Future Pharmacol., Volume 5, Issue 2 (June 2025) – 6 articles

Background: Periodontal disease (PD) is a chronic inflammatory condition associated with dysbiotic biofilm, leading to the destruction of bone and periodontal ligament. Scaling and root planing (SRP) is the gold-standard treatment for PD, but some patients may not respond adequately, necessitating adjunctive therapies. This study investigated the antimicrobial activity of diacetylcurcumin (DAC), a modified curcumin, against multispecies subgingival biofilm associated with periodontitis. Methods: The biofilm, containing 40 bacterial species, was cultured for seven days in the Calgary apparatus. Treatments with DAC (200 μg/mL), 0.12% chlorhexidine (CHX), and a vehicle (control) were applied twice daily for 1 min, starting on the third day. On the seventh day, biofilms were analyzed for metabolic activity (MA) and bacterial counts via DNA-DNA hybridization. DAC toxicity was tested on Galleria mellonella larvae. Results: DAC reduced biofilm metabolic activity by 51%, while CHX achieved 88% reduction compared to the vehicle (p < 0.05). DAC also significantly decreased counts of key periodontal pathogens, including P. gingivalis, T. forsythia, P. intermedia, and A. actinomycetemcomitans (p < 0.05). At the tested concentration, DAC showed no toxicity in larvae. Conclusions: These findings suggest that DAC effectively reduces biofilm activity and periodontal pathogen counts, presenting a promising adjunctive therapy for PD. Full article

Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they are categorized as high-risk for leachables. Method: These external foreign chemical substances (leachables) may adversely affect and alter patient safety. Results: These primary container closure systems and manufacturing process equipment mainly comprise rubber elastomers, polypropylene, resin, ink, adhesives, glass, or plastic material. To establish the ID of detected compounds and their quantity in the finished parenteral drug formulation and then to assess the formulation for toxicological safety, broad-scope non-specific analytical screening methods are required that are capable of screening out and quantifying the predicted/unpredicted leachable compounds at the levels that pose anticipated toxicological concerns for human patients. Before the selection of the final primary packaging system for the parenteral drug product, their extractable screening profile/knowledge is required to minimize leachable compounds in the finished drug product formulation and to develop and manufacture a safe product for human patients. The adverse effect or toxicity of leachables proportionally increases with an increase in the dose of the drug product or the duration of therapy because the volume of the drug product administered to a patient in a larger quantity is directly proportional to the concentration of the detected leachable. Conclusion: This document outlines the detailed process/scientific approach for conducting an organic leachable screening profile for parenteral drug products with respect to the chemical nature of leachables, i.e., polarity, propensity, volatility, and techniques. Full article

Introduction: Decursin is a pyranocoumarin natural phytochemical found in the Angelica gigas Nakai herb, which shows various therapeutic properties and beneficial effects against various diseases. Objective: The aim of this study was to find the anticancer potential of decursin and its molecular mechanisms involved with different anticancer effects. Methodology: All of the relevant data concerning this compound and cancer were collected using different scientific search engines, including PubMed, Scopus, Springer Link, Wiley Online, Web of Science, Scifinder, ScienceDirect, and Google Scholar. Results: This study found that decursin shows anticancer properties through various mechanisms, such as apoptosis, cell cycle arrest, inhibition of cell proliferation, autophagy, inhibition of angiogenesis, cytotoxicity, and the inhibition of invasion and migration against a number of cancers, including breast, bladder, lung, colon, skin, ovarian, prostate, pancreatic, and bone cancers. This study also discovered that decursin has the ability to affect several signaling pathways in the molecular anticancer mechanisms, such as the PI3K/AKT/mTOR, JAK/STAT, and MAPK signaling pathways. Findings also revealed that decursin expresses poor oral bioavailability. Conclusions: Based on the data analysis from this literature-based study, decursin has properties to be considered as a potential candidate in the treatment of cancer. However, more clinical research is suggested to establish proper efficacy, safety, and human dosage. Full article

