Effect of Extract and Synthesized Derivatives of Isolated Compound from Symplocos chinensis f. Pilosa Ohwi on Neuropathic Pain in Mice

Abstract

Neuropathic pain is described as the “most terrible of all tortures that a nerve wound may inflict.” The aim of the present study was to demonstrate the antinociceptive effect of Symplocos chinensis f. pilosa Ohwi water extract (SCW) and synthesized derivatives of the isolated compound. The antinociceptive effect was tested using the acetic acid-induced writhing and 5% formalin tests. Antinociceptive effects on neuropathic pain were evaluated using the von Frey test with chronic constriction injury (CCI) and surgical nerve injury (SNI) models and tail-flick test with a vincristine-induced pain model. An Ames test was also conducted. 5-hydroxymethylfurfural (5-HMF) was isolated and derivatives were synthesized with various acid groups. Among the plant water extracts, SCW showed significantly effective activity. Additionally, SCW presented antinociceptive effects in the neuropathic pain models. The SCW water fraction resulted in fewer writhes than the other fractions, and isolated 5-HMF was identified as an effective compound. Because 5-HMF revealed a positive response in the Ames test, derivatives were synthesized. Among the synthesized derivations, 5-succinoxymethylfurfural (5-SMF) showed the best effect in the neuropathic pain model. Our data suggest that SCW and the synthesized compound, 5-SMF, possess effective antinociceptive activity against neuropathic pain.

5,7-Dimethoxycoumarin ameliorates vincristine induced neuropathic pain: potential role of 5HT3 receptors and monoamines

“…In this regard, a variety of natural and synthetic compounds, primarily those with antioxidant potential in the attenuation of VINP, have been examined ( Khan et al, 2019 ; Chen et al, 2020 ; Lee et al, 2020 ; Starobova et al, 2019 ; Zhou et al, 2020 ; Khan et al, 2021 ; Zhu et al, 2021 ; Khodaei et al, 2022 ; Fouda et al, 2023 ). In our study, VCR administration caused a significant decrease in tail immersion withdrawal latency when assessed on days 10 and 14 of the treatment protocol, and this has also been reported in other studies ( Khan et al, 2019 ; Amirkhanloo et al, 2020 ; Kim H. et al, 2021 ). The suggested mechanisms underlying adverse actions of VINP include: swelling of mitochondria in axons intracellularly, leading to the release of calcium ions and apoptosis; increased substance P levels in the spinal cord ( Chiba et al, 2022 ); an involvement of altered adenosine signaling in pain transmission ( Zhou et al, 2022 ); increased release of substances (TNF-α, an adipocytokine, interleukin-1 [IL-1] and IL-6 (cytokines) and NO in glial cells, macrophages, and Langerhans cells); downregulation of IL-10 in the spinal dorsal horn; increased NOS in the spinal cord dorsal horn, increased 5-HT2A receptors in dorsal horn and dorsal root ganglion neurons; increased ROS, which affect serine protease activity and decrease endorphins in the spinal cord as well as the dorsal root ganglion; and increased serine proteinase that inactivates endorphins ( Thibault et al, 2008 ; Addington and Freimer, 2016 ).…”

“…5,7-DMC suppresses the production of IL-1β, TNFα and IL-8 in the colorectal carcinoma HT-29 cell line ( Lee et al, 2022 ). Similarly, it inhibits the expression of IL-8 in the cystic fibrosis bronchial epithelial IB3-1 cell line ( Borgatti et al, 2011 ), and inhibits the expression of IL-4 in RBL-2H3 cells, which are commonly used in immunological experiments, inflammation and allergy ( Kim H. et al, 2021 ). Furthermore, 5,7-DMC decreases the concentration of monoamine oxidase-A, which is responsible for metabolizing monoamines ( Yang and Wang, 2018 ).…”

Diverse Applications of Biomass‐Derived 5‐Hydroxymethylfurfural and Derivatives as Renewable Starting Materials

“…The library of compounds obtained displayed a moderate inhibition of protein tyrosine phosphatase 1B (PTP 1B), which suggests potential application towards the treatment of diabetes and obesity. The esterification of HMF was also observed in a report by Kim et al., who after structural identification of compounds derived from Symplocos chinensis subsequently synthesized the esterification products identified [42] . The lipase‐catalyzed esterification was done with a variety of carboxylic acids and aided by molecular sieves to obtain a range of esters ( 30 ).…”