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Effect of mangiferin on hyperglycemia and atherogenicity in STZ diabetic rats

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In the present study, the effect of mangiferin (a xanthone glucoside, isolated from the leaves of Mangifera indica) on the atherogenic potential of streptozotocin (STZ)-diabetes was investigated. In addition, the effect of mangiferin on oral glucose tolerance in glucose-loaded normal rats was also determined. The chronic intraperitoneal (i.p.) administration of mangiferin (10 and 20 mg/kg) once daily (o.d.) for 28 days exhibited antidiabetic activity by significantly lowering fasting plasma glucose level at different time intervals in STZ-diabetic rats. Further, mangiferin (10 and 20 mg/kg, i.p.) showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) levels coupled together with elevation of high-density lipoprotein cholesterol (HDL-C) level and diminution of atherogenic index in diabetic rats. In addition, the chronic administration of mangiferin (10 and 20 mg/kg, i.p.) for 14 days significantly as well as markedly improved oral glucose tolerance in glucose-loaded normal rats suggesting its potent antihyperglycemic activity. The accumulating evidences suggest that both pancreatic and extrapancreatic mechanisms might be involved in its antidiabetic or antihyperglycemic action. In conclusion, the present study demonstrates that mangiferin possesses significant antidiabetic, antihyperlipidemic and antiatherogenic properties thus suggesting its beneficial effect in the treatment of diabetes mellitus associated with hyperlipidemia and related cardiovascular complications.
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Journal of Ethnopharmacology 97 (2005) 497–501
Effect of mangiferin on hyperglycemia and atherogenicity
in streptozotocin diabetic rats
S. Muruganandana,, K. Srinivasanb, S. Guptaa, P.K. Guptaa,J.Lala
aDivision of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar 243 122, UP, India
bDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India
Received 8 March 2004; received in revised form 3 November 2004; accepted 7 December 2004
Abstract
In the present study, the effect of mangiferin (a xanthone glucoside, isolated from the leaves of Mangifera indica) on the atherogenic
potential of streptozotocin (STZ)-diabetes was investigated. In addition, the effect of mangiferin on oral glucose tolerance in glucose-loaded
normal rats was also determined. The chronic intraperitoneal (i.p.) administration of mangiferin (10 and 20mg/kg) once daily (o.d.) for 28
days exhibited antidiabetic activity by significantly lowering fasting plasma glucose level at different time intervals in STZ-diabetic rats.
Further, mangiferin (10 and 20mg/kg, i.p.) showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant
decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) levels coupled together with elevation of high-
density lipoprotein cholesterol (HDL-C) level and diminution of atherogenic index in diabetic rats. In addition, the chronic administration of
mangiferin (10 and 20 mg/kg, i.p.) for 14 days significantly as well as markedly improved oral glucose tolerance in glucose-loaded normal rats
suggesting its potent antihyperglycemic activity. The accumulating evidences suggest that both pancreatic and extrapancreatic mechanisms
might be involved in its antidiabetic or antihyperglycemic action. In conclusion, the present study demonstrates that mangiferin possesses
significant antidiabetic, antihyperlipidemic and antiatherogenic properties thus suggesting its beneficial effect in the treatment of diabetes
mellitus associated with hyperlipidemia and related cardiovascular complications.
© 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Mangiferin; Streptozotocin; Atherogenic; Diabetic
1. Introduction
Mangiferin, a xanthone glucoside, is an active phyto-
chemical present in various plants including Mangifera in-
dica L (Family: Anacardiaceae, Genus: Mangifera)(Chopra
et al., 1956). Mangiferin has been reported to possess an-
tioxidant (Sanchez et al., 2000), antitumor (Guha et al.,
1996), antiviral (Zheng and Lu, 1990; Zhu et al., 1993;
Yoosook et al., 2000) and immunomodulatory activities
(Guha et al., 1996; Leiro et al., 2004). The aqueous ex-
Corresponding author. Present address: Department of Biomedical Sci-
ences, Atlantic Veterinary College, UPEI 550, University Avenue, Charlot-
tetown, PE, Canada C1A 4P3.
E-mail address: muruguphyto@yahoo.co.uk (S. Muruganandan).
tract of Mangifera indica leaves has been reported to possess
hypoglycemic activity in glucose-induced hyperglycemic
rats as well as in mice (Aderibigbe et al., 1999, 2001).
Furthermore, the active principle, mangiferin has recently
been shown to have antidiabetic activity in KK/Ay mice,
a genetic model of non-insulin-dependent diabetes mellitus
(NIDDM) with hyperinsulinemia (Ichiki et al., 1998; Miura
et al., 2001a,b). However, there is no experimental evidence
Presently available in the literature with regard to its ef-
fect on plasma glucose and lipid profiles (atherogenic value)
in streptozotocin-induced diabetes mellitus in rats. Hence,
the present study was carried out in an attempt to investi-
gate the possible antidiabetic and antiatherogenic activities
of mangiferin, isolated from the leaves of Mangifera indica
in STZ-diabetic rats. In addition, the effect of mangiferin on
0378-8741/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jep.2004.12.010
498 S. Muruganandan et al. / Journal of Ethnopharmacology 97 (2005) 497–501
oralglucose tolerance in glucose-loaded normal ratswas also
studied.
2. Materials and methods
2.1. Mangiferin
The method of isolation and determination of pu-
rity of mangiferin can be found from our earlier report
(Muruganandan et al., 2002). Briefly, shade-dried and pow-
dered leaves of Mangifera indica were soxhleted for 12h
with petroleum ether (60–80 C). The defatted plant material
was extracted with ethanol under reflux for 16h, which was
further, defatted again with petroleum ether and crystallized
repeatedly in aqueous ethylacetate into pale yellow needles.
The purity was 95.56% mangiferin upon high performance
liquid chromatographic (HPLC) analysis using PDA detec-
tor (254 nm) and a mobile phase of acetonitrile and 3% acetic
acid (16:84) as reported earlier (Muruganandan et al., 2002).
