Ana Claudia Piccinelli

Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuropathic pain model

Abstract Objectives Previous studies have shown that essential oil containing (R)-(+)-limonene and α-phellandrene, extracted from fruits of Schinus terebinthifolius Raddi, exhibit anti-inflammatory activity. This work aimed to verify the antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from S. terebinthifolius fruits in spared nerve injury (SNI) model of neuropathic pain in rats. Methods In the present work, essential oil from fruits of S. terebinthifolius, as well as the pure (R)-(+)-limonene and α-phellandrene compounds, were assayed for their effects on SNI-induced mechanical and cold hyperalgesia, and depressive-like behavior (immobility in forced swim test) in rats. The locomotor activity was evaluated in open-field test. Results Oral administration for up to 15 days of essential oil of S. terebinthifolius (100 mg/kg), (R)-(+)-limonene (10 mg/kg), α-phellandrene (10 mg/kg), and also subcutaneous 10 mg/kg dose of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. On the 15th day of oral treatment, α-phellandrene, but neither the essential oil from S. terebinthifolius nor (R)-(+)-limonene, prevented the SNI-induced increase in sensitivity to a cold stimulus. The oral treatment with essential oil (100 mg/kg) or with compounds (10 mg/kg) did not interfere on locomotor activity. Discussion Together, the results of the present work show that essential oil of S. terebinthifolius and compounds present in this oil, including (R)-(+)-limonene and α-phellandrene, exhibit antihyperalgesic effects against mechanical hyperalgesia, and are antidepressive, while only α-phellandrene inhibited cold hyperalgesia in SNI rats.

Toxicological analysis and antihyperalgesic, antidepressant, and anti-inflammatory effects of Campomanesia adamantium fruit barks.

Objective: This study evaluates the anti-inflammatory, antihyperalgesic, and antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium fruit barks (CAE) on rodents and determines the safety of this plant. Methods: The acute toxicity of CAE was evaluated by oral administration to female rats as single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. In the subacute toxicity test, male and female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior (forced swimming test), and cold hypersensitivity in spared nerve injury (SNI) model in rats. Results: No clinical signs of toxicity were observed in animals from the experimental groups during acute and subacute exposure to CAE. At pleurisy test, the oral administration of CAE significantly inhibited leukocyte migration and protein leakage at all doses tested when compared to control. Oral administration of CAE for 3–15 days significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. Finally, on the 15th day, oral treatment with CAE prevented the increase in sensitivity to a cold stimulus induced by SNI. Discussion: The present study shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and antidepressive properties in rodents without causing toxicity.

Anti-Inflammatory and Antihyperalgesic Activities of Ethanolic Extract and Fruticulin A from Salvia lachnostachys Leaves in Mice.

The anti-inflammatory and analgesic effects of the ethanolic extract (SLEE) and fruticulin A from the leaves of Salvia lachnostachys were evaluated in mice, using experimental models of inflammation (paw oedema and pleurisy induced by carrageenan injection) and hyperalgesia (electronic Von Frey). Oral administration of SLEE (30, 100, and 300 mg/kg) and fruticulin A (0.3 and 3.0 mg/kg) decreased the total leucocytes number in pleural lavage, protein extravasation, and paw oedema. SLEE (100 mg/kg) and fruticulin A (3 mg/kg) also exhibited antihyperalgesic activity in carrageenan induced mechanical hyperalgesia. In addition, fruticulin A (3 mg/kg) prevented mechanical hyperalgesia, inhibiting TNF but not L-DOPA-induced mechanical hyperalgesia. In conclusion, SLEE and fruticulin A display anti-inflammatory and analgesic properties. Therefore, fruticulin A is at least partially responsible for the activity observed in the ethanolic extract of Salvia lachnostachys.

Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice

Aims: We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Main methods: Male Swiss mice received gp120, IL‐1&bgr; or TNF‐&agr; intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3 h after the injection. Spinal cord and blood samples were isolated for protein quantification. Key findings: Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3 h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3 h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL‐1&bgr; and IL‐10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF‐&agr; and IL‐1&bgr;‐induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4 h after intrathecal IL‐1&bgr; injection. Significance: These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL‐1&bgr; and IL‐10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL‐1&bgr; application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF‐&agr; and IL‐1&bgr; emphasizes the anti‐inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.

