Study of nuclear factor-2 erythroid related factor-2 activator, berberine, in paclitaxel induced peripheral neuropathy pain model in rats

Abstract

Objectives The role of nuclear factor‐2 erythroid related factor‐2 (Nrf2) activator, berberine (BBR), has been established in rat model of streptozotocin induced diabetic neuropathy. Around 30–40% of cancer patients, on paclitaxel (PTX) chemotherapy develop peripheral neuropathy. The present study was contemplated with the aim of establishing the neuropathy preventive role of BBR, in paclitaxel induced peripheral neuropathy model in rats. Methods A total of 30 Wistar rats were divided into five groups as follows: Group I: dimethyl sulfoxide; Group II: PTX+ 0.9% NaCl; Group III: Amitriptyline (ATL) + PTX; Group IV: BBR (10 mg/kg) + PTX and Group V: BBR (20 mg/kg) + PTX. Animals were assessed for tail flick latency, tail cold allodynia latency, histopathological scores, oxidative stress parameters, and mRNA expression of the Nrf2 gene in the sciatic nerve. Key findings Berberine significantly increased the tail flick and tail cold allodynia latencies and significantly decreased the histopathological score. BBR reduced oxidative stress by significantly decreasing the lipid peroxidation, increasing the superoxide dismutase and reduced glutathione levels in the sciatic nerve. BBR also increased the mRNA expression of Nrf2 gene in rat sciatic nerve. Conclusions All of these results showed the neuropathy preventing role of BBR in PTX induced neuropathy pain model in rats.

Ameliorative effect of gallic acid in paclitaxel-induced neuropathic pain in mice

“…PT enhances neuronal free radical production. Abundant accumulation of cytosolic free radicals is known to activate lipid peroxidation of the neuronal membrane [33]. In the present study, lipid peroxidation products (TBARS) levels were estimated by a spectrophotometric method [47].…”

“…Ayurvedic herbs have large quantities of GA [26,30,31]. Experimentally, GA has been documented to produce anti-hyperlipidemic, cardioprotective, anti-diabetic activity [32,33]. Furthermore, GA has potential neuroprotective action due to mono and poly-targeted actions [34,35].…”

Effects of alkaloids on peripheral neuropathic pain: a review

“…2) [78]. Singh et al [87] found that berberine was effective in ameliorating the heat hyperalgesia and cold allodynia. Morphometric analysis of sciatic nerves revealed that berberine treatment significantly increased axon diameter and myelin thickness, but the axon number did not be increased compared with the paclitaxel group.…”

“…In oxidative stress, genes encoding antioxidant defending enzymes are activated, especially the nuclear erythroid 2-related factor 2 (Nrf2) gene, which increases the expression of SOD, glutathione peroxidase (GSH-Px), and catalase genes [ 88 ]. Berberine exerted analgesic and neuroprotective effects via upregulating Nrf2 mRNA and further enhancing antioxidant capacity in the sciatic nerve [ 87 ].

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Therapeutic and biological activities of berberine: The involvement of Nrf2 signaling pathway

“…48,50,66 Brb has great efficacy in the treatment of neurological disorders. Sing et al 55 evaluated the protective effects of Brb in paclitaxel (PTX)-induced peripheral neuropathy pain model in rats. They exhibited that Brb administration is associated with an increase in the tail-flick, tail cold allodynia latencies as well as a reduction in histopathological score.…”