Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain.

Rosemary, Rosmarinus (R.) officinalis L. is a well-known plant with several useful properties such as analgesic, anti-inflammatory and anti-neurodegenerative. It has been used in folk medicine to alleviate rheumatic pain, stomachache and dysmenorrhea. Rosemary has several constituents such as rosmarinic acid which can be responsible for therapeutic properties been noted with rosemary. The aim of this study was to investigate the potential anti-inflammatory effects of R. officinalis and rosmarinic acid in a rat model of sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain to verify usage of rosemary in folk medicine. Rats underwent CCI, were treated with either normal saline, ethanolic extract of aerial parts of R. officinalis (400mg/kg, i.p.) or rosmarinic acid (40mg/kg, i.p.) from the day of surgery (day 0) for 14days. The anti-inflammatory effects of R. officinalis extract and rosmarinic acid were evaluated by assessing the levels of some spinal inflammatory markers including cyclooxygenase-2 (COX2), prostaglandin E2 (PGE-2), interleukin 1 beta (IL-1β), matrix metallopeptidase 2 (MMP2) through western blotting and nitric oxide (NO) production via Griess reaction on days 7 and 14 post-surgery. CCI rats exhibited a marked expression in the levels of inflammatory markers (COX2, PGE-2, IL-1β, MMP2 and NO) on both days 7 (p<0.001) and 14 (p<0.001). Rosmarinic acid and ethanolic extract of R. officinalis were able to decrease amounts of mentioned inflammatory markers on both days 7 (p<0.001) and 14 (p<0.001). Our data support the traditional use of R. officinalis as an effective remedy for pain relief and inflammatory disorders. It also suggests that the ethanolic extract of R. officinalis and rosmarinic acid through modulating neuro-inflammation might be potential candidates in treating neuropathic pain and different neurological disorders associated with inflammation.

Ghasemzadeh Rahbardar M ，Amin B ，Mehri S ，Mirnajafi-Zadeh SJ ，Hosseinzadeh H ... -  《-》

Effect of alcoholic extract of aerial parts of Rosmarinus officinalis L. on pain, inflammation and apoptosis induced by chronic constriction injury (CCI) model of neuropathic pain in rats.

According to traditional medicine, rosemary (Rosmarinus officinalis) has been used in many ailments such as dysmenorrhea, rheumatic pain and stomachache. This work was carried out to evaluate putative anti-allodynic and anti-hyperalgesic effects of Rosmarinus officinalis alcoholic extract and some spinal cord molecular changes on a neuropathic pain model in rats. Peripheral neuropathy was induced by chronic constriction injury (CCI) of sciatic nerve. Rats were treated daily with alcoholic extract of aerial parts of R. officinalis (100, 200, and 400mg/kg, i.p.), from the day of surgery (day 0) for 14 days. Mechanical allodynia, cold allodynia and heat hyperalgesia were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of apoptotic factors (bcl-2-like protein (Bax)), cleaved caspases 3 and 9, anti-apoptotic mediator, Bcl2, inflammatory mediators including tumor necrosis factor alpha (TNF-α), inducible isoform of nitric oxide synthase (iNOS), toll like receptor 4 (TLR4), microglial activation marker, ionized calcium-binding adapter molecule 1 (Iba-1) and astroglia activation marker, glial fibrillary acidic protein (GFAP) were measured via western blot on days 7 and 14. CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post-CCI. All three doses of rosemary alcoholic extract were able to attenuate neuropathic behavioral changes as compared with CCI animals that received vehicle. In the vehicle-treated CCI group, a significant increase in levels of Bax, cleaved caspases 3 and 9, Iba1, TNF-α, iNOS and TLR4 levels was detected on both days 7 and 14. Rosemary extract, 400mg/kg significantly decreased the amounts of mentioned apoptotic, inflammatory and glial markers as compared with vehicle-treated CCI animals. Anti-inflammatory and anti-apoptotic processes might contribute to the anti-allodynic and anti-hyperalgesic effects of rosemary following nerve injury. Our findings support the ethnopharmacological use of rosemary as a potential candidate in treating neuropathic pain and different neurological disorders that associate with the activation of apoptosis and inflammatory pathways.

Ghasemzadeh MR ，Amin B ，Mehri S ，Mirnajafi-Zadeh SJ ，Hosseinzadeh H ... -  《-》

Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain: An evidence of anti-oxidative and anti-inflammatory effects.