Background: Cnidoscolus quercifolius, popularly known as “favela”, is used in traditional medicine to treat various conditions, such as infections and inflammations. However, its therapeutic potentials remain underexplored in scientific research. The present study aimed to evaluate the anxiolytic effect, toxicity, and antioxidant activity of methanolic (EMCq) and ethyl acetate (EAECq) extracts of C. quercifolius bark, as well as determine their chemical composition by HPLC/DAD and their levels of phenolic compounds and flavonoids. Methods: Anxiolytic effect and acute toxicity tests were conducted using the zebrafish model, while antioxidant activity was assessed using the DPPH^• and ABTS⁺ methods. The chemical composition was obtained by HPLC/DAD, and phenolic compounds and flavonoids were quantified with the Folin–Ciocalteu reagents and the aluminum chloride colorimetric method, respectively. Results: Caffeic acid, p-coumaric acid, cinnamic acid, pinocembrin, and apigenin were identified and quantified. The results indicated that both extracts exhibited low antioxidant activity, possibly due to their low levels of phenols (0.187 and 0.293 mg GAE/g) and flavonoids (0.84 and 0.64 mg QE/g). However, the extracts did not show acute toxicity (>400 mg/kg) and reduced the locomotor activity of zebrafish at all the doses tested (40 to 400 mg/kg), while increasing the time the animals remained in the light zone, indicating an anxiolytic effect. Conclusions: These findings suggest for the first time that C. quercifolius has anxiolytic properties, warranting further investigation into specific bioactive compounds and their mechanisms of action. Future studies may explore molecular analysis techniques to identify the responsible compounds, as well as investigate safety and clinical efficacy in mammalian models. Full article

Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic approaches, such as antioxidants (Ascorbic Acid), have been explored for their potential to relieve acute pain after surgery, cancer-related pain, and chronic pain not related to cancer with fewer adverse effects. Furthermore, the use of pharmacological combinations is an alternative treatment strategy to obtain a higher efficacy using lower drug concentrations, at which side effects are minimal. Background/Objectives: The aim of this study was to evaluate the pharmacological synergism of ketorolac and ascorbic acid in an inflammatory pain model. Methods: The individual and combined effects of ketorolac and ascorbic acid were evaluated in a formalin-induced pain model in mice. Four experimental groups were established: control (vehicle), ketorolac (KET), ascorbic acid (AA), and combination (KET/AA). Results: The combination of ketorolac and ascorbic acid produced a greater antinociceptive effect compared to the vehicle and individual treatments in the formalin model. Notably, even the lowest dose of the combination (KET 6.26/AA 3.21 µg/paw) exhibited a stronger effect than the maximum doses of each individual treatment KET (100 µg/paw) and AA (100 µg/paw). The effective concentration that produced 30% of antinociception (EC₃₀) for the tested treatments were determined, and an isobologram analysis confirmed the presence of a synergistic interaction in these combinations. Conclusions: These findings suggest that the combination of ketorolac and ascorbic acid produces a synergistic antinociceptive effect in the formalin-induced pain model. The enhanced efficacy of the combination indicates a potential therapeutic advantage in pain management by reducing the required dosage of each compound while maintaining or improving analgesic effects. Full article

The aim of this review is to evaluate the therapeutic possibilities of trifluralin and other 2,6-dinitroaniline herbicides by assessing different aspects of trifluralin’s toxicology (including its mitochondrial toxicity), pharmacokinetics, and environmental fate. The particular features of TFL have triggered a wide range of policies about its properties. Is has been banned in some countries and, at the same time, has been proposed as a drug for the cure of parasitic disease by some scientific research articles. The use of this pre-emergence herbicide to control broadleaf weeds and annual grasses is assumed to rely only on its microtubule depolarization or cytoskeleton disassembly abilities (on-target effect), a fact that justifies its inhibition of a wide range of microorganisms (mostly protozoans), sharing a relatively high degree of conservation in tubulin protein sequences with weeds and grasses. Recent studies have confirmed that TFL also affects mitochondrial function (off-target effect), a hypothesis previously suggested in earlier works. Here, we account for the main issues in TFL toxicology, other potential uses of the herbicide outside crops, and its feasibility for use as an antiprotozoal drug. Full article