Mahboobeh Rahbardar Ghasemzadeh1, Bahareh Amin2, Soghra Mehri3, Seyed Javad Mirnajafi-Zadeh4, Hossein Hosseinzadeh5. 1. Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Islamic Republic of Iran. 2. Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Islamic Republic of Iran. 3. Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran. 4. Department of Physiology, School of Medical Sciences, Tarbiat Modares University, PO Box: 14115-331, Tehran, Islamic Republic of Iran. Electronic address: mirnajaf@modares.ac.ir. 5. Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran. Electronic address: hosseinzadehh@mums.ac.ir.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional medicine, rosemary (Rosmarinus officinalis) has been used in many ailments such as dysmenorrhea, rheumatic pain and stomachache. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional medicine, rosemary (Rosmarinus officinalis) has been used in many ailments such as dysmenorrhea, rheumatic pain and stomachache. AIM OF THE STUDY: 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. MATERIALS AND METHODS: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 tumornecrosis 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. RESULTS:CCIrats 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. CONCLUSIONS: 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.