Antinociceptive activity, elucidation of mechanism of action and identification of bioactive components of muntingia calabura L. Leaf extracts
Research into plant as an alternative treatment for pain has been widely explored due to its potentially low adverse effect with great therapeutic activity. Muntingia calabura L. (Tiliaceae) has recently gained a medicinal status as well as attention from throughout the world. The present study...
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| Format: | Thesis |
| Language: | English |
| Published: |
2016
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/66043/1/FPSK%20%28p%29%202016%206%20IR.pdf |
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| Summary: | Research into plant as an alternative treatment for pain has been widely explored due to its potentially low adverse effect with great therapeutic activity. Muntingia calabura L.
(Tiliaceae) has recently gained a medicinal status as well as attention from throughout
the world. The present study examined the potential antinociceptive activity of
methanol extract of Muntingia calabura (MEMC) leaves using the acetic acid-induced
abdominal constriction, formalin and hot plate test following the determination of its
safety using acute toxicity test. Then the possible involvement of MEMC-induced
antinociception through capsaicin, glutamate, bradykinin, opioidergic, dopaminergic
serotonergic, noradrenergic, adenosisnergic, protein kinase C (PKC), nitric oxide
(NO)/cyclic guanosine monophosphate (cGMP) and potassium channel pathway was
evaluated. Experimental animals (n=6) were pretreated orally with 10% dimethyl
sulfoxide (DMSO; negative control), 5 mg/kg morphine or 100 mg/kg aspirin (positive
control) or 100, 250, and 500 mg/kg of MEMC, followed by the administration of
receptor antagonists and/or induction of nociception. The crude MEMC extract was
further partitioned into three fractions: petroleum ether extract (PEMC), ethyl acetate
extract (EAMC) and aqueous extract (AEMC). The antinociceptive profiling
demonstrates PEMC produced a significantly better activity than EAMC and AEMC.
Possible mechanism of PEMC action was studied using the same assays. Result on the
acute toxicity study shows no mortality and significant behavioural and physiological
changes detected. Oral administration of MEMC and PEMC shows a dose-dependent
inhibition in acetic acid-induced abdominal constriction test, formalin-, capsaicin-.
glutamate-, bradykinin- and PMA-induced paw licking test, while only the highest dose
produced significant pain inhibition in hot plate test. Furthermore, the antinociception
caused by MEMC and PEMC in acetic acid-induced abdominal constriction test was
significantly attenuated by intraperitoneal treatment of naloxone (non-specific opioid
receptor antagonist; 5 mg/kg), naltrindole (δ opioid receptor antagonist; 1 mg/kg) norbinaltorphimine
(κ opioid receptor antagonist; 1 mg/kg), β-funaltraxamine (μ opioid
antagonist; 10 mg/kg), pindolol (5-HT1A receptor antagonist; 1 mg/kg), caffeine (nonselective
adenosine receptor antagonist; 3 mg/kg) and yohimbine (α2 adrenoceptor
antagonist; 0.15 mg/kg). While both extracts did not act on dopaminergic receptor
system, PEMC, but not MEMC, was significantly reversed by i.p. injection of atropine (non-selective cholinergic antagonist; 10 mg/kg). At the same time, MEMC and PEMC
were found to inhibit pain through NO/cGMP/PKC as well as potassium channel
pathways. The potential antinociceptive activity seen was probably due to synergistic
effect of flavonoids, tannins, polyphenolic compounds, triterpene and steroid present in
the extracts based on their phytochemical screening. High performance liquid
chromatography analysis shows several peaks, detected at different wavelengths of the
chromatogram, which were suggested to be flavonoid-based compounds. In conclusion,
the synergistic effects of various bioactive components suggested to be responsible in
the antinociceptive activity of MEMC as well as the semi-purified PEMC extract which
involved in central and peripheral pain pathways. The activation of potassium pathway
as well as opioid, adenosinergic, noradrenergic and serotonergic receptors while
inhibits NO/cGMP/PKC pathways, TRPV1, glutamate and bradykinin receptors might
be the possible mode of action of both the extracts in exerting their analgesic effect. |
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