This document discusses recent advances in human biology that are relevant to understanding Panchakarma therapies in Ayurveda. It describes the ketogenic diet and how it relates to snehapana, the heat shock response and how it may explain the effects of svedana, the human microbiome and how panchakarma therapies like vamana and basti could act on gut microbes, the gut-brain axis and how the gut is connected to the brain and mind, gut hormones, and the enteric nervous system as the "brain of the gut." It poses new questions about how these recent insights can help explain the physiological basis of panchakarma procedures and their therapeutic effects.

1. Physiology and
Mechanistic basis of
Panchakarma
Kishor Patwardhan
BAMS, MD(Ay), PhD
Associate Professor and Head
Department of Kriya Sharir
Faculty of Ayurveda
Banaras Hindu University
Varanasi

2. Panchakarma: FAQs
 Does Basti Dravya (enema) get absorbed? If yes, through which vein?
 Does Abhyanga (oil massage) cause absorption of the drugs through
skin?
 Which Vamana Dravya (emetic) acts centrally and which one
peripherally?
 How do different Virechana dravyas (laxatives/ purgatives) produce
purgation?
 Does Nasya (Nasal instillation) get absorbed into the circulation?
 Does it directly stimulate the brain? Why is ‘Nasa hi Shiraso
Dvaram’?

3.  This presentation will pose few more new questions
based on the recent advances in human biology
 These newer questions might render the old ones
redundant!

4. Recent insights
 Ketogenic diet
 The Heat-Shock Response
 The Microbiome
 The gut-brain axis (GBA)
 Gut hormones
 Enteric Nervous System
 Probiotics and Prebiotics

5. Ketogenic diet
 The CNS normally utilizes glucose, not fat
 However, if one does not consume carbohydrates
for 3–4 days, the CNS is ‘forced' to find alternative
energy sources
 This alternative energy source is derived from the
overproduction of acetyl coenzyme A

6.  This is seen when a person is on in high-fat / low-
carbohydrate diet
 It leads to the production of higher-than-normal
levels of ketone bodies
 This process is called ketogenesis
 Occurs principally in the mitochondrial matrix in the
liver.

8.  Ketogenic diet has been in use since the 1920s as
a therapy for epilepsy
 From the 1960s onwards it is being used as one of
the common methods for obesity treatment.
 Recent work has provided evidence of the
therapeutic potential of ketogenic diet in many
pathological conditions
Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate
(ketogenic) diets. European Journal of Clinical Nutrition. 2013;67(8):789-796. doi:10.1038/ejcn.2013.116.

9. Therapeutic potential of ketogenic diet
 Overweight
 Diabetes
 Polycystic ovary syndrome
 Acne
 Neurological diseases
 Cancer
 Amelioration of respiratory and CVS disease risk
factors

10. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate
(ketogenic) diets. European Journal of Clinical Nutrition. 2013;67(8):789-796. doi:10.1038/ejcn.2013.116.

11. Question-1
 Why do we go for Snehapana (drinking ghee) ?
 Why Arohana (incremental) Snehapana?
 Does Snehapana act like ketogenic diet?

12. Heat Shock Response
 The heat-shock response is a set of well-ordered and
regulated responses to stress in the cell
 There occurs the production of a group of proteins known
as the heat-shock proteins (hsps)
 These proteins can protect the cell by helping it survive
under conditions that would normally be lethal
Powers Marissa V. and Workman Paul(2007), Inhibitors of the heat shock response: Biology and
pharmacology, FEBS Letters, 581, doi: 10.1016/j.febslet.2007.05.040

13.  Heat-shock response in a cell can be triggered when a person is
exposed to a elevated temperature, heavy metals, ischemia,
inflammation, infection and oxidative stress
 Most HSPs are molecular chaperones that interact with diverse
protein substrates to assist in their folding
 Their role is critical during cell stress to prevent the appearance
of folding intermediates that lead to misfolded molecules
Powers Marissa V. and Workman Paul(2007), Inhibitors of the heat shock response: Biology and
pharmacology, FEBS Letters, 581, doi: 10.1016/j.febslet.2007.05.040

14.  Heat Shock Factors mediate Heat Shock Response
 HSF1 gene is essential for HSP expression
 Celastrol, a natural triterpene derived from a Chinese
herb, Trypterygium wilfordii, activates HSF1
 Antioxidant, anti-inflammatory, anti-cancer, anti-obesity
effects of this compound are known
Allison, A. C.; Cacabelos, R.; Lombardi, V. R. M.; Alvarez, X. A.; Vigo, C. (2001). "Celastrol, a potent antioxidant and anti-
inflammatory drug, as a possible treatment for Alzheimer's disease". Progress in Neuro-Psychopharmacology and
Biological Psychiatry 25 (7): 1341–1357. doi:10.1016/S0278-5846(01)00192-0.
Liu, Junli; Lee, Jaemin; Salazar Hernandez, Mario Andres; Mazitschek, Ralph; Ozcan, Umut (May 2015). "Treatment of
Obesity with Celastrol". Cell 161 (5): 999–1011. doi:10.1016/j.cell.2015.05.011.

