ketoconazole exhibited no inhibitory effect on Staphylococcus aureus at the tested concentration.

Conclusion: N10-acetyl-3,4-dimethylacridone (Compound 3) exhibits considerable antibacterial and antifungal properties, surpassing conventional antibiotics such as gentamicin in efficacy against Pseudomonas aeruginosa and Escherichia coli. The results indicate that Compound 3 may serve as an effective antibacterial agent and necessitates further exploration for therapeutic use in addressing bacterial and fungal illnesses.

Purpose: To evaluate the protective effects of Tamarillo (Solanum betaceum Cav) extract on lead acetate-induced testicular germ cell apoptosis in male mice.

Methods: A post-test-only control group experimental study was conducted on Balb/c mice. Thirty-five male mice 12 weeks old were randomly divided into 5 groups: two control groups (K-, K+) and three treatment groups (P1, P2, P3). The K- received distilled water, and the K+ received 75 mg/kg lead acetate. The P1, P2, and P3 received 100, 200, and 400 mg/kg of Tamarillo crude extracts (TCE), respectively for 35 days, and on the fourth day, were given lead acetate 75 mg/kg one hour after the TCE administration by gavage tube. The effect of TCE against lead-induced oxidative stress in mice was determined by the expression of mouse testicular apoptosis using terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) assay, the expression of Caspase-3, and SOD.

Results: TCE at the dose of 400 mg/kg showed comparable apoptosis and SOD expression to the negative control group (K-). Notably, the level of Caspase-3 among treatment groups showed lower expression than the K- group despite the injection of lead acetate.

Conclusion: This study demonstrated that TCE exhibits antioxidant activity and protects the reproductive system by inhibiting lead acetate to induce oxidative damage and testicular damage.

Objective: To evaluate the therapeutic benefits of dapagliflozin and liraglutide as treatments for type 2 diabetes mellitus and their combined effects on T2DM-related complications, specifically cardio-renal injury.

Methods: Thirty rats were randomly allocated into two groups, with the first group serving as the control group, which had 6 rats. The second group was the experimental group, which had 24 rats administered a high-fat diet for four weeks, followed by a single dose of streptozotocin (STZ) to induce diabetes mellitus (DM). This, combined with a high-fat diet, a low dose of STZ was used to cause sub-lethal damage to beta cells. HFD/STZ is an easy method to successfully create a rat model resembling human T2DM, causing insulin resistance, but it does not fully capture the complexity of human T2DM. The experimental group was randomly divided into a positive control group, a liraglutide (0.4 mg/kg, s.c) group, a dapagliflozin (1 mg/kg, orally) group, and a combination of Dapa and lira group, which were administered daily for four weeks. Blood samples were analyzed for glucose, insulin, and cardiac and kidney function markers. Cardiac and kidney tissue were examined to assess redox balance, glutathione (GSH), catalase (CAT), and malondialdehyde (MDA).

Results: Dapa and/or lira administration improved the body weight, lipid profile, cardiac and kidney function markers. Furthermore, all treating groups exhibited restoration of the balance between oxidants and antioxidants. Histological studies also revealed a reduction in cardiorenal tissue injury caused by diabetes. Interestingly, the combined management of Dapa and Lira showed a more beneficial protective effect than individual treatments. This study uniquely explores the simultaneous impact on cardiac and renal systems in a diabetic model, offering novel insights into cardiorenal interaction and the combined therapeutic potential of Dapa and Lira.

Conclusion: These findings suggest that the combination of dapagliflozin and liraglutide provides superior protection against diabetes-induced cardiorenal injury compared to either treatment alone, highlighting their potential as adjunctive therapies in reducing type 2 diabetes mellitus complications.

Background: In this study, the efficacy of three essential oil extraction techniques steam entrainment, Soxhlet extraction, and supercritical fluid extraction (SCF) was evaluated.

Aim: Determine the most effective method for obtaining bioactive compounds from Cymbopogon citratus, Origanum vulgare, and Coriandrum sativum, plant species recognized for their antimicrobial and anti-inflammatory properties with potential applications in dentistry. The selected plants, identified based on scientific evidence, were certified and lyophilized prior to extraction. The efficiency of each technique was assessed in terms of essential oil yield, purity, and biological activity.

Methodology: The plant species were selected for their therapeutic properties based on scientific reports, certified, and lyophilized before proceeding with the different extraction methods. The efficacy of each technique was compared in terms of the purity and yield of the essential oils obtained. The statistical analysis was performed using SPSS version 25.