2.2. Chemicals
Streptozotocin (Sigma Chemicals, St. Louis, MO, USA),
heparin (SRL, Mumbai), insulin (highly purified bovine
porcine insulin, Eli-Lilly Ranbaxy, New Delhi) were used
in the study. Mangiferin was the isolated compound from
Mangifera indica leaves as described above.
2.3. Experimental animals
Wistar male rats (100–125g) were procured from the
Laboratory Animal Resource Section of Indian Veterinary
Research Institute (IVRI), Izatnagar, UP, India. The ani-
mals were maintained on standard ration and provided with
clean drinking water ad lib. The animals were kept in air-
conditioned room (temperature 22±2C) and acclimatized
for a period of 7 days.
2.4. Induction of experimental diabetes
Fasted male Wistar rats (100–125g) were rendered dia-
betic by the single injection of STZ (55mg/kg, i.v.) through
tail vein. STZ was dissolved in ice-cold citrate buffer (pH
4.5) and injected immediately within few minutes to avoid
degradation. The development of hyperglycemia in rats was
confirmed by plasma glucose estimation 48h post STZ in-
jection. The rats with fasting plasma glucose level of above
250 mg/dl at 30 days post STZ injection were considered di-
abetic and only uniformly diabetic rats were included in the
study.
2.5. Experimental design
The experiment was designed to determine the ef-
fect of mangiferin on hyperglycemia and atherogenesis in
streptozotocin-induced uniformly diabetic rats.
Previousexperimentalpharmacokineticstudiesrevealthat
mangiferin has poor bioavailability through oral route in rats
(Geodakyan et al., 1992). The compound was reported to
show pharmacological effects when administered at the dose
level of 10mg/kg through intraperitoneal route (Guha et al.,
1996). Also, our preliminary studies showed that rats exhibit
behaviouralsigns of depression whenmangiferin was admin-
istered with doses beyond 100 mg/kg through intraperitoneal
route. Thus, an intraperitoneal route of administration with
the dose level of 10 and 20 mg/kg that did not show any gross
sign of toxicity was selected for the study.
The rats were divided into five groups consisting of six
rats each. Group 1 (normal control) consisted of normal rats
that neither received STZ nor any drug. Group 2 served as
negative control (diabetic control). Group 3 was given stan-
dard drug, insulin (6U/kg, i.p.) that served as positive con-
trol. Groups 4 and 5 were administered with test compound,
mangiferin (10 and 20mg/kg, i.p.), respectively. The drugs
were given once daily for 28 days. Blood samples were col-
lected from 18h fasted rats at 1h after the last dose admin-
istration and analyzed for plasma glucose, total cholesterol,
HDL-cholesterol (HDL-C) and triglycerides using kits ob-
tained from M/s Qualigens Diagnostics, Mumbai, India. In
addition, the changes in body weight were recorded in both
the control and treated groups.
2.6. Oral glucose tolerance test
The effect of mangiferin on oral glucose tolerance was
also studied in glucose-loaded normal rats. There were three
groups consisting each of six normal rats used. First group
servedas control rats given normal saline (1 ml/kg, i.p.) while
the other two groups were treated with mangiferin (10 and
20mg/kg, i.p.), respectively, once daily for 14 days. All the
rats were fasted for 18h before subjecting them to oral glu-
cosetolerance test. On the 14th day of thestudy,the last acute
dose of vehicle normal saline (1ml/kg, i.p.) and mangiferin
(10 and 20 mg/kg, i.p.) was administered 30min prior to oral
glucose load (2g/kg at 4ml/kg dissolved in normal saline)
to the respective groups. The blood samples were collected
from each group just before (0min) compounds administra-
tion and at 30, 60, 90 and 120 min after glucose challenge for
the plasma glucose analysis. The percent induced glycemia
(%IG) following oral glucose load at different time intervals
was calculated for the control and treated groups as follows:
%IG =GxG0
G0×100
where G0is the initial glycemia (mg/dl) and Gxthe
glycemia (mg/dl) at different time intervals after the oral
glucose load. From the %IG versus time plot, the area un-
der the glucose tolerance curve (AUGTC 0–120min) was
calculated using trapezoidal method. The total antihyper-
glycemic response (AUGTC 0–120min) was expressed as
mean±S.E.M. (Leonhardt et al., 2004).
S. Muruganandan et al. / Journal of Ethnopharmacology 97 (2005) 497–501 499
2.7. Biochemical analysis
The plasma was separated from heparinized blood sam-
ples immediately after collection and analyzed for glucose,
totalcholesterol, HDL-C and triglycerides using standard en-
zymatic colorimetric kits obtained from M/s Qualigens Di-
agnostics, Mumbai, India. Plasma glucose was estimated by
O-toluidine method. Total cholesterol and triglycerides were
estimated by enzymatic methods of CHOD-PAP and GPO-
PAP, respectively.
LDL-C was calculated by using the following formula
(Noda et al., 2000):
LDL-cholesterol =total cholesterol
HDL-C +triglycerides
5
Atherogenic index was calculated by using the following
formula (Kayamori and Igarashi, 1994):
atherogenic index =total cholesterol HDL-C)
HDL-C
2.8. Statistical analysis
The results were expressed as mean ±S.E.M. All the data
were analyzed by one way analysis of variance followed by
multiple comparison test (Tukey’s test) at the 5% level of
significance. A value of P<0.05 was considered statistically
significant.
3. Results
Streptozotocin treatment caused significant weight re-
duction in rats as compared to the vehicle treated nor-
mal rats at day 30 of injection (163.33±10.54 g ver-
sus 206.67±13.18g). However, the chronic treatment of
mangiferin (10 and 20mg/kg, i.p.) for 28 days significantly
(P<0.05) restored the body weight loss as compared to the
vehicle treated diabetic control rats observed at the end of 28
daysof treatment period (191.67 ±15.35 gand200 ±10.72 g
versus 130±5.16 g, respectively). However, the standard
drug insulin (6 U/kg, i.p.) also exhibited significant improve-
ment in body weight loss of the diabetic animals following
28 days of treatment (196.67±8.37 versus 130±5.16).