15. Question-2
 Does Svedana Karma (sudation) act through Heat
Shock Response?
 Do we have drugs like Celastrol?
 Could Svedopaga / Svedana Dravya s be having a
similar activity?

16. Human Microbiome
 Microbe: tiny living organism, such as bacterium, fungus,
protozoan, or virus
 Microbiome: collectively all the microbes in the human
body; a community of microbes
 Biofilm: a community of microbes that live together on a
surface

17.  According to a recent National Institutes of Health
(NIH) estimate, 90% of cells in the human body are
bacterial, fungal, or otherwise non-human
 The NIH's ongoing initiative, the Human Microbiome
Project, aspires to catalog the human microbiome,
also referred to as the human metagenome
http://mpkb.org/home/pathogenesis/microbiota

18. The microbial life on human body
Nasya
Kavala / Gandusha
Abhyanga/ Svedana /Lepa
/Avagaha
Vamana/Virechana/Basti
Uttara Basti
http://nihroadmap.nih.gov/hmp/

19. Microbes in the Human Microbiome include
http://commons.wikimedia.org/wiki/File:Tree_of_life.svg

20. • The interior lining of the nose contains mucous secreting
glands
• A wide variety of microbes are normally found there
• There is a delicate balance of microbes
• Staphylococcus epidermidis bacteria forms a biofilm that
coats the mucosal lining
• Staphylococcus aureus bacteria is fine when kept under
control by a protease found in S. epidermidis, but if left to
grow out of control, S. aureus can become pathogenic and
cause infection
Nose
outreach.mcb.harvard.edu/Microbiome/download/Microbiome.pptx

21. Oral Cavity
• A wide variety of microbes regularly enter the oral cavity
• Saliva, pH, temperature, immune system prevent many
species from surviving
• Symbiosis of the oral microbes that are able to survive
these conditions form a scaffold that lives on the tooth
enamel and at the interface with the gums
• It forms a barrier for incoming bacteria
outreach.mcb.harvard.edu/Microbiome/download/Microbiome.pptx

22. Skin
• There are several skin environments: oily, dry, moist.
• Some microbes prefer one over another
• The skin has natural defenses including slightly acidic sweat
and antimicrobial peptides
• There is a normal balance of microbes on the skin
• Damaged skin gives opportunities for microbes to invade the
bloodstream and cause illness
outreach.mcb.harvard.edu/Microbiome/download/Microbiome.pptx

23. Urogenital Tract
• Urinary system is almost sterile due to urea and other
chemicals
• Urine often flushes out microbes that find their way in
• Introducing a catheter into the urethra can introduce
microbes directly into the bladder, where a biofilm can
grow and cause bladder infection
• The vagina has a low pH due to Lactobacillus secreting
lactic acid and hydrogen peroxide.
outreach.mcb.harvard.edu/Microbiome/download/Microbiome.pptx

24. Gut Microbiota
• The microbe population living in our intestine
• Gut Microbiota plays an important role in our lives and in
the way our bodies function
• The composition of gut microbiota is unique to each
individual, just like our fingerprints!
• Our gut microbiota contains tens of trillions of bacteria –
ten times more cells than in our body!
http://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

25. • There are more than 3 millions microbial genes in our
gut microbiota, 150 times more genes than in the
human genome
• Microbiota, in total, can weigh up to 2 kg
• More than 1,000 different known bacterial species can
be found in human gut, but only 150 to 170
predominate in any given subject
http://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

26. • It helps the body to digest certain foods that the stomach
and small intestine have not been able to digest
• It helps with the production of some vitamins (B and K)
• It helps us combat aggressions from other microorganisms
• Japanese people, can digest seaweeds, thanks to specific
enzymes that their microbiota has acquired from marine
bacteria
http://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

27. An Organ?
• Experts nowadays consider it as an “organ”.
• It is an “acquired” organ, as babies are born sterile;
that is, intestine colonization starts right after birth
and evolves as we grow.
• The newborn’s digestive tract is quickly colonized by
microorganisms from the mother (vaginal, faecal, skin,
breast, etc.), the environment in which the delivery
takes place, the air, etc.
http://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

28. • A loss of balance in gut microbiota is called Dysbiosis.
• Dysbiosis may be linked to health problems such as
functional bowel disorders, inflammatory bowel disease,
allergies, obesity and diabetes
• Many studies have demonstrated the beneficial effects of
prebiotics and probiotics on our gut microbiota
http://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

29. Probiotics and Prebiotics
 Probiotics are defined as the live microorganisms that can
provide benefits to human health when administered in
adequate amounts, which confer a beneficial health effect on
the host.
 Prebiotics are substances that induce the growth or activity
of microorganisms (e.g., bacteria and fungi) that contribute
to the well-being of their host.
http://www.ncbi.nlm.nih.gov/books/NBK57065/

30.  Milk products such as butter milk and curd are
probiotics
 Several herbs contain pre-biotic fibers such as Garlic,
Onion, Asparagus
Slavin J. Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients. 2013;5(4):1417-1435.
doi:10.3390/nu5041417.

