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Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats.

ABSTRACT: Context. The stem bark of the savanna tree Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. Objective:This study seeks to investigate the possible antiallodynic and antihyperalgesic effects of the hydroethanolic stem bark extract of B. africana in a vincristine-induced peripheral neuropathy model in rats. Materials and Methods. 0.1?mg?kg-1 vincristine was administered intraperitoneally for 5 days followed by 2 days break and continued for another 5 days to establish peripheral neuropathy in Sprague Dawley rats. Effects of Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. p.o.) and pregabalin (10-100?mg?kg-1,?i.p.) were assessed on tactile, intermediate, mechanical, cold, and hot allodynia as well as in the Randall-Sellito test. Moreover, the levels of total proteins, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in sciatic nerve tissue homogenates were assayed. Results:BAE (50-1000?mg?kg-1 p.o.) showed significant antiallodynic and antihyperalgesic effects similar to pregabalin by increasing paw withdrawal latency and paw withdrawal threshold in all the behavioral tests used. Also, the extract decreased the levels of MDA (a lipid peroxidation product) as well as MPO and caused a significant increase in endogenous antioxidants (GSH) and antioxidant enzymes (SOD and CAT) in tissue homogenates of treated rats. Conclusions:Results from this study indicate that the hydroethanolic stem bark extract of B. africana exhibits antiallodynic and antihyperalgesic effects in vincristine-induced peripheral neuropathy in rats.B. africana in a vincristine-induced peripheral neuropathy model in rats.

SUBMITTER: Jibira Y

PROVIDER: S-EPMC7094176 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats.

Jibira Yakubu Y Boakye-Gyasi Eric E Kofi Mensah Abotsi Wonder W Amponsah Isaac Kingsley IK Adongo Donatus Wewura DW Woode Eric E

Advances in pharmacological and pharmaceutical sciences 20200212

Context. The stem bark of the savanna tree Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases.<h4>Objective</h4>This study seeks to investigate the possible antiallodynic and antihyperalgesic effects of the hydroethanolic stem bark extract of B. africana in a vincristine-induced peripheral neuropathy model in rats. Materials and Methods. 0.1 mg kg-1 vincristine was ad ...[more]

PMID: 32259104

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Project description:Peripheral polyneuropathy is a common and dose-limiting side effect of many important chemotherapeutic agents. Most such neuropathies are characterized by early axonal degeneration, yet therapies that inhibit this axonal destruction process do not currently exist. Recently, we and others discovered that genetic deletion of SARM1 (sterile alpha and TIR motif containing protein 1) dramatically protects axons from degeneration after axotomy in mice. This finding fuels hope that inhibition of SARM1 or its downstream components can be used therapeutically in patients threatened by axonal loss. However, axon loss in most neuropathies, including chemotherapy-induced peripheral neuropathy, is the result of subacute/chronic processes that may be regulated differently than the acute, one time insult of axotomy. Here we evaluate if genetic deletion of SARM1 decreases axonal degeneration in a mouse model of neuropathy induced by the chemotherapeutic agent vincristine. In wild-type mice, 4 weeks of twice-weekly intraperitoneal injections of 1.5 mg/kg vincristine cause pronounced mechanical and heat hyperalgesia, a significant decrease in tail compound nerve action potential amplitude, loss of intraepidermal nerve fibres and significant degeneration of myelinated axons in both the distal sural nerve and nerves of the toe. Neither the proximal sural nerve nor the motor tibial nerve exhibit axon loss. These findings are consistent with the development of a distal, sensory predominant axonal polyneuropathy that mimics vincristine-induced peripheral polyneuropathy in humans. Using the same regimen of vincristine treatment in SARM1 knockout mice, the development of mechanical and heat hyperalgesia is blocked and the loss in tail compound nerve action potential amplitude is prevented. Moreover, SARM1 knockout mice do not lose unmyelinated fibres in the skin or myelinated axons in the sural nerve and toe after vincristine. Hence, genetic deletion of SARM1 blocks the development of vincristine-induced peripheral polyneuropathy in mice. Our results reveal that subacute/chronic axon loss induced by vincristine occurs via a SARM1 mediated axonal destruction pathway, and that blocking this pathway prevents the development of vincristine-induced peripheral polyneuropathy. These findings, in conjunction with previous studies with axotomy and traumatic brain injury, establish SARM1 as the central determinant of a fundamental axonal degeneration pathway that is activated by diverse insults. We suggest that targeting SARM1 or its downstream effectors may be a viable therapeutic option to prevent vincristine-induced peripheral polyneuropathy and possibly other peripheral polyneuropathies.

Dataset Information

Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats.

Publications

Hydroethanolic Stem Bark Extract of <i>Burkea africana</i> Attenuates Vincristine-Induced Peripheral Neuropathy in Rats.

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