Dr. K.V.G.S. Murty discloses his interests in herbal research companies and formulations including Cardorium Plus. Cardorium Plus is manufactured by Alakananda Herbals and marketed by Ayurveda One to address vascular endothelial dysfunction. World health statistics show increases in conditions like hypertension, diabetes and obesity globally that are associated with endothelial dysfunction. An interim report discusses an ongoing clinical trial of Cardorium Plus that shows improvements in endothelial function markers like augmentation pressure and augmentation index in subjects taking Cardorium Plus compared to placebo after 3 months. The report concludes Cardorium Plus may benefit those with conditions like hypertension, heart disease and diabetes by improving endothelial function.

1. DR KVGS MURTY, MBBS
AYURVEDA ONE PVT LTD.,
NIZAM’S INISTITUTE OF
MEDICAL SCINCES,
HYDERABAD,
INTERIM REPORT
14.03.2016
KOLKATA

2. DISCLOSURE OF INTEREST:
DR. K.V.G.S. MURTY, MBBS
DIRECTOR, KALAGA HERBAL RESEARCH LABS
DIRECTOR, ALAKANANDA HERBALS PVT LTD
FORMULATOR OF CARDORIUM PLUS®
CARDORIUM PLUS® MANUFACTURED BY M/S
ALAKANANDA HERBAL PVT LTD., HYDERABAD,.
TELANGANA
CARDORIUM PLUS® MARKETED BY AYURVEDA ONE
PVT LTD., BANGALORE

4. The World health statistics 2012 (WHO)
One in three adults worldwide has raised blood pressure – a condition
that causes around half of all deaths from stroke and heart disease.
One in 10 adults has diabetes, left untreated, diabetes can lead to
cardiovascular disease, blindness and kidney failure.
Dramatic increase in the conditions that trigger heart disease and
other chronic illnesses, in particular low-and middle-income
countries.
“In every region of the world, obesity doubled between 1980 and
2008,” “Today, half a billion people (12% of the world’s population) are
considered obese.”
(ONE INTERESTING OBSERVATION IS ALL THE ABOVE CONDITIONS
ARE ASSOCIATED WITH VASCULAR ENDOTHELIAL DYSFUNCTION)

10. Endothelial Dysfunction
(Vascular Dysfunction)
and Various Diseases
This slide shows the extent of
involvement of endothelial
dysfunction in various diseases,
much like a high blood pressure
measurement or fever that is
indicative of different problems.
This is why we believe
endothelial function monitoring
will be adopted as part of
routine vital sign monitoring,
not as an indicator of an acute
condition but rather for chronic
health and preventive
maintenance.

18. AYURVEDIC SOLUTION FOR MANAGEMENT
OF ENDOTHEILIAL DYSFUNCTION
ROOT CAUSE OF MANY DISEASES
INCLUDING HYPERTENSION, OBESITY
DIABETES AND MANY
OTHER DISEASES

19. A poly herbal proprietary Herbal Ayurvedic liquid decoction
manufacutred by M/S Alakananda Herbals Pvt. Ltd., made out of
Arujuna, Pushkarmool, Gokru, Kokum, Burans, Jatamansi and Ames
to address vascular endothelial dysfunction and Atherosclerosis.
CARDORIUM PLUS®
Cardorium Plus® is available in Liquid form in 300 Ml Pet Bottles.

20. Mechanism of Action of Cardorium Plus®
•Relaxes blood vessels
•Anti inflammatory and Anti oxidant action
•Anti Platelet action (Blood thinner) Improves blood
circulation
•Improves cardiac function in particular Left Ventricular
Systolic Ejection Flow
•Anti-Hyperglycemic action in particular reduction of
insulin resistance
•Normalizes lipid ratios
•Protects Liver
•Prevents/reduces blockages in both micro and macro
blood vessels by preventing the lipid accumulation and by
improving vascular endothelial function and lipid efflux
action on existing blockages - through maintaining
adequate availability of Nitric Oxide at Vascular
endothelium (Tunica intima)

21. Phase I studies of Cardorium Plus®
Animal Trials - Cardorium Plus® Beneficial effects on
Dysplipidemia and Inflammation in Hyperlipidemic
Chick model, oxidative stress in Hyperlipidemic chick
model, Complete toxicity studies and feretility studies
were conducted under the guidance of Dr. A. Ramesh,
M.Pharm, Ph.D, Professor in Pharmacology and Sri
Devarakonda SSGPMR Murthy, Shri Vishnu College of
Pharmacy, Vishnupur. Bhimavaram, Andhra Pradesh in
the years 2009 to 2010.
Phase II studies (Clinical Trials) of Cardorium Plus®
Human Trials – Completed at Government Ayurvedic
Medical College at Bangalore, Karnataka State, India.

