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Therapeutic validation of Ipomoea digitata tuber (Ksheervidari) for its effect on cardio-vascular risk parameters

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Ipomoea digitata Linn. (Ksheervidari) is a well known medicinal plant used in Ayurveda for its health promoting effects in human beings. Its tuber powder was evaluated first time in a single blinded, placebo controlled study for its antihypertensive potential and its effect on lipid profile, fibrinolytic activity and total antioxidant status in individuals with stage 1 hypertension. Administration of 3 gm tuber powder significantly (p<0.001) decreased systolic, diastolic and mean blood pressure, increased fibrinolytic activity and total antioxidant status with a significant reduction (p<0.05) in serum total cholesterol, LDL cholesterol and atherogenic index at the end of 12 weeks. It was tolerated well without any significant side effect. In the placebo group, there were no significant alterations in any of the parameters at the end of study. Ipomoea digitata Linn. syn. Ipomoea paniculata (L.) R.Br. (Fig.1) is a member of family Convolvulaceae and called as Bilai-kand, Bhui-khola, Ksheervidari, Payasvinee, Bhumi-kumra, Bhumi-kushmanda in various languages 1 . Plant and its medicinal properties has been well mentioned in the ancient literature 2 as follows:
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Indian Journal of Traditional Knowledge
Vol.10 (4), October 2011, pp. 617-623
Therapeutic validation of Ipomoea digitata tuber (Ksheervidari) for
its effect on cardio-vascular risk parameters
Jain1 Vartika, Verma2* SK & Katewa1 SS
1Laboratory of Ethnobotany and Agrostology, Department of Botany, University College of Science,
Mohan Lal Sukhadia University, Udaipur, Rajasthan, India
2Indigenous Drug Research Center, Department of Medicine, RNT Medical College, Udaipur, Rajasthan
E-mails: vartikajain31@gmail.com, skvermaster@gmail.com
Recieved 01.10.09; revised 05.01.10
Ipomoea digitata Linn. (Ksheervidari) is a well known medicinal plant used in Ayurveda for its health promoting effects
in human beings. Its tuber powder was evaluated first time in a single blinded, placebo controlled study for its
antihypertensive potential and its effect on lipid profile, fibrinolytic activity and total antioxidant status in individuals with
stage 1 hypertension. Administration of 3 gm tuber powder significantly (p<0.001) decreased systolic, diastolic and mean
blood pressure, increased fibrinolytic activity and total antioxidant status with a significant reduction (p<0.05) in serum total
cholesterol, LDL cholesterol and atherogenic index at the end of 12 weeks. It was tolerated well without any significant side
effect. In the placebo group, there were no significant alterations in any of the parameters at the end of study.
Keywords: Hypertension, Bhumi-kushmanda, Fibrinolysis, Antioxidant
IPC Int. Cl.8: A01D 14/01, A01D 14/02, A01D 14/03, A01D 14/04, A01D 14/05, A01D 14/06, A01D 14/07, A01D 14/08,
A01D 14/09, A01D 14/10
Abbreviations: Atherogenic index, AI, Blood pressure, BP;
Ischemic heart disease, IHD; Body mass index, BMI; Joint
national committee, JNC; Gram, gm; High density lipoprotein
cholesterol; HDL-C; Low density lipoprotein cholesterol, LDL-C;
Total antioxidant status, TAS; Very low density lipoprotein
cholesterol, VLDL-C.
Ipomoea digitata Linn. syn. Ipomoea paniculata (L.)
R.Br. (Fig.1) is a member of family Convolvulaceae
and called as Bilai-kand, Bhui-khola, Ksheervidari,
Payasvinee, Bhumi-kumra, Bhumi-kushmanda in
various languages1. Plant and its medicinal properties
has been well mentioned in the ancient literature2
as follows:
Its tubers are eaten raw in Midnapore district of
West Bengal, India3. Raw tuber is also taken to
treat blood dysentery and used as an astringent.
Juice of its tubers with one glass of cow milk is given
for 7 days to increase lactation by Kandha tribe of
Orissa4. Sun-dried root powder, boiled in sugar and
butter is administered to promote weight gain and to
moderate menstrual discharge. Tubers have also been
used for treatment of debility, spermatorrhoea, fever,
bronchitis, scorpion stings and menorrhagia5.
