Beijing 2014

SYNERGISTIC ROLE OF BROMELAIN, CURCUMIN AND BOSWELLIC
ACID IN MANAGEMENT OF PLEURAL OEDEMA IN A CASE OF
CARCINOMA OF THE LUNGS STAGE 3B
26/08/2014 International Conference On Traditional & Alternative Medicine
- 2014, Beijing, China
Ayushya Varsha Clinics and Health Café’s
Dr. Nitin Chaube
Ayushya Varsha Clinics and Ayurveda Health Café

Lung cancer
INTRODUCTION
Carcinoma of lungs presents with Oedema and
inflammation as co-dependent conditions. It is more
prevalent in males with a growth of 13 % of all newly
diagnosed cases. The pathophysiology of CA lungs
suggests formation of a proteinous gradient influencing
the ionic environment across the microvasculature and
lymphatic drainage of the lungs which induces ionic
polarity, thus increasing the rate of pleural filteration
and reduces reabsorption. This causes effusion due to
impaired hydrostatic and ionic gradients.
Pulmonary oedema

Turmeric (Curcuma longa)
INTRODUCTION
vitiate pitta by
different
mechanisms
Pine Apple (Anana squamosal)
Shallaki (Boswellia serrata)
TRAUMATISED
TISSUE
+
reduce jal and
prithvi
mahabhoot’s,
the vitiated and
trapped vata
moves out of the
srotas
Anti-Oedematic activity
+
+

MATERIAL
Material
The clinical observational study included using extracts in the form of Bromelain,
Boswellic Acid and curcumin.

INDIVIDUAL INGREDIENTS

(BROMELAIN)
Bromelain –
extract derived from the stems of pineapples has -
anti-inflammatory effects
might interfere with the growth of tumor cells and
slow blood clotting.
Ayurvedic constitution –
In the Ayurvedic sense since it has an
enzymatic property which is catabolic in
character (a Pitta-Vataja function) representing
lyasing activity and replacement (a vataja
property)
The anti–oedematic property may likely be due
to the nature of chemical bonding and covalent
characters of the carbon chain and nitrogen in
the context of proteins.

Boswellic Acid –
Boswellic acids are pentacyclic
triterpene molecules found in
the resin of the plant that
exudes them.
(BOSWELLIC ACID)
Ayurvedic constitution –
The Ayurvedic context of Boswellic acid would
present this complex group of chemicals with an
amla attribute which again is pittaja in function.
The pathway of action of these molecular
substrates is entirely different and is likely to be
pitta-vata dominated; since their action is likely to
be classically similar to traditional enzymatic
activity of catabolism.

Curcumin is the principal curcuminoid of turmeric and is a natural
phenol.
curcumin, as an antioxidants, can be a "double-edged sword" and may
have carcinogenic and pro-oxidant effects in addition to anticancer and
antioxidant effects.
Curcumin is known to be anti-inflammatory, antioxidant,
chemopreventive and chemotherapeutic
(CURCUMIN)

Ayurvedic Constitution –
In the Ayurvedic context curcumin may be understood to have pittaja properties.
The chemical character of curcuminoids is that of Alkaloids which are primarily
lipid derivatives and usually lipid soluble or emulsifiable constituents.
This may be a reason for its anti-inflammatory response coupled with anti-pyretic
responses at the same time.
This combination of the activity may signify a pitta-kaphaja coexistence and may
explain the bilateral activity of curcuminoids acting both as anti-inflammatory
and anti-pyretic at the same time.
(CURCUMIN)

What changes happen so as to cause pleural oedema?

Concept of ion mechanisms for pleural fluid accumulation

The pleural space contains approximately 0.3 mL.kg-1 of hypooncotic fluid
approximately 1 g.dL-1 protein.
Pleural fluid turnover is estimated to be approximately 0.15 mL.kg-1.h-1.
Pleural fluid is produced at parietal pleural level, mainly in the less dependent regions
of the cavity.
Reabsorption is accomplished by parietal pleural lymphatics in the most dependent part
of the cavity, on the diaphragmatic surface and in the mediastinal regions.
The flow rate in pleural lymphatics can increase in response to an increase in pleural
fluid filtration, acting as a negative feedback mechanism to control pleural liquid
volume.
This can control a huge change if at all, as a 10 fold increase in filtration rate would only
result in a 15% increase in pleural liquid volume.
In man, maximum pleural lymph flow could attain 30 mL.h-1, equivalent to
approximately 700 mL.day-1 (approximately 40% of overall lymph flow).
Ion Exchange Mechanisms

