Characterization and formulation of bio-active fraction of Moringa oleifera Lam. leaves extract and its protective potential against acetaminophen toxicity
Moringa oleifera (MO) is a well-known and widely distributed tropical species of Moringaceae family. Its leaves possess an excellent nutritional profile and an impressive range of therapeutic properties. Recently, the investigations on pharmaceutical properties of MO leaves get expanded due to it...
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| Format: | Thesis |
| Language: | English |
| Published: |
2016
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/67066/1/IB%202016%2017%20IR.pdf |
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| Summary: | Moringa oleifera (MO) is a well-known and widely distributed tropical species
of Moringaceae family. Its leaves possess an excellent nutritional profile and
an impressive range of therapeutic properties. Recently, the investigations on
pharmaceutical properties of MO leaves get expanded due to its enriched
antioxidant potential. Though numerous study reports focused on its
therapeutic efficacy, the responsible active compounds and its underlying
molecular mechanism of action has not been determined yet which hold a
setback for researchers to explore its exact therapeutic potential.
Acetaminophen (APAP) overdose is a worldwide leading cause of acute
liver failure and drug-induced hepatotoxicity. During APAP overdose,
majority of the drug is converted by the cytochrome P450 (CYP 450 -
2E1/1A2) enzymes to the reactive toxic metabolite, N-acetyl-pbenzoquinoneimine
(NAPQI) that depletes GSH level and covalently binds
to the other cellular proteins and induce hepatocyte death/acute liver
failure. Currently, the most effective therapy for APAP overdose is Nacetylcysteine
(NAC), which replenishes glutathione level and enhances
hepatic recovery. However, NAC has few significant limitations such as time
constraints and reversal of GSH level alone may not be sufficient to arrest
progress of APAP hepatotoxicity. This drives scientists/researchers in
exploring for an alternative safe and effective therapy. In this study, the optimal MO gradient leaf extract has been obtained as 90%
hydro-ethanolic solution based upon in vitro antioxidant assays and the
active compounds responsible for its elite activity has been determined as
quercetin, kaempferol, apigenin and multiflorin-B through chromatographic
analysis. The underlying mechanism of action of 90% hydro-ethanolic MO
leaf extract has been evaluated in Balb/c mice inflicted with lethal dose of
APAP for hepato- and nephro-toxicity. The MO leaf extract effectively
protects the liver through suppression of CYP 450 isoenzymes and in both
liver and kidney through regulation of antioxidant enzymes level and
modulation of inflammatory cytokines thereby hindering the further
exacerbation of necrotic and renal tubular damage respectively. Further, 90%
MO leaf crude extract was fractionated through liquid-liquid partition
technique. Among the obtained solvent fractions, ethyl acetate (EA) fraction
revealed the highest antioxidant activity evidently due to the presence of
quercetin, kaempferol and apigenin which has been identified and
quantified with commercial standards using HPLC analysis. Wherein,
kaempferol was expressed in higher concentration with 263.86 μg, followed
by apigenin and quercetin with 82.64 and 66.89 μg respectively, per mg of
MO leaves EA fraction. Soy phosphatidylcholine (PC) is a bifunctional
complex comprises of lipophilic phosphatidyl moiety and hydrophilic
choline moiety. Naturally, flavonoids and phenolic compounds got affinity
to bind with PC molecule resulting in a cell like lipid compatible molecular
complex. In accordance, the EA fraction and its three major flavonoids
quercetin, kaempferol and apigenin has been successfully loaded in PC
molecule to retain its synergism and enhance bioavailability. Further its
physico-chemical parameters, invitro drug release and hepato-protective
potential against APAP inflicted hepatotoxicity in HepaRG cell line has been
evaluated.
The findings of this study has evidently suggested that MO leaves extract
and its EA fraction loaded phospholipid complex can be implied as an
effective antidote against APAP intoxication as it
hinders/suppresses/modulates various key biomarkers involved in APAP
hepatotoxicity pathway. |
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