Streptozotocin treatment resulted in significant elevation
of plasma glucose, triglycerides, total cholesterol, LDL-C
and reduction in HDL-C levels as compared to the normal
controlrats as noted at differentperiodsof the study (Table1).
The chronic administration of mangiferin (10 and
20mg/kg, i.p.) resulted in significant (P<0.05) reduction in
plasma glucose level at different periods in the experimental
duration of 28 days in STZ-diabetic rats with the maximum
percent reduction of plasma glucose being 49.77 and 51.89,
respectively on 28th day of treatment. However, the standard
drug insulin (6 U/kg, i.p.) exhibited significant and more po-
tent antidiabetic activity with maximum percent reduction of
plasmaglucose67.54on28thday as compared to the diabetic
control group (Table 1).
There was a significant reduction in plasma triglycerides,
total cholesterol and LDL-C levels of diabetic rats treated
Table 1
Effect of mangiferin on fasting plasma glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol and atherogenic index in STZ-diabetic rats
Parameter Days Group 1 Group 2 Group 3 Group 4 Group 5
Glucose (mg/dl) 0 75.92 ±2.36 320.84 ±28.24#320.97 ±32.78 323.05 ±23.41 305.21 ±19.92
14 78.03 ±9.81 324.58 ±19.88#112.69 ±5.6*180.03 ±13.81*160.67 ±12.62*
28 72.72 ±3.90 329.79 ±14.19#107.04 ±7.89*165.66 ±16.18*158.65 ±8.45*
Triglycerides (mg/dl) 0 76.51 ±11.87 127.61 ±13.34 118.70 ±20.12 126.50 ±13.60 131.11 ±16.96
14 75.51 ±4.59 110.5 ±11.40 98.19 ±5.70 93.70 ±7.73 86.57 ±9.25
28 85.3 ±5.78 131.5 ±8.3#68.58 ±4.25*80.88 ±4.00*82.07 ±3.23*
Total cholesterol (mg/dl) 0 122.49 ±2.06 207.92 ±7.15#206.53 ±11.59 203.46±4.96 215.40 ±9.13
14 138.52 ±12.33 226.78 ±8.58#136.34 ±9.45*144.98 ±9.99*123.22 ±6.64*
28 124.00 ±6.80 296.91 ±23.40#115.80 ±13.31*128.50 ±7.45*128.50 ±9.53*
LDL cholesterol (mg/dl) 0 57.06 ±10.12 141.05 ±3.15#142.75 ±17.13 142.40 ±10.34 143.17 ±3.71
14 71.68 ±13.83 160.19 ±7.04#80.28 ±9.02*89.86 ±12.19*57.94 ±8.89*
28 52.79 ±5.61 230.28 ±16.60#57.80 ±14.51*69.09 ±15.44*64.45 ±8.36*
HDL cholesterol (mg/dl) 0 49.99 ±0.95 41.44 ±1.91 39.48 ±1.26 41.65 ±0.73 42.19 ±1.21
14 54.94 ±2.11 43.57 ±2.87 44.76 ±2.19 46.19 ±3.59 53.38 ±5.43
28 53.86 ±3.48 37.43 ±1.08#44.93 ±1.67*46.61 ±1.15*48.90 ±0.84*
Atherogenic index (units) 0 1.59 ±0.23 4.03 ±0.28#4.16 ±0.26 3.88 ±0.09 4.05 ±0.12
14 1.5 ±0.10 4.27 ±0.29#2.09 ±0.28*2.13 ±0.46*2.46 ±0.33*
28 1.26 ±0.12 4.82 ±0.70#1.67 ±0.18*1.74 ±0.09*1.70 ±0.10*
n= 6/group. Values are mean±S.E.M. Group 1: normal control (normal saline 1 ml/kg); Group 2: diabetic control; Group 3: positive control (diabetic +insulin
6 U/kg); Group 4: diabetic+ mangiferin (10 mg/kg); Group 5: diabetic+ mangiferin (20 mg/kg).
#P< 0.05, Group 1 vs. Group 2.
P< 0.05, treated diabetic groups vs. diabetic control group.
500 S. Muruganandan et al. / Journal of Ethnopharmacology 97 (2005) 497–501
Fig. 1. Effect of mangiferin on oral glucose tolerance test in glucose-loaded
normal rats. Left panel indicates time course of action while the right
panel indicates the total antihyperglycemic response (AUGTC 0–120min)
of mangiferin. () Vehicle (Veh) (2ml/kg, i.p.); () mangiferin (10mg/kg,
i.p.); () mangiferin (20 mg/kg, i.p.). Man: mangiferin, n=6/group. Values
are mean ±S.E.M. *P<0.05 vs. control group.
with mangiferin (10 and 20 mg/kg, i.p.) as comparable to in-
sulin (6U/kg, i.p.) at various time intervals (Table 1). How-
ever, there was a significant (P< 0.05) elevation in the HDL-
C level in mangiferin (10 and 20mg/kg, i.p.) treated diabetic
rats on 28th day as compared to the diabetic control group
(Table 1). In addition, mangiferin (10 and 20mg/kg, i.p.)
showed significant (P<0.05) reduction in atherogenic index
starting from the 14th day of treatment period as comparable
to insulin (6U/kg, i.p.).
The chronic administration of mangiferin (10 and
20mg/kg, i.p.) for 14 days in normal rats resulted in
significant improvement in oral glucose tolerance follow-
ing oral glucose load as shown by the significant reduc-
tion in %IG at 60min interval of OGTT (14.72±6.46
and 5.89±3.27 versus 91.62±13.46) with the (AUGTC
0–120min) of 1442.38±193.53 and 1335.58±137.77 ver-
sus 5088.08±542.59, as compared to the control group, re-
spectively (Fig. 1). However, mangiferin treatment for 14
days did not alter basal plasma glucose level at any time of
the study (data not shown).
4. Discussion
Owing to the reported antidiabetic and hypolipidemic
properties of mangiferin, a xanthone-C-glucoside in non-
insulin dependent KK/Ay mice with hyperinsulinemia, the
present study was carried out in an attempt to elucidate its
effects on hyperglycemia and atherogenesis in STZ-diabetic
rats.
