Ashwagandha - Anti-inflammatory Mechanism

Summary

In this informative talk, the host delves into the ancient herb Ashwagandha, used for centuries in Indian and African medicine, particularly for stress relief and adaptogenic behavior. Despite mixed feelings due to a lack of robust studies, the host explores its anti-inflammatory properties, noting its potential benefits for neurological symptoms and overall inflammation reduction. The discussion highlights Ashwagandha's modulation of the nuclear Factor Kappa B pathway, which plays a crucial role in cell survival and inflammation. The host also touches on potential side effects and drug interactions, emphasizing the need for caution and consultation with healthcare professionals. The talk is complemented with engaging cartoons and a special announcement about Dr. Bean's upcoming courses and pricing changes.

Takeaways

• 🌿 Ashwagandha is an Indian and African herb with a history of use going back 3000 years.
• 🧬 Despite limited strong human studies, ashwagandha has been used extensively in India and is part of Ayurvedic medicine.
• 🤔 The speaker has mixed feelings about ashwagandha due to a lack of robust evidence but acknowledges its traditional use.
• 📈 Ashwagandha is primarily used for stress relief and adaptogenic behavior, helping the body adapt to various stressors.
• ⚠️ There are potential side effects and contraindications with ashwagandha, especially for pregnant women and those with certain health conditions.
• 🤰 Ashwagandha may not be safe for pregnant women and its safety for nursing mothers is unknown.
• 💊 It can interact with various drugs, including those for diabetes, hypertension, and immune system suppression.
• 💤 Ashwagandha might cause drowsiness and should be used cautiously with sedative hypnotic drugs.
• 🔍 The script discusses the anti-inflammatory effects of ashwagandha and its mechanism of action on the nuclear Factor Kappa B pathway.
• 🐠 The talk humorously includes a Finding Nemo reference to explain the process of ubiquitination in the context of the nuclear Factor Kappa B pathway.

Q & A

What is the primary use of ashwagandha?

The primary use of ashwagandha is for stress relief and adaptogenic behavior, meaning it helps a person adapt to stressors such as age, disease, or other stresses without getting overwhelmed.

What are the mixed feelings the speaker has about ashwagandha?

The speaker has mixed feelings about ashwagandha because, despite its long history of use, they do not see strong studies supporting its efficacy, mostly finding in vitro studies or mouse models rather than robust clinical trials.

What is the significance of ashwagandha being part of ayurvedic medicine?

Ashwagandha is significant in ayurvedic medicine because it has been used for approximately 3000 years, indicating a long-standing cultural tradition of its use for various health benefits.

What are some of the side effects and contraindications of ashwagandha mentioned in the script?

Some side effects and contraindications of ashwagandha include its potential unsafety for pregnant women due to the risk of miscarriage, unknown effects on nursing mothers, possible irritation of the digestive tract, drug interactions with neurological and immune systems, lowering blood sugar levels, lowering blood pressure, and possible interference with immune-suppressing drugs.

What is the recommended dosage for ashwagandha?

The recommended dosage for ashwagandha is 1000 milligrams per day, with long-term usage beyond 12 weeks having less supporting evidence.

What is the role of the nuclear Factor Kappa B (NF-κB) pathway in inflammation?

The nuclear Factor Kappa B (NF-κB) pathway plays a crucial role in inflammation as it is activated by stressors, such as pathogens or cellular stress, leading to the production of inflammatory mediators. Ashwagandha is believed to modulate this pathway, thereby reducing inflammation.

How does ashwagandha interact with the NF-κB pathway?

Ashwagandha is thought to modulate the NF-κB pathway by suppressing it, which in turn reduces the production of inflammatory mediators and leads to a decrease in inflammation.

What are some of the potential benefits of ashwagandha for long COVID patients as mentioned in the script?

For long COVID patients, ashwagandha may provide benefits such as relaxation and improvement in neurological symptoms, potentially due to its anti-inflammatory effects on the brain.

