Tagitinin F has anti-inflammatory, anti-nociceptive and anti-matrix metalloproteinase properties: An in silico, in vitro and in vivo study.

Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 µM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.

A New Crystalline Ketoprofen Sodium Salt: Solid-State Characterization, Solubility, and Stability.

Ketoprofen (KTP) is an Active Pharmaceutical Ingredient (API) that has low solubility in aqueous solvents. The use of KTP salts has attracted attention due to its improvements in terms of solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a crystalline KTP sodium salt (coded as KTP-Na) was successfully obtained and widely characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), solubility and accelerated stability studies. XRD results showed that KTP-Na is not yet reported in the literature. Moreover, FTIR, DSC and TGA were useful for differentiation of KTP-Na from the KTP commercialized form (coded as KTP-R1). The solubility of KTP-Na in water was about 80 times greater than the KTP-R1. However, KTP-Na showed lower physical stability in storage conditions at 40 ± 2°C/ 75% ± 5% RH when compared to KTP-R1, which was shown to be related to a high hygroscopicity of KTP-Na. Therefore, due to its higher solubility, KTP-Na may be a viable alternative for use in solid dosage forms. However, the presence of moisture must be strictly controlled to avoid water absorption and consequent amorphization.

Impact of sesquiterpene lactones on the skin and skin-related cells? A systematic review of in vitro and in vivo evidence.

Although anti-inflammatory properties are attributed to sesquiterpene lactones (SL), cutaneous hypersensitivity reactions are proposed as limitations for SL-based therapies. Thus, the impact of SL on the skin and skin-related cells was systematically reviewed. Studies indexed in electronic databases were screened from the PRISMA strategy. The risk of bias in all studies was verified from the SYRCLE's tool. Thirty original studies were recovered and analyzed. Mice and guinea pig, keratinocytes and fibroblasts were predominantly investigated from in vivo and in vitro studies, respectively. In vivo studies indicated that most SL induced contact dermatitis associated with edema, erythema, and inflammatory infiltrate. Conversely, in vitro evidence was consistent with a dose-dependent anti-inflammatory effect of SL in response to reduced cytokines, 5-LOX, and COX-2 levels or activity in keratinocytes, fibroblasts, macrophages and dendritic cells; which are events potentially triggered by downregulation of gene expression and/or inhibition of the NF-κB signaling pathway. In vivo studies presented uncertain to high-risk of bias mainly associated with underreporting of randomization and experimental blinding. The current evidence supports potent cutaneous immunomodulatory properties of SL. Although in vitro and in vivo studies indicate opposite anti- or proinflammatory effects, this contradiction exhibits a dose-dependent component. In addition, the anti-inflammatory pathways activated by SL are better understood from in vitro evidence. However, additional studies are required to elucidating specific anti-inflammatory and proinflammatory mechanisms triggered by SL in vivo. Thus, controlling the sources of bias described in this review can contribute to improving the quality of the evidence in further investigations.