Abstract
Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy. Repeated administrations significantly reduced oxaliplatin-dependent hypersensitivity with 50%HA, the most effective, fully preventing mechanical and thermal hypersensitivity. Ex vivo, 50%HA reduced morphometric and molecular alterations induced by oxaliplatin in peripheral nerve and dorsal-root-ganglia. In the spinal cord and in brain areas, 50%HA significantly decreased activation of microglia and astrocytes. Furthermore, 50%HA prevented the nephro- and hepato-toxicity induced by the anticancer drug. The protective effect of 50%HA did not alter oxaliplatin-induced apoptosis in colon tumors of Pirc rats, an Apc-driven model of colon carcinogenesis. The hydroalcoholic extract (50%HA) of Astragali radix relieves pain and promotes the rescue mechanisms that protect nervous tissue from the damages triggering chronic pain. A safe profile strongly suggests the usefulness of this natural product in oxaliplatin-induced neuropathy.
Highlights
Neurotoxicity is a major side effect of platinum derivatives both during and after treatment
The pro-allodynic effect of oxaliplatin was significantly reduced by Aqu and totally prevented by both 20%HA and 50% hydroalcoholic dried extract (50%HA) (Fig. 1B)
Given the neuroprotective properties of 50%HA, we examined its potential protective effects against hepatic and renal toxicity induced by oxaliplatin treatment
Summary
Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy. Chemotherapy-induced neuropathy can limit therapeutic options for patients and result in dose reduction. During survival, it might greatly affect the patient’s quality of life[7]. The prevention or treatment of oxaliplatin-induced neuropathy (as well as other chemotherapy induced neuropathies) is a relevant therapeutic need. In this context, a scientific approach to the study of medicinal plants may help to identify adjuvant treatments able to reduce the side effects of chemotherapy. Bioactivity of crude drugs or vegetal extracts is a summation of antagonistic and/or synergistic effects on bioavailability, cellular transport processes, compound metabolism and pharmacodynamic mechanisms[12]
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