Yaogika cikitsa and Dravya guna has mentioned
its usefulness in patients with hypertension and
heart disease. Their recommendations are based
on ethnomedicinal observations in Rarh region.
A teaspoonful of powdered tuber if given twice a
day with honey is beneficial for the patients of high
blood pressure and heart disease6,7.
There are many drugs available for management
of hypertension which is a common cardiovascular
risk factor for IHD. However, drug treatment of mild
hypertension has been associated with metabolic
alterations that increase the risk of cardiovascular
diseases, resulting in stand off or even a negative
overall effect. In this regard dietary spices and various
plant products have been evaluated from time to
——————
*Corresponding author
INDIAN J TRADITIONAL KNOWLEDGE, VOL. 10, No. 4, OCTOBER 2011
618
time8. Ksheervidari is one such medicinal plant which
has shown some promise against hypertension as
shown in animal models9, yet it has not been
scientifically validated in human studies. In this
regard, this study is an attempt to evaluate the tubers
of Ipomoea digitata on various cardiovascular risk
parameters in hypertensive individuals.
Methodology
Tubers of Ipomoea digitata were procured
from the forests of West Midnapore, Bengal and
cultivated under the vigilance of Society for
Microvita research and Integrated Medicine
(SMRIM) at Udaipur (Figs.1 a & b). After noting
whole taxonomic characters and identification10 ,
voucher specimen of the plant was deposited in
the Herbarium at Laboratory of Ethnobotany and
Agrostology, Department of Botany, ML Sukhadia
University, Udaipur, Rajasthan (India) for
authentication of information and future reference.
Herbarium number to voucher specimen was
also provided (EA-540*) (EA—Ethnobotany and
Agrostology Herbarium number)
Tubers were thoroughly washed under running tap
water, and cut into small pieces (Fig. 1c). They were
airdried in shade at an ambient temperature. The dried
material was ground in an electrical grinder to make a
fine homogenous powder which was filled in gelatin
capsules. Each capsule contained 750 mg of the dried
powder. Placebo contained lactose powder filled in
similar gelatin capsules. It was selected because it
doesn’t alter the biochemical parameters.
After approval from institutional ethical committee
(No.RNT/State/2008/F.comn/597), 60 newly diagnosed
male individuals having essential hypertension
(Primary hypertension), between the ages of 40-50 yrs
(BMI<25), who attended medical out patient
department of Maharana Bhopal General Hospital
attached to RNT Medical College, Udaipur during
January 2008 to March 2009 were enrolled for
the study.
All the patients selected were of stage 1 (140/90
to 159/99 mm Hg) hypertension of JNC VII11. The
patients with stage 2 (160/100 mm Hg) hypertension
of JNC VII, secondary hypertension, diabetes,
ischemic heart disease, renal and endocrine diseases
were not included in the study. Similarly, the patients
who were smokers, alcoholics, on lipid lowering
drugs, dietary restrictions or weight reduction
program were excluded from this study.
After informed consent, the selected individuals
were randomly categorized to the following two
groups. The study subjects, however, were unaware of
this categorization.
Group I (n=30) Treated group: They were
administered I. digitata tuber powder filled in
capsules, in a dose of 1.5 gm twice daily for a period
of 12 weeks.
Group II (n=30) Placebo group: They received
matched placebo capsules in the same doses for 12
weeks. However, 10 individuals dropped out during
the study period. Therefore, final results are based on
20 individuals.
The placebo and tuber powder filled capsules
were similar in size, shape and weight; hence the
patients were blinded for that matter. During the study
period, the patients were advised not to alter their
dietary and exercise habits. They were also instructed
not to take any medication without prior consultation.
Blood pressure was measured by a mercury
sphygmomanometer (Pagoda Delux) with a standard
Fig. 1 (a)—Twining plant; (b) Ipomoea digitata Linn. Tuber; (c) Ipomoea digitata Linn. sliced tuber
JAIN et al.: THERAPEUTIC VALIDATION OF IPOMOEA DIGITATA TUBER
619
size cuff as per recommendations of JNC VII.