Inthe present study,STZ(55mg/kg,i.v.)producedsignifi-
cantfastinghyperglycemiaand bodyweightloss. Mangiferin
showed significant and consistent reduction in fasting blood
glucose levels and also significantly improved the body
weight loss at different intervals throughout the period of
experiment as compared to the vehicle treated diabetic con-
trolsindicatingitspotentantidiabetic activity.Inour previous
study, we showed that the chronic treatment of mangiferin
(10 and 20mg/kg, i.p.) caused significant as well as moder-
ate reduction in the glycosylated hemoglobin levels in STZ-
diabetic rats further substantiating its potential in the long
term glycemic control of diabetes mellitus (Muruganandan
et al., 2002). Since STZ (55mg/kg, i.v.) effectively destroys
pancreatic cells and causes persistent hyperglycemia, the
mechanismof antidiabeticactionof mangiferin mightinvolve
actions other than pancreatic cells insulin release/secretion
(insulinotropic effect), i.e. possibly through other extrapan-
creaticactions in these STZ-diabetic rats (Bwititi etal., 2000;
Jouadet al., 2000). Theextrapancreaticactions perhaps might
includethe stimulation of peripheralglucoseutilization or en-
hancing glycolytic and glycogenic processes with concomi-
tantdecreaseinglycogenolysisandgluconeogenesis (Saxena
and Vikram, 2004). Furthermore, it is also likely that it might
reduce blood glucose level by inhibiting the glucose absorp-
tion from the intestine. The latter hypothesis could be sup-
ported by the recent findings that mangiferin inhibits glu-
cosidase enzymes (sucrase, isomaltase, maltase) (Yoshikawa
et al., 2001) which are involved in the digestion of carbo-
hydrate into simple sugars in the gut leading to delay or
inhibition of carbohydrate breakdown and subsequent glu-
cose absorption from the intestine (Emelien et al., 1999).
Although, in the present study mangiferin was administered
intraperitoneally, the inhibition of -glucosidase enzymes by
the mangiferin excreted through bile into gut, i.e. through
enterohepatic circulation cannot be ruled out. Also, in our
preliminary investigation, we found that both the single and
chronic administration of mangiferin did not have any sig-
nificant effect on the basal fasting plasma glucose level in
normal rats (data not shown). Nevertheless, chronic adminis-
tration of mangiferin (10 and 20 mg/kg, i.p.) significantly im-
proved oral glucose tolerance in glucose-loaded normal rats
indicating its potent antihyperglycemic activity. This result
is in accordance with the previous results conducted with the
aqueous extract of Mangifera indica leaves further suggest-
ing that the active principle, mangiferin might be responsible
for the glucose lowering action on oral glucose tolerance test
(Aderibigbe et al., 1999, 2001). These evidences tempt us to
speculatethat apart from the aforementioned probable insulin
independent extrapancreatic actions, the other possible pan-
creatic mechanism, i.e. stimulating insulin release from the
pancreatic cells might contribute in improving oral glucose
tolerancein the glucose-loaded normal rats. Takentogether,it
canbe summarized as mangiferin might possessboth pancre-
aticand extrapancreaticmechanisms in its antidiabetic action
andsuch apparent dual pancreaticandextrapancreatic actions
of mangiferin would be more advantageous to the existing
oral antidiabetic monotherapy.
In our study, STZ (55mg/kg, i.p.) treated diabetic rats
exhibited clear-cut abnormalities in lipid metabolism as evi-
denced from the significant elevation of plasma total choles-
terol, triglycerides, LDL-C, atherogenic index and reduc-
tion of HDL-C levels. Treatment with mangiferin (10 and
20mg/kg, i.p.) for 28 days significantly and greatly reduced
S. Muruganandan et al. / Journal of Ethnopharmacology 97 (2005) 497–501 501
plasmatotalcholesterol,TGand LDL-C associated with con-
comitantsignificant increase in HDL-C levelsand decrease in
atherogenic index in diabetic rats indicating its potent antihy-
perlipidemic and antiatherogenic activity. The glucose low-
ering action of the mangiferin can be due to the consequence
of an improved lipid metabolism apart from the direct inter-
action with glucose homeostasis. The triglycerides lowering
property of mangiferin could indirectly contribute to the over
all antihyperglycemic activity through a mechanism of so-
called glucose–fatty acid cycle (Randle et al., 1963). Accord-
ingtothe Randle’sglucose–fatty acid cycle, increased supply
of plasma triglycerides per se could constitute a source of in-
creased free fatty acid (FFA) availability and oxidation that
can impair insulin action, glucose metabolism and utilization
leading to development of hyperglycemia. Therefore, the re-
duction of triglycerides following treatment with mangiferin
wouldalsofacilitatetheglucose oxidation and utilization and
subsequently the reduction of hyperglycemia. In our earlier
study, we found that mangiferin significantly reduced mal-
onaldehyde (MDA) level, a marker of lipid peroxidation in
different organs viz., heart, liver and kidney by ameliorating
changes in the antioxidant enzymes indicating its possible
antioxidant activity which is advantageous in treatment of
diabetic complications (Muruganandan et al., 2002).
In conclusion, the present study demonstrates that
mangiferin (10 and 20mg/kg, i.p.) at the dose levels
tested exhibits potent antidiabetic, antihyperlipidemic
and antiatherogenic activities in STZ-diabetic rats and
also shows the improvement in oral glucose tolerance in
glucose-loaded normal rats without inducing hypoglycemic
state. The agent with these multiple advantageous properties
viz., antidiabetic, antihyperlipidemic, antiatherogenic and
antioxidant properties without causing hypoglycemia would
be of greater therapeutic benefit in the management of DM
associated with abnormalities in lipid profiles and merits
further detailed investigation to find out its mechanism
of action and to establish its therapeutic potential in the
treatment of diabetes and diabetic complications.
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... In the next section, the basic reproductive number of the mathematical model shall be obtained using the next generation matrix [11]. ...