23. Endo-PAT2000 is the leading medical device for noninvasive
endothelial function assessment. It is FDA-cleared, CE-
marked and used in preeminent clinical institutions,
research centers and Pharmaceutical clinical phase studies
in over 40 countries. (Test based on NO bioavailability)

24. ENDOPAT 2000 STUDY Cardorium plus
DATE Name Before Date After
Cardorium plus Cardorium plus
Test Result
28.11.2013 1 RHI : 1.46 04.03.2014 RHI : 1.57
F 50 Yr BMI - 27 Endothelial Endothelial
Metabolic Syndrome Dysfunction Dysfunction
28.11.2013 2 RHI : 1.62 04.03.2014 RHI : 1.82
M 54 Yr BMI - 29 Endothelial Normal Endothelial
Metabolic Syndrome Dysfunction Function
29.11.2013 3 RHI : 1.42 05.03.2014 RHI : 1.82
M 45 Yr BMI - 25.2 Endothelial Normal Endothelial
Diabetes with BP Dysfunction Function
28.11.2013 4 RHI : 1.98 04.03.2014 RHI : 1.96
M 62 Yr BMI - 24.2 Normal Endothelial Normal Endothelial
Diabetes Function Function
(Earlier used
Cardorium Plus)
Cardorium Plus® 15Ml Twice a day after food for a period of 90 days given, without changing their
existing modern treatment package, which they are taking regularly for the past 12 to 36 months.

25. CLINICAL STUDY OF CARDOIRUM PLUS® - INTERIM REPORT
(Joint Clinical Study by Nizam’s Institute of Medical Sciences and
Dr.B.R.K.R.Govt. Ayurvedic Medical College, Hyderabad, Telangana State)
Dr.C.H. Ravikumar, MD (Ay), Professor & HOD, Department of Dravyaguna,
Dr.B.R.K.R. Govt. Ayurvedic Medical College, Hyderabad, Telangana, Dr. C.
Prabhakar Reddy, MD, Assist. Professor, Department of Clinical Pharmacology,
Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana.
Study Title - A randomized, double-blind, parallel group study to evaluate
the effect of CARDORIUM PLUS® on Vascular Endothelial Function, arterial
stiffness and on biomarkers of inflammation, thrombosis, oxidative stress,
coagulation, lipids and insulin sensitivity in subjects with Vascular
Endothelial Dysfunction (type 2 diabetes mellitus, cardiovascular disease
and chronic kidney disease).
The study was initiated with Institutional Ethical Committee clearance from
Dr.B.R.K.R. Govt. Ayurveda Medical College (1) and PABC clearance from
Nizam’s Institute of Medical Sciences. (2) and AYUSH approval.

28. Primary parameters:
The primary parameters are evaluated three times in the study, at the baseline, at
the end of study drug administration i.e. at 12 weeks and lastly at end of 4 week
follow-up i.e. at 16 weeks.
1.Endothelial dysfunction
a.cf Pulse Wave Velocity
b.Changes in Augmentation Index (AIx) with administration of endothelium-
dependent β2 agonist Salbutamol and of endothelium-independent
vasodilator Nitroglycerine.
c.Levels of Nitric Oxide
2.Oxidative stress markers:
a.Malonaldehyde
b.Protein carbonyl
c.Glutathione
3.Inflammatory markers:
a.Highly sensitive C-Reactive protein
b.Tissue necrosis factor- α
c.Interleukin-6
4.Thrombosis markers:
a.von Willibard factor
b.Platelet aggregation test
5.Insulin sensitivity:
6. Lipid parameters:

