The Effects And Mechanism Of Action Of Garcinia Atroviridis Extracts On The Lipid Profile And Antioxidant Status Of Chemically- And High Fat Diet-Induced Hyperlipidemic Rats
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Date
2017-08
Authors
Al-Mansoub, Majed Ahmed Kacem
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Garcinia atroviridis, a member of Clusiaceae family, has gained much
attention in recent years due to its ability to reduce body weight. The objective of this
study was to investigate the effect and mechanism of action of G. atroviridis extracts
on the lipid profile and antioxidant status of chemically- and high fat diet (HFD)-
induced hyperlipidemic rats. Aqueous and methanolic extracts of different parts of
G. atroviridis namely: ripe fruit with seeds, ripe fruit rind, unripe fruit with seeds,
unripe fruit rind, leaves, and stem were used in this study. Generally, in the poloxamer-
407 (P-407)-induced acute hyperlipidemic rat model, the aqueous extracts showed
better antihyperlipidemic activity than the methanol extracts. Of all the extracts, the
aqueous extract of ripe fruit with seeds (AqE-RFS) showed the most potent
antihyperlipidemic effect, comparable to that of atorvastatin (60 mg/kg). The AqERFS
significantly decreased serum TC, TG, LDL and VLDL levels and AC at dose of
1000 mg/kg compared to that of hyperlipidemic control group at 58 hr after
hyperlipidemia induction. Rats fed on HFD had significantly higher levels of serum
lipid profile and elevation of serum and liver MDA associated with a significant
decrease in GSH content and antioxidant enzymes activities. Daily treatment of HFD
rats with AqE-RFS at 1000 and 500 mg/kg for six weeks showed significant reductions
in TC, TG, and VLDL as compared to the HFD control rats. The AqE-RFS at 1000
mg/kg showed significant reduction in LDL. Likewise, the AC was also significantly
reduced after treatment with 1000 and 500 mg/kg compared to HFD control group.
Similarly, AqE-RFS treatment (1000 mg/kg) for six weeks significantly reduced lipid
peroxidation as shown by decreased MDA level and increased GSH content as well as
improvement in antioxidant activities of SOD, CAT, GPx and GR in liver and serum
against oxidative damage in HFD rats. In contrast, for in vitro antioxidant screening,
methanol extracts of the stem and leaves showed higher antioxidant activities than the
fruits. A reversed phase (RP)-HPLC analysis for determination of two marker
compounds, HCA and HCAL in all G. atroviridis extracts revealed that aqueous and
methanol extracts of both unripe and ripe fruit rind contain the highest total contents
of these markers, respectively. Elucidating of possible mechanism of action revealed
that the AqE-RFS exhibited significant reduction on the activity of HMG-CoA
reductase and moderate effect on pancreatic lipase. On the synthesis and excretion of
lipids, the AqE-RFS significantly reduced the contents of liver TC and TG, as well as
significantly increased fecal TC and bile acids excretion in a dose dependent
manner. Safety assessment showed that AqE-RFS is non-toxic up to the dose of 2000
mg/kg for acute administration. Meanwhile, rats given chronic oral doses of AqE-RFS
(250, 500 or 1000 mg/kg) survived the 3 months of dosing and showed no significant
changes in general behaviour, hematological and biochemical parameters as well as
histopathological observations of liver and kidney structures. In conclusion, these
findings demonstrate the beneficial effect of AqE-RFS against hyperlipidemia and
may be potential for development as antihyperlipidemic phytopharmaceuticals.
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Keywords
The effect and mechanism of action of G. atroviridis extracts , on the lipid profile and high fat diet