What is the significance of the term 'Ganda' in ashwagandha?

The term 'Ganda' in ashwagandha refers to the fragrance of the plant's root, which is due to the presence of flavonoids. This fragrance is associated with stress reduction, similar to the effects of being in a forest or jungle.

What are some of the active components in ashwagandha?

Some of the active components in ashwagandha include withanolides, alkaloids like somniferin and somnin, and flavonoids, which contribute to its various health benefits.

What is the connection between ashwagandha and the character 'Nemo' from the script?

The connection between ashwagandha and 'Nemo' is a play on words related to the NF-κB pathway. In the pathway, a protein called Nemo gets ubiquitinated and destroyed, which is part of the process that ashwagandha may modulate to reduce inflammation.

Outlines

00:00

🌿 Introduction to Ashwagandha and its Traditional Usage

The speaker begins by introducing the topic of the video, which is the discussion of ashwagandha, an herb used in Indian and African medicine for approximately 3000 years. Despite the long history of use, the speaker expresses mixed feelings due to a lack of strong modern scientific studies supporting its efficacy. The primary uses of ashwagandha are highlighted as stress relief and adaptogenic behavior, helping individuals adapt to various forms of stress. The speaker also mentions their family's background in traditional medicine, specifically ayurvedic medicine, and their personal connection to the herb. Additionally, the speaker promotes an upcoming change in pricing for their courses and provides some references and side effects of ashwagandha, such as its potential risks during pregnancy and its impact on the digestive system.

05:00

💊 Ashwagandha's Interactions and Effects on the Body

This paragraph delves into the effects of ashwagandha on the immune system, noting that it can boost immunity and potentially lower blood sugar levels, which could interfere with certain medications. The speaker also addresses the herb's impact on blood pressure and its contraindications with immune-suppressing drugs. Furthermore, ashwagandha's potential to cause drowsiness and its effects on thyroid hormone levels are discussed. The speaker emphasizes the importance of consulting with healthcare professionals before using ashwagandha, especially for long-term use beyond the studied 12 weeks.

10:02

🌲 Exploring Ashwagandha's Stress-Relief and Immune-Boosting Properties

The speaker explores the stress-relief and immune-boosting properties of ashwagandha, referencing a study that compared the stress levels and immune responses of people in forests versus a city environment like Tokyo. The study findings suggest that natural environments rich in phytochemicals and fragrances, such as forests, can reduce stress hormones and enhance immune function. This is likened to the effects of ashwagandha, which contains flavonoids that may contribute to its stress-reducing and immune-boosting capabilities. The speaker also lists various areas where ashwagandha has been studied, including its potential neurological, sedative, adaptogenic, sleep-inducing, anti-inflammatory, antimicrobial, cardioprotective, anti-diabetic, and reproductive benefits.

15:04

🧬 The Anti-Inflammatory Mechanism of Ashwagandha

Here, the speaker focuses on the anti-inflammatory effects of ashwagandha, particularly its impact on the nuclear Factor Kappa B (NF-κB) pathway, which is associated with cell survival and stress responses. The NF-κB pathway can be activated by external stressors, such as pathogens or toxins, or internal stressors, like changes in cell shape or pH levels. The speaker simplifies the complex cellular mechanisms involved in this pathway, explaining how ashwagandha may modulate it to reduce inflammation. The discussion also touches on the concept of gliosis, the overproduction of brain tissue cells in response to inflammation, and how ashwagandha might help in reducing brain inflammation.

20:05

🐠 The Cellular Pathway and the Role of 'Nemo' in Inflammation

In this section, the speaker continues the discussion on the NF-κB pathway, focusing on the activation and regulation of proteins within the cell. The narrative takes a creative turn by incorporating the story of 'Finding Nemo,' using it as an analogy to explain the process of protein ubiquitination and destruction. The speaker describes how certain proteins, once activated, can lead to the production of inflammatory mediators. Ashwagandha's role in modulating this process is highlighted, suggesting that it can suppress the inflammatory response by affecting the activation of NF-κB. The speaker also mentions a study that provides evidence for ashwagandha's anti-inflammatory effects.

