Umbelliprenin relieves paclitaxel-induced neuropathy

Abstract

Objectives Umbelliprenin (UMB) is a prenylated coumarin that acts as an in vitro antioxidant and inhibits lipoxygenase managing the inflammation pathways, while in vivo it exerts anti-inflammatory activities. Methods In this study, neuropathic pain was induced by four intraperitoneal doses of 2 mg/kg per day of paclitaxel (PTX) on days 1, 3, 5 and 7. Here, 49 male mice were randomly divided in the following groups: sham (not treated animals), negative control (PTX-treated receiving normal saline), single-dose UMB 6.25, 12.5 and 25 mg/kg groups (PTX-treated receiving UMB 6.25, 12.5 and 25 mg/kg, respectively), prevention (PTX-treated receiving PTX along with UMB 12.5 mg/ kg on days 1, 3, 5 and 7) and positive control group (PTX-treated receiving imipramine 10 mg/kg as acute treatment). Hot-plate test was done to assess response to heat. Finally, interleukin (IL)-6 levels in the sciatic nerve and lipid peroxidation in sera were assessed. Key findings Umbelliprenin was found equally effective for acute treatment with imipramine, when comparing the prevention group and the positive control group. Single, 25 mg/kg UMB effectively attenuated hyperalgesia, lipid peroxidation and IL-6 levels. Conclusions Umbelliprenin alleviated neuropathic pain, and decreased serum IL-6 levels and oxidative stress. UMB deserves further investigations, especially in clinical settings.

Auraptene Alleviates Paclitaxel-induced Neuropathy in Mice

“…In this assay, animals were put on the hot plate device in order to calculate the time they start licking, lifting paws, or jumping from the surface (i.e., response latency). The cut-off time (the maximum time that can put animals on the hot plate device) was considered 45 s (Shahraki et al, 2020). Latencies were measured at 30, 60, 90, and 120 min after AUR and imipramine 10 mg/kg i.p.…”

Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy

“…Among the approved drugs, duloxetine, lacosamide, pregabalin, and rosuvastatin have also been reported to reverse PIPN via their antioxidant effects [23,28,32]. Moreover, many agents, which have antioxidant effects, inhibit PIPN in preclinical studies [19,22,[24][25][26][29][30][31]33,34].…”

“…Inflammatory cytokines (e.g., interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) and chemokines (e.g., chemokine (C-X-C motif) ligand (CXCL) family) were elevated in the peripheral sites, spinal cord, and of paclitaxeltreated animals, and many agents reduced the peripheral neuropathy symptoms via their anti-inflammatory effects [19,21,22,24,25,27,28,[32][33][34][35][36][37][38][39]41,42,[44][45][46][47][49][50][51][52][53][54]56]. Activations of astrocytes and microglia were also observed in the spinal dorsal horn after paclitaxel administrations, and many agents including minocycline attenuated PIPN via the inhibition of these spinal changes and prevented neurological damage [40,43,44,48].…”

Attenuation of Hyperalgesia and Allodynia by some Phenolic Acids in Paclitaxel Induced Neuropathy

“…Currently, modern chemotherapy is emerging to treat various complicated malignancies, which is increasing survival rate in cancer. But along with this, these chemotherapeutic agents are resulting into many adverse effects (Shahrak et.al., 2020). Taxanes are first-line group of antineoplastic drugs used to treat breast, lung, prostate and other gynecological malignancies.…”

“…Neuropathic pain is commonly observed adverse effect of chemotherapeutic agents which may affect patient’s life quality. Recently, many natural products are getting research attention due to their protective biological and pharmacological actions (Shahrak et.al., 2020). Various plants and their phyto-constituents are selectively studied in the treatment of neuropathy in rats (Ozyurt et.al., 2006).…”