Neuropathic pain (NP) is the most prevalent and debilitating form of chronic pain, caused by injuries or diseases of the somatosensory system. Since current first-line treatments only provide poor symptomatic relief, the search for new therapeutic strategies for managing NP is an active field of investigation. Multiple mechanisms contribute to the genesis and maintenance of NP, including damage caused by oxidative stress. The naturally occurring antioxidant alpha-lipoic acid (ALA) is a promising therapeutic agent for the management of NP. Several pre-clinical in vitro and in vivo studies as well as clinical trials demonstrate the analgesic potential of ALA in the management of NP. The beneficial biological activities of ALA are reflected in the various patents for the development of ALA-based innovative products. This review demonstrates the therapeutic potential of ALA in the management of NP by discussing its analgesic effects by multiple antioxidant mechanisms as well as the use of patented ALA-based products and how technological approaches have been applied to enhance ALA’s pharmacological properties.

The "witch broom disease" caused by the fungus called Moniliophthora perniciosa is one of the most important cocoa diseases in Latin America, causing around 70% production reduction in the southern Bahia. In attempt to solve the problem, many cultivars resistant to the disease have been recommended to farmers. On the other hand, the chocolate flavour is composed by many compounds whose formation depends on the genetic background, environment where cocoa is grown and processing operations. Therefore, this work aimed at determining the monomeric phenolic compounds, methylxanthines and antioxidant activity of cocoa mass and dark chocolate from cocoa cultivars resistant to "witch broom disease" and non resistant to the disease. The total phenolic compounds in cocoa mass did not vary among cultivars with values ranging from 23.95mg g-1 to 25.03mg g-1. Chocolates made from non resistant cultivars showed higher total phenolic compounds (19.11mg g-1) than SR162 and PH16 with 16.08mg g-1 and 15.46mg g-1, respectively. Epicatechin had higher content than catechin and the levels of these two compounds were higher in SR162. There were significant differences among samples of cocoa mass analyzed for caffeine. Chocolate made from SR162 had the highest amount of monomeric compounds due to its high concentration of catechin and epicatechin. The chocolate sample with the highest antioxidant activity was the SR162, followed by non resistant blend and PH16, showing relationship between the antioxidant activity and monomeric phenolics content.

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56–100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED₅₀ values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56–25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund’s adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE₂ levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production.

Carvacryl acetate (CA) is a monoterpene obtained from carvacrol, which exhibits anti-inflammatory activity. However, its low solubility in aqueous media limits its application and bioavailability. Herein, we aimed to develop a carvacryl acetate nanoemulsion (CANE) and assess its anti-inflammatory potential in preclinical trials. The optimized nanoemulsion was produced by ultrasound, and stability parameters were characterized for 90 days using dynamic light scattering after hydrophilic–lipophilic balance (HLB) assessment. To evaluate anti-inflammatory activity, a complete Freund’s adjuvant-induced inflammation model was established. Paw edema was measured, and local interleukin (IL)-1β levels were quantified using ELISA. Toxicity was assessed based on behavioral changes and biochemical assays. The optimized nanoemulsion contained 3% CA, 9% surfactants (HLB 9), and 88% water and exhibited good stability over 90 days, with no signs of toxicity. The release study revealed that CANE followed zero-order kinetics. Dose–response curves for CA were generated for intraperitoneal and oral administration, demonstrating anti-inflammatory effects by both routes; however, efficacy was lower when administered orally. Furthermore, CANE showed improved anti-inflammatory activity when compared with free oil, particularly when administered orally. Moreover, daily treatment with CANE did not induce behavioral or biochemical alterations. Overall, these findings indicate that nanoemulsification can enhance the anti-inflammatory properties of CA by oral administration.