25:07

📉 Summarizing Ashwagandha's Anti-Inflammatory Mechanism

The speaker summarizes the anti-inflammatory mechanism of ashwagandha, emphasizing its ability to reduce the production of inflammatory proteins by modulating the NF-κB pathway. The summary includes a brief overview of the various inflammatory mediators that ashwagandha may help regulate, such as interleukin-12, interleukin-6, interleukin-8, tumor necrosis factor alpha, interleukin-1 beta, and nitric oxide. The speaker concludes by reminding viewers of the upcoming price change for their courses and encourages viewers to like, subscribe, and share the video for support.

Keywords

💡Ashwagandha

Ashwagandha is an Indian and African herb that has been used for approximately 3000 years. It is primarily known for its stress relief and adaptogenic properties, meaning it helps the body adapt to stressors such as aging or disease. In the video, the speaker discusses the mixed feelings about ashwagandha due to a lack of strong studies to support its use, despite its long history of traditional use.

💡Inflammation

Inflammation is a protective response of the body to infection or injury. In the context of the video, ashwagandha is discussed for its potential anti-inflammatory effects. The speaker focuses on how ashwagandha may reduce inflammation in the brain and body, which is a significant aspect of its traditional use in medicine.

💡Adaptogenic

Adaptogenic refers to substances that help the body manage stress by promoting balance and resistance to various stressors. In the video, ashwagandha is described as an adaptogen, which helps individuals cope with stress without becoming overwhelmed, as it allows the body to adapt and mount an effective response.

💡Nuclear Factor Kappa B (NF-kB)

NF-kB is a protein complex that controls transcription of DNA, cytokine production, and cell survival. In the video, the speaker explains that ashwagandha's anti-inflammatory effects may be due to its modulation of the NF-kB pathway, which is a key player in the body's inflammatory response. By suppressing this pathway, ashwagandha could potentially reduce inflammation.

💡Stress relief

Stress relief is the process of reducing or managing stress. The video discusses ashwagandha's traditional use as a means of stress relief, suggesting that it can help mitigate the negative impacts of stress on the body, which aligns with its adaptogenic properties.

💡Phytochemicals

Phytochemicals are chemicals naturally found in plants that have protective properties. The video mentions that ashwagandha contains various phytochemicals, including flavonoids, which are thought to contribute to its stress-reducing and anti-inflammatory effects.

💡Flavonoids

Flavonoids are a group of phytochemicals that have antioxidant and anti-inflammatory properties. The script describes how the presence of flavonoids in ashwagandha might be responsible for its fragrance and potential stress-reducing effects, as they are associated with a reduction in stress hormones.

💡In vitro studies

In vitro studies are conducted outside of a living organism, often using isolated cells or tissues. The video script mentions that most of the studies on ashwagandha are in vitro, which the speaker views as less compelling than in vivo or clinical studies, but still a part of the evidence base for its effects.

💡Mouse models

Mouse models are laboratory experiments using mice to study biological phenomena or disease. The speaker in the video expresses mixed feelings about the effectiveness of ashwagandha, noting that many studies are conducted on mouse models, which may not always translate directly to effects in humans.

💡Drug interactions

Drug interactions occur when two or more drugs affect each other's action or metabolism. The video discusses potential drug interactions with ashwagandha, cautioning that it could interfere with medications for blood sugar, blood pressure, and immune system suppression, among others.

💡Ubiquitination

Ubiquitination is a process in which proteins are tagged for degradation. In the video, the speaker uses the example of the protein Nemo being ubiquitinated and destroyed as part of the NF-kB pathway's regulation, illustrating how ashwagandha might suppress this pathway and reduce inflammation.

