In this paper, I described impressive affair about changes of official journals of the Japanese Society of Pharmacognosy (JSP) during April 2001 to March 2021, including adoption of JSPS KAKENHI (Enhancement of International Dissemination of Information (B)) and process of the publishing contract with Springer.

The process of the transformation of the Japanese Society of Pharmacognosy to the general incorporated association was reviewed.

The Science Council of Japan has developed a Master Plan for Large-Scale Research Programs to guide important research initiatives across academic fields in the country. Starting from the 2014 Master Plan, the council has been regularly soliciting and selecting concrete project proposals from the scientific community, aided by scientific committees, at three-year intervals. The members of Japanese Society of Pharmacognosy participated in the 2014 Master Plan and continued as a priority large-scale research project in the 2017 and 2020 iterations. This article outlines the development and history of this process.

In this review, I would like to introduce the details of the research work conducted by three departments (Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, Research Center for Medicinal Plant Resources, National Institutes of Biomedical Innovation, Health and Nutrition and the Kochi Prefectural Makino Botanical Garden) for more than 30 years with the aim of promoting the domestic cultivation of medicinal plants. As a result of our research project, we published “The Guideline for Cultivation and Quality Evaluation of Medicinal Plants Part 1-13” from 1992 to 2019, including 68 monographs on medicinal plants; we also we established the Comprehensive Medicinal Plant Database and made it available to the public in 2013. However, the domestic cultivation of medicinal plants is only halfway through, as there are still many issues to be overcome. We continue to actively promote the cultivation of medicinal plants in cooperation with other organizations, so as to contribute to the stable procurement of raw materials for Kampo medicines.

ISO/TC249 standardizes traditional Chinese medicine (TCM), including Japanese Kampo medicine. Working Group 1 covers raw materials for TCM and their traditional processing methods. Working Group 2 covers TCM products including Kampo products. The author has continuously participated in ISO/TC249 since 2011. The standard proposed by the author himself has become an international one. Here I will describe my experience of international standardization in ISO/TC249. I will also describe the preparatory work for the standardization of Kampo medicines that I did before the establishment of ISO/TC249. This will serve as a reference for future generations.

The pharmaceutical approval system in Japan is basically designed to deal with chemically synthesized drugs. Since natural medicines such as Kampo medicines are multi-component complexes with diversity, it is not easy to develop new natural medicines under a unified pharmaceutical approval system that does not distinguish between chemical drugs and natural medicines. In this review, I will discuss the approval standards for the OTC natural medicines and the application guidelines for approval of the prescription natural medicines, which were established to overcome this hurdle in the pharmaceutical approval system.

Since 2002, the academic societies of pharmacognosy in Japan (JSP), Korea (KSP), and China (CCTCNM/CSP) have organized 11 Trilateral Joint Symposiums (TSs). This review describes the history and holding of the TSs, with particular emphasis on the recent 9th, 10th, and 11th TSs. A Joint Seminar on Pharmacognosy between Japan and Korea (1985-1998), which mainly consisted of plant collecting activities, became more academia-oriented to lead the Japan meeting in 2000, the Japan-Korea Joint Seminar on Pharmacognosy. The Chinese society members joined the following 2002 symposium in Korea to eventually become the first TS. Since then, the TS has continued on an annual or biennial basis, with the International Symposium Committee in charge as far as JSP is concerned. The 11th seminar hosted by the JSP (2021) was the first time that the industry associations related to crude drugs and Kampo medicines organized a special TS session aimed at industry-government-academia collaboration, entitled Traditional East Asian Medicinal (TEAM) Products: Current and Future Trends in TEAM Products for an Aging Society. It is hoped that a TS will continue as an opportunity for the three societies to further strengthen their collaboration as TEAM partners in academic activities, medical treatment and health promotion.

Quality assurance of crude drugs has been one of the most important issues since ancient times. In this article, by reviewing the history of Pharmacognosy and Kampo medicine, the future of education and research in this field will be discussed.