31. Question-3
 What is meant by Sahaja Krimi? Do they refer to human
microbiome?
 Does the composition of microbiota vary according to
Prakriti?
 Do Vamana, Virechana, Basti (Asthapana / Anuvasana /
Uttara Basti), Nasya act on microbiota and help in
correcting the dysbiosis?

32.  Why is Takra indicated in diseases like Grahani?
 How does Takra Basti act?
 Are Asava / Arishta probiotics?
 How do Kavala / Gandusha act?
 Does the composition of microbiome vary according
to individual Koshtha /Agnibala ?

33. Enteric Nervous System
 It is the brain of gut, consisting of 100 million neurons,
extends from esophagus to anus. ENS is arranged in
two plexuses:
 Myenteric plexus
 Submucosal plexus

34. ENS & CNS: similarities
 Glial instead of Schwann cells (similar to astrocytes in CNS)
 All neurotransmitters so far known in ENS are there in CNS
too:
 Acetylcholine, Norepinephrine, Adenosine triphosphate,
Serotonin, Dopamine, Cholecystokinin
http://www.scholarpedia.org/article/Enteric_nervous_system#ENS-CNS_interactions
http://www.psyking.net/id36.htm

35. ENS & CNS: similarities
 Similar sensitivity to toxins, drugs, and diseases
 Antidepressants:  5-HT re-uptake in brain & ENS - nausea,
diarrhea, then constipation (desensitization)
 Antidepressants can be used to “calm down” the gut (ENS
more sensitive than CNS)
 Lewy’s bodies (Parkinson’s disease) & amyloid plaques &
neurofibrilar clusters (Alzheimer’s disease) are also seen in the
gut (Gut biopsy may serve the diagnostic purpose)
 GI & psychic problems often co-exist
http://www.authorstream.com/Presentation/Dario-47285-Motilita-GITus-Motility-gastrointestinal-tract-Slide-2-
Regulation-Entertainment-ppt-powerpoint/

36. ENS & CNS: similarities
ENS can learn:
Hirschsprung’s disease - genetically determined absence
of nerves in the most distal GIT part - inability to
defecate
Within 18 months after resection of the defect, the
more proximal part “learns” to defecate (it couldn’t do it
at the beginning)
http://www.authorstream.com/Presentation/Dario-47285-Motilita-GITus-Motility-gastrointestinal-tract-Slide-2-
Regulation-Entertainment-ppt-powerpoint/

37. The gut-brain axis (GBA)
 Bidirectional communication between the
central and the enteric nervous system
 Links emotional and cognitive centers of
the brain with peripheral intestinal
functions.
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions
between enteric microbiota, central and enteric nervous systems. Annals of
Gastroenterology : Quarterly Publication of the Hellenic Society of
Gastroenterology. 2015;28(2):203-209.

38.  This interaction is through signaling from gut-microbiota to
brain and from brain to gut-microbiota by means of Neural,
endocrine, immune, and humoral links.
 This axis mediates several peripheral intestinal functions
and mechanisms such as immune activation, intestinal
permeability, enteric reflex, and entero-endocrine
signaling.
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota,
central and enteric nervous systems. Annals of Gastroenterology : Quarterly Publication of the Hellenic
Society of Gastroenterology. 2015;28(2):203-209.

39. Gut hormones
 The gastrointestinal tract is the body's largest endocrine
organ and releases more than 20 different regulatory peptide
hormones
 They influence a number of physiological processes and act
on tissues including exocrine glands, smooth muscle and the
peripheral nervous system
 Most of these hormones are sensitive to gut nutrient content,
and short-term feelings of hunger and satiety are mediated
by coordinated changes in circulating gut hormone levels
http://www.nature.com/nature/journal/v444/n7121/full/nature05484.html

40. Question-4
 Is Pakvashaya the primary seat of Vayu because of these
interactions?
 Is ENS relevant in understanding the Samana Vayu?
 Why is the ‘Gut’ therapeutic target irrespective of the
disease?
 Why is there a role of Ahara in most of the diseases?

41. “Physiology to Application” is a process:
 Observation
 Hypothesis
 Experimentation
 Clinical Research
 Establish the theory
 Apply

42. An interesting work

43. Thanks!