21ST CENTURY HERBAL ALCHEMY
A new study: Inonotus obliquus conks growing on Alnus incana has remarkable properties
IMAGE: BLACK FUNGUS (INONOTUS OBLIQUUS) PARASITIZING ON ALDER TREE. view more
CREDIT: AHTO TÄPSI
A study led by researchers of the Estonian University of Life Sciences demonstrated that Inonotus obliquus, parasitizing on Alnus species, has comparable properties to the fungus growing on Betula species.
Inonotus obliquus is the fungus known to parasitize on Betula. I. obliquus grows in the Northern Hemisphere and belongs to the family of Hymenochaetaceae in the order Hymenochaetales and causes stem rot on several broadleaved tree species.
In Estonia, the fungus grows primarily on Betula pendula, Betula pubescens, Alnus incana and Alnus glutinosa. Sterile conks of I. obliquus contain bioactive compounds known to have anti-cancer effects, e.g. against proliferation of cells of leukemia and lung and colon adenocarcinoma, hepatocellular carcinoma of the liver, oral epidermoid carcinoma and prostate cell carcinoma.
The bioactive compounds extracted from the I. obliquus, especially betulin, betulinic acid and inotodinol inhibit the development of cancer cells. Previous studies have concentrated on the I. obliquus on birch trees, but it is not known whether the conks parasitizing on other tree species can offer equivalent properties.
As known, the current study is the first to determine the bioactive compounds of the I. obliquus parasitizing on alder species. The results demonstrate convincingly that conks of I. obliquus parasitizing on A. incana, which is growing well in Estonia, contain betulin, inotodiol and lanosterol to a similar extent as I. obliquus on B. pendula.
Surprisingly, the A. incana conks contained even up to 30 times higher betulinic acid than the conks parasitizing on B. pendula, 474–635 µg/g and 20–132 µg/g, respectively. The conks parasitizing on grey alder contained more beta-glucans, polyphenols and flavonols compared to the conks on silver birch. However, betulinic acid, betulin and inotodiol are more important in terms of anti-cancer effect.
Therefore, there is no substantive difference whether I. obliquus grows on a grey alder or a silver birch. However, further research is still needed to establish the potential effect of I. obliquus conks on alder on various cancer cell lines. Preliminary research also suggests the possibility that I. obliquus may have other valuable properties, such as effects on the immune system.
So what is the importance of the research for forestry and landowners? Alder is growing well in Estonia, for example, A. incana dominated the stands cover by approximately 9%, and of the private forest area, A. incana covers 14.1%. It would increase the still comparatively low economic value of grey alder generally considered suitable mostly for firewood by cultivating this host I. obliquus and would offer landowners, especially small landowners, an opportunity to earn.
The article is not calling for mass inoculation of trees with a pathogenic fungus, the risks and best practices for inoculating trees need to be researched before a tree inoculation campaign, and only then one can proceed to cultivation. The study shows that grey alder is not a worthless tree species, but rather an important resource that can be valued in many ways.
The study was conducted by researchers from the Institute of Forestry and Rural Engineering at the Estonian University of Life Sciences, the Institute of Agricultural and Environmental Sciences, and the Institute of Pharmacy at the University of Tartu.
Article: Comparative Analyses of Bioactive Compounds in Inonotus obliquus Conks Growing on Alnus and Betula. R. Drenkhan, H. Kaldmäe, M. Silm, K. Adamson, U. Bleive, A. Aluvee, M. Erik, A. Raal.
JOURNAL
Biomolecules
METHOD OF RESEARCH
Meta-analysis
SUBJECT OF RESEARCH
Not applicable
ARTICLE TITLE
Comparative Analyses of Bioactive Compounds in Inonotus obliquus Conks Growing on Alnus and Betula
21 CENTURY HERBALISM/SPAGYRICS
Antiviral substances discovered within native plants in South Korea
Two saponins were identified to be highly effective in blocking the ability of SARS-CoV-2 variants including Omicron to enter the cells
Peer-Reviewed PublicationIMAGE: TOP) ASTER KORAIENSIS AND BOTTOM) CODONOPSIS LANCEOLATA, WHICH ARE NATIVE PLANTS IN SOUTH KOREA. view more
CREDIT: INSTITUTE FOR BASIC SCIENCE
Codonopsis lanceolata, more commonly referred to as “deodeok”, is used as a medicinal herb in South Korea. It is cultivated in large quantities and has been an integral part of Korean cuisine across history. Aster koraiensis, or Korean starwort, is a common flower that resembles a daisy, which is only found in the Korean peninsula. What can these two different types of plants have in common?
A team of researchers led by Director C. Justin LEE from the Life Science Institute (Center for Cognition and Sociality) within the Institute for Basic Science (IBS), South Korea, recently announced the discovery of new antiviral compounds derived from these two Korean native plants. The researchers discovered that the saponins found within these plants were particularly effective at inhibiting SARS-CoV-2 infection by blocking membrane fusion, which allows the viruses to invade the host cells. These findings were published in Antiviral Research in October 2022 and Antimicrobial Agents and Chemotherapy in November 2022.
