Pharmaceuticals

Background: Periplaneta americana grease (PAG), a lipid-rich fraction with documented wound-repair properties, remains challenging. This study aimed to develop a stable and patient-friendly film-forming agent (PAP) from PAG for topical wound management. Methods: The chemical profile of PAG was characterized with GC-MS. The formulation was optimized via single-factor and orthogonal experimental design. Comprehensive physicochemical characterization was performed. A vehicle control (film without PAG) was used to isolate PAG’s bioactive effects. In vitro, antioxidant (DPPH/ABTS assays) and antibacterial activity were evaluated. In vivo efficacy was assessed using a murine full-thickness wound model (mice, 150 µL applied 3 times daily for 10 days), with bFGF and Kangfuxin solution as positive controls. Histological analysis was conducted on healed tissue. Results: GC-MS revealed PAG’s complex composition, rich in sterols, terpenoids, and heterocyclic compounds. The optimized PAP formed a uniform, flexible film with suitable mechanical strength and shear-thinning rheology. PAP showed significant antioxidant activity and selective antibacterial activity against Staphylococcus aureus. In the wound model, PAP treatment significantly accelerated wound closure, achieving a 98.2% healing rate by day 10, comparable to positive controls and significantly superior to the vehicle control. Histology demonstrated enhanced re-epithelialization, reduced inflammation, and improved collagen organization. Conclusions: PAP was successfully formulated into a multifunctional film-forming agent that addresses key barriers to healing—infection, oxidative stress, and tissue regeneration. The results demonstrate its potential as an innovative therapeutic strategy for wound care.

Background: Opioid receptors are a commonly used target for treatment of pain conditions. Most opioids used in therapy are linked to adverse effects such as tolerance, dependence, and respiratory depression. Indole alkaloids acting on opioid receptors may provide a novel molecular mechanism to confer analgesic effects. Results: Indole alkaloids such as ibogaine and mitragynine act on μ-opioid receptors as biased full or partial agonists that do not, or much less strongly, recruit β-arrestin compared to non-biased agonists. The recruitment of β-arrestin has been linked to adverse effects, most notably substantial respiratory depression. The molecular mechanism of biased activation has been proposed to be associated with accommodation of the indole structure that leads to a different spatial orientation of amino acid residues in transmembrane regions 2 and 3 of the μ-opioid receptor as well as extracellular helix 8. Conclusions: Naturally occurring indole alkaloids show biased G-protein coupled activation of opioid receptors with limited recruitment of β-arrestin, thus limiting commonly observed adverse effects. Indole alkaloids may present a feasible structure to develop new biased opioid modulators with an improved risk-to-benefit ratio.

Background: Numerous plant-derived products have shown notable potential in preclinical studies and traditional use for the management of periodontitis, although clinical studies validating their efficacy remain scarce. The present study investigated the efficacy of a polyherbal phytopreparation as an adjunctive therapy to scaling and root planing (SRP) in patients with periodontitis, and further examined its underlying mechanisms of action, pharmacokinetic behavior, and toxicological profile using in silico approaches. Methods: Eighty patients with moderate periodontitis (stage II, grade A) were randomly assigned to two groups: a control group (n = 40) treated with SRP alone, and an experimental group (n = 40) receiving SRP followed by topical phytotherapeutic treatment with the polyherbal Tinctura paradentoica^®. Efficacy was evaluated using the gingival index, periodontal pocket depth, and cytomorphometric analysis of gingival cells before treatment and one month after. The in silico analysis, guided by HPLC profiling, included MolDock-based docking to assess interactions of bioactive compounds with cyclooxygenase isoforms COX-1 and COX-2 as anti-inflammatory targets, and evaluation of their pharmacokinetic and toxicity properties (ADME/Tox) using SwissADME, ProTox-3.0, and pkCSM. Results: Compared with SRP treatment, the experimental treatment significantly reduced the gingival index and periodontal pocket depth (p < 0.05), as well as the assessed cytomorphometric parameters (nuclear area, perimeter, and Feret’s diameter values) (p < 0.001). Rerank analysis revealed van der Waals-driven isoform selectivity: compact phenolic acids and aglycones favored COX-1, whereas bulky glycosides (e.g., rutin, narcissoside) were optimized for COX-2, with luteolin-7-O-glucoside showing near-balanced engagement. The ADME/Tox analysis indicated generally favorable pharmacokinetic and safety characteristics of phenolic compounds from the phytopreparation, including low systemic absorption and no predicted mutagenicity or skin sensitization potential. Conclusions: The topical application of the polyherbal phytopreparation demonstrated significant potential to enhance the efficacy of conventional SRP therapy by promoting the regression of gingival inflammation in patients with moderate periodontitis, further supported by in silico findings.