Average of two or more readings with the gap of
5 minutes was taken at each time of blood pressure
recording. Blood pressure was recorded in sitting
position initially and at every 4th week for 12 weeks.
Mean BP and Pulse pressure was calculated from
the following formula12:
Mean blood pressure = Diastolic blood pressure +
1/3rd of pulse pressure.
Pulse pressure = Systolic blood pressure - Diastolic
blood pressure
Blood samples were collected in a fasting state,
initially and at the end of 4th, 8th and 12th week for
analysis of plasma fibrinolytic activity, serum lipid
profile and total antioxidant status. Fibrinolytic
activity13 was assessed as euglobulin lysis time as
described by Buckell and Elliot. It is based on the
principle that euglobulin fraction clotted with
thrombin and the time taken for clot lysis is estimated
and expressed in units by multiplying the reciprocal
of lysis time in minutes by 10000.
Blood cholesterol14, Triglycerides15 and HDL-C16
were estimated colorimetrically by enzymatic
methods employing standard diagnostic kits (Reckon
Diagnostics P. Ltd., Baroda). VLDL-cholesterol
(VLDL – C) and LDL-cholesterol (LDL – C) were
calculated by Friedwald formula17 as follows:
VLDL – C = Triglycerides / 5
LDL – C = Total Cholesterol - (HDL-C + VLDL-C)
Total antioxidant status was assessed using
standard kit supplied by Randox, UK where the color
produced by ABTS (2,2’-Azino-di-[3-ethylbenz
thiazoline sulphonate]) radicals is measured at
600 nm in a spectrophotometer (Milton Roy Co.)
which is proportional to concentration of antioxidants
present in the sample18.
All the values were expressed as mean ± standard
error (SE). Results were statistically analyzed with
student’s t-test for paired data and a p’ value of less
than 0.05 was considered as significant.
Results and discussion
Administration of Ipomoea digitata tuber powder
in a dose of 1.5 gm twice daily significantly decreased
systolic (p<0.001), diastolic (p<0.01) and mean
(p<0.001) blood pressure at the end of 4 weeks.
Although the reduction in blood pressure was
statistically significant at the end of fourth week
yet the levels of systolic blood pressure did not reach
up to the normal values of less than 120 mm Hg.
At the end of 8 weeks there was further decrease
observed in systolic, diastolic and mean blood
pressure and systolic blood pressure lowered to
126.4 ± 1.83 from 157.6 ± 1.16 mm Hg. At the end of
the study, the systolic (118.8 ± 0.34 mm Hg) and
diastolic (76 ± 2.45 mm Hg) blood pressure reached
within the range of normal level ( 120/80 mm Hg)
as defined by JNC VII criteria (Table 1). The placebo
controlled group did not show any significant
alteration in systolic, diastolic and mean blood
pressure at any stage of the study (Fig. 2).
On an average, there was a fall of 38.8 mm
Hg in systolic and 19.2 mm Hg in diastolic blood
pressure at the end of 12 weeks in treated
group (Fig. 3). This statistically significant decrease
in blood pressure is important in terms of its
long term morbidity and mortality from
cardiovascular diseases. Randomized controlled
trials have shown that in patients with mild
hypertension, lowering of 5-6 mm Hg in diastolic
and 10 mm Hg in systolic blood pressure reduces
stroke risk by about one third and risk of coronary
events by about one sixth19.
Table 1—Effect of Ipomoea digitata tuber powder (3 gm) on blood pressure in stage 1
hypertensive individuals (n=30)
BLOOD PRESSURE
(mm Hg)
INITIAL
(I)
4 WEEKS
(II)
8 WEEKS
(III)
12 WEEKS
(IV)
SYSTOLIC 157.60 ± 1.16 129.2 ± 2.58 a 126.4 ± 1.83 b 118.80 ± 0.34 c,d
DIASTOLIC 95.20 ± 1.49 85.2 ± 2.33e 78.00 ± 2.00 b 76.00 ± 2.45 c,d
MEAN 115.99 ± 1.34 97.19 ± 1.65 a 93.73 ± 1.12 b 90.26 ± 1.48 c,d
Values are expressed as Mean ± SE
Mean Blood Pressure = Diastolic blood pressure + 1/3rd of pulse pressure.