Anti-hyperalgesic and Anti-inflammatory Activity of Alternanthera Maritima Extract and 2″-O-α-l-rhamnopyranosylvitexin in Mice

Alternanthera maritima are used in Brazilian popular medicine for the treatment of inflammatory and infectious diseases. Species of Alternanthera have demonstrated biological activities in previous scientific studies. The aim of this study was to determine whether the ethanol extract of the aerial parts of A. maritima (EEAM) and the isolated compound 2″-O-α-l-rhamnopyranosyl-vitexin inhibit mechanical hyperalgesia and parameters of inflammation in mice. The oral administration of EEAM significantly inhibited carrageenan (Cg)-induced paw edema and reduced leukocyte migration into the pleural cavity. 2″-O-α-l-rhamnopyranosylvitexin significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. Both EEAM and 2″-O-α-l-rhamnopyranosylvitexin significantly prevented the Cg-induced hyperalgesia. Local administration of 2″-O-α-l-rhamnopyranosylvitexin significantly prevented the Cg- and tumor necrosis factor (TNF)-induced hyperalgesia. In conclusion, this study demonstrated that EEAM is an anti-inflammatory and anti-hyperalgesic agent, and the results suggested that 2″-O-α-l-rhamnopyranosylvitexin is responsible for the effects of EEAM and the mechanism involves the TNF pathway.

Antidepressive and antinociceptive effects of ethanolic extract and fruticuline A from Salvia lachnostachys Benth leaves on rodents

Objectives This study investigated the antidepressant and antinociceptive effects of ethanolic extract (SLEE) and pure fruticuline A obtained from Salvia lachnostachys leaves on rats and mice. Methods In this study, SLEE (100 mg/kg, p.o. route) was evaluated for its effects on spared nerve injury (SNI) in rats. The animals were submitted to mechanical sensitivity, forced swim (FST) and cold sensitivity tests 10 and 15 days after surgery. SLEE (100 mg/kg, p.o.) and fruticuline A (3 mg/kg, p.o.) were also evaluated with respect to nociceptive behavior induced by formalin. In addition, clonidine-induced depressive-like behavior was also analyzed. Results The oral administration of SLEE for up to 15 days and the subcutaneous injection of 10 mg/kg of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and decreased immobility in the FST. On the 15th day of oral treatment, SLEE prevented the SNI-induced increase in cold sensitivity. In the formalin test, SLEE and fruticuline A significantly reduced the frequency of paw licking during the first and second phases and decreased the formation of edema. In locomotor analysis (open field test without clonidine treatment), SLEE and fruticuline A did not alter the response. SLEE and fruticuline A significantly attenuated clonidine-induced suppression of spontaneous locomotor activity (squares invaded and licking) and emotionality (grooming and freezing) compared with controls, similar to the naive group. Conclusion SLEE exhibits antihyperalgesic, antidepressant, and antinociceptive effects, and fruticuline A appears to be at least partly responsible for the effects of SLEE. Together, these results demonstrate the antidepressive effects of SLEE and fruticuline A and indicate that both derivatives obtained from S. lachnostachys act against spontaneous neuropathic pain.

Subacute and Reproductive Oral Toxicity Assessment of the Hydroethanolic Extract of Jacaranda decurrens Roots in Adult Male Rats

Jacaranda decurrens subsp. symmetrifoliolata Farias & Proença (Bignoniaceae) is a species traditionally used for the treatment of inflammatory and infectious diseases. Previous findings from our group reported scientifically that J. decurrens has anti-inflammatory efficacy. However, more toxicological studies are needed to support and ensure its safe use. The present study was carried out to evaluate the toxic effects of a prolonged treatment with hydroethanolic root extract of J. decurrens (EJD) on hematological, biochemical, and reproductive parameters in adult male rats. The animals received by oral gavage 0; 250; 500; or 1000 mg/kg body weight of EJD for 28 days. After the treatment, biochemical, hematological, histopathological, and reproductive parameters were analyzed. The EJD treatment did not cause adverse effects on body weight gain, feed and water consumption, hematological and biochemical profiles, or histopathological analysis of liver and kidney. Similarly, there were no statistically significant differences in reproductive parameters, such as sperm production, number of sperm in the epididymis, and sperm morphology. These results demonstrate the absence of subacute toxicity as a result of the oral treatment with EJD for 28 days in adult male rats. However, other studies should be performed to evaluate the total safety of this plant.