Results: It was shown that FSC extraction is the method that allows obtaining essential oils with the highest purity and yield, followed by steam entrainment, with the Soxhlet method being the least efficient. However, in the microbiological analysis, the essential oil obtained by steam entrainment showed a greater inhibitory effect against Candida albicans ATCC 90028.

Conclusion: In this study, the FSC and steam entrainment techniques are the most suitable for obtaining essential oils for therapeutic applications in dentistry, since they allow better preservation of the bioactive components and reduce the environmental impact. These results position FSC and vapor entrainment extraction as promising options for the development of therapeutic products in dentistry.

Peperomia pellucida (L.) Kunth, a tropical herb belonging to the Piperaceae family, is used in traditional medicine for various therapeutic applications. This review aims to comprehensively analyze preclinical evidence (in silico, in vitro, in vivo, cytotoxicity, and toxicity) supporting the pharmacological activities of P. pellucida and elucidate its mechanisms of action and therapeutic potential. Articles were searched in the PubMed and Scopus databases, filtered to those published between 2014 and 2025, to guarantee the most updated research on this plant. These findings indicate that P. pellucida should be explored globally. The bioactive compounds contained in this plant could interact with numerous proteins, such as estrogen receptors, NOS, NF-κB, PPAR-gamma, ACE, aldose reductase, alpha-glucosidase, alpha-amylase, DPP-IV, insulin receptor, and AChE. It was reported in vitro studies that the extracts and essential oils of this plant exerted their pharmacological effects through multiple pathways, such as inhibiting COX, NF-κB, and NOS, and scavenging free radicals, which are driven by terpenoids, phenolics, and flavonoids. The in silico and in vitro studies were in agreement with the in vivo studies, which delineated antihypertensive, anti-inflammatory, antinociceptive, antiplasmodial, and osteogenic activity. As expected, P. pellucida was not toxic towards normal cells or animal models, confirming its safety. Moreover, several articles describe ethnobotanical studies of this plant in Singapore, India, Myanmar, Nigeria, and Indonesia. However, despite promising pharmacological evidence, the clinical applications of P. pellucida remain limited owing to a lack of human studies and open challenges in determining its safety, dosage, and long-term effects. Further research for clinical validation is essential to assess its potential as a therapeutic agent.

Purpose: The use of medicine plants in the management of various human ailments have gained lots of attention in recent time; hence, the present study aimed to investigate the impact of Bidens pilosa on the behavioral, oxidative stress and cerebellar cortical histoarchitectural alterations during bisphenol A exposure in mice.

Methods: Thirty (30) adult male mice were divided into six groups. Group 1 received distilled water (2 mls/kg b.w). and group 2 was treated with (bisphenol A) BPA (100 mg/kg body weight). Groups 3-5 were co-treated with varying doses of Bidens pilosa (250 mg/kg, 500 mg/kg, and 1000 mg/kg b.w). and group 6 received vitamin C (60 mg/kg b.w). along with BPA. The animals underwent neurobehavioral tests (beam walking and wire hang). Other parameters evaluated included body weight, oxidative stress biomarkers, and cerebellar histology.

Results: Animals treated with high doses of Bidens pilosa spent less time crossing the beam during the beam walking test and more time in the wire hang test than those treated with BPA alone. Lowered malondialdehyde level and higher catalase and superoxide dismutase activity was observed in Bidens pilosa treated groups than in the BPA-only group. Histological examination revealed a significant improvement in the cerebellar tissue structure in Bidens pilosa treated groups, particularly at higher doses.

Conclusion: Bidens pilosa demonstrated potential protective effects against BPA-induced oxidative stress and negative histological changes in the cerebellar cortex, suggesting its therapeutic potential for mitigating BPA neurotoxicity. Further research is needed to explore the therapeutic applicability.

Breast cancer remains one of the most prevalent and life-threatening diseases worldwide, affecting millions of individuals and their families. While current treatments such as chemotherapy, radiation, and targeted therapies have improved survival rates, they often come with severe side effects and limitations. This has led to a growing interest in natural compounds derived from medicinal plants as safer and potentially more effective alternatives. These plant-based compounds have shown promise in targeting key cancer pathways, including EGFR, PI3K/AKT/mTOR, NF-κB, JAK-STAT3, RAF/MEK/ERK, BCL-2, p53, and SKP/p21, helping to inhibit tumor growth, induce cancer cell death, and prevent metastasis. Research combining computational, in vitro, and in vivo studies has revealed that bioactive compounds such as flavonoids, alkaloids, and phenolics can provide meaningful therapeutic benefits. However, challenges such as ensuring proper absorption, stability, and clinical application remain. By addressing these limitations through advanced drug formulations and integration into existing treatment plans, plant-based therapies could play a vital role in improving outcomes for breast cancer patients. This review sheds light on the potential of natural compounds to offer hope for more effective and less harmful cancer treatments in the future.

