Camila Camponogara

Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice

This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases.

Hydrogel containing silibinin-loaded pomegranate oil based nanocapsules exhibits anti-inflammatory effects on skin damage UVB radiation-induced in mice

The present study shows the development of a topical formulation (hydrogel) containing silibinin-loaded pomegranate oil based nanocapsules suspension and its evaluation as an alternative for the treatment of cutaneous UVB radiation-induced damages. For this, an animal model of skin injury induced by UVB radiation was employed. Gellan gum was used as gel forming agent by its direct addition to nanocapsules suspension. The hydrogels showed adequate pH values (5.6-5.9) and a silibinin content close to the theoretical value (1mg/g). Through vertical Franz diffusion cells it was demonstrated that nanocapsules decreased the silibinin retention in the semisolid formulation. All formulations were effective in reducing mice ear edema and leukocyte infiltration induced by UVB radiation 24h after the treatments. After 48h, only the hydrogels containing nanocapsules or silibinin associated with pomegranate oil demonstrated anti-edematogenic effect, as well as the positive control (hydrogel containing silver sulfadiazine 1%). After 72h, the hydrogel containing unloaded pomegranate oil based nanocapsules still presented a small activity. In conclusion, the results of this investigation demonstrated the feasibility to prepare a semisolid formulation presenting performance comparable to the traditional therapeutic option for skin burns (silver sulfadiazine) and with prolonged in vivo anti-inflammatory activity compared to the non-nanoencapsulated compounds.

Antinociceptive activity and mechanism of action of hydroalcoholic extract and dichloromethane fraction of Amphilophium crucigerum seeds in mice

ETHNOPHARMACOLOGICAL RELEVANCE The medicinal plant generally known as monkeys comb (Amphilophium crucigerum) has been popularly described for the treatment of neuropathic and inflammatory pain, specially seeds preparations. AIM OF THE STUDY The goal of the present study was to evaluate the antinociceptive effect of the crude extract (Crd) and dichloromethane fraction (Dcm) of A. crucigerum seeds, and investigate the involvement of transient receptor potential vanilloid 1 (TRPV1) receptor in this effect. MATERIALS AND METHODS Male Swiss mice were used in this study. The effects of Crd and Dcm was tested on capsaicin-induced Ca2+ influx or the specific binding of [3H]-resiniferatoxin. Moreover, after treatment with Crd or Dcm, animals were exposed to acute pain (hot water tail-flick and capsaicin intraplantar test) or chronic pain models (injection of complete Freunds adjuvant or partial ligation of the sciatic nerve). Acute adverse effects were also noted: locomotor activity, corporal temperature, hepatic or renal damage, gastrointestinal transit alteration, and ulcerogenic activity. RESULTS The oral administration of Crd or Dcm resulted in an antinociceptive effect in the hot water tail-flick (48°C) and capsaicin intraplantar tests. Furthermore, these preparations exhibited antinociceptive and anti-inflammatory effects in a chronic inflammatory pain model, and antinociceptive effects in a neuropathic pain model. Moreover, Crd and Dcm reduced capsaicin-induced Ca2+ influx and diminished the [3H]-resiniferatoxin specific binding to spinal cord membranes. Acute adverse events were not found with Crd or Dcm administration. CONCLUSION In conclusion, our results support the analgesic effect of A. crucigerum and suggest the presence of compounds that may act as TRPV1 antagonists.

Solanum paranense Extracts and Solanine Present Anti-Inflammatory Activity in an Acute Skin Inflammation Model in Mice

The aim of the study was to evaluate the anti-inflammatory activity of the S. paranense crude extract, S. paranense alkaloid fraction, and solanine alkaloid. These samples reduce the croton oil-induced ear edema in a dose-dependent manner and a maximum inhibition of 81%, 98%, and 80% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Moreover, the samples inhibit the MPO activity with an inhibition maximum of 51%, 40%, and 46% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Similar results were found for dexamethasone 0.10 mg/ear (positive control), which showed inhibitions of ear edema and MPO activity of 100% and 65%, respectively. These results found probably are related to the presence of solanine which is present in significant quantity in the alkaloid fraction and others as rutin and rosmarinic, chlorogenic, and gallic acids. These results support the use of S. paranense for the treatment of inflammatory skin disorders.

α‐Spinasterol: a COX inhibitor and a transient receptor potential vanilloid 1 antagonist presents an antinociceptive effect in clinically relevant models of pain in mice

Postoperative pain is one of the most common manifestations of acute pain and is an important problem faced by patients after surgery. Moreover, neuronal trauma or chemotherapeutic treatment often causes neuropathic pain, which induces disabling and distressing symptoms. At present, treatments of both painful conditions are inadequate. α‐Spinasterol, which is well characterized as a transient receptor potential vanilloid 1 antagonist, has anti‐inflammatory, antioxidant and antinociceptive effects. Therefore, we investigated its antinociceptive potential on postoperative and neuropathic pain, as well as its effect on COX‐1 and COX‐2 activities.

