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Indian J Med Res 134, August 2011, pp 168-173

A pilot study on the effects of a polyherbal formulation cream on


diabetic foot ulcers
Vijay Viswanathan, Rajesh Kesavan, Kavitha K.V. & Satyavani Kumpatla

WHO Collaborating Centre for Research, Education & Training in Diabetes, M.V. Hospital for Diabetes &
Diabetes Research Centre, Chennai, India

Received April 12, 2010


Background & objectives: Diabetic foot ulcers are the most common cause of non-traumatic lower
extremity amputations in developing countries. The aim of this pilot study was to evaluate the safety
of using a polyherbal formulation in healing diabetic foot ulcers in comparison with standard silver
sulphadiazine cream among patients with type 2 diabetes.
Methods: A total of 40 (M:F=29:14) consecutive type 2 diabetes patients with foot ulcers were enrolled in
this study. They were randomly assigned to two groups of 20 each; Group 1 was treated with polyherbal
formulation and group 2 with silver sulphadiazine cream. All the patients were followed up for a period
of 5 months. The baseline ulcer size was noted and photograph of the wound was taken at the baseline
and at each follow up visit. Number of days taken for healing of the wound was recorded.
Results: The mean age of patients, duration of diabetes and HbA1c% were similar in both the study
groups. The mean length and width of the ulcers was also similar in both the groups at baseline visit.
There was a significant decrease in the size of the wound (length and width) in both the study groups
(P<0.001). The mean time taken for the healing of the ulcer was around 43 days in both groups.
Interpretation & conclusions: Diabetic wound cream prepared by using polyherbal formulation was
found to be effective as well as safe in healing diabetic foot ulcers like the standard silver sulphadiazine
cream.
Key words Diabetic foot ulcers - polyherbal formulation - treatment - type 2 diabetes

cause of non-traumatic lower extremity amputations


in the industrialized world. Foot infection is a leading
cause for hospital admission among diabetes patients
in India2,3. The risk of lower extremity amputation is 15
to 46 times higher in diabetes patients than in persons
who do not have diabetes4,5.

Type 2 diabetes is a chronic disorder and its


prevalence is projected to increase globally. The
increasing prevalence of type 2 diabetes and its
complication are among the most serious public health
concerns around the world. Developing countries,
especially India, face a major problem due to high
prevalence of diabetes1. Diabetic foot disease is the most
significant complication of diabetes and it is a common

Foot ulceration is a disabling complication of


diabetes, and the lifetime risk of a person with diabetes
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VISWANATHAN et al: EFFECT OF POLYHERBAL CREAM ON DIABETIC FOOT ULCERS

developing this complication may be as high as 25 per


cent6. The most frequent underlying aetiologies are
neuropathy, trauma, deformity, high plantar pressures
and peripheral arterial disease7. More than 80 per cent
of amputations in patients with diabetes are preceded
by non-healing foot ulcers8.
Wound may be produced by physical, chemical,
thermal, microbial or immunological insult to the
tissue. Diabetic foot wounds are defined as any break
in the cutaneous barrier, usually extending through the
full thickness of the dermis9. There have been different
methods for infection control and treatment of diabetic
foot ulcers. Their main goal is to accelerate the wound
healing and tissue repair. The process of wound healing
consists of integrated cellular and biochemical events
leading to reestablishment of structural and functional
integrity with regain of strength of injured tissue.
Various herbal products have been used in the
management and treatment of wounds over the years.
Many substances like tissue extracts10, vitamins and
minerals and a number of plant products11 have been
reported to possess pro-healing effects. Wound healing
herbals encourage blood clotting, fight infection and
accelerate the healing of wounds. The aim of this pilot
study was to evaluate the safety of using a polyherbal
formulation cream in promoting the healing of diabetic
foot ulcers in comparison with the standard silver
sulphadiazine cream among type 2 diabetes patients.
Material & Methods
This study was a uni-centre, open label, phase III,
comparative study. Consecutive type 2 diabetes patients
who presented with an ulcer up to Wagners grade III
classification12 (Grade I, superficial ulcer; grade II deep
ulcer probing to tendon, capsule or bone; grade III deep
ulcer with abscess, osteomyelitis or joint sepsis;) were
enrolled in this study at Diabetes Research Centre,
Chennai, between August 2008 and February 2009.
Subjects who had clinical signs of severe infection,
wound that had exposed bone and unwillingness
to participate in the study were excluded. The study
protocol was approved by the ethics committee of the
institution. The patients were fully informed regarding
the composition of the cream and its role in treating
infection. All the study participants gave written
informed consent.
Active ingredients of diabetic wound care cream:
(Polyherbal formulation):
Glycyrrhiza glabra 0.20 per cent (Yastimadhu
Athimathuram) - It improves normal cell multiplication

