Fighting COVID-19 With Kampo Medicine

Join us as we explore Medical Frontiers.

From the shells of shellfish and insects to plants, animals and minerals, various natural ingredients are used to create formulations aimed at healing the body

in the Japanese traditional medicine called "Kampo."

Many people think that Kampo medicine is a traditional Chinese medicine.

But it's actually Japanese and it's based on ancient Chinese medicine that entered Japan and developed independently from the original version.

In recent years, there have been increasing studies in Japan that prove the efficacy of Kampo.

Today we look out for Kampo can be used for COVID-19.

The Kitasato University Oriental Medicine Research Center in Tokyo has the longest history of studying Oriental medicine in Japan.

It has been conducting research to establish Kampo as a science-based medicine.

The center is currently looking at how to use Kampo to treat and prevent COVID-19.

Dr. Odaguchi, such a great pleasure to meet you. Thank you so much for your time today.

You're welcome.

The center is headed by Hiroshi Odaguchi.

There're so any different drawers here.

How many are there?

I guess these are for your Kampo medicine formulations.

About 200.

What is this one here, for example?

Cicada shells.

What's the one next to it?

"Shiso," or perilla leaves.

The drawers each contain a different "crude drug," or ingredient, for Kampo medicines.

Crude drugs are dried versions of natural products that have medicinal properties.

In Kampo, they're blended into formulations.

Kampo has its roots in this early-3rd-century Chinese classic.

It explains how to treat acute infectious illnesses.

The Japanese used the information in this text to adapt crude drug formulations and diagnoses to fit the local climate and people's physical constitutions.

The product of their efforts is the traditional Japanese medicine known as Kampo.

How do you know, how do you mix them and formulate for each patients?

There are commonly used, standard formulations.

We start with these formulations and make changes.

- So there're thousands of potential of different combinations.
- Combinations are limitless.

At the research center, specialists examine each patient's constitution and symptoms, then combine crude drugs into a custom-made medicine.

Formulations are packed into individual doses.

Patients boil the formulations in hot water to extract the medicinal properties.

They divide the liquid into two or three portions and drink it over the day.

This is how Kampo is taken traditionally.

What are some of the key differences between Western medicine and Kampo medicine?

In Western medicine, pills or tablets
tend to contain one key ingredient.

They have one strong ingredient,
mixed with additives.

But in Kampo, each crude drug, such as this one,
has hundreds of medicinal properties.

We combine them into a formulation
that has thousands of medicinal properties.

Kampo and Western medicine
are completely different.

In Western medicine, doctors prescribe specific drugs for specific symptoms.

However, Kampo combines crude drugs that each contain several medicinal properties.

Kampo formulations can therefore be effective for a variety of symptoms.

Many people globally are suffering from so-called "long COVID," or long-term effects of coronavirus infection.

Its more than 50 symptoms include fatigue, headache, difficulty breathing, joint pain and impaired sense of taste.

Symptoms can vary from patient to patient.

In January 2021, the research center established an outpatient clinic dedicated to long COVID.

70 percent of the 170 patients it treated showed an improvement in symptoms.

The causes of long COVID are unknown,
but it leads to many symptoms.

Kampo can treat symptoms with unknown causes.
This is difficult for Western medicine.

Therefore, Kampo is a suitable for long COVID.

20-year-old dancer Takai Nanami struggled with long COVID.

She was infected with the coronavirus in August 2021.

A few days after recovering from COVID-19, she began to notice abnormalities.

It was painful to speak loudly.
I couldn't be my cheerful self.

I didn't feel like talking.
I could barely mumble.

That continued for a while.
I think these were aftereffects.

One day, my parents asked me,
"Aren't you going to your dance class?"

I used to love dancing,
but I guess I stopped going.

My parents worried about me,
and did some research.

She also experienced memory loss.

Two weeks after she began having the mysterious symptoms, she visited the research center's clinic.

I had joint pain that worsened
around the time I started going to the clinic.

That was the most difficult time for me.
I kept massaging my legs like this.

In addition to joint pain, she also had symptoms such as fatigue, cough, and headache.

Kampo practitioners check the patient's pulse, tongue, and stomach.

They also try to identify the patient's constitution by checking blood flow and the presence of allergies, diarrhea and constipation.

Listening to the patients' complaints is critical.

In an examination, it's important to
listen carefully to what the patient has to say.

Finding out what symptoms appeared,
and in what order they appeared, is crucial.

It's necessary to listen attentively.

Kampo practitioners classify the progress of disease accompanied by fever into six stages, from the initial stage to the life-threatening stage.

At the far left is the initial stage of an illness.

It involves headache and joint pain, like the first signs of a cold.