Pleural and interstitial lung fluid volumes are strictly controlled and maintained at the
minimum because of the ability of lymphatics to match the increase in filtration rate.
In the pleural cavity, fluid accumulation is easily accommodated by retraction of lung
and chest wall; the increase of lymph flow per unit increase in pleural fluid volume is
high due to the great extension of the parietal lymphatic.
However, for the lung interstitium, the increase in lymph flow to match increased
filtration does not need to be so great.
Increased filtration only causes a minor increase in extravascular water volume (<10%)
due to a marked increase in interstitial pulmonary pressure which, in turn, buffers
further filtration.
Accordingly, a less extended lymphatic network is needed.
The efficiency of lymphatic control is achieved through a high lymphatic conductance in
the pleural fluid and through a low interstitial compliance for the lung interstitium.
Fluid volume in both compartments is so strictly controlled that it is difficult to detect
initial deviations from the physiological state; thus, a great physiological advantage
turns to be a disadvantage on a clinical basis as it prevents an early diagnosis of
developing disease.
Concept of Partial Pressures

The air blood barrier is a gas exchanger and is well designed to fulfill this task as its
main feature.
The hydraulic pressure in the lung interstitium is approximately -10 cmH2O and reflects
the equilibrium between the lymphatic absorption pressure and the microvascular
filtration through the basement membrane whose hydraulic permeability is kept very
low due to the macromolecular organization of heparansulphate proteoglycans (HS-PGs).
When microvascular filtration is increased, the increase in extravascular water is
minimal in face of a considerable increase in interstitial pressure (up to approximately 5
cmH2O) because of the high elastance of the extracellular matrix thanks to the
mechanical role of matrix chondroitin sulphate proteoglycans (CS-PGs).
This increase in pressure buffers microvascular filtration.
Hypoxia causes fragmentation of CS-PGs of the extracellular matrix and of HS-PGs of
the basement membrane: the result is a decrease in tissue elastance and an increase
in permeability of the endothelial and epithelial barriers.
When the overall PGs fragmentation overcomes a critical threshold, severe lung edema
develops.
Concept of Partial Pressures Contd.

Diagramatic Representation of the aforesaid -

In the Ayurvedic context in case of cancer due to unnatural trauma caused by the
diseased state the parthiv and the jalaj attributes which together with akash form the
major of the 5 panchmahabhoots get distorted
vayu and agni take predominance proteoglycan structurechanges
distorted distribution ratios of the parthiv attributes across the pleural membranes
different pressure gradients across the membrane.
varied jal conditions
the body tries to restore
increased flow into the pleural cavity.
Vata forms an awarana
prevents flow back of the fluid into the
lymphatic system.
Ayurvedic View
Reduced resorption into
the lymphatic system.
Pleural oedema

THE CASE WHERE THE AFORESAID CHANGES WERE OBSERVED

THE CASE -
STAGE 3B CA LUNGS PREDIAGNOSED -
PATIENT 43 Year old Female
Very Weak
REPORTS FIRST SEEN IN JULY 2013
ANY SURGICAL INTERVENTIONS REFUSED AT NAGPUR AND NEW DELHI AS
WELL
GEFITINIB GIVEN BY MODERN MEDICINE DOCTORS
SEVERE DYSPNOES DUE TO PLEURAL EFFUSION
HIGH PERSISTENT FEVER
GASTRITIS
PATIENT SEEKS AYURVEDIC SUPPORT -

THE CASE (Contd. THE PRESCRIPTION) -
CAP CARSONA 2 TID WITH SARIVADYARISHTHA AS AN
ANTICANCER. ASKED NOT TO STOP GEFITINIB
CAP (BROMELAIN, CURCUMIN AND BOSWELLIC ACID)
2 TID WITH COLD MILK FOR OEDEMA AND SUPPORT
SYP HIMCOCID 2 TSF QID
SUVARNA VASANTA MALINI ONCE DAILY WITH HONEY
TULI+GILOY+SHUNTHI+RICE BRAN (ARK)+GOMUTRA FOR
IMMUNE SUPPORT
GEFITINIB ASKED TO CONTINUE. PATIENT DISCONTINUED
SELF HOWEVER ASKED TO RECONTINUE AND NOT STOP
SINCE WE DO NOT CLAIM ANY CHEMOTHERAPEUTIC
TREATMENTS AT THIS STAGE OF ADVANCEMENT
TAPPING AS A SURGICAL PROCEDURE ADVISED TO BE
DONE WITH CATHETERIZATION FOR CONTINUING
DRAINAGE -