... R 0 is a dimensionless number and not a rate that would have units per time [9,10]. [11] Hefferman et al provided a nice readable introduction for calculating R 0 in structured population models [12,13]. Using the next generation matrix method, the basic reproductive number is defined as the spectral radius of the next generation matrix of the form , where F is a nonnegative matrix that consists of the rate of new infections and matrix V consists of the rate of recovery. ...
... [14] Hefferman et al provided a nice readable introduction for calculating R 0 in structured population models [12,13]. Using the next generation matrix method, the basic reproductive number is defined as the spectral radius of the next generation matrix of the form , where F is a nonnegative matrix that consists of the rate of new infections and matrix V consists of the rate of recovery, deaths and other transitions from one compartment to another given in the form and where x 0 is the disease free equilibrium state and R 0 is the dominant eigenvalue of the matrix [11]. Consider the system of equations (6) to (10). ...
... In the next section, the basic reproductive number of the mathematical model shall be obtained using the next generation matrix [11]. ...
... R 0 is a dimensionless number and not a rate that would have units per time [9,10]. [11] Hefferman et al provided a nice readable introduction for calculating R 0 in structured population models [12,13]. Using the next generation matrix method, the basic reproductive number is defined as the spectral radius of the next generation matrix of the form , where F is a nonnegative matrix that consists of the rate of new infections and matrix V consists of the rate of recovery. ...
... [14] Hefferman et al provided a nice readable introduction for calculating R 0 in structured population models [12,13]. Using the next generation matrix method, the basic reproductive number is defined as the spectral radius of the next generation matrix of the form , where F is a nonnegative matrix that consists of the rate of new infections and matrix V consists of the rate of recovery, deaths and other transitions from one compartment to another given in the form and where x 0 is the disease free equilibrium state and R 0 is the dominant eigenvalue of the matrix [11]. Consider the system of equations (6) to (10). ...
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Mango with the botanical name of Mangifera Indica (MI) (Linn.) is one of the traditionally used herb trees in the third-world country used for different curative and prophylaxis measure for different health challenges. This article presents updated information on its mathematical modeling using ordinary differential equations (S,E,I,P,R) for theoretical/analytical methods and epidemiological applicability of therapeutic/pharmacological efficacy of Mangifera indica (MI) (Linn.) against selected recalcitrant diseases in third-world countries. To introduce the mathematical model that connects all the necessary parameters and variables on the epidemiological applicability of therapeutic /pharmacological efficacy of the Mango (Mangifera Indica (MI)(Linn.)leaf and stem bark, to cure the Original Research Article Osuntokun et al.; SARJNP, 5(1): 43-52, 2022; Article no.SARJNP.88572 44 ravaging health challenges. The basic reproductive number of the model was obtained. This parameter was obtained to show that, the use of the (Mangifera Indica (MI))(Linn.) leaf and stem bark can cure the health challenges mathematically such that, as the use of the mango leaf and stem bark increases, the rate of the ravaging health challenges among the populace reduces. It is a fact that the medicinal plant is a good source of medicine for developing countries especially in the third world like Africa and Asia, taking Nigeria as a case study. This write-up is premeditated from the fact that there should be a cure for recalcitrant ailments like high blood pressure, diabetes and etc. without the use of conventional medicine. We should be able to use the local herbs for the known health debacle without any side effects. As scientists, we decided to research various medicinal plants that can be used. During the process of search, mango leaf shines like a bright star and there is a need to make a thorough and further searchlight for the wonderful medicinal plant, because of its various therapeutic uses on ravaging health challenges in Nigeria and other third world countries.
... The rise in the incidence of colorectal cancer (CRC) has made it a concerning disease and currently represents approximately 10% of malignant growth-related mortality in western countries. The 'ascent' of CRC worldwide is due to the increase in unhealthy dietary propensities, and an increment in hazard factors like smoking, low actual exercise, and obesity [1][2][3][4][5][6][7][8][9][10]. CRC is caused by the stepwise interaction of hereditary and epigenetic modifications, leading to the change of ordinary colonic mucosa into intrusive malignant growth [11,12]. ...
... Although benign colon cancer is often successfully removed by surgery, the high-level illness requires aggressive treatment that has lower efficacy. Around 30 to 75% of patients with colon malignant growth utilize correlative and elective medication (CAM) [1][2][3][4][5][6][7][8]. Many clinical trials suggest that bioactive components from plants in combination with chemotherapy reduced the side effects of chemotherapeutic drugs and improved the survival rates in colon cancer as compared with chemotherapy alone [4][5][6][7][8][9][10]. ...
... Around 30 to 75% of patients with colon malignant growth utilize correlative and elective medication (CAM) [1][2][3][4][5][6][7][8]. Many clinical trials suggest that bioactive components from plants in combination with chemotherapy reduced the side effects of chemotherapeutic drugs and improved the survival rates in colon cancer as compared with chemotherapy alone [4][5][6][7][8][9][10]. ...
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Background Mangiferin is a C-glycoside xanthone molecule having a wide range of therapeutic properties. Hence, the present study aims to understand the efficacy of mangiferin against colorectal cancer (CRC) and to elucidate the mechanisms of action of mangiferin on colorectal cancer. Method The molecular mechanism of mangiferin against colorectal cancer was studied using Autodock Vina software. Pharmacophore analysis of mangiferin concerning five COX-2 inhibitor drugs was carried out using the PharmaGist server to analyze the possibility of using mangiferin as a COX-2 inhibitor. In vitro analysis of Mangiferin against various cancer cell lines was performed. Results The molecular mechanism of action of mangiferin against CRC was assessed by docking with multiple target proteins involved in the progression of CRC. Docking studies showed good binding scores (kcal/mol) ranging from − 10.3 to − 6.7. Mangiferin showed a good affinity towards enzymes like COX-2 and LA4H involved in Arachidonic acid (AA) metabolism with a binding score(kcal/mol) of − 10.1 and − 10.3 respectively. The pharmacophore feature assessment of mangiferin was done for COX-2 inhibitor drugs, which further confirmed that mangiferin poses the same pharmacophore feature as that of COX-2 inhibitor drugs. Furthermore, the binding affinity of mangiferin was compared with five COX-2 inhibitor drugs to prove its efficacy as an inhibitor. Mangiferin also had a cytotoxic effect against colorectal cancer (HT 29), cervical cancer (HeLa), and breast cancer (MCF 7) cell lines. The study could establish that Mangiferin might be a promising candidate for the treatment of colorectal cancer. Conclusion In short, these studies exploited the possibility of mangiferin as a lead molecule to develop anticancer/anti-inflammatory drugs for the treatment of CRC.
