Phyllanthin from Phyllanthus amarus exerts neuroprotective effects against spinal cord injury in experimental rats

TL;DR

Phyllanthin from Phyllanthus amarus helps protect the spinal cord in injured rats by reducing inflammation and nerve damage.

Contribution

This study identifies phyllanthin in Phyllanthus amarus as a potential neuroprotective agent for spinal cord injury.

Findings

Phyllanthin reduced SCI-induced hyperalgesia and improved nerve conduction in rats.

PAME treatment lowered inflammatory markers IL-1β, IL-6, and TNF-α in spinal cord tissue.

Phyllanthin ameliorated apoptotic signaling by modulating Bax and caspase-3 protein expressions.

Abstract

Spinal cord injury (SCI) results in changes in autonomic function, impacting an individual's movement, sensory perception, and overall quality of life. Phyllanthin, a lignan from
Phyllanthus amarus
, is known for its neuronal protective effects.

To evaluate the potential of phyllanthin identified in
P. amarus
methanolic extract (PAME) against SCI in experimental rats.

The lignan was identified in PAME using high-performance liquid chromatography (HPLC). Spinal cord injury was induced in Sprague-Dawley rats using the laminectomy clip compression method. Rats received either a vehicle (distilled water) or methylprednisolone (30 mg/kg) or PAME (50, 100, and 200 mg/kg) orally for 4 weeks after SCI. Behavioral, histological, and molecular parameters were assessed to evaluate the neuroprotective effects of phyllanthin.

During the HPLC analysis of PAME, phyllanthin was present at a retention time of 25.30 minutes with 75.22% weight per weight (w/w). The administration of standardized PAME (100 and 200 mg/kg) effectively ameliorated the alterations induced by SCI in thermal and mechano-tactile hyperalgesia, locomotor activity, and nerve conduction velocity (
p
 < 0.05 each). The SCI-induced elevation in spinal interleukins (ILs: IL-1β and IL-6) and tumor necrosis factor alpha (TNF-α) protein levels was also effectively (
p
 < 0.05) reduced by PAME. The PAME treatment markedly (
p
 < 0.05) ameliorated SCI-induced alterations in protein expressions of B-cell leukemia/lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax), and caspase-3 in the spinal cord. Aberrations, such as inflammatory infiltration, edema, congestion, and necrosis induced in the spinal cord, were also effectively reduced by the PAME treatment (
p
 < 0.05).

Phyllanthin identified in
P. amarus
showed neuroprotective potential against SCI by moderating impairments in behavioral (allodynia, hyperalgesia, and nerve conduction velocity) parameters, elevated inflammatory mediators (IL-1β, IL-6, and TNF-α), and deactivating the apoptotic signaling (Bax/caspase-3) pathway.

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