Coronaviruses are known to enter human cells via endosomes or fusion at the plasma membranes. In both of these two pathways, a process known as “membrane fusion” must occur between the coronavirus envelope and the cell membrane. The research team revealed that two saponins (astersaponin I and lansemaside A) found within the two beforementioned plants are capable of blocking this fusion of the membrane between the coronavirus and human cells, thereby effectively blocking all the ways that the virus can infect its host.
The research team first made a SARS-CoV-2 infection model using human lung cells overexpressing ACE2 receptor protein and a pseudovirus that expresses the viral spike protein on its surface, which can be used in the relatively less restrictive biosafety level 2 research facility. The cells were treated with astersaponin I and lansemaside A to test the compounds’ inhibitory effect on virus infection. Both saponins were found to have an IC50 value (half maximal inhibitory concentration) of 2 μM, indicating that they were highly effective at stopping the coronavirus from entering the cell. The same results were confirmed in subsequent experiments using actual authentic coronaviruses, and infection was suppressed with almost the same efficiency. More importantly, the inhibitory effect was identical for all SARS-CoV-2 variants, such as the Omicron.
Astersaponin I and lansemaside A are triterpenoid saponins. They both have central ringed hydrocarbon (or core) structures very similar to that of cholesterol, which is the main component of cell membranes. in addition to a polysaccharide chain attached to one side. The central part of these saponins readily binds to the cell membrane thanks to their similarity to cholesterol. When the molecule penetrates into the cell membrane, the long sugar chain on protrudes out of the cell membrane. It is believed that this protruding sugar is what blocks the cell membrane from fusing with the coronavirus envelope.
SARS-CoV-2 variants such as Omicron are more infectious than original onedue to the mutations in the spike protein, which enhances their binding affinity with the ACE2 cell receptor. However, no matter how much the SARS-CoV-2 variants to increase its affinity, it will be unable to enter the cell if the whole membrane fusion process, which occurs after viral binding to the receptor, is blocked. That is, the membrane fusion inhibitor can effectively prevent the infection of SARS-CoV-2 variants regardless of the their affinity to human cell receptor.
In the past, the IBS team worked jointly with Dr. KIM Seungtaek from Korea Pasteur Institute and discovered another natural triterpenoid saponin called platycotin D from the balloon flower. This saponin was also found to be effective against SARS-CoV-2 infection. This research was published in the journal Experimental & Molecular Medicine in May 2021.
Armed with this knowledge, the IBS researchers in collaboration with Prof. HAN Sunkyu’s team from Korea Advanced Institute for Science and Technology (KAIST) explored the creation of synthetic saponins with potentially even more powerful effects. The joint team made and tested a dozen synthetic saponins possessing different polysaccharide chains with varying lengths and types of sugars. One of these saponins was found to have up to twice higher activity as that of platycodin D. This research was published in the 2022 October issue of the journal Bioorganic Chemistry.
Director C. Justin LEE stated, “Natural saponins contained in these plants are major constituents in many foods and herbal medicines that are readily accessible in everyday life. When ingested, it can be delivered at high concentrations to the epithelial cells of the upper respiratory tract, which means it can be effective in an asymptomatic or early stage of COVID-19 infection.” He added, “While their effects have been confirmed only in vitro at the moment, clinical trials may be possible in the future if positive results are obtained in animal tests.”
Senior Researcher KIM Taeyoung from the IBS said, “Historically, many important drugs such as penicillin, aspirin, or the antimalarial drug artemisinin have been derived from natural organisms. As these saponins’ mechanism of action relies on inhibiting membrane fusion, it may even be possible to develop broad-spectrum antiviral drugs based on this principle.”
Astersaponin I prevents COVID-19 infection in a dose-dependent manner, with an IC50 value of 2 μM. The saponin worked equally as well against all variants of SARS-CoV-2, due to its ability to block membrane fusion.
Coronaviruses enter cells through membrane fusion between the virus envelope and cell membrane. When cells expressing coronavirus spike protein (green) are cultivated with human lung cells (red), membrane fusion followed by fusion between the two cells can be observed. Lansemaside A inhibits this membrane fusion, thereby confirming that its mechanism is based on blocking membrane fusion.
Astersaponin I, lancemaside A, and platycodin D are triterpenoid saponins with central ringed hydrocarbon structures similar to that of cholesterol. This allows one side of the saponin to become readily embedded within the cell membrane. It is believed that the polysaccharide chain protruding from the cell membrane is what prevents membrane fusion from occurring.
Left) 12 different synthetic saponins were synthesized using Platycodin D as the base. Right) One of the synthetic saponins showed twice higher ability to inhibit SARS-CoV-2 infection.