Highlights

Ashwagandha is an Indian and African herb used for about 3000 years.

It is primarily used for stress relief and adaptogenic behavior.

Mixed feelings due to lack of strong studies, mostly in vitro or mouse models.

The presenter's family has a history of practicing Ayurvedic medicine.

Ashwagandha is being discussed due to audience request.

The presenter will focus on the anti-inflammatory aspect of ashwagandha.

Ashwagandha might be unsafe for pregnant women due to miscarriage risk.

It can irritate the digestive tract in some individuals.

Ashwagandha affects the neurological and immune systems.

It might lower blood sugar levels, impacting its use with anti-hyperglycemics.

It can also lower blood pressure, affecting its use with anti-hypertensives.

Ashwagandha may interfere with immune-suppressing drugs.

It might cause drowsiness or sleepiness due to its calming effect on the brain.

Ashwagandha may increase thyroid hormone levels.

The recommended dosage for ashwagandha is 1000 milligrams.

Ashwagandha has been studied for various effects including neural protection, sedative effect, and anti-inflammatory properties.

The active components of ashwagandha include retinoids, alkaloids, and flavonoids.

Ashwagandha affects the nuclear Factor Kappa B pathway, which is involved in cell survival and inflammation.

Ashwagandha modulates the nuclear Factor Kappa B pathway to reduce inflammation.

The study discussed shows modulation of various inflammatory mediators by ashwagandha.

The course page at DrBean.com is launching with finalized descriptions and prices.

The price for Dr Bean's courses will increase from $67 to $97 on Monday.

The presenter shares cartoons to illustrate the discussion on ashwagandha.