169

in a wound and in combination with ketaki and Shorea


robusta (kumkilium) it forms a fine protective layer
over the wound, accelerating the growth of normal
tissue, which gets absorbed into the tissue later.
Musa paradisiaca 19.42 per cent (Kadali
vazhaikilangu Kadali) - It tightens the open wound,
reduces the wound area and accelerates wound healing.
It also reduces the kelloid growth and accelerates the
normal tissue growth.
Curcuma longa 2.43 per cent (Manjal turmeric) - It
possess anti-inflammatory activity, antiseptic and helps
in wound healing. It effectively controls normalcy of
tissue glucose level in the wound area. It helps in the
natural repair of micro vascular structure.
Pandanus odaratissimus 9.70 per cent (Thazhai
/ Chevuda Ketaki) - This contains natural fibres with
microcrystalline calcium embedded in it which forms
foundation layer for the tissue growth like natural
fibrogen network over which normal dermal layer can
grow.
Aloe vera 4.85 per cent (Sothukathazhai) - It
increases the cytogenesis, cleanses the wound and
controls the tissue glucose level. Various constituents of
aloe vera have been shown to have anti-inflammatory
activity as well as it stimulates the wound healing.
Cocos nucifera oil (Kera thailam, coconut milk) It supplies nutrition and polysaccharides and enhances
the growth of the tissue.
A total of 40 (M: F=26:14) patients with type 2
diabetes were randomly assigned into two groups:
group 1 (n=20) was treated with diabetic wound cream
(a polyherbal formulation prepared by Cholayil Product
and Services, Chennai, India); group 2 (n=20) was
treated with silversulphadiazine cream. The enrollment
of the subjects was done after the debridement of the
ulcer. The polyherbal formulation cream had various
constituents having antimicrobial, anti-inflammatory
properties. Cream was employed in the treatment
owing to its assured safety and efficacy.
Age and duration of diabetes was recorded
for all patients. HbA1c % was estimated by
immunoturbidimetric method13. The diagnosis of
lower-extremity vascular insufficiency was made
clinically on the basis of absence of both pedal pulses
of the involved foot and/or an ankle-brachial pressure
index of <0.914. Neuropathy was diagnosed by vibration
perception threshold (VPT)15 and a value of >25 V was
considered as abnormal. The anatomic location of the

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INDIAN J MED RES, AUGUST 2011

wound, tissues and vascular status was recorded for all


the patients. All the patients were followed for a period
of 5 months.

Friedmans non parametric repeated measures


comparison were used to test the significance, and
P<0.05 was considered significant.

The baseline ulcer size was between 2-50 cm2.


The ulcer tracing was done for each patient in a sterile
acetate sheet. The photographs of the wound was
taken at the baseline i.e., before the application of the
cream and at each follow up visit. The ulcers greatest
length and width was measured at baseline and follow
up. Patients were initially seen in the diabetic foot
clinic on a weekly basis and were provided with the
best possible care for their ulcers at each visit. Broad
spectrum antibiotics were prescribed if ulcers showed
clinical signs of infection. The dressings were changed
daily after a wash with normal saline followed by the
local application of the diabetic wound cream or silver
sulphadiazine cream as a thin layer. Patients were
advised to do dressing daily, either in the out patient
clinic of our hospital or nearby local hospital or with
the aid of the community nurse who provides home
care for patients with ambulatory problems.

Results

Duration of ulcer before enrollment in the study


and the number of days taken for healing of the wound
were recorded. Offloading of the wounds was done by
standard method in both the groups. Clinical outcome
was documented as a part of routine practice. Healing
was defined as complete epithelialization either by
secondary intention or by split skin graft.
Statistical analysis: SPSS package (version 10.0)
was used for doing statistical analysis. MeanSD for
continuous variables and proportions were reported
as relevant. Students t test, Chi-square test and