p Value –
<0.001- a II v/s I, b III v/s I, c IV v/s I,
<0.01 – e II v/s I,
NS –d IV v/s III
INDIAN J TRADITIONAL KNOWLEDGE, VOL. 10, No. 4, OCTOBER 2011
620
There were 80 % of individuals who attained
the optimum level of diastolic blood pressure
( 80 mm Hg) at the end of 4 weeks and all the
individuals achieved the optimum level at the end
of 8 weeks. However, in systolic blood pressure,
initially there were 20 % of individuals who attained
the optimum level of systolic blood pressure of 120
mmHg at the end of 4 weeks. The percentage reached
to 100 % at the end of 12 weeks.
Mean BP is the product of cardiac output and
peripheral vascular resistance. Administration of 3 gm
Ipomoea digitata tuber powder also significantly
reduced mean blood pressure (22.18 %) at the end
of the study (Table 1). Pulsatile pressure is also
dependent on large and small artery compliance,
a reduction of which contributes to a progressive
increase in systolic pressure with aging. The pressure
difference between systolic and diastolic provides
a crude guide to stiffness of the large conduit
arteries20,21.
Hypertension and atherosclerosis often co-exist
in individual patients. Hypertension and its
complications, its modifications seem to be an
attractive means to favorably affect the development
of cardiovascular events in hypertensive patients.
However, recent large clinical trials still emphasize
that the main drives of clinical benefit from blood
pressure lowering therapy is the magnitude of blood
pressure reduction22.
Hypertension is usually associated with an
abnormal level of antioxidant status and reduced
fibrinolysis23. Increased blood lipids further add to its
risk in producing coronary atherosclerosis. In this
regard, various dietary compounds and some plant
materials are important as they have effect on blood
pressure as well as other risk factors of endothelial
dysfunction24-26. Ipomoea digitata not only lowers
blood pressure; but also affects other parameters
inductive to atherogenesis with a wide safety profile.
In the present study, administration of Ipomoea
digitata tuber powder has led to significant (p<0.001)
rise in fibrinolytic activity which is an important
factor responsible for maintaining a perfect
haemorrheological state (Table 2). The fibrinolytic
activity is considered to be a major physiological
means of disposing fibrin after its haemostatic
function has been fulfilled. The process is of great
importance in wound healing and re-canalization of
the thrombosed vessels. If the fibrin is not removed
properly then its organization and fatty deposition on
the artery involved, result in atheroma formation27.
The antioxidant status in humans reflect the
dynamic balance between antioxidant defense and
prooxidant conditions and have been suggested as a
Fig. 2—Pattern of blood pressure change after administration of
Ipomoea digitata (Group I) and matched placebo (Group II) in
hypertensive individuals
Fig. 3—Reduction in blood pressure (mm Hg) at the end of
4th, 8t h and 12th weeks after daily administration of 3 gm
Ipomoea digitata tuber powder in stage 1 hypertensive
individuals (n=30)
JAIN et al.: THERAPEUTIC VALIDATION OF IPOMOEA DIGITATA TUBER
621
useful tool in estimating the risk of oxidative
damage28,29. Ipomoea digitata; besides its blood
pressure lowering and fibrinolysis enhancement
properties, has also demonstrated significant
(p<0.001) improvement in serum total antioxidant
status (TAS) after 12 weeks of its administration in
stage 1 hypertensive individuals (Table 2). TAS was
progressively increased by 39, 90 and 103 % at the
end of 4, 8 and 12 weeks respectively after
administration of 3 gm tuber powder in two divided
doses (Fig. 4).
Favorable reductions were also observed in serum
total cholesterol (26.11 %), triglycerides (16.06 %),
VLDL-C (16.06 %) and LDL-C (32.54 %) levels at
the end of 12 weeks in treated (group I) hypertensive
individuals (Table 3). The levels of reduction attained
statistical significance with total cholesterol and
LDL-C while the changes in triglycerides, HDL-C
and VLDL-C were statistically not significant.