Transcripts

welcome to one more show in the talk

today we'll talk about horses and Nemo

you know the Finding Nemo the fish and

other such things and in this process

we'll discuss ashwagandha

this is a uh an Indian

an African herb that has been used for

about 3000 years

after reading the literature I have

mixed feelings about it I have not used

it for myself however this topic was

very much requested so let's look at

this topic it is actually fascinating to

look at this Urban how it works I'm only

going to take one part or one kind of a

section today and that is the

inflammation although its primary use is

for stress relief and for adaptogenic

Behavior meaning it allows a person not

to stress out because of something that

is bothering them for example let's say

stress of age stress of disease or other

stresses it helps them adapt

why I said I have mixed feelings is that

I do not see

strong studies for this

so from a studious point of view from an

Evidence point of view I see mostly in

vitro studies or Mouse models however be

aware that it has been used in India

India is a very large population it has

been used there for 3000 years my own

family

of course we are from Pakistan but our

ancestors were in Combined Indian

continent and my maternal side practiced

local medicine

ayurvedic medicine for 400 years and

these kind of herbs are of course part

of that process of practicing so let's

start

I have drawn some very cool cartoons for

you today as well so I hope you like

them

so first of all they say Dr bean.com in

the description of this video there is a

um link to get access to Dr bean.com we

have finally reached a point that our

courses page has become ready now all

descriptions are correct and all prices

are final Monday we will launch this so

this one this page will be uh changed on

Monday to move the price from 67 to 97

and then a week later that will be

retired as well and we will only be

offering the courses

so with this if you wanted to take

advantage of that you can this gives you

access to everything once we go towards

the courses you continue to be

grandfathered in the system so with this

here are some of the references and as I

have always done with the herbs

I try to put the side effects first so

that you are aware of what are the

contraindications because many of the

articles that talk about some herbs they

do not usually put the side effects

having said that I I know that you are

aware that side effects for every

medicine

are studied in Pharmacology every

medicine has side effects that doesn't

mean that medicine is not used usually

the dosage that is used for a drug and

the frequency of the use

provides us the best

effect with least side effects the

dosage for this is 1000 milligram

and let me show you some of the side

effects and contraindication and then we

look at the anti-inflammatory mechanism

there are many people who use it on

daily basis I have seen many long covet

patients using it and feeling better and

then there are some for whom it does not

work very well so ashwagandha here this

is Merc Manuel is a small evergreen

shrub that grows in India Middle East

and Africa the botanical name is this I

want to go to the

the side effects so ashwagandha is

probably unsafe for pregnant women

because it might increase the risk of

miscarriage whether nursing mothers

should take it or not we do not know

because there are no studies for nursing

mothers and it can irritate digestive

tract in some people

the drug interactions remember that it

is it affects on the neurological system

it affects on the immune system it

actually boosts so when you talk about

boosting the immune system this is a

drug that actually boosts it it makes

the innate arm

a little more active and more strong if

we can use that as a as a flexible

medical term

so uh ashwagandha might lower blood

sugar levels

and thus make it unsafe to use with

anti-hyperglycemics

then it it can lower blood pressure as

well so be careful to use it with

anti-hypertensives then it seems to

change the immune system's activity and

it might interfere with those immune

system drugs that are suppressing the

immune system so drug is let's say we

are taking drugs to suppress immune

system and then we take ashwagandha it

can reduce their activity by boosting

the immune system

and those cool beans who've been here

with me for a long time they know that I

do not like to use the word boosting

because boosting actually means moving

the immune system

above and beyond its normal expected

behavior however this drug actually does

boost the immune system

and because of that drugs like

cyclosporines or microfenolate

Etc prednisolans it does not work very

well with them or should not be taken it

can shave off some of that effect

ashwagandha might take might make people

drowsy or sleepy because it does have an

effect on the brain and calming effect