Of the 40 patients enrolled in this study, 38 adhered


to the protocol (group 1; n=19 and group 2; n=19). One
patient in group 1 was excluded from the study because
of severe infection and one patient in group 2 died
during the study period (unrelated cause). The follow
up period in both the groups was five months. There
were no adverse events reported in both the groups.
All the study patients had the presence of
neuropathy. More than 60 per cent of patients had
plantar forefoot ulcers in both the study groups.
There was no significant difference in the location of
the wound between the groups. The distribution of
ulcers according to Wagners grade was also similar
in both the study groups. Wagner grade I and II foot
ulcers were viable and grade III ulcers were non-viable
tissues. Ulcers with abscess had foul odour. Presence
of osteomyelitis and peripheral arterial disease among
the study patients was similar in both the groups.
Duration of ulcer before enrollment in the study did not
differ between the groups (Table I). Age and duration
of diabetes was similar in both the groups. HbA1c%
was also similar in both the groups (Table II). Table
III shows the details of size of the wound at baseline
and during follow up visits (after one, 3, 5 months).
The mean length of the wound and mean width was
similar between the groups at baseline. There was a
significant decrease noted in the size of the wound viz.,
length and width in both the study groups at follow up

Table I. Details of foot ulcers at baseline and presence of peripheral arterial disease among the study groups

Location of the wound

Group 1
polyherbal formulation cream (n = 19)
N (%)

Group 2
silver sulphadiazine cream (n = 19)
N (%)

Plantar forefoot

12 (63.2)

13 (68.4)

Plantar mid foot

5 (26.3)

4 (21.1)

Plantar hind foot

2 (10.5)

2 (10.5)

Forefoot dorsum

Mid foot dorsum

5 (26.3)

6 (31.6)

II

5 (26.3)

7 (36.8)

III

9 (47.4)

6 (31.6)

Presence of osteomyelitis

3 (15.8)

4 (21.1)

Peripheral arterial disease

5 (26.3)

4 (21.1)

14.9 13.6

14.0 8.4

Wagners grade classification


of ulcers

Duration of ulcer before enrollment (days) (mean SD)

VISWANATHAN et al: EFFECT OF POLYHERBAL CREAM ON DIABETIC FOOT ULCERS

171

visit (P<0.001). The healing of wound and the decrease


in wound size was shown in the Fig. (Panel a; group 1,
Panel b; group 2). Number of days taken for healing of
the wound was similar in both the groups. The mean
time taken for the healing of the wound was around
43 days in both the groups. There was no significant
difference in healing time between the study groups.
Recurrence of ulcers was similar in both the groups.
Discussion
Wound healing is a complex process that involves
expression of growth factors that promote various
cellular processes, production of new connective tissue
matrix and collagen deposition16. This process is delayed
in diabetes patients due to vascular insufficiency and
decreased blood flow17,18. Various methods have been
used for promotion of wound healing. Recent clinical
Table II. Characteristics of the study groups
Parameters

Group 1
Group 2
polyherbal
silver
formulation cream sulphadiazine cream
(n=19)
(n=19)
Mean age (yr)
59.4 8.6
58.7 4.6
HbA1c (%)
10.5 1.58
10.9 1.5
Duration of diabetes (yr)
13.7 6.5
12.1 4.4
Values are mean SD
Table III. Length and width of the wound at the baseline and
during follow up visits in each group
Wound
length x width

Polyherbal
formulation
cream
Group 1
(n = 19)

Silver
sulphadiazine
cream
Group 2
(n = 19)

4.98 1.5

4.3 1.4

Follow up
1st month

4.51 1.6

4.27 1.4

3rd month

3.99 1.51

3.7 1.5

5 month

3.39 1.8

2.8 2.0*

Width (in cm2)


Baseline

3.54 1.4

3.0 0.98

Follow up
1st month

3.2 1.3

2.95 0.95

3 month

2.75 1.3

2.37 0.97

5th month

2.38 1.4*

1.9 1.3*

43.1 26.8

43.6 30.7

9 (47.4)

8 (42.1)

Length (in cm2)


Baseline

th

rd

Number of days taken for


healing
Recurrence of ulcers n (%)

Values are mean SD. *P<0.001 compared to baseline

Fig. Panel a: Wound healing in the group 1. (i) Pre application of


the polyherbal cream (ii) 28th day of application Panel b: Wound
healing in group 2 (i) Pre application of the silver sulphadiazine
cream (ii) 29th day of application.

