Euphorbia bicolor(Euphorbiaceae) Latex Extract Reduces Inflammatory Cytokines and Oxidative Stress in a Rat Model of Orofacial Pain

Abstract

Recent studies have reported that the transient receptor potential V1 ion channel (TRPV1), a pain generator on sensory neurons, is activated and potentiated by NADPH oxidase-generated reactive oxygen species (ROS). ROS are increased by advanced oxidation protein products (AOPPs), which activate NADPH oxidase by upregulating Nox4 expression. Our previous studies reported that Euphorbia bicolor (Euphorbiaceae) latex extract induced peripheral analgesia, partly via TRPV1, in hindpaw-inflamed male and female rats. The present study reports that E. bicolor latex extract also can evoke analgesia via reduction of oxidative stress biomarkers and proinflammatory cytokines/chemokines in a rat model of orofacial pain. Male and female rats were injected with complete Freund’s adjuvant (CFA) into the left vibrissal pad to induce orofacial inflammation, and mechanical allodynia was measured by the von Frey method. Twenty-four hours later, rats received one injection of E. bicolor latex extract or vehicle into the inflamed vibrissal pad. Mechanical sensitivity was reassessed at 1, 6, 24, and/or 72 hours. Trigeminal ganglia and trunk blood were collected at each time point. In the trigeminal ganglia, ROS were quantified using 2′,7′-dichlorodihydrofluorescein diacetate dye, Nox4 protein was quantified by Western blots, and cytokines/chemokines were quantified using a cytokine array. AOPPs were quantified in trunk blood using a spectrophotometric assay. E. bicolor latex extract significantly reduced orofacial mechanical allodynia in male and female rats at 24 and 72 hours, respectively. ROS, Nox4, and proinflammatory cytokines/chemokines were significantly reduced in the trigeminal ganglia, and plasma AOPP was significantly reduced in the trunk blood of extract-treated compared to vehicle-treated rats. In vitro assays indicate that E. bicolor latex extract possessed antioxidant activities by scavenging free radicals. Together our data indicate that the phytochemicals in E. bicolor latex may serve as novel therapeutics for treating oxidative stress-induced pain conditions.

Euphorbia species latex: A comprehensive review on phytochemistry and biological activities

“…Analysis by UPLC-ESI-MS/MS of latex methanolic extract samples from E. bicolor collected in Denton County, TX, USA identified two diterpenes (36) and (37) ( Basu et al, 2019 ) responsible for the anti-inflammatory ( Fernandez et al, 2001 ) and analgesic activity, respectively.…”

“…The DPPH and NO radical scavenging activities of the extract show strong correlation with phenolic compounds and terpenoids contents. On the other hand, the H 2 O 2 radical scavenging activity shows weak correlations with polyphenols contents ( Basu et al, 2019 ).…”

“…Figure 12 shows a proposed model of the non-opioid mechanism that contributes to the peripheral analgesia induced by E. bicolor latex extracts. It shows that local injection of phytochemicals from E. bicolor latex at the site of injury may be effective in reducing oxidative stress by reducing the plasma levels of advanced oxidation protein products (AOPP) and increasing the expression of the Nox4 protein, which leads to a decrease in the levels of reactive oxygen species and consequently, the release of the pro-inflammatory peptide ( Basu et al, 2019 ).…”

“… Proposed model of the mechanisms involved in E. bicolor latex extract-evoked peripheral, nonopioid analgesia ( Basu et al, 2019 ). …”

Therapeutic Agents for the Treatment of Temporomandibular Joint Disorders: Progress and Perspective

“…In this process, its role in antioxidant activities matters. Basically, the extract downregulated the level of advanced oxidation protein product (AOPP), leading to fewer reactive oxygen species (ROS) produced via Nox4, which would be followed by a consequential decrease in activation of TRPV1 as the peripheral pain generator (Basu et al, 2019). The molecule provided a cure for both acute and chronic pain and functioned independently of the opioid receptors, which indicate its medical potential (Basu et al, 2019).…”