The Antinociceptive Potential of Camellia japonica Leaf Extract, (−)-Epicatechin, and Rutin against Chronic Constriction Injury-Induced Neuropathic Pain in Rats

Abstract

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been explored. We examined the antinociceptive efficacy and underlying mechanism of C. japonica leaf extract (CJE) in chronic constriction injury (CCI)-induced neuropathic pain models. To test the antinociceptive activity of CJE, three types of allodynia were evaluated: punctate allodynia using von Frey filaments, dynamic allodynia using a paintbrush and cotton swab, and cold allodynia using a cold plate test. CCI rats developed neuropathic pain representing increases in the three types of allodynia and spontaneous pain. In addition, CCI rats showed high phosphorylation levels of mitogen-activated protein kinases (MAPKs), transcription factors, and nociceptive mediators in dorsal root ganglion (DRG). The ionized calcium-binding adapter molecule 1 levels and neuroinflammation also increased following CCI surgery in the spinal cord. CJE and its active components have potential antinociceptive effects against CCI-induced neuropathic pain that might be mediated by MAPK activation in the DRG and microglial activation in the spinal cord. These findings suggest that CJE, (−)-epicatechin, and rutin could be novel candidates for neuropathic pain management.

Protective effect of epicatechin in diabetic-induced peripheral neuropathy: A review

“…to the nociceptive mice, after pretreatment with naloxone (2 mg/kg s.c.), glibenclamide (mg/ kg s.c.), ketanserin (0.3 mg/kg s.c.), yohimbine (0.15 mg/kg s.c.), pindolol (1 mg/kg s.c.), and atropine (0.1 mg/kg s.c.) exhibited reverse antinociceptive effect. The result indicates the participation of opioid receptors and potassium channels sensitive to ATP, as well as serotoninergic (receptors 5HT1A and 5HT2A), adrenergic (α2 receptor), and cholinergic receptors in the alleviation of pain receptors and might be useful in the management of diabetic neuropathy (Lopes et al, 2012). The above findings suggest that epicatechin having anti-oxidant activity can be employed to ameliorate neuropathic pain by modifying the complementary biochemical processes.…”

“…In this context, myristate 13-acetate was used to induce NF-κB in Jurkat T cells 4.6-fold more. In vitro results show that pretreatment with epicatechin (20 nM) reduced the expression of NF-κBup to 78% via preventing the NF-κBto gene, suggesting the modulating properties of epicatechin could affect the immune function properties of diabetic neuropathy individuals (Mackenzie et al, 2004). Recent discoveries demonstrate that ER stress plays a significant role in the O n l i n e F i r s t development of diabetic neuropathy and points to a potential new treatment target.…”

“…for 2 weeks reduced formalin-induced nociception (Quinonez-Bastidas et al, 2013). Recently, in chronic constriction injury-induced neuropathic pain models, researchers looked at the antinociceptive efficacy and underlying mechanism of Camellia japonica leaf extract having epicatechin and rutin, and found C. japonica leaf extract and its active components might have antinociceptive benefits against CCI4-induced neuropathic pain, which may be mediated through DRG MAPK activation and spinal microglial activation (Lim et al, 2022). Furthermore, epicatechin activates the NO-cyclic GMP-K + channel, 5-HT1A/1B/1D/5A serotonin receptors, and opioid receptors to produce antinociception (Quiñonez-Bastidas et al, 2018).…”

“…Similarly, (-)-epicatechin has demonstrated significant anti-diabetic activity by altering the relative expression of the GLUT 3 and TNF-proteins in an in vivo high fat, STZ-induced diabetic model, suggesting that it may alleviate neuropathy (Gonzalez, 2014). Lopes et al (2012) studied the mechanism of antinociceptive action of epicatechin isolated from the hydroalcoholic fraction of Combretum leprosum using Swiss albino mice model. Initially, the nociception was induced in the paw of animals by using 20 µmol of glutamate.…”

Quercetin Derivatives in Combating Spinal Cord Injury: A Mechanistic and Systematic Review

“…This adjuvant therapy increased MPO; and reduced spinal cord MDA and ROS, indicating the anti-inflammatory and antioxidative stress mechanism of rutin in alleviating SCI complications [76,77]. The anti-nociceptive and neuroprotective responses of rutin-containing compounds have also been shown to pass through MAPK activation [78]. As another quercetin complex, trihydroxyethyl rutin showed neuroprotective responses, improving nerve electrophysiological parameters and limb motor function following SCI, maintaining microvascular density, and decreasing injury area and demyelination degree [79].…”