Beijing 2014

Ayushya Varsha Clinics and Health Café’s

26/08/2014 International Conference On Traditional & Alternative Medicine

- 2014, Beijing, China

SYNERGISTIC ROLE OF BROMELAIN, CURCUMIN AND BOSWELLIC

ACID IN MANAGEMENT OF PLEURAL OEDEMA IN A CASE OF

CARCINOMA OF THE LUNGS STAGE 3B

Dr. Nitin ChaubeAyushya Varsha Clinics and Ayurveda Health Café




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

Lung cancer




INTRODUCTION

vitiate pitta by

different

mechanisms

Pine Apple (Anana squamosal)

Shallaki (Boswellia serrata)

Turmeric (Curcuma longa)

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




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.

INDIVIDUAL INGREDIENTS (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

INDIVIDUAL INGREDIENTS (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.

INDIVIDUAL INGREDIENTS (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.

Ayurvedic View

Reduced resorption into

the lymphatic system.

Vata forms an awarana

prevents flow back of the fluid into the

lymphatic system.

Pleural oedema




THE CASE WHERE THE AFORESAID CHANGES WERE OBSERVED




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 -




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 -




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 CASE (Contd. THE PRESCRIPTION) -




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

DaysTotal Volume in

litresCoulour 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

locus150 0.28 Whitish clear

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




CELL SURFACE ENVIRONMENT –

The lipoproteinous environment of cell membrane -

Proteins in the Ayurvedic context may be interpreted as

(Prithvi+Agni+Akash).

ROLE OF BROMELAIN ACCORDING TO AYURVEDA -




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]Lipoprotein(P(pr)+Ag(pr)+Ak(pr))




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 -




ROLE OF BOSWELLIC ACID -




Boswellic

(rich in Agni, Jal and

Vayu Mahabhoot’s


environment


+

Under Treatment Lipoprotein

(P(ut)+Ag(ut)) + (J + V)


AYURVEDIC HYPOTHESIS OF ACTION OF BOSWELLIC ACID -




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 –




ROLE OF CURCUMIN –




HYPOTHESIS FOR THE AYURVEDIC MODEL OF ACTION OF CURCUMIN –


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]

Heat

Heat + Jal as

Sweat

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] Lipoprotein(P(pr)+Ag(pr)+Ak(pr))




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.

Health & Medicine

Beijing 2014