one part of that side effect could be

sleepiness

some combining sedative hypnotic drugs

used to help with the Sleep ashwagandha

might take make people too sleepy in

them

ashwagana may increase thyroid hormone

levels so doctors carefully monitor the

thyroid functions so Merc manual says no

recommendation they don't think it is

useful but that is Merck Manual take

that with a grain of salt

this is WebMD and what is important here

is the dosing so if you see here WebMD

says ashwagandha has most often been

used by adults in doses up to thousand

milligram daily for up to 12 weeks speak

with a healthcare doctor so more than 12

weeks or three months usage there are

not much studies

once again people have been using it for

a long time

there are all of these links are present

in the description of this video

this is the study this is 2023 in

pharmaceutics and this study was uh 6

February 2023 is when it was received

and now it is accepted in 20 March 2023

and published on 24 March so it's a very

recent write-up this study is what I'm

gonna take one part at a time and

discuss if you would like more

discussions about ashwagandha if there

isn't much interest then I would leave

it after this discussion

so today I'm gonna talk about

anti-inflammatory but there are other

effects here as well

with this I have some other

links in the description as well that

would help you see or read various

components of actual panda with this

I'm gonna now go to

this

sometimes I forgot to re forget to reset

it so these are gifts for Humanity and

they're continuing

this is what we're talking about

ashwagandha it is an it is called Indian

ginseng ginseng it is called Indian

winter cherry it is not actually the

winter cherry it is just called Indian

winter cherry it is called vitinia

sluggered or withinia somnifera

the root is the actual

um

component that is used for medical

purposes or medicinal purposes ashwa so

I do not know how to pronounce it very

well I'm not from India so I do not know

exactly how to pronounce it ashwa means

horse and this is my depiction of force

whatever it means I know that the nose

is a little crooked but anyways that is

horse and Ganda means fragrance so its

root has at fragrance of the plants

because of flavonoids in them and so it

is horse and fragrance remember this

that wherever we have flavonides and

flavonus there is going to be stress

reduction uh remember that study from

Japan where they sent out a few people

to Forest and another few people to

Tokyo and they gave the people going to

Tokyo they gave them money to party and

relax and the people who went to Forest

they were also

us to relax and have fun when they came

back

they thought that people who went to

Tokyo they would have better

relaxation and they would be in a better

shape compared to those who went to the

jungle and it turned out

that because of the Phantom sites

because of the phytochemicals and the

fragrance in the jungle or the forest

the people who went to the forest they

had lower stress hormones lower cortisol

levels lower norepinephrine epinephrine

levels and they had a higher volume or

concentration or count of natural killer

cells so their immune system was

performing better and their stress

hormones were performing

meaning going down on the other hand the

people who went to Tokyo they did not

have this change although they were also

relaxed and having fun so that means

that if you are near plants that

actually relaxes you more and that

boosts your immune system

so this is a plant as well with its

fragrance whenever you have a plant's

fragrance that means you are actually

inhaling the flavonals and flavonoids

flavonoids actually so that is

ashwagandha

so areas of study there are many areas

in which it has been studied nowadays

for neural protection sedative effect

adaptogenic effect as I said before

sleep

anti-inflammatory antimicrobial

cardioprotective anti-diabetic

and possible reproductive outcomes

and hormone modulations today I tried to

write it in my cursive handwriting and

you can see it is so difficult to read

even I cannot read my own Android and it

is yet a clean end in writing anyways

Active Components

so there are many phytochemicals that

are present it's a plant right so it is

going to have phytochemicals or plant

chemicals in it the important ones are

retinoids and alkaloids and there are

for example with anolites are

retinopharyn a retinolides a to Y with

henon and so on similarly there are

alkaloids as well we tendin somniferin

somnin Etc it has flavonoids II and

these are the kind of flavonides that

are present

so it has good chemicals that are

present in it now I'm gonna go through

anti-inflammatory effect

this is where we'll talk we have already

talked about horse I promised you that

we'll talk about horse I just hope that

CDC does not put a tweet out tomorrow

that you are not a horse so don't take