CREDIT
Institute for Basic Science
JOURNAL
Antiviral Research
METHOD OF RESEARCH
Experimental study
SUBJECT OF RESEARCH
Cells
ARTICLE TITLE
Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibits the infection of SARS-CoV-2 variants and syncytium formation
8TH CENTURY ALCHEMY
Tracing the origin of Kampo, Japan’s traditional medicine
The origin, surprisingly, could be in 8th century, suggests new study by researchers in Japan and China
Peer-Reviewed PublicationIMAGE: KAMPO CAN TRACE ITS ORIGINS TO AN 8TH CENTURY CHINESE MONK, JIANZHEN, WHO BROUGHT TO JAPAN WISDOM ON BUDDHISM AS WELL AS TRADITIONAL CHINESE MEDICINE. view more
CREDIT: TOSHIHIKO MATSUO FROM OKAYAMA UNIVERSITY
Traditional Chinese medicine (TCM) has been around for centuries. With a history of almost 3000 years dating back to the early Zhou Dynasty, it has been incorporated into China’s present medical system. The traditional practice involves the use of plants, animals, and minerals. It works on the principle of maintaining the delicate balance between ‘yin’ and ‘yang’—the opposite but interconnected forces said to be at the core of all creation—to prevent diseases and maintain health. Originating in China, TCM is practiced widely today, including in Japan.
It has long been considered that TCM was introduced in Japan by the monk, Jianzhen or Ganjin, who visited Japan in the 8th century to promote the teachings of Buddhism on the invitation of two Japanese clerics. Born in Yangzhou, the monk Jianzhen was well-versed in TCM and was proficient in Buddhism. When he arrived in Japan in 753 CE, it is said that he had with him 36 kinds of herbal medicines, each with different pharmacological effects and recipes for different combinations to treat a variety of diseases. Along with his Buddhist teachings, whether Jianzhen imparted his pharmacological and medical knowledge, thereby influencing existing traditional Japanese medicine, remains debated.
Now, researchers from Japan and China, led by Professor Toshihiko Matsuo of the Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, have conducted an extensive review of available Chinese, Japanese, and English literature to shed light on this longstanding mystery. The team comprised of Shihui Liu, former assistant professor in Okayama University, visiting research fellow Chie Matsuo, and senior assistant professor Takumi Abe, both from Okayama University. Their article, published on 18 October 2022 in the journal Compounds, offers interesting insights on the life of Jianzhen as seen through the lens of his ethnopharmacological knowledge.
On his trip to Japan, Jianzhen gathered and brought with him things he found on his way, things as insignificant as stalactites and Zixue (a TCM component), while also bringing traditional ingredients from China, including musk, agarwood, snail, rosin, dipterocarp, fragrant gall, benzoin, incense, dutchman’s pipe root, Pistacia lentiscus, Piper longum, Terminalia chebula/haritaki, asafetida, sugar, sucrose, 10 bushels of honey, and 80 bunches of sugar cane. In their article, the researchers have reviewed the 36 herbal medicines and their therapeutic effects that were brought to Japan. Local lore suggests Jianzhen also had with him a book called Jianshangren (Holy Priest Jianzhen)’s Secret Prescription, which has been lost for centuries. The team also reports being successful in tracking down a copy of another book that holds the same prescriptions.
Most interestingly, their findings show that the prescriptions by Jianzhen form the basis of herbal medicinal practice in Japan, popular under the name of Kampo. The herbal medicinal practice is very much integrated into the fabric of Japan’s current healthcare system. Kampo medicines are prescribed alongside Western medicine and modern drugs and is covered by the reimbursement of the national health insurance.
“People in Japan can buy Kampo medicines as over-the-counter drugs at pharmacies. This unique system in Japan has derived from a long history of systematic prescription of Kampo medicines and would have an origin in Jianzhen’s prescription in the 8th century,” observes Prof. Matsuo with much excitement.
He hopes for the spread of the use of Kampo medicine beyond Japan. “People in other countries also have a chance to use Kampo medicines in combination with Western medicines.” His inspiration in saying so is possibly, Jianzhen, again. “Jianzhen is one of the first people to bring Chinese traditional medicine to Japan. He is considered an ancestor of Kampo medicine, who molded Chinese traditional medicine to suit the needs of Japanese people,” reflects Prof. Matsuo. In the age of globalization, the journey of traditional medical knowledge that took 11 years to reach Japan from China may be accomplished in less than 11 seconds with the click of a button.
We live in that hope.
About Okayama University, Japan
As one of the leading universities in Japan, Okayama University aims to create and establish a new paradigm for the sustainable development of the world. Okayama University offers a wide range of academic fields, which become the basis of the integrated graduate schools. This not only allows us to conduct the most advanced and up-to-date research, but also provides an enriching educational experience.
Website: https://www.okayama-u.ac.jp/index_e.html
About Professor Toshihiko Matsuo from Okayama University, Japan
Professor Toshihiko Matsuo is a professor at the Graduate School of Interdisciplinary Science and Engineering in Health System, Okayama University, Japan. His areas of interest include Ophthalmology, Uveitis, Oncology, and Vitrectomy.
JOURNAL
Compounds
METHOD OF RESEARCH
Literature review
SUBJECT OF RESEARCH
Not applicable
ARTICLE TITLE
Traditional Chinese Medicines and Prescriptions Brought from China to Japan by a Monk (Jianzhen, Japanese: Ganjin): A Historical Review
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