Analgesic Effects Of Annona Muricata Leaf Extract In Paclitaxel And Streptozotocin-Induced Diabetic Neuropathy In Murine Models.
Date
2022-08
Authors
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Publisher
University Of Ghana
Abstract
Background: Annona muricata have demonstrated antinociceptive and anxiolytic effects in animal
models through its leaf extracts. This study evaluates the aqueous leaf extract of the plant for possible
analgesic properties in hyperalgesia and allodynia associated with paclitaxel-induced neuropathy in
mice and streptozotocin (STZ)- induced diabetic neuropathy in rats.
Methods:10kg of the coarse crushed leaves was soaked in 3 liters of distilled water to make a
decoction, cooled, filtered and freeze dried for use. Sub-acute toxicity test was carried out for 14-
days after which blood samples were taken and examined for haematological analysis.
Phytochemistry of the extract was conducted and analgesic property was accessed using hot plate
test. Irwin test was also conducted to observe alterations in behavior and physiological activity,
neurotoxicity and mortality. Diabetic- induced neuropathy in Sprague-Dawley rats was
accomplished by injecting 55mg/kg body weight of STZ followed by 120mg/kg body weight of
nicotinamide to achieve type 2 diabetes mellitus. Paclitaxel-induced neuropathy was also achieved
by injecting ICR mice with 2mg/kg body weight body weight of paclitaxel continuously for 5 days.
Parameters which include cold allodynia mechanical hyperalgesia and thermal hyperalgesia were
measured before the administration of paclitaxel and on day 1 – 5 and after the administration of
paclitaxel. In STZ-induced diabetic neuropathy experiment parameters were measured before the
administration of STZ and after the administration of STZ on day 2, 4, 6, 8, 10, 12 and 14. These
animals were then treated with Annona muricata extract (AME) (30, 100 and 300 mg/kg body
weight), pregabalin (10, 30 and 100 mg/kg body weight) and distilled water as a vehicle daily for 5
days and 14 days continuously in paclitaxel- and diabetic-induced peripheral neuropathy
respectively. Pain thresholds were measured on day 1, 2, 3 and 5 in paclitaxel-induced neuropathy
experiment and that of STZ-induced - diabetic neuropathic experiment, it was measured from day 1-7.
Results: Annona muricata Extract (AME) showed no toxicity as no death were observed during the
14-day study period in sub-acute toxicity studies. Preliminary phytochemical screening of the extract
indicated the presence of secondary metabolites which includes alkaloids, saponins, flavonoids,
tannins, glycosides, triterpenoids and sterols. The extract showed analgesic property during the hot
plate test. CNS safety pharmacology using Irwin test indicated no mortality when experimental
animals were observed for 24 hours after various treatment doses were employed. Observable
physiological/ pharmacological effects were noted which include straub tail, defecation, sniffing
among others. Relative organ weight of the experimental animals also indicated no obvious
abnormally when compared to the control during Irwin’s test. AME and pregabalin produced
analgesic properties which was exhibited in paclitaxel and STZ-induced - neuropathy as increased
paw withdrawal latencies to mechanical, cold-water stimuli and thermal hyperalgesic tests.
Conclusions: The findings from this study suggest that aqueous extract of Annona muricata is sub
acutely safe with observable CNS physiological effect and no observable CNS toxicity. Again, the
extract possesses an analgesic property as seen in both paclitaxel- and STZ-induced diabetic
neuropathy in animal models which may contribute to its traditional use in managing neuropathic
pain.
Description
MPhil. Pharmacology
Keywords
Annona Muricata, Streptozotocin-Induced Diabetic Neuropathy, Murine Models