THE CASE (Contd. THE PRESCRIPTION) -
OEDEMA REDUCED
RATE OF FLUID FORMATION REDUCED
COLOUR OF FLUID CHANGED FROM RED TO PALE
APPETITE IMPROVED
SITE OF TAPPING CHANGED AS PREVIOUS TAPPING
DONE AT THE NEAREST MEDICAL COLLEGE WAS
RELATIVELY HIGHER AND STILL FLUID PERSISTING IN
THE PLEURAL REGION
AT THIS TIME I HAVE ASKED THE PATIENT TO RESTART
GEFITINIB WHEN UPON INTERROGATION HE REPORTED
THAT IT WAS STOPPED; TELLING HIM CLEARLY THAT WE
HAVE NOT ASKED HIM TO STOP IT
X RAYS SHOW REDUCED PLEURAL FLUID

THE OBSERVATIONS
The changes observed in fluid volume drained by thoracentesis in case of CA Lungs when
using the combination of Bromelain, Curcumin and Boswellic Acid
Days
Total Volume in
litres
Coulour Fluid Thoracentesis
Before
Treatment
0 3 RED
Done from a single
locus
8 3.5 RED
15 4 RED
24 4 RED
30 3 RED
After initiation
of the
combination
0 3 RED
Done from a single
locus
15 3 Yellowish Red
30 2 Yellowish
50 0.75 Light Yellow
65 0.5 Light Yellow
90 0.3 Whitish clear
120 0.2 Whitish clear Done from a multiple
150 0.28 Whitish clear locus
The patient lived for another 180 days with 2 more episodes of fluid tapping
each of which was about 0.3l

MECHANISM OF ACTION OF INDIVIDUAL INGREDIENTS AND
SYNERGIES

BROMELAIN

ROLE OF BROMELAIN ACCORDING TO AYURVEDA -
CELL SURFACE ENVIRONMENT –
The lipoproteinous environment of cell membrane -
Proteins in the Ayurvedic context may be interpreted as
(Prithvi+Agni+Akash).

HYPOTHESIS OF CHANGES TO CELL STRUCTURE IN TRAUMA -
Post Traumatic Lipoprotein
environment
(P(tr)+Ag(tr)+V(tr)+J(tr)) + Ak)
Lipoprotein(P(pr)+Ag(pr)+Ak(pr))
+ Trauma (V(t)
Post Traumatic freshly
oedematised Lipoprotein
environment
(P(tr)+V(tr)+J(tr))
Post Traumatic oedematised Lipoprotein
environment (P(tr)+J(tr))
(Vata and Jal due to
induction of microvascular
injuries take the place of
Akash)
(combine with Prithvi to
create a stiff and
lesioned site with
rubour)
(Prithvi is reduced and
Agni is replaced with Jal
component which is
increased)

UNDER TREATMENT HYPOTHESIS FOR BROMELAIN -
Bromelain (Agni and Vata)
(P(br)+Ag(br)+V(br)
Post Traumatic oedematised Lipoprotein
environment (P(tr)+J(tr))
+
Under Treatment
Lipoprotein Environment
(P(ut)+Ag(ut)+V(ut)+J(ut))
[stage 1]
Under Treatment
Lipoprotein
Environment
(P(ut)+Ag(ut)+V(ut))
[stage 2]

SUMMARY OF EVENTS -
Protein(P(pr)+Ag(pr)+Ak(pr)) + Trauma (V(t) Post Traumatic Protein
environment (P(tr)+Ag(tr)+V(tr)+J(tr)) + Ak) Post Traumatic freshly
oedematised Protein environment (P(tr)+V(tr)+J(tr)) Post
Traumatic oedematised Protein environment (P(tr)+J(tr)) + Bromelain
(P(br)+Ag(br)+V(br) Under Treatment Protein Environment
P(ut)+Ag(ut)+V(ut)+J(ut)) [stage 1] Under Treatment Protein
Environment (P(ut)+Ag(ut)+V(ut)) [stage 2]
Protein(P(pr)+Ag(pr)+Ak(pr))

MODEL OF AYURVEDIC ACTION OF BROMELAIN -
Fig. 1. – Proposed model for Action of Bromelain in a traumatised tissue.

