Background/Objectives: The antinociceptive and anti-inflammatory effects of a patent-pending ointment containing plant extracts from Eucalyptus globulus, Curcuma longa, Hamamelis virginiana, Echinacea purpurea, and Zingiber officinale were evaluated. Methods: Plant extracts were chemically characterized by gas chromatography–mass spectroscopy. The antinociceptive activity of the ointment was assessed using the hot plate, tail flick, and formalin tests, whereas the anti-inflammatory activity was measured using the acute and chronic TPA-induced ear edema tests. Mechanisms of action were evaluated using inhibitors from signaling pathways related to pain response and by using histological analysis and assessing the expression and activity of pro-inflammatory mediators. Results: The ointment showed antinociceptive and anti-inflammatory effects like those observed with diclofenac gel (1.16% v/v) and ketoprofen gel (2.5% v/v). The antinociceptive actions of the ointment are mediated by the possible participation of the opiodergic system and the nitric oxide pathway. The anti-inflammatory response was characterized by a decrease in myeloperoxidase (MPO) activity and by a reduction in ear swelling and monocyte infiltration in the acute inflammation model. In the chronic model, the mechanism of action relied on a decrease in pro-inflammatory mediators such as COX-2, IL-1β, TNF-α, and MPO. An in-silico study with myristic acid, one of the compounds identified in the ointment’s plant mixture, corroborated the in vivo results. Conclusions: The ointment showed antinociceptive activities mediated by the decrease in COX-2 and NO levels, and anti-inflammatory activity due to the reduction in IL-1β and TNFα levels, a reduction in MPO activity, and a decrease in NF-κB and COX-2 expression.

The present study describes the synthesis of an analog of the anti‐inflammatory drug fenbufen, a compound which has recently attracted of renewed interest in the treatment of chronic degenerative diseases such as cancer and rheumatoid arthritis. The molecule under consideration, 4‐(4‐methoxyphenyl)‐4‐oxobutanoic acid, is distinguished from fenbufen by the absence of the biphenyl moiety. This characteristic results in the generation of nontoxic metabolites during biotransformation. The incorporation of aromatic amino acid residues (phenylalanine and tyrosine) led to the modulation of the hybrid NSAID–amino acid and NSAID–peptide derivatives, thereby altering their biological activity and safety profile. The inhibitory activity against the dual cyclooxygenase‐2/5‐lipoxygenase system was evaluated using molecular docking, free energy calculations, and per‐residue decomposition analysis based on molecular dynamics simulations. Compounds containing a tyrosine residue or the Tyr‐Phe dipeptide exhibited strong drug–receptor binding affinities and long‐term stability during our simulations, in some cases outperforming the reference drugs celecoxib and zileuton. The values of the free energy (Δ G ) obtained through the Boltzmann equation demonstrated a strong correlation with the energy decomposition data, particularly for the lead compounds, which exhibited stabilizing interactions with the heme prosthetic group and the Fe ²⁺ ion. These findings provide substantial support for the identification of these molecules as promising candidates for further preclinical development.

Parkinson’s disease is the second most common neurodegenerative disease in the world. Natural products can offer a possible option of neuroprotective agents for preventing neurodegenerative diseases. D-Pinitol is a cyclic polyol with anxiolytic and antidepressant effects in acute assays. This work aimed to evaluate the effects of D-Pinitol (10, 50, and 100 mg/kg p.o.) in a chronic reserpine-induced depression model (19 days), using the forced swimming and tail suspension tests in female Balb/c mice, and the neuroprotective effects in an MPTP-induced Parkinsonism model (30 days) in male C57bL/6 mice, using behavioral tests such as wire grip, rotarod, catalepsy, and others. D-Pinitol showed low antidepressant-like effects in the reserpine-induced chronic depression model, compared to amitriptyline (25 mg/kg p.o.). D-Pinitol protected MPTP-treated mice from motor impairment with similar effects to those shown by L-Dopa (25 mg/kg p.o.) as evaluated in different behavioral tests. The inhibition of oxidative stress markers, increase in dopamine levels, and avoidance of apoptosis in neuronal cells were the mechanisms by which D-Pinitol protects MPTP-treated mice from motor impairment.

In this paper, the synthesis of compounds based on a hybrid structure combining a fenbufen analog (a nonsteroidal anti-inflammatory drug, NSAID) with amino acids or peptides is described. Additionally, a detailed molecular docking analysis was performed to investigate their drug–receptor interactions with inflammation-related enzymes COX-2 and 5-LOX. The hybrid compound that demonstrated the best interaction was further evaluated through molecular dynamics simulations, and its binding free energy (ΔG) was calculated using the Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) method.