Piperine-hydroxybenzoate as phytochemistry antiosteoarthritis combination: Structural, solubility, and in vivo antiinflammatory study

Abstract

This study discusses the composition and structure determination of a new multicomponent system from antiinflammatory natural ingredients, consisting of piperine (Pip) and 4-hydroxybenzoic acid (HBA), named Pip-HBA. In addition, this research studied its solubility and anti-inflammatory activity. After screening the stoichiometric proportions, this multicomponent system formation reaction was carried out using the solvent-dropped grinding and evaporation methods. Characterizations using solid analysis including differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR), confirmed the formation of Pip-HBA. These multicomponent systems showed different thermograms and diffractograms. Furthermore, the FTIR spectrum of Pip-HBA multicomponent system differs from the physical mixture and its constituent components. Single crystal diffractometry (SCXRD) determined Pip-HBA to be a new multicomponent system structure in three dimensions. Pip-HBA showed increased solubility and anti-inflammatory activity compared to single piperine. Therefore, Pip-HBA multicomponent system has quite potential for further preparation development.

Keywords: 4-Hydroxybenzoic acid; Antiosteoarthritis; Piperine; Piperine-hydroxybenzoate; Solid-phase multicomponent.

Fig. 1

The structure of (a) Piperine (Pip) and (b) 4-hydroxybenzoic acid (HBA) [40,41].

Fig. 2

Crystals form (a) Piperine (b) HBA, and (c) Pip-HBA under 10× magnification.

Fig. 3

DSC thermogram of Pip-HBA multicomponent system compared to its constituent components (Pip and HBA), and physical mixture (Pip-HBA PM)

Fig. 4

Pip-HBA diffractogram compared to the constituent compounds (Piperine and HBA).

Fig. 5

FTIR spectra of Pip-HBA compared to piperine, HBA, and its PM

Fig. 6

Thermal ellipsoid plot of Pip-HBA cocrystal with 50 % probability. Hydrogen bonds were shown as blue lines. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 7

Packing diagrams of Pip-HBA (green: piperine; red & blue: HBA). The light blue color represents hydrogen bonds. (a) Pip-HBA ribbon structure, (b) Parallel part ofPip-HBA ribbon viewed along c-axis, (c) Pip-HBA layered structure. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 8

Solubility of (a) piperine in Pip-HBA and single piperine (Pip), (b) HBA in Pip-HBA and single HBA; (n = 3); RSD≤2; P < 0.05

Fig. 9

Percentage of inflammation of Na CMC, diclofenac sodium (diclo), piperine (Pip), 4-hydroxybenzoic acid (HBA), and Pip-HBA (three dosage variations) on carrageenan-induced inflammation.