Antinociceptive effects of oleuropein in experimental models of neuropathic pain in male rats

Abstract

Background: The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. Methods: Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 μg/kg) was injected for 10 days to develop neuropathic pain. The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H 2 S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. Results: Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H 2 S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H 2 S, CSE and CBS. Conclusions: Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H 2 S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.

N-type calcium channel blockers: a new approach towards the treatment of chronic neuropathic pain

“…Mitragyna speciosa [181,182], Momordica charantia [183], and Nigella Sativa [184,185] (Table 4). Acmella oleracea Asteraceae Leaves and flowers [187] Acorus calamus Araceae Rhizomes [188] Alstonia scholaris Apocyanaceae Milky juice of plant [189] Butea monosperma Fabaceae Leaves [190] Crocus sativus Iridaceae Flower [191] Curcuma longa Zingiberaceae Roots [192] Emblica officinalis Phyllanthaceae Fruit [193] Euphorbia tirucalli Euphor-biaceae Latex, root, bark [194] Gelsemium elegans Loganiaceae Seeds, stems [195,196] Ginkgo biloba Ginkgoaceae Herbal extract [197,198] Momordica charantia Cucurbitaceae Fruit [199] Nauclea latifolia Rubiaceae Roots [200,201] Ocimum sanctum Lamiaceae Leaves [202] Olea europaea Oleaceae Oil and leaves [203] Paederia scandens Rubiaceae Roots, leaves, bark, and fruits [204] Punica granatum Punicaceae The juice, whole fruit, flowers, and roots [205] Senna spectabilis Fabaceae Flowers, fruits and leaves [206] Thymus caramanicus Jalas Lamiaceae Aerial parts [207] Tribulus terristris Zygophylla-Ceae Complete herb [208] Trigonella foenum-graecum Fabaceae Seeds [209] Vernonia cinerea Asteraceae Whole plant [210] Future prospective of N-type VGCC blockers…”

The Effects of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (Nrf2) Activation in Preclinical Models of Peripheral Neuropathic Pain

“…Alkaloid levo-corydalmine [ 94 ], antioxidant alphalipoic acid [ 95 ], mitoquinone [ 96 ], endogenous fatty acid amide palmitoylethanolamide (PEA) in association with oxazoline forming the 2-pentadecyl-2-oxazoline of palmitoylethanolamide (PEA-OXA) [ 97 ], curcumin [ 98 ], quercetin [ 99 ], resveratrol [ 100 ], formononetin [ 101 ], berberine [ 102 ], dimethyl fumarate and its metabolite monomethyl fumarate [ 103 ], and oleuropein [ 104 ] can reduce pain and inflammation associated with CIPN by activating the Nrf2 pathway. In addition to these Nrf2 inducers, Zhang and Xu shed light on the effects of bromodomain-containing protein 4 (BRD4) on the alleviation of vincristine-induced PN [ 105 ].…”

“…In addition to the active constituents of garlic oil, several other natural compounds, including bromelain [ 113 ], a major protease from pineapple ( Ananas comosus ) [ 114 ], oleuropein, [ 104 ], paeoniflorin [ 115 ], a bioactive compound isolated from the dried roots of Paeonia lactifora Pallas or P. veitchii Lynch [ 115 ], the extracts from Thymus algeriensis and T. fontanesii ( Lamiaceae ) [ 116 ], quercetin [ 117 ], plumbagin [ 118 ], poly (ADP-ribose) polymerase (PARP) inhibitor 4-amino 1, 8-naphthalimide (4-ANI) [ 117 ], DOR agonist UFP-512 [ 119 ], and RTA-408 (a novel synthetic triterpenoid under clinical investigation) [ 120 ] ameliorated CCI-induced neuropathic pain. Targeted mechanisms reported involved either increasing the Nrf2 activity [ 104 , 114 , 116 , 117 , 119 , 120 ], enhancing the translocation of Nrf2 while suppressing the spinal NOD-like receptor protein 3 (NLRP3) inflammasome and NF-κB [ 115 ], or inhibiting PARP activation [ 117 ]. For example, Arruri et al reported that carvacrol attenuated CCI-induced neuropathic pain by inhibiting NLRP3 and activating autophagy via the Keap1/Nrf-2/p62 forward-feedback loop and augmenting mitochondrial quality control (MCQ) [ 121 , 122 ].…”