Can the dietary fat type facilitate memory impairments in adulthood? A comparative study between Mediterranean and Western-based diet in rats

A balanced intake of fatty acids (FA) of both omega-6 (n-6) and -3 (n-3) series is essential for memory. The Mediterranean diet (MD), rich in n-3 polyunsaturated FA (PUFA) and low n-6/n-3 PUFA ratio, has shown beneficial influences on health. Inversely, the Western diet contains saturated fats, including hydrogenated vegetable fat (HVF, rich in trans fat) and interesterified fat (IF), making the n-6/n-3 PUFA ratio high. Due to the health impairments caused by HVF, it has been replaced by IF in processed foods. We compared an MD (balanced n-6/n-3 PUFA ratio) with Western diets 1 (WD1, rich in trans fat) and 2 (WD2, rich in IF) on memory process per se and following scopolamine (SCO) administration, which induces amnesia in rats. While MD exerted protective effects, WD1 and WD2 showed declined memory per se, showing higher susceptibility to SCO-induced memory deficits. In addition, WD1 and WD2 showed increased proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, IL-6] and decreased anti-inflammatory cytokines (IL-10) in plasma. IL-1β was higher in the hippocampus of WD1, which was reflected on histological assessments. Significant correlations between cognitive decline and inflammatory markers reinforce our hypothesis: MD-like fats may act preventively on cognitive loss, while WD-like fats may facilitate this.

Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain: Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain

There is a major, unmet need for the treatment of cancer pain, and new targets and medicines are required. The transient receptor potential ankyrin 1 (TRPA1), a cation channel expressed by nociceptors, is activated by oxidizing substances to mediate pain‐like responses in models of inflammatory and neuropathic pain. As cancer is known to increase oxidative stress, the role of TRPA1 was evaluated in a mouse model of cancer pain. Fourteen days after injection of B16‐F10 murine melanoma cells into the plantar region of the right hind paw, C57BL/6 mice exhibited mechanical and thermal allodynia and thigmotaxis behavior. While heat allodynia was partially reduced in TRP vanilloid 1 (TRPV1)‐deficient mice, thigmotaxis behavior and mechanical and cold allodynia were absent in TRPA1‐deficient mice. Deletion of TRPA1 or TRPV1 did not affect cancer growth. Intrathecal TRPA1 antisense oligonucleotides and two different TRPA1 antagonists (HC‐030031 or A967079) transiently attenuated thigmotaxis behavior and mechanical and cold allodynia. A TRPV1 antagonist (capsazepine) attenuated solely heat allodynia. NADPH oxidase activity and hydrogen peroxide levels were increased in hind paw skin 14 days after cancer cell inoculation. The antioxidant, α‐lipoic acid, attenuated mechanical and cold allodynia and thigmotaxis behavior, but not heat allodynia. Whereas TRPV1, via an oxidative stress‐independent pathway, contributes partially to heat hypersensitivity, oxidative stress‐dependent activation of TRPA1 plays a key role in mediating thigmotaxis behavior and mechanical and cold allodynia in a cancer pain model. TRPA1 antagonists might be beneficial in the treatment of cancer pain.

Topical treatment with a transient receptor potential ankyrin 1 (TRPA1) antagonist reduced nociception and inflammation in a thermal lesion model in rats

&NA; Thermal injury promotes tissue inflammation and pain, which is difficult to control. Different peripheral mechanisms seem to be involved in burn pain, such as free radical‐induced damage, but further study is still needed to understand how oxidant substances induced nociceptor sensitization. The transient receptor potential ankyrin 1 (TRPA1) is an ion channel activated by oxidants substances, and it could be sensitized after tissue inflammation. This study evaluated the TRPA1 involvement in nociception and inflammation produced by a thermal injury model. Male Wistar rats were used. The concentration of the TRPA1 antagonist (HC‐030031, 0.05%) on base cream was chosen using allyl isothiocyanate intraplantar test. Then, the base cream containing HC‐030031 was tested on the thermal injury model (induced by warm water immersion of hind paw, under anesthesia), and silver sulfadiazine (1%) was used as a positive control. Cream treatments on the hind paw were done daily (200 mg/paw) for 6 days after thermal injury. Also, nociception (static and dynamic mechanical allodynia, heat allodynia, and spontaneous pain) or edema were evaluated. On day 6, inflammatory and oxidative parameters were assessed. The base cream containing HC‐030031 produced antinociceptive and anti‐inflammatory effects (reduced the edema and inflammatory cells infiltration) and decreased the levels of hydrogen peroxide, or superoxide dismutase and NADPH oxidase activities after thermal injury. Thus, this study showed the involvement of the TRPA1 receptor in the nociception and inflammation caused by thermal injury and suggested that TRPA1 antagonists might be useful as novel treatments for pain and inflammation by topical application.