trials proved that herbal extracts are also safe and


effective for treatment of diabetic foot ulcers19,20. The
results of the present study showed that diabetic wound
care cream prepared by using polyherbal formulation
was found to be effective as well as safe in healing
of diabetic foot ulcers. The healing process of the
wound with polyherbal formulation cream in diabetic
foot ulcers was similar when compared with subjects
treated with silver sulphadiazine cream. There was a
significant decrease in wound size in both the study
groups.
Evidence showed that healing progression at 2nd
to 4th wk predicts eventual wound closure17,21. Our
study showed that time taken for healing of wound was
approximately 43 days in both the herbal cream treated
versus silver sulphadiazine cream treated subjects. The
healing process was similar in both the study groups. It
has been reported that a herbal drug named ANGIPARS
(daily intravenous infusion) was effective in treating
diabetic foot ulcers without any adverse side effects.
The wound size was reduced 50 per cent during a 8 wk
period22.
It has been proved that silver has bactericidal action
against a number of microorganisms. In the last few
years, a number of silver- containing dressings have
been developed and used to treat acute and chronic
wounds23. In the first randomized controlled trial of
silver dressings in diabetic foot ulcers, 134 patients
with neuropathic foot ulcers were randomly assigned

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INDIAN J MED RES, AUGUST 2011

to either Aquacel Ag (AQAg; ConvaTec, Chester,


UK) or Algosteril calcium alginate (CA) (Smith &
Nephew, Hull, UK) dressings and a secondary foam
dressings. The mean time to healing was 53 days in the
AQAg-treated ulcers and 58 days for the CA treated
ulcers. Ulcers treated with AQAg, however, showed
greater depth reduction than CA-treated ulcers24.
The polyherbal formulation cream used in this study
showed similar effects compared to silver containing
cream treated subjects with diabetic foot ulcers.
The herbal formulation cream used in this study
contains Glycyrrhiza glabra, Musa paradisiaca,
Curcuma longa, Pandanus odaratissimus, Aloe vera
and Cocos nucifera oil ingredients of plant origin. These
ingredients are known to possess anti-inflammatory and
anti-bacterial action. Polyherbal preparations containing
Glycyrrhiza glabra have been reported to promote gain
in tensile strength in incision wound model, but do not
modify the granulation phase of healing25. Curcumin
(difeurloylmethane) from curcuma rhizomes showed
faster closure of wounds and increased collagen, TGF1 and fibronectin in animal studies26. Curcuma longa
also contains protein, fats, vitamins all of which have
an important role in would healing and regeneration.
The anti-inflammatory property and the presence of
vitamin A and proteins result in the early synthesis of
collagen fibres27. Aloe vera has been historically used
for many of the same conditions for which it is used
todayparticularly minor cuts and burns. Test tube
studies suggest polysaccharides, such as acemannon,
help promote skin healing by anti-inflammatory,
antimicrobial, and immune-stimulating actions. Aloes
effects on the skin may also be enhanced by its high
concentration of amino acids, as well as vitamin E,
vitamin C, zinc, and essential fatty acids28. The daily
application of polyherbal cream with all the above
ingredients may promote wound healing in diabetes
patients with foot ulcers. Usage of this cream is not
cumbersome and it does not involve complicated
dressing procedures. Diabetes is a major public health
problem in developing countries and is associated with
high costs of treating diabetic foot problems. So, usage
of this cream may have an impact on treatment of
diabetes foot ulcers in India.
There were a few limitations in the present study.
First, the small sample size, secondly the microbiological
investigations were not done. The prolonged use of the
herbal cream which may have beneficial or probable
side effects was not assessed. Lastly, this study was not
a randomized clinical trial.

In conclusion, daily application of polyherbal


cream could reduce the wound size significantly
approximately in a mean period of 6 wk without any
adverse side effects. The polyherbal cream may be
effective in treating diabetic foot ulcers along with
current standard care. It may be an alternative to silver
sulphadiazine cream used in healing diabetic foot
ulcers. It must however, be stressed that good wound
care practices including sharp debridement, infection
control and offloading play an important role in healing
a diabetic foot ulcer.
Acknowledgment

The authors thank Cholayil Product and Services, Koyambedu,
Chennai, India for providing the polyherbal cream with their
formulation.

Conflict of interest: None.


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Reprint requests: Dr Vijay Viswanathan, Diabetes Research Centre (WHO Collaborating Centre for Research, Education & Training in
Diabetes), 5, Main Road, Royapuram, Chennai 600 013, India

e-mail: drvijay@mvdiabetes.com