29. INTERIM REPORT
The study is under progress and
has recruited around 100 subjects
against target of 120 subjects. In
this interim report we are
concentrating assessment of
Vascular Endothelial Function by
SphygmoCor on 38 subjects, in
which 23 were randomized to
Cardoirum Plus® and 15
randomized to placebo and these
subjects have completed 3 months
of drug/placebo intake followed by
one month follow-up.
CARDORI
UM
n=23
PLACEB
O
n=15
Age
(Mean) 48.80 52.4
Male:
Female 0.67 08:07
DM 23 15
Hypertensi
on 12 4
CAD 4 1
DM alone 13 11
DM+HTN 6 3
DM+CAD 4 1

30. Pulse wave analysis (PWA) is a
simple and noninvasive
technique that has been widely
used in epidemiological and
interventional studies. PWA
provides useful information
regarding the mechanical
properties of the arterial tree and
the ventricular-vascular
interaction and can also be used
to assess endothelial function.
PWA is a simple, valid, reliable,
and inexpensive technique,
offering great clinical and
epidemiological potential.
Electronics module
(SphygmoCor device,
AtCorMedical, Sydney,
Australia).

31. The figure shows typical features of the
aortic pulse pressure waveform, from
which can be derived augmentation
pressure (AP), augmentation index (AIx),
and arrival time of reflected waves at the
central aorta (Tr). Tr represents the time
from the onset of the ejected pulse
waveform to the onset of the reflected
wave and reflects aortic pulse wave
velocity. AP is the additional aortic
systolic pressure generated by the return
of the reflected waves at the central
aorta, expressed in absolute terms. AIx is
the AP as a percentage of central pulse
pressure and is a composite measure of
aortic wave reflection and systemic
arterial stiffness. Although the timing of
the arrival of the reflected wave at the
proximal aorta is largely determined by
large artery PWV, AIx is not
interchangeable with PWV.

32. Central pressure waveform.
The central (aortic) pressure
waveform as derived from
the radial artery waveform
(via a validated transfer
function (as provided by the
SphygmoCor™).
Identification of early and
late systolic peaks allows for
central SBP, PP, AP and AIx.
(Adapted from: Woodman RJ
and Watts GF. Measurement
and application of arterial
stiffness in clinical research:
focus on new methodologies
and diabetes mellitus. Med
Sci Monitor 2003;9: RA101-
109.)

33. Endothelial function can be assessed noninvasively by evaluating
the effects of inhaled salbutamol on the AIx. AIx is a measure of
systemic arterial stiffness. Notably, NO, considered the central molecule
governing endothelial function, is a key modulator of arterial stiffness.
Chowienczyk et al. demonstrated that salbutamol, a β2 agonist and
endothelium dependent vasodilator, in part reduces wave reflection by
activation of the L-arginine-NO pathway.
Wilkinson et al. and Hayward et al. evaluated the effects of inhaled
salbutamol and sublingual GTN on the AIx. Investigators observed a
significant correlation between the salbutamol-mediated reductions in Aix
and increase in forearm blood flow during infusion of acetylcholine that
was abolished by coadministration of NGmonomethyl-L-arginine (L-
NMMA), an endothelial NO synthase inhibitor, suggesting that this may
represent a valid approach for assessing endothelial function.
Salbutamol-mediated effects on Aix can be used to estimate endothelial
function.

34. CARDORIUM (n=23)
AP (mm of Hg) A Ix(mm of Hg)
Pre Sal Post Sal Pre Sal Post Sal
Baseline 11.6 12.9 25.4 25.1
Std ± 3.48 ± 3.67 ± 6.32 ± 6.48
3 Months 7.1 2.6 18.7 11.3
Std ± 2.69 ± 1.75 ± 6.02 ± 4.76
Follow-up 9.1 6.2 20.8 16.7
Std ± 3.48 ± 3.46 ± 6.58 ± 5.92
p > 0.05 at baseline for both AP and A Ix and also for changes with salbutamol inhalation .
p < 0.001 for Changes in AP from baseline to 3 months of treatment and >0.05 between
baseline and at follow-up, p < 0.001 for Changes in AP with salbutamol inhalation, p <
0.05 between end of treatment and 01 month of follow-up and at end of 3 months the p <
0.05 for Changes in AP with salbutamol inhalation.