However, the ratio of HDL-C and LDL-C was
significantly (p<0.05) increased at the end of 12
weeks. Impressively, atherogenic index, the marker of
atherogenesis was also found to be continuously
decreasing by 10.15, 14 and 25.15 % at the end of 4,
8 and 12 weeks of the study, respectively (Fig. 5)
but the statistically significant (p<0.05) reduction
was observed only at the end of the study. In the
placebo treated hypertensive individuals, the lipid
fractions, fibrinolysis and total antioxidant status
were significantly unaltered throughout the study
(Tables 2 & 3).
Looking at the temporal profile of the effects
of Ksheervidari on various cardiovascular risk
parameters, its therapeutic potential has become
more apparent. In the present study, administration of
I. digitata in hypertensive individuals has enhanced
fibrinolysis, decreased systolic and diastolic pressure
significantly even at the end of fourth week, whereas
the significant reduction of atherogenic lipids was
not observed. To counteract the lipid factor in
inflicting injury to endothelium in the process of
atherosclerosis, the TAS has started increasing
significantly even at the end of 4 weeks; possibly
preventing oxidation of LDL-C. The plant therefore
counteracts the risk parameters and interacts with
the situations of endothelial dysfunction, thereby
improving its functions which are important for
cardiovascular health.
Tubers of Ipomoea digitata has been reported to
yield compounds as taraxerol, taraxerol acetate,
umbelliferone, scopoletin, scoparone, β-sitosterol and its
3-0-β-D-glucoside, 1-o-ethyl-β-D glucopyranoside9,30.
Many of these chemical compounds possess
pharmacological activities, involved in protection
against endothelial dysfunction. Scopoletin, a
coumarin present in the tubers of I. digitata has been
shown to cause hypotension in animal study31.
It relaxes the smooth muscles by dilating blood
vessels and also acts as a non-specific spasmolytic
Fig. 4—Percent increase in total antioxidant status after daily
administration of Ipomoea digitata tuber powder (3 gm) in stage 1
hypertensive individuals
Fig. 5—Percent change in HDL-C/LDL-C ratio and atherogenic
index (AI) after daily administration of 3 gm Ipomoea digitata
tuber powder in stage 1hypertensive individuals (n=30)
INDIAN J TRADITIONAL KNOWLEDGE, VOL. 10, No. 4, OCTOBER 2011
622
agent like papaverine. Moreover, it also possesses
in vitro antioxidant activity as shown by Shaw and
associates 32.
An ether soluble fraction from the tubers of
I. digitata has also been reported to possess
hypotensive, myocardium depressant and muscle
relaxant activities. Administration of 5 and 10 mg/kg
ether soluble drug intravenously in normotensive
anesthetized dogs reduced blood pressure by 20 and
32 mm Hg, respectively. Moreover, this hypotensive
effect was not modified by ganglionic, adrenergic,
cholinergic blockade, antihistaminic drugs or bilateral
cervical vagotomy9.
Umbelliferone, a benzopyrone present in the
tubers of Ipomoea digitata is a well known
natural antioxidant33. β-sitosterol is another
important sterol present in this plant which has
been shown to possess antioxidant34, antimicrobial35,
anti-cancer36, angiogenic37, antihyperglycemic38
and hypocholesterolemic39 properties. However, the
specific bioactive molecule from Ksheervidari
responsible for its hypotensive and antioxidant
properties should be isolated for its maximum
therapeutic benefit.
The present single blinded placebo controlled
study therefore, suggests that Ksheervidari possesses
components due to which its long term
administration significantly lowers blood pressure
and blood lipids, and enhances fibrinolysis and
antioxidant status in stage 1 hypertensive
individuals. Looking to its beneficial effects with a
wide safety profile, it can be developed as a safe and
economical plant derived hypotensive agent with its
multifaceted benefits.