flavonus or ashwagandha but now I'm

going to talk about Nemo as well as

we're gonna see if we can find Nemo

so anti-inflammatory effect so what it

does is basically it affects the nuclear

Factor Kappa B pathway

so before I go and discuss one of the

pathway just one there are actually many

Pathways I'm only going to talk about

one to kind of make a point here

the nuclear Factor Kappa B pathway is

usually said to be the cell survival

pathway

the mechanisms that are orchestrated

inside a cell imagine for a second the

gears turning in the cell

they become active in this pathway

nuclear Factor Kappa B pathway

either because of stressors outside of

the cell

for example

presence of the pathogens presence of

bacteria presence of viruses presence of

toxins presence of foreign material that

the cell doesn't like those can activate

uh pathogen recognition receptors or PR

one important one is called tall like

receptor or tlr4 and that inside is

connected with nuclear Factor Kappa B

Gears of the system and that produces an

inflammatory response from the cell

just a survival Behavior similarly

within the cell as well and surrounding

the cell there may be an absence of the

foreign material but still

stressors on the cell for example

extraordinary stretch or skew of the

cell or the pH is different or the

oxygen levels are not correct so other

stresses of the cell can also cause

nuclear Factor Kappa B to become active

this is why we say that nuclear Factor

Kappa B system can become activated

as a canonical system or canonical

pathway which means the pathogen comes

in or foreign material comes in or some

some offending agent from outside is

introduced in our body and our body is

now going to respond with the survival

Instinct or survival mechanism and not

just the Instinct but also the molecules

and that will be the canonical nuclear

Factor Kappa B pathway the non-canonical

pathway is where the body and the cells

are activating this pathway nuclear

Factor Kappa B but for

internal stressors

so how does it work let's start from

here

and actually before my diagram I want to

show you

to if you go to this link

this is a diagram where the this part

here is the nuclear Factor copper B this

p50 and p65 are actually the ones and

you can see that there are many Pathways

that would activate it I am only going

to talk about these two Pathways and

still within this I'm only going to talk

about this one area this one I'm I'm

gonna remove or ignore tram I'm going to

ignore all of this as well but I want to

make sure that it is in front of you

that there are more ways to activate the

nuclear Factor Kappa B the point I'm

making is ashwagandha actually

modulates this pathway and suppresses it

so that the inflammatory state is

reduced when this state is taken up in

the brain then the brain's inflammatory

State responds by gliosis gliosis is

overproduction of the brain's tissue

cells which are going to respond with

inflammation and ashwagandha suppresses

that too because of that it can in

theory from a mechanism point of view

reduce brain's inflammation and also

reduce inflammation in the body

I think this is why it may have been

um for some long covet patients who've

been saying that hey when I take

ashwagandha that allows me to number one

be relaxed and number two my

neurological symptoms improve so maybe

these are the combinations so back here

imagine that in here this is all a cell

inside this is the cell membrane on the

membrane we have tall like receptor four

and we also have interleukin receptor

so the cells respond to interleukins

this is interleukin one receptor that

also activates the nuclear Factor Kappa

B and call like receptor four that would

uh that would Identify some pathogen in

the environment

now if we go in here the tall like

receptor 4 on the inside of the cell it

is connected to a couple of proteins

called

tirap and tram

I am gonna go this pathway as I said t i

r a p

when become active how when we have

something here let's say a pathogen a

gram negative bacterial

lipopolysaccharide some toxins on the

bacteria they are here it's all like

receptor four becomes active when it

becomes active it activates both of them

I'm only going to be here so let's say

tirap becomes active when that becomes

active it activates another protein

called my d88

my d88 so my d88

so today

your takeaway are going to be two basic

things one is ashwagandha can be used to

reduce inflammation in the brain and in

the tissues and second is the the

pathway that it uses is nuclear Factor

Kappa B pathway it suppresses that so

now there are just some fun characters

my d88 protein when that becomes

activated it causes another set of

proteins which are called irak4 and

irak5 one

it activates them or we use also the

term it recruits them it activates them

it brings them in action so it recruits

them with the irak

it is another protein attached to them

called traf 6.

