Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.

The antipyretic potential of viscosine, a natural product isolated from the medicinal plant Dodonaea viscosa, was investigated using yeast-induced pyrexia rat model, and its structure–activity relationship was investigated through molecular docking analyses with the target enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments showed a progressive dose-dependent reduction in body temperatures of the hyperthermic test animals when injected with viscosine. Comparison of docking analyses with target enzymes showed strongest bonding interactions (binding energy −17.34 kcal/mol) of viscosine with the active-site pocket of mPGES-1. These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E₂ in brain through its mPGES-1 inhibitory action and make it a potential lead compound for developing effective and safer antipyretic drugs for treating fever and related pathological conditions.

Antibacterial resistance is considered to be one of the major causes for mortality in coming years. In recent years green nanotechnology played a key role in addressing this problem. Biocompatible metal nanoparticles have gained popularity owing to their excellent therapeutic effects and minimal side effects. We report the synthesis of AgNPs and their amoxicillin conjugates (Ag-amoxi) using Micromeria biflora crude flavonoid extracts. The physicochemical properties of the synthesized NPs and Ag-amoxi conjugates were systematically evaluated using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and X-ray diffraction (XRD) analysis, Fourier transform infrared (FTIR), and UV-visible (UV-Vis) spectroscopic techniques. The average sizes of AgNPs and Ag-amoxi conjugates were 45 and 62 nm, respectively. We have also explored the antibacterial, antioxidant, anti-inflammatory, and analgesic properties of the AgNPs and Ag-amoxi conjugates through in vivo and in vitro analysis. The Ag-amoxi conjugates showed better antibacterial potential against Streptococcus Pneumoniae (S.P), Staphylococcus aureus (S.A), Pseudomonas aeruginosa (P.A), and Methicillin resistance Staphylococcus aureus (MRSA) strain both the drug and AgNPs. Similarly, in vivo anti-inflammatory studies revealed that both Ag-amoxi (68 %) and AgNPs (64 %) had strong anti-inflammatory effects, with (***p < 0.001) significance at a dose of 10 mg kg^-1 body weight as compared to standard, amoxicillin (45 %), and flavonoids extract (48 %) at a dose of 100 mg kg^-1. The findings of the antinociceptive activities (writhing and hot plate tests) demonstrated that the Ag-amoxi conjugates produced fewer writhing (15 in 20 s) and a shorter latency time of 22 s as compared to vehicle-treated (tramadol) animals, amoxicillin, and P.E at much lower doses. In vitro antioxidant studies revealed that the Ag-amoxi conjugate has the potential to be used as an antioxidant with an IC₅₀ value of 43.58, compared with AgNPs (46.34), amoxicillin (58.17), compared to the standard of ascorbic acid (34.14). These results reveals that these biologically inspired AgNPs and Ag-amoxi conjugate could be used to improve antibiotic efficiency and could play a critical role in addressing the multidrug resistance problem in coming years.