... The below mentioned therapeutic properties have been described regarding xanthones which were obtained from other sources shown in Fig. 9: anti-malarial [7,[70][71][72], antidiabetes, anti-hyper lipidemic, and antiatherogenic [56,73]; antibacterial [56]; anticancer [73]; antitumoral [56]; hepato-protective, antifungal, antiulcer, immunomodulator, antiviral, and anti-inflammatory [56]; and cardioprotective [42,56]. ...
... The below mentioned therapeutic properties have been described regarding xanthones which were obtained from other sources shown in Fig. 9: anti-malarial [7,[70][71][72], antidiabetes, anti-hyper lipidemic, and antiatherogenic [56,73]; antibacterial [56]; anticancer [73]; antitumoral [56]; hepato-protective, antifungal, antiulcer, immunomodulator, antiviral, and anti-inflammatory [56]; and cardioprotective [42,56]. ...
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The Garciniamangostana Linn (Mangosteen) is also called as “Queen of Fruits” in Malaysia. It is found in the region of Southeast Asia. It is a medicinal plant that has been used to treat cancer in a variety of cell lines. The mangosteen pericarp possesses distinctive biological properties like anticancer or antitumoral and antioxidant. It has a distinct sweet and sour taste, rich in biological compounds like xanthones. It exhibits various properties like apoptotic in tumor cells which leads to the suppression of their growth and results in their various sizes. The primary purpose of this review article is to summarize the valuable results covered by the researchers so far in the Garcinia mangostana extract and its compound like xanthones. Our focus was to explain the role of the phytoconstituent molecules in invading the cancer pathways to combat the expansion of cells. Furthermore, we still feel that there is a scope for more in silico and in vivo studies to understand and identify the specific site of action in tumoral cells and their mechanistic pathways. In conclusion, Garcinia mangostana can act as an anticancer agent by attacking various molecular pathways. Graphical abstract
... Mangiferin (1) provides protection against a wide range of physiological disorders (Telang et al. 2013), and it exhibits many pharmacological activities such as antidiabetic (Muruganandan et al. 2005); anti-inflammatory by acting as a potent inhibitor of cyclooxygenase-2 (COX2), interleukins (IL-6 and IL-8), X-linked inhibitor of apoptosis protein (XIAP), intercellular adhesion molecule 1 (ICAM1), chemokine receptor type 4 (CXCR4), tumor necrosis factor (TNF), and nuclear factor kappa B (NFκB) (Garcia-Rivera et al. 2011); analgesic (Ojewole 2005); immunomodulatory (Leiro et al. 2004); and antiviral (Wang et al. 2011). The antioxidant and free radical scavenging activity of mangiferin is mainly due to the polyphenolic groups in its structure (Saha et al. 2016). ...
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Nutraceuticals have recently gained interest owing to their valuable contribution in the treatment of several diseases, with high safety margin and low incidence of side effects. However, their efficacy is limited by some challenges, namely poor solubility, low permeability, and, consequently, low bioavailability. Delivery carriers have proven that they can overcome almost all the aforementioned limitations, leading to improvement in the pharmacological efficacy of nutraceuticals. Among the promising nutraceuticals that have currently evoked considerable interest is mangiferin from mango tree, which is a polyphenol exhibiting many favorable pharmacological actions, but unfortunately suffers from poor aqueous solubility and other limitations that lower its bioavailability and halter its efficacy. This review summarizes the pharmacological actions of mangiferin and provides an insight on how delivery carriers for mangiferin (lipidic, vesicular, polymeric, inorganic, and protein nanoparticles, as well as complexes) can overcome its pharmaceutical challenges, hence reflecting on its improved therapeutic effects in treatment of different diseases. Graphical Abstract
... Antibacterial, antifungal, anthelmintic, antiparasitic, anticancer, anti HIV, antibone resorption, antispasmodic, antipyretic, antidiarrheal, immunomodulation, hypolipidemia, antimicrobial, hepatoprotective, and gastroprotective properties have all been researched by many researchers and experts. (Samantha et al.,2019) Hypoglycemic activity of Mangiferin (10 and 20 mg/kg, i.p. once daily for 28 days) in STZinduced diabetic rats and improvement in oral glucose tolerance in glucoseloaded normal rats after chronic administration (10 and 20 mg/kg, i.p.) for 14 days, via intestinal glucose absorption reduction and pancreatic and extrapancreatic mechanisms (Murugananda et al., 2005). ...
Chapter
The wound healing process is made up of interconnected cellular and molecular stages that work together to heal the wound. Wound healing can be defined as a succession of processes completed by the body, with each stage increasing the likelihood of microbial infection. Improved wound healing can be attained by shortening the healing time or reducing the number of inappropriate events. To aid wound healing, the medicines were administered locally or systemically. Antibiotics, antiseptics, desloughing agents, extracts, and other compounds have been used to promote wound healing. Some synthetic medications are restricted due to their harmful effects. Plants or plantderived mixtures are required to explore, identify, and formulate for wound healing treatment and management. Because of the fewer side effects and management of wounds, there has been an increase in interest in using medicinal herbs in wound healing throughout the years. In research, medicinal herbs were found to help diabetic, infected, and open wounds heal faster. Medicinal plants have been shown to aid in wound healing through a variety of processes. This chapter will go through some therapeutic plants as well as reported active ingredients with pharmacological efficacy in formulations
... Mangiferin (10 and 20 mg/kg, ip) showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) levels, together with elevation of high-density lipoprotein cholesterol (HDL-C) level and diminution of atherogenic index in diabetic rats (210) . ...
