Vijay Arruri1, Prashanth Komirishetty2, Aparna Areti1, Siva Kumar Naik Dungavath1, Ashutosh Kumar3. 1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India. 2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India; Division of Neurology & Neuroscience and Mental Health Institute, Department of Medicine, University of Alberta, Edmonton, AB, Canada. 3. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India. Electronic address: ashutosh@niperhyd.ac.in.
Abstract
BACKGROUND: Plumbagin is known to exhibit a broad range of biological activities including anti-cancer, antimicrobial and has been widely used traditionally. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) inhibitory and Nuclear factor (erythroid derived-2) like-2 (Nrf2) modulatory activities of Plumbagin have been reported already. In nerve injury model of neuropathy in rats, the role of NF-κB upregulation and declined antioxidant defence has been well recognized. So, we evaluated neuroprotective potential of Plumbagin in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in male Sprague-Dawley rats. METHODS: Animals were tested for functional, behavioural and biochemical changes. Various markers associated with oxidative stress and inflammatory changes were assessed in the sciatic nerve and dorsal root ganglion (DRG) of the animals exposed to CCI mediated nerve injury. RESULTS: CCI induced nerve injury led to long-lasting mechanical hyperalgesia, loss of hind limb function and abnormal pain sensation. Plumbagin treatment (10 and 20mg/kg, po) significantly and dose-dependently reversed mechanical hyperalgesia and other functional deficits. There was a marked increase in NF-κB and reduced Nrf2 levels in sciatic nerve and DRG following nerve injury. Plumbagin strengthened the antioxidant defence by improving Nrf2 levels and checked the neuroinflammation by decreasing NF-κB levels in sciatic nerve and DRG. CONCLUSIONS: Together, these results suggested that Plumbagin alleviated CCI-induced neuropathic pain via antioxidant and anti-inflammatory mechanisms. Hence, the study suggests that Plumbagin may be useful for the management of trauma-induced neuropathic pain.
BACKGROUND: Plumbagin is known to exhibit a broad range of biological activities including anti-cancer, antimicrobial and has been widely used traditionally. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) inhibitory and Nuclear factor (erythroid derived-2) like-2 (Nrf2) modulatory activities of Plumbagin have been reported already. In nerve injury model of neuropathy in rats, the role of NF-κB upregulation and declined antioxidant defence has been well recognized. So, we evaluated neuroprotective potential of Plumbagin in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in male Sprague-Dawley rats. METHODS: Animals were tested for functional, behavioural and biochemical changes. Various markers associated with oxidative stress and inflammatory changes were assessed in the sciatic nerve and dorsal root ganglion (DRG) of the animals exposed to CCI mediated nerve injury. RESULTS:CCI induced nerve injury led to long-lasting mechanical hyperalgesia, loss of hind limb function and abnormal pain sensation. Plumbagin treatment (10 and 20mg/kg, po) significantly and dose-dependently reversed mechanical hyperalgesia and other functional deficits. There was a marked increase in NF-κB and reduced Nrf2 levels in sciatic nerve and DRG following nerve injury. Plumbagin strengthened the antioxidant defence by improving Nrf2 levels and checked the neuroinflammation by decreasing NF-κB levels in sciatic nerve and DRG. CONCLUSIONS: Together, these results suggested that Plumbagin alleviated CCI-induced neuropathic pain via antioxidant and anti-inflammatory mechanisms. Hence, the study suggests that Plumbagin may be useful for the management of trauma-induced neuropathic pain.
Authors: Jiahe Li; Jiacheng Ma; Michael J Lacagnina; Sabina Lorca; Max A Odem; Edgar T Walters; Annemieke Kavelaars; Peter M Grace Journal: Anesthesiology Date: 2020-02 Impact factor: 7.892
Authors: Larissa Staurengo-Ferrari; Stephanie Badaro-Garcia; Miriam S N Hohmann; Marília F Manchope; Tiago H Zaninelli; Rubia Casagrande; Waldiceu A Verri Journal: Front Pharmacol Date: 2019-01-11 Impact factor: 5.810