1) Several guidelines for medicinal plants conservation and utilization are published by WHO’s herbal medicines regulatory network. 2) The medicinal plants used in Japan and China are different in quality. Scientists in both countries exchange views about their knowledge and materials. 3) Philippine and Myanmar pharmacopoeia are published by Japanese experts with scientific advice. 4) Medicinal plant cultivation instead of opium has been carried out as the Myanmar Drug Eradication Project by Japanese experts.

Quantitative NMR (qNMR) is a useful technique to determine the purity of organic compounds and is now recognized as a new absolute quantification method in multiple fields such as pharmaceuticals, foods, and food additives. This review outlines why and how qNMR has been implemented as an official method in the Japanese Pharmacopoeia and other social standards. In addition, it addresses difficulties to introduce NMR as a quantitative method and how to resolve them.

My history in field investigations in Asia and pharmacognosy research on natural resources obtained is being introduced to encourage promoting collaboration and benefit sharing between Japan and other countries. In my first overseas expedition to explore traditional medicines and medicinal resources in the Nepalese Himalayas as a graduate student, I learned from my professor, Dr. Tsuneo Namba, how to prepare plant specimens, to conduct interviews on medicinal plants with traditional Tibetan physicians, and to return the scientific results to a community. As an assistant- and associate-professor, my field investigations in China followed by studies on authentication and quality evaluation of Chinese crude drugs were performed with support of the international network comprising Dr. Namba’s former students. When I led a laboratory, our primary goal was to develop a strategy for the sustainable use of crude drug resources. Thus, we conducted analyses on the genetic and chemical diversity of medicinal plants. These plants were collected during a field survey in Asia. Before such collaborative studies, international cooperative research activities of both our university and institute, and cooperation agreements with foreign institutions were necessary. Recently, our project in Mongolia needed to establish mutually agreed terms with a Mongolian researcher and to obtain prior informed consent.

In the chairman’s speech at the 52nd annual meeting of the Japanese Society of Pharmacognosy, I talked about the separation and independence of Natural Medicines as a new division to be the core course as well as aiming to launch an English-language journal. The vice president was Prof. Honda of Kyoto University, but we two were a good fit and met with Prof. Shibasaki of the University of Tokyo, who was the president of the Pharmaceutical Society of Japan at the time, to beg for independence. At the subsequent Board of Directors meeting of the Pharmaceutical Society of Japan, the matter was recognized. Meanwhile, Prof. Takeda, who was familiar with Springer, was able to successfully publish the Journal, and it was launched as the Journal of Natural Medicines.

I introduce achievements of Dr. Hiromu Ohashi (1927-2007), a pioneer in the study of medicinal crop cultivation and the founder of the Japanese Society of Research for the Cultivation of Medicinal Plants.

In the 1960s, many hippies brought marijuana into Japan, increasing marijuana crimes. The Ministry of Health and Welfare asked if it was possible to improve non-toxic cannabis, and this led to the start of marijuana research. Cannabis sativa is a dioecious annual herb belonging to the Cannabinaceae family, and has been cultivated throughout the world since ancient times. The marihuana research on the cannabinoid started in 1940 with the structural determination of cannabinol, and with the advancement of analytical methods, new cannabinoids have been isolated and their structures elucidated, resulting in more than 120 species. Breeding research was conducted on non-toxic cannabis, and eight years later, a non-toxic cannabis species containing almost no tetrahydrocannabinolic acid (THCA) was successfully bred, i.e., cannabidiolic acid (CBDA) strain. The biosynthetic pathway of cannabinoids was demonstrated through studies using labeled compounds, followed by purification and cloning of the biosynthetic enzymes, and finally, expression, crystallization, and X-ray analysis of THCA synthase were performed to clarify the entire protein of the enzyme. This enzyme is a flavoenzyme and its enzymatic reaction mechanism was cleared. In addition, two endogenous ligands and two receptors were identified, and extensive research has been conducted to date. Pharmacological studies of THC and CBD have also progressed, and both are now available as pharmaceuticals. Currently, research is being conducted on the anti-cognitive activity of cannabis, which has the potential to become a pharmaceutical product. The two-fold nature of marijuana is a major challenge. Cannabis is a “gateway drug” to narcotics and other drugs, and its repeated use causes psychiatric disorders and anxiety, symptoms of which are called cannabis psychosis. Recently, an epidemiological study in the Netherlands reported that cannabis consumption in young people can induce psychosis. Considering the merits and demerits of marijuana as described above, it is imperative that the laws regarding marijuana should be revised.