The second stage is accompanied by the kinds of symptoms that appear when a cold worsens.

They include cough and fatigue.

Takai complained of symptoms belonging to the first and second stages.

A common formulation for such patients is "saikokeishito."

It's a combination of nine crude drugs, including a parsley-family plant called "saiko," jujube fruit, and ginseng root.

Takai took saikokeishito twice a day.

It was bitter - incredibly bitter.
But I finally got used to it.

One month after she started taking the medicine, her joint pain disappeared.

And after another month, she was feeling like her old self.

I was so happy. I wonder what would've
happened if my symptoms continued.

My parents and I thought I'd never dance again.

But now, I can dance, and I've regained
my normal life. I'm really happy.

With Western medicine, treatment of an illness
is not possible without knowing the cause.

We often get patients who were told that.

With Kampo, there are always clues we can use
to find a way to treat patients.

That's the strength of Kampo.

Kampo developed based on experience over a long period.

But critics have said there is a lack of scientific evidence for its use.

Kampo specialists have conducted various studies to overcome this, and produced promising results.

"Kososan" is one of the scientifically verified Kampo formulations.

It's made of five plant-based crude drugs, including the peel of a Japanese citrus; shiso, or perilla leaf; and the roots and stems of ginger.

Kososan is prescribed to patients who complain of depressive symptoms, that have increased amid the pandemic.

The effects were verified in an experiment using mice, and the results were published in a journal in 2022.

Naoki Ito is one of the authors.

Kososan has been used clinically for
patients with depressive symptoms.

But there was no scientific proof on
its efficacy, nor the reason for its efficacy.

We also wanted to show kososan's
effects on pre-symptomatic patients.

That's why we began this research.

The researchers used two types of kososan.

The only difference was the type of citrus peel they contained.

One was a regular kososan containing the peel of a Japanese citrus called "unshiu."

The other contained the peel of a citrus that's rich in a substance called nobiletin.

In the experiment, they used a strain of mice that age faster than usual.

These mice age at about 1.5 times faster than regular mice, and develop depression 17 weeks after birth.

Ito labeled the fast-aging mice at seven weeks of age as being in a pre-symptomatic state.

From this point, the group started giving the mice either water, kososan, or nobiletin-rich kososan, and compared the changes in them.

The mice were exposed to stress in their 19th week of age, when they were expected to have depression.

Healthy mice move around to escape stress.

But those with depression give up and remain immobile for long periods.

This graph shows the lengths of time the mice remained still.

Compared with the mice that were given water, those given either type of kososan had shorter periods of immobility.

The kososan-fed mice were more resistant to stress and more active.

In addition, the fast-aging mice given nobiletin-rich kososan were immobile for about the same period of time as regular mice.

In other words, they aged fast, but were just as active as regular mice.

Start taking a Kampo formulation
before abnormalities are found, and disease development can be prevented.
I think the data have shown that.

Ito also looked at brain inflammation, which can cause depressive symptoms.

He measured the amount of an inflammation-causing substance in the brains of the mice.

The fast-aging mice that were given nobiletin-rich kososan had a small amount of this substance, similar to regular mice.

This showed that taking nobiletin-rich kososan can suppress brain inflammation.

Western drugs cannot cure
mental disorders like depression.

Antidepressants have many side effects,
and need to be taken for a long time.

But many Kampo formulations have
few side effects, even if taken for long periods.

Kampo formulations don't need to be taken alone.

Combining them with Western drugs
would provide the best effect.

I hope our research will help enable that.

It's becoming clear that Kampo can also prevent the worsening of COVID-19.

A team led by Sumiko Hyuga is researching this topic.

The team focused on a crude drug called "mao," or Ephedra herb.

Its extract is known to be effective against influenza and contains ephedrine alkaloids, which have medicinal properties.

However, the alkaloids also have side effects.

Its side effects include high blood pressure,
palpitations, insomnia and urination trouble.

Hyuga's team developed "ephedrine alkaloids-free Ephedra Herb extract," or EFE, to prevent side effects.

Her team tested EFE's effects against influenza, and discovered that it could suppress infection.

People assumed ephedrine alkaloids were responsible
for all of mao's benefits and side effects.

Because of this, no one ever thought of
removing ephedrine alkaloids from mao.

Without them, it was believed there would be
neither benefits nor side effects.

But through our research, we discovered that
mao is effective even without ephedrine alkaloids.

We therefore removed them
and started researching EFE.

Hyuga's team investigated whether EFE had any effects on COVID-19.

When the team added a small amount of the coronavirus to a culture medium with cells in it, the virus infected the cells and multiplied exponentially.