this protein once it is activated what

it does is there is another complex of

three proteins

actually this complex of two proteins

called Tab 2 3 and take one tab take so

we are we are getting near a fish so you

open up a tab in your in your restaurant

and take one fish so tab two three and

take one when these become activated or

tack one not take when these become

activated what they do is there is

another protein called Nemo

when they will become these two guys

will become active they will activate

Nemo

now here is an interesting thing when

Nemo is activated

there is ubiquitination of Nemo what

does that mean Nemo will be destroyed

ubiquitination inside ourselves mean and

I've done a complete discussion about

ubiquitination and autophagy in terms of

intermittent fasting mechanisms

in the ubiquity Nation our cells can try

to destroy

proteins in two ways

it can destroy proteins as a regular

mechanism which you would see here for

example Nemo will be destroyed as a

normal function of the cell this is like

opening a door so the cell would not

open the door it would just destroy the

door but that doesn't mean there is a

disaster happening that simply means

that is a function it is trying to open

a door inside and it broke it and to

open it

then so this would be called autophagus

sorry ubiquitination

ubiquitination does not cause alarm in

the cell that proteins are breaking this

is a normal mechanism

the other one is that we have done

autophagy which can pick up the raw

material or the or the bad detangled

d-shaped denatured proteins and break

them down and that actually causes alert

as well so back here the Nemo protein

gets ubiquini ubiquitinated that means

it gets marked to be destroyed

so of course it then gets destroyed when

it gets destroyed then this stack won

this is such a funny story this stack

one then sneaks beyond the Nemo and goes

and connects with this pathway do you

see there are two proteins here let me

make them bigger

there are two proteins this is ikkb and

this is ikk Alpha and you see this

little DAC has snuck in and now it is

phosphorylating phosphorylating means

putting a phosphate many times when we

are activating a protein in our cells we

put a phosphate on them we give them

currency we give them money to become

active so here tack one has come in near

ikk Alpha and beta and it is now

phosphorylating ikk beta that

phosphorylation would activate this one

ikk beta which in turn will take a

phosphate and phosphorylate this little

guy so do you see that they are in turn

phosphorylating and activating each

other some of them are just going poof

they are disappearing like Nemo so if

this was a movie Finding Nemo you will

not find Nemo because Nemo would get

destroyed so here ikk beta when that

becomes active it would phosphorylate

this ik beta Alpha this guy this little

thing here where there is a protein

you can see probably that this little

protein is holding on to two baby

proteins

this is a very common pattern in our

cells where a protein protects the other

protein and prevents it from functioning

by hugging it and binding with it

so imagine that

in your home there is a refrigerator

you do not want the refrigerator to be

opened there is a delicious cake in

there yummy cake

so what you do is you go and hug the

refrigerator

so now the refrigerator is not

accessible to others because you are

hugging it or you are sequestering it

that is what's happening here this

little protein is called ik beta alpha

or ikk

it is

sequestering or binding with two more

proteins called p50 and p65 this whole

complex together is the nuclear Factor

Kappa B complex in this complex one

protein is The Binding protein to

protect these two active ones these two

little baby proteins are actually the

active ones

they are protected by this guy

and why do you think we are protecting

them very simple these two proteins

are the ones that would cause the cell

to produce inflammatory mediators

so if you let them be

free like little naughty children in the

cell they're gonna run in the nucleus

and ask the nucleus to make inflammatory

proteins

we don't want them to do that so what do

we do we bind them to this bigger mommy

protein

so now this complex

is present and when ikk beta here

becomes active it will attach a

phosphate to this proteins when this

protein gets the phosphate attached to

it that causes this protein to become

destroyed

or degraded by ubiquitination

when this gets so who got destroyed here

Nemo and ikk

when that gets destroyed guess what

proteins become free the p50 and p65

become free these are the actual active

nuclear Factor Kappa B transcripting

proteins why do we call them

transcripting proteins because they

would go in the nucleus they will bind

with the DNA and they would open up the

DNA for transcription or gene expression

so as soon as this mother protein got

destroyed or ubiquitinated these two

children protein became free they ran

into the nucleus

and they bound to their corresponding

genes

and once they got bound there we would

say Gene promotion they will promote the

gene now to become expressive so Gene

will open up and the messenger RNA will

be produced this messenger RNA will then

come out of the cell and will attach

with the ribosome with the Golgi

operators and it would so smooth and

rough endoplasmic reticulum would be the

one with the ribosome that would then

produce the actual proteins that are the

responsive proteins and various kind of

inflammatory proteins will be produced

now various Pathways produce some more

than the others for example the the tall

like receptor pathway produces these

ones more

compared to the other Pathways that

might produce these more

but in any event when the ashwagandha is

given and it is modulating the nuclear

Factor Kappa B pathway all of these can

be reduced what are these interleukin-12

inflammatory

interleukin-6 quite through inflammatory

actually interleukin-6 blockers are

given all the time for controlling the

inflammation interleuking eight tumor

necrosis Factor Alpha interleukin One

beta interleukin once sorry six and then

I wrote six here as well nitric oxide

stress

enzymes as well

that will produce the reactive oxygen

species reactive nitric oxide species

so these would all start going down the

result of that is that the inflammation

will go down and now just very quickly

this is the mechanism I just explained

one tiny part of this whole thing now if

I go back here to this study

in this study

I'm not going to read the whole

paragraph but this is the section

for

okay so I lost the section one second

here so this is the anti-inflammatory

section here all of these color

variations that I have are because they

have various in vitro or Mouse model

studies in which they said that this

study was done and that study showed the

modulation of these inflammatory

mediators that it just showed and I

showed you the pathway for how these get

modulated

so this is the discussion thank you very

much for listening in

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