Background: Gingerols and shogaols are the main active constituents in Zingiber officinale var. sunti Valeton has been reported for its anti-anxiety activity. Anti-anxiety drugs, such as benzodiazepines, alleviate anxiety disorders by enhancing the activity of gamma-aminobutyric acid type A (GABA_A) receptors through positive allosteric regulation at the α1/γ2 interface extracellular domain.

Purpose: To elucidate the binding energy and stability of gingerols and shogaols toward human GABA_A receptor (hGABA_AR), compared to their known allosteric agonist (diazepam), and further phytochemical analysis in the ethanol extract of Z. officinale var. sunti Valeton rhizome (EEZO).

Methods: The ligands, namely gingerols (6-, 8-, and 10-gingerol) and shogaols (6-, 8-, and 10-shogaol), were evaluated by pre-ADMET screening tools and molecular docking simulation towards hGABA_AR α1/γ2 subtype (PDB ID: 6X3X). Compounds with the best pre-ADMET profile and affinity were subjected to a 200 ns molecular dynamics (MD) simulation. The UPLC analysis was performed to detect and quantify gingerol and shogaol in EEZO.

Results: The best pre-ADMET prediction was shown by 6-gingerol, whereas the molecular docking simulations revealed that the best binding affinity and stability were shown by 6-gingerol (-7.41 kcal/mol) and 10-shogaol (-8.24 kcal/mol), which are comparable to that of diazepam. They build hydrogen bonds with α1 Ser206 and pi interaction with γ2 Phe77. The MD simulation confirmed that the stability of the 10-shogaol/hGABA_AR and 6-gingerol/hGABA_AR complexes is equal to that of diazepam/hGABA_AR. The UPLC analysis resulted in a level of 44.98 µg/mL for 6-gingerol and 2.52 µg/mL for 10-shogaol.

Conclusion: 6-Gingerol and 10-shogaol of EEZO may have the potential to be developed as novel allosteric agonists of human GABA_A receptors, thus explaining their anti-anxiety activity. However, the activity towards the human GABA_A receptor is lower than diazepam, its known allosteric agonist.

Background: Ethanol consumption by oral route can induce gastric cell necrosis and vascular damage due to excessive reactive oxygen species (ROS) production. ROS activates the translocation of NF-κB to the nucleus and increases iNOS expression, an enzyme that catalyzes nitric oxide (NO) production, eventually disrupting gastric protective mechanisms and contributing to ulcer formation. Etlingera elatior inflorescence, which has been traditionally used to alleviate stomach discomfort, was reported to possess anti-inflammatory activity. However, such a study on the downregulation of the iNOS expression is lacking.

Purpose: To confirm the gastro-protective and anti-ulcer effects of the E. elatior inflorescence (EEIE) extract via downregulation of iNOS expression in ethanol-induced gastric ulcer rats.

Methods: The fresh inflorescence petals were collected from West Java, Indonesia, and were extracted using 70% ethanol. The effects of 5 days of oral administration of EEIE were studied in ethanol-induced adult male Wistar rats by examining the weight gain percentage, feed residue, stomach ratio index, and microscopic and macroscopic evaluation of gastric mucosal damage. Subsequently, the iNOS expression in the rats' stomach was Western blotted by employing β-actin as the loading control.

Results: EEIE reduced weight gain percentage but did not show a significant difference in feed residue. EEIE increased the stomach ratio index, and at a dose of 625 mg/kg BW, significantly reduced the ulcer index, providing 100% protection (p < 0.05) to rats while decreasing inflammatory cell infiltration. EEIE inhibited the expression of iNOS in both cleaved and full-length forms at this dose.

Conclusion: Etlingera elatior inflorescence may have the potential to mitigate acute gastric ulcers by downregulating the expression of iNOS in ethanol-induced Wistar rats. However, further studies are needed to confirm its role in alleviating chronic ulcer models.