The researchers tried adding EFE under the same conditions.

They confirmed EFE could suppress viral proliferation.

The blue graph indicates the amount of the coronavirus when EFE is absent.

The team found that a higher concentration of EFE led to a lower rate of viral multiplication.

But they discovered more than that.

I asked fellow researchers to test
EFE against coronavirus variants.

They confirmed EFE is effective in
curbing the growth of variants as well.

Hyuga's team investigated why EFE could prevent even mutated viruses from multiplying.

They found that a substance it contained, called "ephedra herb macromolecule condensed-tannin," or EMCT, was responsible.

It's a mixture of high-molecular
mass condensed tannins.

Tannin, the astringent substance?

Yes, it's a type of polyphenol.

EMCT has a high molecular mass,
so it may have sites that can bind to proteins.

EMCT is a very large molecule.

It comes in various complex structures, like puzzle pieces with numerous bumps and dips.

The researchers predicted EMCT can bind to coronavirus spike proteins.

The spike proteins are projections on the surface of the coronavirus.

They bind to receptors on cells' surfaces.

The spikes are like keys, and the receptors are like locks.

The virus uses its spikes to infect and enter cells, and multiply rapidly.

Because EMCT has such a complex structure, researchers believe it is able to fit spike proteins.

They believe EMCT binds to the spikes and prevents infection.

Viral mutations occur in the spike protein.

Even if the virus mutates, EMCT can still bind to it because it has other sites that can fit the spikes.

The research team conducted an experiment using human receptors and coronavirus spikes.

They usually bind to each other immediately.

However the researchers confirmed that the addition of EMCT inhibits the spikes from binding to the receptors.

They tested the efficacy of EMCT in various concentrations and discovered that even in low concentrations, EMCT can inhibit infection.

EMCT binds to spike proteins,
averting infection of healthy cells.

That prevents severe symptoms.

The first few cells may be damaged,
but the healthy ones nearby are saved.

It keeps the infection mild.

A clinical trial is underway on about 150 mild covid patients.

The research team aims to turn EFE into a scientifically proven medicine in the near future.

If the trial confirms that EFE is effective,
and it is approved as a drug, patients will be able to take it
without worrying about side effects.

We hope that day will come quickly.

EFE could also be given as a preventive measure.
Patients in the early stage of infection can take it.

So can family members and others
who've come in close contact.

Taking EFE early may keep them from
getting infected or developing symptoms.

Kitasato University has been doing a lot of researches in different areas.

How do you think it's gonna change perceptions going forward for Kampo medicine?

Kampo formulations and crude drugs contain
many substances that we are unaware of.

They have huge potential, and
we'd like to explore them further.

Instead of just passing on knowledge,
we should expand it for future generations.

We want Kampo to be a
traditional medicine that keeps evolving.

Today, we'll introduce a recipe for a juice using the leaves of red perilla, or "aka shiso."

Pharmacist Chiaki Ogata will explain how to make it.

So this is perilla herb.

Red perilla is coming into season.

It's obviously, we can't get it overseas.

So instead of perilla leaves or red shiso, or purple shiso, what else has the same compounds of similar compounds overseas?

Perilla contains rosmarinic acid.

This is also found in rosemary,
as the name suggests.

Mint is in the same family as shiso,
so I suggest using that too.

Red perilla seeds are available at major online retailers, so you can also try growing the plant yourself.

What is the medicinal effect of perilla herb?

Perilla has many effects.
It can bring about relaxation.

It can also help to prevent colds.
It's included in Kampo formulations very often.

When I was an exchange student in Kyushu in many many years ago, my grandmother, my homestay grandmother, she used to make shiso juice every summer.

I've never made perilla juice myself,
so I'm looking forward to it.

First, let's wash the perilla leaves.

Next, put the leaves in boiling water, make sure they're submerged, and simmer them for 10 minutes.

Strain the liquid into a heat-resistant container with sugar.

Add vinegar and lemon slices, and it's done!

Store the juice in the refrigerator and finish drinking it within two weeks.

Such a beautiful color! Gorgeous!

Wow, delicious. Not too sweet, not too sour. For me this is perfect.

But I think for some people who don't like sour, probably less lemon and less vinegar and add a little bit more sugar.

Wow, this is so good! Getting relaxed already.

"Shiso" is written using two characters that
together mean "purple color revives."

Drinking this will revive your body.
It provides power and energy.

This is gonna be my favorite summer drink.

Red perilla juice will help you
get through the summer.

Kampo is a medical science which is based on incredible history over thousands years.

And all the emerging research will certainly take Kampo medicine to a new level.

And I very much hope that many more people would be able to receive amazing benefits of Kampo medicine.