35. 0
5
10
15
20
25
30
Baseline
3months
Follow-up
Baseline
3months
Follow-up
AP A Ix
Pre Sal
Post Sal
CHANGES IN AP AND A Ix WITH CARDORIUM

36. At Base line before starting of Cardoirum plus® the subjects are
having endothelial dysfunction and even with salbutamol the
response is minimal in both Augmentation Pressure (AP) and
Augmentation Index (Aix), indicating confirmation of endothelial
dysfunction.
After completion of three months of usage of Cardorium Plus®
10ml twice a day, there is considerable improvement even at base
line values of both Augmentation Pressure (AP) and Augmentation
Index (Aix), and also with salbutamol the improvement is recorded,
indicating improvement in the endothelial function and increase in
the availability of Nitric oxide.
At the end of fourth month i.e. absence of Cardorium Plus® for one
month there was a small reduction in the values of both
Augmentation Pressure (AP) and Augmentation Index (Aix), and
also with salbutamol but the improvement of endothelial function is
there in comparison with baseline values.

37. PLACEBO (n=15)
AP (mm of Hg) A Ix(mm of Hg)
Pre Sal Post Sal Pre Sal Post Sal
Baseline 9.5 11.4 20.7 21.8
Std ± 4.16 ± 4.24 ± 6.31 ± 5.53
3 Months 12 10.7 20.8 21.5
Std ± 4.26 ± 4.19 ± 6.67 ± 6.78
Follow-up 11.5 12.4 21.7 20.8
Std ± 3.31 ± 3.4 ± 7.11 ± 7.85
p > 0.05 for all changes with salbutamol inhalation.

38. 0
5
10
15
20
25
Pre Sal Post Sal Pre Sal Post Sal
AP A Ix
Baseline
3 Months
Follow-up
CHANGES IN AP AND A Ix WITH PLACEBO
With placebo in 15 subjects there are minimal changes in the
Augmentation Pressure (AP) and Augmentation Index (Aix), in fact
there is some progress in dysfunction after three months showing
disease progress.

39. Conclusion: The above interim report is provisionally
encouraging and showing improvement of endothelial
function in all subjects randomized to Cardorium
Plus® . The study is under progress by completion of
this clinical trial we will be in a position to provide
more evidence based data.
Inclusion of Cardorium Plus® in the treatment
protocol will benefit Hypertensive subjects, Coronary
Heart Disease Subjects, Diabeteic subjects, Obesity
subjects, Geriatric subjects (both male and female)
and apart from many other diseases and disorders.

40. Cardorium plus® and Ayurveda
Cardorium plus® is a potent drug bringing
VATHANULOMATHA in the circulatory system.
It removes SROTHORODHA.
It prevents DHAMANIPRATHICHAYA.
It corrects MEDODUSHTI.
It reduces the risk of complications associated with
PRAMEHA.
In a single word Cardorium Plus is a JEEVANA Drug.

41. Arjuna and Pushkaramoola which correct Dhamaniprathichaya. Arjuna is a
Hridya Drug - cardio protective.
Pushkaramoola removes Kapha vitiation and inhibits the process of
Srothorodha, since Kapha Dosha is mainly responsible for Srothorodha.
Burans acts against Kapha Dsoha, Vyana Vatha Dsoha, Medodushti and
improves raktha vaha srotas.
Vrikshamla is a proven drug against Medodushti which prevents
Dyslipidemia and Atherosclerosis.
Gokshura is a potent Vatha pacifying herb with Rasayana quality.
Rasayana drugs like Amlavetas will boost the immune system in the body
and scavenges free radicals in addition Amlavetas also act against Vyana
Vatha Dosha, Medodushti and improves Raktha vaha srotas.
Jatamansi acts against Vyana Vatha Dosha and helps to maintain normal
Raktha vaha srotas.

42. DR. K.V.G.S. MURTY, MBBS,
DIRECTOR (R&D), KALAGA HERBAL RESEARCH LABS,
DIRECTOR (R&D), M/S ALAKANANDA HERBALS PVT. LTD.
FLAT NO.501, BRINDAVAN APRTMENTS, C.E.COLONY,
BAGH AMBERPET, HYDERABAD – 500 013 (A.P) INDIA
MOBILE: +91 9849870762 E-mail: drkvgsmurty@gmail.com
kalagaherbalresearchlabs@gmail.com