Nature is a very important resource for not only new drug discovery but also application of traditional medicines. The Japanese Society of Pharmacognosy has greatly contributed to the use of natural resources and human health. Kampo (Japanese traditional) medicines have been used as the traditional formula in which multi-active ingredients may attack multiple target sites to address complicated symptoms caused by disturbance of the body systems such as immune, neural and endocrine systems. Therefore, their multilateral actions are suitable to treat multifactorial diseases. The present article reminisces about the memory of the Society and our research on scientific elucidation of Kampo medicines to clarify their action mechanism and active ingredients.

My research life was reviewed and some thoughts together with ideas which have not been realized are described.

Because the seeds of Swertia japonica (Schult.) Makino, the source plant of the crude drug Swertiae herba, are tiny, they are conventionally sown by suspending them in water. However, this method has the disadvantage that the seeds are sown irregularly and often too densely, which can lead to stunted growth and plant disease susceptibility. To control the seed density of S. japonica, we manufactured pelleted seeds, and investigated seeding conditions using a commercially available vegetable seeder. The germination rate of pelleted seeds was as high as that of untreated seeds. Of the two types of pelleted seeds we produced, the larger, with a long axis of 2.324 mm and a short axis of 2.096 mm, was suitable for mechanical seeding. The weight of 100 grains was 636.7 mg, or about 148 times that of untreated seeds. Both sowing depth and covering the soil surface with a perforated polyethylene film after sowing had significant effects (p<0.01) on the rate of germination and the size of rosette leaves in the first year of growth. Of the four combinations of 0 cm or 1 cm seeding depth and with or without the perforated polyethylene film, we found that a sowing depth of 0 cm and the use of film was most suitable: the number of seedlings was 3.6 times higher and the rosette leaf diameter was 1.3 times larger than in the least suitable condition of a sowing depth of 1 cm and without the film. In contrast, the yield in the second year of cultivation was highest, at 4.1 g per plant or 647.1 g/m², with the 1 cm sowing depth and without the film. The quality of the harvested product was evaluated according to the Japanese Pharmacopoeia 18th edition, and all test plots met the criteria for quality.

A phytochemical investigation was conducted on the underground parts of Alternanthera philoxeroides, designated by Japan as an invasive alien species, to find new candidates for anti-cancer drugs. As a result, nine oleanane-type triterpene glycosides (1－9), including two new ones (1 and 2), and five noroleanane-type triterpene glycosides (10－14) were collected. The structures of 1 and 2 were determined by analysis of their NMR spectral data and enzymatic hydrolysis. Compounds 1－14 were evaluated for their cytotoxicity toward 　SBC-3 human small-cell lung cancer cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Compounds 1, 4, 7, and 11 exerted cytotoxicity against SBC-3 cells with IC₅₀ values ranging from 1.2 M to 16 M. This study implies that invasive alien species could be potential resources for new pharmaceutical seeds.

Several researchers have reported changes in the ginsenoside content of Panax ginseng during its cultivation period, but their results were not consistent. This may be explained in part by root diameter or localization of ginsenosides in the main root. In the present study, the ginsenoside content in the periderm and inner part of the main root were analyzed and compared between different ages. The results showed higher ginsenoside content in the periderm than in the inner part of the main root and the compositions of ginsenosides were different between these parts. Ginsenoside content was the highest in 1-year-old root and lowest in 2-year-old root. In 3- to 6-year-old roots, the ginsenoside content was almost the same.

The chemical constituents of Allium macrostemon Bunge tissue cultures were first determined. Coniferyl alcohol (1), coniferin (2), allimacronoid A (3), tuberonoid A (4) and 1-O-(E)-feruloyl-β-D-glucopyranose (5) were isolated from the root tissues of plantlets grown on 1/2 Murashige and Skoog solid medium. In the HPLC analysis, 3 and 4 were detected in the leaves of the cultures. On the other hand, five compounds (1-5) were not detected in the bulb. Compounds 1 and 2 were isolated from A. macrostemon Bunge for the first time.