Table 2—Effect of Ipomoea digitata tuber powder and placebo (3 gm) on fibrinolytic activity (FA)
and total antioxidant status (TAS) in stage 1 hypertensive individuals
PARAMETER GROUP INITIAL(I) 4 WEEKS(II) 8 WEEKS(III) 12 WEEKS(IV)
TREATED 85.71 ± 7.35 101.08 ± 8.70 a 101.86 ± 6.45 b 125.25 ± 11.02 c,d
FA
(Units) PLACEBO 78.96 ± 4.56 80.50 ± 7.46 * 82.69 ± 5.65 * 80.97 ± 10.46 *
TREATED 0.59 ± 0.05 0.82 ± 0.08 a 1.12 ± 0.06 e 1.20 ± 0.11 c,f
TAS(mM/L)
PLACEBO 0.61
±
0.07 0.75
±
0.07
*
0.70
±
0.08
*
0.70
±
0.05
*
Values are expressed as Mean ± SE NS-Not significant
p Value –
<0.05 - a II v/s I, d IV v/s III
<0.02 - b III v/s I
<0.001 – c IV v/s I
<0.01 - e III v/s I
NS – f IV v/s III, *As compared to initial.
Table 3—Effect of Ipomoea digitata tuber powder and placebo (3 gm) on lipid profile in stage 1 hypertensive individuals
PARAMETERS GROUP INITIAL(I) 4 WEEKS(II) 8 WEEKS(III) 12 WEEKS(IV)
Cholesterol(mg/dl) Treated 262.21 ± 34.26 219.05 ± 28.22 a 225.03 ± 24.65 b 193.74 ± 22.30 c, d
Placebo 255.46 ± 15.88 245.26 ± 18.67 a 250.14 ± 13.99 b 240.91 ± 16.03 e
Triglycerides(mg/dl) Treated 169.40 ± 17.31 156.82 ± 15.53 a 139.35 ± 11.51 b 142.19 ± 17.38 d, e
Placebo 174.70 ± 19.56 166.64 ± 3.50a 170.45 ± 16.06 b 164.50 ± 15.45e
HDL-C(mg/dl) Treated 40.91 ± 3.63 38.04 ± 2.97 a 40.90 ± 2.60 b 40.40 ± 4.04 d, e
Placebo 45.57 ± 3.95 48.57 ± 3.40 a 48.69 ± 2.26 b 46.92 ± 3.14 e
VLDL-C(mg/dl) Treated 33.87 ± 3.58 31.36 ± 3.10 a 27.96 ± 2.23 b 28.43 ± 3.47 d, e
Placebo 34.94 ± 2.91 33.32 ± 2.67 a 34.09 ± 3.16 b 32.9 ± 2.85 e
LDL-C(mg/dl) Treated 185.16 ± 31.66 149.65 ± 27.88 a 156.02 ± 26.73 b 124.90 ± 22.86 c, f
Placebo 174.95 ± 17.55 163.37 ± 15.67 a 167.36 ± 19.57 b 170.09 ± 18.45 e
HDL-C/ LDL-C Treated 0.22 ± 0.11 0.25 ± 0.10 a 0.26 ± 0.09 b 0.32 ± 0.17 c, d
Placebo 0.26 ± 0.04 0.29 ± 0.08 a 0.29 ± 0.07 b 0.27 ± 0.09 e
Atherogenic index (AI) Treated 6.40 ± 0.43 5.75 ± 0.54 a 5.50 ± 0.98 b 4.79 ± 0.62 c, d
Placebo 5.60 ± 0.46 5.04 ± 0.57 a 5.13 ± 0.58 b 5.32 ± 0.96 e
Values are expressed as Mean ± SE, NS - Not significant, AI=Total cholesterol/HDL-C
p Values-
NS – a II v/s I, b III v/s I, d IV v/s III, e IV v/s I
<0.05 - c IV v/s I, f IV v/s III.
JAIN et al.: THERAPEUTIC VALIDATION OF IPOMOEA DIGITATA TUBER
623
Acknowledgement
One of the authors (Vartika Jain) is highly thankful
to CSIR, New Delhi, India for providing financial
assistance.
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... Ipomoea digitata (I. digitata), a flower locally named as Giant Potato, have been well known for its use to lower the blood pressure and for the treatment of poor digestion, tuberculosis and liver complications [5] [29] [30] . Allamanda cathartica (A. ...
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