BOSWELLIC ACID

ROLE OF BOSWELLIC ACID -

AYURVEDIC HYPOTHESIS OF ACTION OF BOSWELLIC ACID -
Boswellic
(rich in Agni, Jal and
Vayu Mahabhoot’s
environment
+
Under Treatment Lipoprotein
(P(ut)+Ag(ut)) + (J + V)

Lipoprotein(P(pr)+Ag(pr)+Ak(pr)) + Trauma (V(t) Post Traumatic
Lipoprotein environment (P(tr)+Ag(tr)+V(tr)+J(tr)) + Ak) +Boswellic Acid
(Ag(ba)+J(ba)+V(ba)) Under Treatment Lipoprotein (P(ut)+Ag(ut))
+ (J + V) [Stage 1] Lipoprotein(P(pr)+Ag(pr)+Ak(pr))
SUMMARY OF EVENTS-

MODEL OF AYURVEDIC ACTION OF BOSWELLIC ACID -
Fig. 2. – Proposed model for Action of Boswellic Acid in a traumatised tissue.

CURCUMIN

ROLE OF CURCUMIN –

HYPOTHESIS FOR THE AYURVEDIC MODEL OF ACTION OF CURCUMIN –
Heat
Heat + Jal as
Sweat
environment
+
Under Treatment Lipoprotein (P(ut)+Ag(ut)) +
J(ut) + V(ut) +Ak) [Stage 1]
Curcumin
(P(cr)+Ag(cr)+J(cr)+V(cr))
Under Treatment Lipoprotein
(P(ut)+Ag(ut)) +Ak )+(J+V) [Stage 2]
Jal as Sweat

SUMMARY OF EVENTS -
Lipoprotein(P(pr)+Ag(pr)+Ak(pr)) + Trauma (V(t) Post Traumatic
Lipoprotein environment (P(tr)+Ag(tr)+V(tr)+J(tr)) + Ak) + Curcumin
(P(cr)+Ag(cr)+J(cr)+V(cr)) Under Treatment Lipoprotein
(P(ut)+Ag(ut)) + J(ut) + V(ut) +Ak) [Stage 1] Under Treatment
Lipoprotein (P(ut)+Ag(ut)) +Ak )+(J+V) [Stage 2]

MODEL OF AYURVEDIC ACTION OF CURCUMIN -
Fig. 3. – Proposed model for Action of Curcumin in a traumatised tissue.

SYNERGY

Protein(P(pr)+Ag(pr)+Ak(pr)) + Trauma (V(t) Post Traumatic Protein
environment (P(tr)+Ag(tr)+V(tr)+J(tr)) + Ak) Post Traumatic freshly
oedematised Protein environment (P(tr)+V(tr)+J(tr)) Post Traumatic
oedematised Protein environment (P(tr)+J(tr)) + Bromelain
(P(br)+Ag(br)+V(br) +Boswellic Acid (Ag(ba)+J(ba)+V(ba)) + Curcumin
(P(cr)+Ag(cr)+J(cr)+V(cr)) Under Treatment Protein Environment
(P(ut)+Ag(ut)+V(ut)+J(ut)) + [(Heat + stiffness)V(ut)+P(ut)] [stage 1]
Under Treatment Protein Environment (P(ut)+Ag(ut)+V(ut)) [stage 2]
Protein(P(pr)+Ag(pr)+Ak(pr))
THE SYNERGY -

THE SYNERGY -
Fig. 4. The mechanism of action of the combination

CONCLUSION

CONCLUSION –
On the basis of the likely models and the clinical table posted above it is of significance to
note that as an adjuvant it is an effective combination –
in the management of oedema.
The likely models of activities and their synergies present with a wide range of possibilities
as in trauma or trauma like conditions which may be induced for varied reasons as in case
of cancer it is a self destructive condition inducing a self trauma.

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