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Hyperlipidemia refers to elevated levels of lipids and cholesterol in the blood. It plays an important role in the development of atherosclerosis, the main cause of death in the world. Medicinal plants can lower blood lipids by many mechanisms included inhibition of the expression of fatty acid synthase, decreasing free fatty acid release, inhibition of HMG-CoA reductase, increasing the fecal excretion of fat and cholesterol, inhibition of the activity of pancreatic lipase and inhibition of cholesterol absorption. The current review will highlight the hypolipidemic effects of medicinal plants as promising effective and safe therapies.
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This study aimed to determine the effect of synbiotic Musa acuminata skin extract (MASE) and Streptococcus salivarius K12 (K12) on Candida species biofilm formation. Liquid chromatography quadrupole time-of-flight (LC-Q-TOF-MS) was conducted to characterize MASE. To determine the effect of synbiotic on Candida biofilm, 200 µL of RPMI-1640 containing Candida, K12, and MASE were pipetted into the same well and incubated at 37 °C for 72 h. A similar protocol was repeated with K12 or MASE to determine the probiotic and prebiotic effects, respectively. Dimorphism, biofilm biomass, and Candida total cell count (TCC) were determined. A total of 60 compounds were detected in MASE. C. albicans (ALT5) and Candida lusitaniae exhibited the highest reduction in biofilm biomass when co-cultured with prebiotic (77.70 ± 7.67%) and synbiotic (97.73 ± 0.28%), respectively. All Candida spp. had decreased TCC and hyphae when co-cultured with synbiotic. In conclusion, MASE and K12 inhibit Candida biofilm formation.
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Diabetes mellitus is a chronic complication that affects people of all ages. The increased prevalence of diabetes worldwide has led to the development of several synthetic drugs to tackle this health problem. Such drugs, although effective as antihyperglycemic agents, are accompanied by various side effects, costly, and inaccessible to the majority of people living in underdeveloped countries. Medicinal plants have been used traditionally throughout the ages to treat various ailments due to their availability and safe nature. Medicinal plants are a rich source of phytochemicals that possess several health benefits. As diabetes continues to become prevalent, health care practitioners are considering plant-based medicines as a potential source of antidiabetic drugs due to their high potency and fewer side effects. To better understand the mechanism of action of medicinal plants, their active phytoconstituents are being isolated and investigated thoroughly. In this review article, we have focused on pharmacologically active phytomolecules isolated from medicinal plants presenting antidiabetic activity and the role they play in the treatment and management of diabetes. These natural compounds may represent as good candidates for a novel therapeutic approach and/or effective and alternative therapies for diabetes.
Article
Purpose The aim of this study is to provide a review of the research studies that took place in the previous years regarding Mangiferin and its potential use in the treatment of various disorders such as diabetes, cardiovascular diseases, cancer and human immunodeficiency virus. Design/methodology/Approach Mangiferin can be easily extracted from the plant at a very low cost to treat some common as well as deadly diseases, which will be a miracle in herbal treatment. In support of this, the recent related articles were considered to understand the bioactive compound “Mangiferin” to treat lifestyle diseases. Various review articles and research papers were collected from international and national journals, and internet sources were also being used to compile the current manuscript. Findings Mangiferin has been shown to have the potential to mitigate many life style diseases such as diabetes, obesity, hypertension, fatty liver, atherosclerosis, dyslipidemia and diabetes-related end-organ complications such as retinopathy, neuropathy and nephropathy. Originality/value In this comprehensive review, this study evaluates Mangiferin and its lifestyle disease-modifying properties for nutraceuticals purposes.
Article
The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats, In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of;Mangifera indica possess hypoglycaemic activity, This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded. Copyright (C) 1999 John Wiley & Sons, Ltd.
Article
The effects of nasunin, a major anthocyanin in eggplant, and its aglycone, delphinidin, on the serum cholesterol conpentration were determined in rats fed with a cholesterol-enriched diet. The serum total cholesterol and HDL-cholesterol concentrations tended to be decreased and increased, respectively, by feeding nasunin and delphinidin, while the fecal excretion of both cholesterol and bile acids tended to be increased by feeding with the anthocyanins. There was no difference between the nasunin and delphinidin activity to decrease serum total cholesterol, nor to increase serum HDL-cholesterol or the fecal excretion of cholesterol and bile acids. These results suggest that the slightly lower serum total cholesterol concentration in rats fed with nasunin and delphinidin may in part be due to inhibition of the intestinal absorption of both cholesterol and bile acids by these anthocyanins, and that the delphinidin moiety of nasunin mainly contributes to this activity.
Article
Mangiferin, three catechins, and two catechin dimers were isolated from the roots of Salacia reticulata (SRE), and examined their inhibitory activities against several carbohydrate metabolize enzymes (sucrase, maltase, isomaltase, (alpha -amylase, and aldose reductase). Among them, mangiferin was found to inhibit sucrase, isomaltase, and aldose reductase from rat with IC50 values of 87, 216 and 1.4 mug/ml, respectively. The inhibitory activities of mangiferin are competitive for sucrase and isomaltase with inhibitor constant (K-i) 55 mug/ml and 70 mug/ml, respectively. In order to determine the mangiferin contents in the water extracts from the roots of S. reticulata, a quantitative analytical method by means of HPLC was developed and the mangiferin contents in SRE were determined to be in the range of 0.9-2.3% by the application of this method. A high linear correlation (r=0.934) was observed between the mangiferin contents and the sucrase inhibitory activity. In addition, this analytical procedure of mangiferin was found to be applicable for other Salacia species (S. oblonga, S. chinensis, and S. prinoides). Thus, the quantitative HPLC analysis of mangiferin was supposed to be suitable for the quality control of Salacia species and its products.
