Pharmacological Evaluation Of Orthosiphon Stamineus Extract And Development Of Analgesic Meter For Arthritic Rat Model
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Date
2012-01
Authors
Yam, Mun Fei
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Abstract
Orthosiphon stamineus Benth. is a genus of herb of the family Labiatae or
Lamiaceace traditionally used for treatment of many diseases such nephritis,
nephrolithiasis, hydronephrosis, vesical calculi, arteriosclerosis, rheumatism,
inflammation, gout and diabetes. Despite the availability of modern medications,
the use of traditional medicine is growing throughout the world, indicating a need
for scientific investigations into the therapeutic effects of medicinal plants and their
underlying mechanisms. While no previous investigation has thoroughly reported
its pharmacological activities such as anti-ulcer, anti-inflammatory, anti-pyretic,
analgesic, hepatoprotective and toxicological effect of such a widely used
medicinal herb, this investigation set out to further characterize the traditional
claims. The O. Stamineus leaves were dried, pulverized and successively
extracted with 50% methanol using maceration method. The extract was dried
under reduced pressure and freeze-dried. The yield of lyophylized 50 % methanolic
extract of O. Stamineus (SEOS) was found to be 6%. HPLC analysis showed that
SEOS contains 0.46%, 1.12%, and 0.94% of 3’-hydroxy-5,6,7,4’-
tetramethoxyflavone, sinensetin and eupatorin, respectively.
In acute toxicity study, up and down method (limit dose) was adapted. A
single dose of 5000 mg/kg of SEOS was given orally to 5 healthy Sprague Dawley
(SD) male and female adult rats. The rats were observed for mortality and clinical
signs for 3 h and then periodically for 14 days. In the subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg per day for
28 days to female and male SD rats, respectively. The animals were sacrificed,
followed by examination of their organs and blood serum. The results in the acute
study showed that SEOS at a dose of 5000 mg/kg caused neither visible signs of
toxicity nor mortality. All five rats survived until the end of observation period. While
in subchronic toxicity, administration of the SEOS at 1250, 2500, and 5000 mg/kg
for 28 days did not produce any mortality and there were no significant differences
in the general condition, growth, organ weights, hematological parameters, clinical
chemistry values and macroscopic appearance of the organs from the treatment
groups as compared to the control group.
DPPH radicals scavenging, Fe3+-induced lipid peroxidation inhibiting
activities and trolox equivalent antioxidant capacity (TEAC) of SEOS were
determined. The results indicated that SEOS exhibited antioxidant, lipid
peroxidation inhibition and free radical scavenging activities. The hepatoprotective
activity of the SEOS was studied using CCl4-induced liver toxicity in rats. The
activity was assessed by monitoring liver function tests in histopathological study
and measurement of alanine transaminase (ALT) and aspartate transaminase
(AST). SEOS at the dose of 1000 and 500 mg/kg significantly inhibited the
increase of serum ALT and AST activities and prevent the liver necrosis.
Absolute ethanol-induced gastric membrane lesions model was used in antiulcer
study. Oral administration of SEOS (125, 250, 500 and 1000 mg/kg) was
found to significantly decrease the ulcer index (P<0.01, P<0.001, P<0.001, and
P<0.001, respectively). Histological study of a section of the rat stomach also
showed a marked improvement in the gastric mucosal damage in groups receiving
SEOS. In order to further investigate the gastroprotective mechanism of SEOS, mucus secretion and lipid peroxidation level were estimated in vitro and ex vivo.
SEOS exhibited dose-dependent stimulation of mucus secretion and inhibition of
lipid peroxidation in rat gastric mucosal homogenates (both in vitro and ex vivo).
Description
Keywords
Analgesics , Medicinal plants