We aimed to investigate the potential prophylactic and curative effects of rosmarinic acid, one of the main constituents of rosemary, on the neuropathic pain induced by chronic constriction injury (CCI) in rats. CCI was used to induce peripheral neuropathic pain. In prophylactic groups, rosmarinic acid (10, 20, and 40 mg/kg, i.p.) was administered from the day of surgery (day 0) for 14 days. In treatment group, rosmarinic acid (40 mg/kg) was given from day 5 (after the pain was established), for 7 days. The degree of mechanical allodynia, cold allodynia, and heat hyperalgesia were measured on days 0, 3, 5, 7, 10 and 14 post-surgery. The open field test was carried out to assess locomotor activity of animals. Lumbar spinal cord levels of astroglia activation marker, glial fibrillary acidic protein (GFAP), microglial activation marker, ionized calcium-binding adapter molecule 1 (Iba-1), toll-like receptor 4 (TLR-4), tumor necrosis factor alpha (TNF-α), inducible isoform of nitric oxide synthase enzyme (iNOS) and apoptotic factors were quantified via western blot on days 7 and 14. CCI rats showed a significant mechanical allodynia, cold allodynia and thermal hyperalgesia, compared to sham ones on day 3, persisted up to day 14 post-CCI. Rosmarinic acid was able to prevent and also attenuate CCI-induced behavioral features in prophylactic as well as treatment groups, respectively. A significant increase in the levels of TNF-α, iNOS, apoptotic factors (Bax, caspases 3, 9), Iba-1, TLR-4, and GFAP was observed on both days 7 and 14, which was suppressed by 14 days administration of rosmarinic acid. These findings further support the use of rosemary in traditional medicine to alleviate pain. Rosmarinic acid could be a promising compound in prophylaxis and treatment of neuropathic pain. Anti-apoptotic and anti-inflammatory effects of rosmarinic acid may have important roles in the observed antinociceptive properties.

Rahbardar MG ，Amin B ，Mehri S ，Mirnajafi-Zadeh SJ ，Hosseinzadeh H ... -  《-》

Anti-inflammatory effect of rosmarinic acid and an extract of Rosmarinus officinalis in rat models of local and systemic inflammation.

Rosmarinic acid is a polyphenolic compound and main constituent of Rosmarinus officinalis and has been shown to possess antioxidant and anti-inflammatory properties. We aimed to evaluate the anti-inflammatory properties of rosmarinic acid and of an extract of R. officinalis in local inflammation (carrageenin-induced paw oedema model in the rat), and further evaluate the protective effect of rosmarinic acid in rat models of systemic inflammation: liver ischaemia-reperfusion (I/R) and thermal injury models. In the local inflammation model, rosmarinic acid was administered at 10, 25 and 50 mg/kg (p.o.), and the extract was administered at 10 and 25 mg/kg (equivalent doses to rosmarinic acid groups) to male Wistar rats. Administration of rosmarinic acid and extract at the dose of 25 mg/kg reduced paw oedema at 6 hr by over 60%, exhibiting a dose-response effect, suggesting that rosmarinic was the main contributor to the anti-inflammatory effect. In the liver I/R model, rosmarinic acid was administered at 25 mg/kg (i.v.) 30 min. prior to the induction of ischaemia and led to the significant reduction in the serum concentration of transaminases (AST and ALT) and LDH. In the thermal injury model, rosmarinic acid was administered at 25 mg/kg (i.v.) 5 min. prior to the induction of injury and significantly reduced multi-organ dysfunction markers (liver, kidney, lung) by modulating NF-κB and metalloproteinase-9. For the first time, the anti-inflammatory potential of rosmarinic acid has been identified, as it causes a substantial reduction in inflammation, and we speculate that it might be useful in the pharmacological modulation of injuries associated to inflammation.

Rocha J ，Eduardo-Figueira M ，Barateiro A ，Fernandes A ，Brites D ，Bronze R ，Duarte CM ，Serra AT ，Pinto R ，Freitas M ，Fernandes E ，Silva-Lima B ，Mota-Filipe H ，Sepodes B ... -  《-》

Systemic administration of Rosmarinus officinalis attenuates the inflammatory response induced by carrageenan in the mouse model of pleurisy.

Rosmarinus officinalis, also named rosemary, is a native plant from the Mediterranean region that is useful for the treatment of inflammatory diseases. Studies using experimental models and/or in vitro tests have shown the important biological effects of rosemary. In this context, the mechanism of the anti-inflammatory activity of rosemary must be investigated to support the discovery of new substances with anti-inflammatory effects. The aim of the present study was to investigate the anti-inflammatory effects of crude extract oil free obtained from the leaves of rosemary in an animal model of inflammation, thus evaluating its medicinal use for the treatment of inflammatory conditions. Also its ethanol, hexane, and ethyl acetate fractions, as well as its isolated compounds carnosol and rosmarinic acid were analyzed. Swiss mice were used for the in vivo experiments. The effect of this herb on the inhibition of the leukocytes, exudation, myeloperoxidase, and adenosine-deaminase activities, nitrite/nitrate, interleukin 17A, and interleukin 10 levels and mRNA expression was determined. The crude extract and its derived fractions, in addition to its isolated compounds, inhibited leukocytes and decreased exudation and myeloperoxidase and adenosine-deaminase activities, as well as nitrite/nitrate and interleukin 17A levels and mRNA expression, besides increasing interleukin 10 levels and mRNA expression. Rosemary showed important anti-inflammatory activity by inhibiting leukocytes and decreasing exudation. These effects were associated with a decrease in the proinflammatory parameters (myeloperoxidase, adenosine-deaminase, nitrite/nitrate, and interleukin 17A) and an increase in the anti-inflammatory cytokine (interleukin 10). This study confirms the anti-inflammatory properties of rosemary and validates its use in folk medicine to treat inflammatory diseases such as rheumatism and asthma.

da Rosa JS ，Facchin BM ，Bastos J ，Siqueira MA ，Micke GA ，Dalmarco EM ，Pizzolatti MG ，Fröde TS ... -  《-》