Article
The pharmacokinetics of mangiferin (the main component of the drug ‘Alpizarin’) was studied by HPLC in rats after intravenous injection of the drug in a single dose of 0.3, 1, 3, 10 and 30 mg/kg and after its oral administration in a single dose of 50–500 mg/kg. It was shown that the mangiferin pharmacokinetics for the above dose levels was nonlinear, and within each dose could be described by a two-compartmental model. Its nonlinearity might be associated with saturated binding and metabolism of the compound.
Article
Using tissue culture techniques the present study assured us of the merits of mangiferin and isomangiferin in the antiviral action against HSV-1. Utilizing 4 main patterns for evaluating drug effectiveness (ie intratube drug-on-virus direct action, simultaneous addition of drug-virus-inoculum to cell bottle, virus inoculation preceding drug addition, and drug addition followed by virus inoculation), it was readily found by logarithm determination of HSV-I inhibition that isomangiferin was superior to such control drugs as acyclovir, idoxuridine, and cyclocytidine in logarithm by 0.27-0.50, and that mangiferin was lower than isomangiferin in logarithm by 0.53. The average plaque reduction rates of mangiferin and isomangiferin were 69.5% and 56.8%, respectively. All in all, the antiviral effect of mangiferin and isomangiferin was attributed presumably to their capability to inhibit virus replication within cells.
Article
The effect of mangiferin, a tetrahydroxy pyrrolidone saponin extracted from the leaves of mango (Mangifera indica), against herpes simplex virus type 2 (HSV-2) in vitro was studied. The 50% effective concentration (EC50) of it against HSV-2 plaque formation in HeLa cells was 111.7 micrograms.ml-1, and the concentrations of 33 and 80 micrograms.ml-1 reduced the virus replicative yields by 90% (EC90) and 99% (EC99), respectively. The therapeutic index (IC50/EC50) was 8.1. Mangiferin did not directly inactivate HSV-2. The results of the drug addition and removal tests suggest that mangiferin inhibits the late event in HSV-2 replication.
Article
Mangiferin, a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside) purified from plant sources was shown to have in vivo growth-inhibitory activity against ascitic fibrosarcoma in Swiss mice. Following in vivo or in vitro treatment, it also enhanced tumor cell cytotoxicity of the splenic cells and peritoneal macrophages of normal and tumor-bearing mice. In vitro treatment of the splenic cells of tumor-bearing mice with mangiferin resulted in augmented killing of tumor cells, both resistant and sensitive to natural killer cells. Mangiferin was also found to antagonize in vitro the cytopathic effect of HIV. The drug appears to act as a potent biological response modifier with antitumor and antiviral effect.
Article
Mangiferin (MF) and its glucosides (mangiferin-7-O-beta-glucoside) (MG) isolated from Anemarrhena asphodeloides Bunge rhizome, were tested for their antidiabetic activity in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM). MF and MG lowered the blood glucose level of KK-Ay mice after oral administration. However, no affect on the blood glucose level in normal mice was seen, indicating that MF and MG are useful in treating NIDDM. In addition, MF or MG improved hyperinsulinemia in KK-Ay mice. From these findings, it seems likely that MF and MG exert their its antidiabetic activity by increasing insulin sensitivity.
Article
Glycaemic control in Type 1 diabetes has been proven efficient in preventing microvascular and neurological complications. The assumption that good control of hyperglycaemia may also have significant impact on alleviation of complications in Type 2 diabetes has gained growing support in recent years. Measures such as body weight reduction and exercise improve the metabolic defects, but pharmacological therapy is most frequently used. The sulphonylureas stimulate insulin secretion. Metformin and troglitazone increase glucose disposal and decrease hepatic glucose output without causing hypoglycaemia. Acarbose helps to spread the dietary carbohydrate challenge to endogenous insulin over time. These pharmacological treatments can improve blood glucose regulation in Type 2 diabetes patients. However, the key to strict glycaemic control with use of exogenous insulin lies in the creation of delivery methods that emulate physiologic insulin secretion. Insulin lispro, a recombinant insulin analogue, is identical to human insulin except for the transposition of proline and lysine at positions 28 and 29 in the C-terminus of the B chain. Evidence suggests that patients perceive their quality of life to be improved with insulin lispro when compared with regular human insulin, and that satisfaction with treatment is greater with the insulin analogue. Numerous new pharmacological approaches are under active investigation, with the aim of promoting insulin secretion, improving the action of insulin, or slowing carbohydrate absorption. With respect to continuous subcutaneous insulin infusion therapy and implantable pumps, despite that this approach is not widely utilised, it appears to bring us as close to achieving glycaemic control as is feasible with current treatment approaches. However, general application of such technology requires significant improvements in several areas, such as improvement of patency of catheter, pump failures due to early battery depletion incidents, and pump miniaturisation. Future perspective resides on insulin analogues with longer half-lives that would provide better basal insulin coverage in association with fast-acting analogues.
Delphinidine-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin was isolated as purple colored crystals from eggplant peels, Solanum melongena L. 'Chouja'. Using an electron spin resonance spectrometer and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), spin trapping, hydroxyl (.OH) or superoxide anion radicals (02*-) generated by the Fenton reaction or the hypoxanthine-xanthine oxidase system were measured as DMPO-OH or DMPO-OOH spin adducts. L-Ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetra-methyl-2-(4,8,12-trimethyltridecyl)-2 H-1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) and bovine erythrocyte superoxide dismutase (SOD) were used as standards for .OH and O2*-, respectively. Nasunin directly scavenged O2*- with a potency of 143+/-8 SOD-equivalent units/mg), and inhibited formation of DMPO-OH (0.65+/-0.07 EPC-K1 micromol/mg). A spectrophotometric study showed that nasunin formed an iron complex with a molar ratio of nasunin : Fe3+ of 2 : 1. Therefore, hydroxyl radical scavenging by nasunin is not due to direct radical scavenging but inhibition of .OH generation by chelating iron. Nasunin (1 microM) significantly protected against lipid peroxidation of brain homogenates (p<0.001) as measured by malonaldehyde and 4-hydroxyalkenals. These findings demonstrate that nasunin is a potent O2*- scavenger and iron chelator which can protect against lipid peroxidation.