There are five cultivated, and more than 20 wild, species of Capsicum pepper, of which C. annuum is the most widely distributed, cultivated, and used in the world. C. annuum was also introduced into Japan in the Azuchi-Momoyama period (1568-1600), but the Japanese did not have a strong pungent taste culture. However, around 1984, strongly pungent foods became popular and triggered the "1st Super Spicy Boom". This was followed by the fourth boom in 2018 and beyond. The third boom in hot and spicy food was the period when the "diet with hot peppers", which was the result of research on capsicum, became a hot topic of conversation, and after that Japanese researchers have continued to make great progress in their research on capsicum peppers.

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The unique pungency of chili peppers is due to capsaicinoids, including capsaicin, which are produced and accumulate in the fruit in the placenta and septum. Because of this capsaicinoid-derived pungency, chili peppers are used as a spice, condiment, and seasoning in many parts of the world. When used as a seasoning, capsaicinoids are often soaked in oil, vinegar, or alcohol because they are oil-soluble. While the non-pungent or very weakly pungent pepper varieties, such as bell peppers, are also used as vegetables around the world, in the Kingdom of Bhutan, even the hot pepper varieties are used as vegetables. In addition, hot peppers are not only required to be pungent, but in regions where hot peppers are widely used, such as Korea and Mexico, they are also required to have other tastes besides pungency, such as Umami or sweetness. In fact, the glutamate and sugar content of some chili peppers is higher than that of tomatoes.

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Capsicum species consist of five cultivated species, C. annuum, C. baccatum, C. chinense, C. frutescens and C. pubescens. Among these five cultivated Capsicum species, C. pubescens (rocoto) has morphological characteristics that are very different from those of other Capsicum species, such as purple flowers, fine pubescence on stems and leaves, bright red, orange or yellow mature fruits, black seeds, and bell-shaped fruits that resemble bell peppers. Rocoto is a pepper cultivated in high altitude regions from Mexico to Peru, with its origins in the Andes of Peru and Bolivia. It is cultivated as a perennial plant in these regions, and is said to grow into a bush with a height of more than 2 m. Rocoto is considered to be one of the oldest cultivated plants in the Americas, having been cultivated since around 6000 BC. When rocoto is grown in an open field in Japan, it flowers but does not bear fruit. The fruiting difficulty of rocoto was investigated, and it was found that this species is a self-incompatible pepper that does not self- fruit by self-pollination. Colchicine treatment of rocoto seeds yielded tetraploids, which were self-fertile. The maximum leaf width and petal length of tetraploid loci were significantly larger than those of diploids, and the number of petals was around 6 in diploids, whereas most tetraploids had 7 to 8 petals. Pollen grain size was also significantly larger in tetraploids than in diploids. Fruit size was not significantly different between diploids and tetraploids, but tetraploids tended to have slightly thicker fruit flesh. Unlike "Taka-no-tsume", which is mainly composed of capsaicin in Japan, rocoto is a hot pepper characterized by its stimulating spiciness that hits the back of the throat, mainly from its dihydrocapsaicin content. It is said that the higher the dihydrocapsaicin content, the less sharp and pungent the taste becomes, and the pungent taste lingers in the mouth, making it undesirable. However, the "lingering spiciness" of rocoto may become a new attraction in the recent boom in hot peppers.

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Capsaicinoids are acid amides of vanillylamine and fatty acids, and are the main spicy component in chili peppers. Although capsaicinoids show beneficial biological activities, their utilization is limited due to intense pungency. The research on various chili pepper strains have identified two groups of low-pungency analogs (capsinoid and capsiconinoid). While capsinoids are esters of vanillyl alcohol and fatty acids, capsiconinoids are esters of coniferyl alcohol and the identical fatty acids. They exhibit similar biological properties to capsaicinoid, and have potential for food utilization, due to low pungency. The content of the low-pungency analogs varies greatly among the chili pepper strains. The mutations in putative aminotransferase (pAMT) gene have been identified as the key factor to accumulate capsinoid. The loss-of-function of pAMT suppresses the production of vanillylamine and capsaicinoid from vanillin, and accumulates vanillyl alcohol and capsinoids instead. Recently, it has been demonstrated that the synthesis of vanillyl alcohol from vanillin is carried out by cinnamyl alcohol dehydrogenase (CAD), which is ubiquitously involved in the lignin biosynthesis pathway in plants. The low-pungency analogs may be regarded as "by-products", which is produced when ubiquitous enzymes are involved in the biosynthetic pathway of specific secondary metabolites. Further understanding of capsaicinoid biosynthesis pathway may lead to rational manipulation of the biosynthesis pathway to increase low pungency analogs and the industrial value of chili pepper fruit.

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Pungency is not taste, but pain. Accordingly, it was thought that isolation of a capsaicin receptor would lead to the development of novel antipungent and antinociceptive agents. After fierce world-wide competition, a gene for capsaicin receptor TRPV1 was isolated by Dr. David Julius at the University of California at San Francisco in 1997. Dr. David Julius was awarded the 2021 Nobel Prize in Physiology and Medicine for his discovery of the receptor for temperature (TRPV1 and TRPM8). TRPV1 was found to be activated not only by capsaicin, but also heat stimulus over 43 degree C, which is known to cause pain in humans and monkeys. Therefore, TRPV1 is a molecule activated by multiple nociceptive stimuli, indicating that TRPV1 can explain polymodal nociceptive neurons. It was also found that mice lacking TRPV1 don't feel pungency or pain upon exposure to capsaicin or noxious heat stimulus, indicating that TRPV1 works as a pain sensor at an in vivo level. Despite extensive efforts, no chemical targeting TRPV1 has become available in the market for controlling pain. The structure of TRPV1 at an atomic level was clarified with Cryo-EM by the David Julius and Yifan Cheng group in 2013. However, It has not yet been clarified how heat stimulus opens TRPV1. We need more research to develop antipungent or antinociceptive agents targeting TRPV1 in the future.

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Cannabis sativa L. is an annual dioecious plant belonging to the Cannabaceae family that has been cultivated for thousands of years. Research on cannabinoids started in the 1940s, and more than 100 cannabinoids have been structurally elucidated recently. Among these cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major active components in marijuana, and they have already been approved as drugs in the United States and Europe. The mechanisms of THC and CBD-related anti-dementia activities, including animal experiments and clinical studies, have been reported, resulting in the possibility that THC and CBD could be therapeutic and preventive drugs for Alzheimer's disease. As medical marijuana continues to spread around the world and CBD has been imported freely to Japan and used in fields as wide as food and cosmetics, it will be debated whether CBD is a product of Cannabis or not. For these reasons, we recommend that the Cannabis Control Law and related regulations be corrected at an early stage. As the number of marijuana users in the world increases, the negative effects of marijuana use, especially for young people, are discussed in detail. Recently it has become evident from epidemiological studies that marijuana use later induces psychosis. The biosynthetic pathway has been described, including purification and isolation of the biosynthetic enzyme, followed by cloning, expression of the enzyme protein, crystallization, and X-ray analysis of the THCA synthase protein. The biosynthetic mechanism of THCA synthase relating to a flavo-enzyme was confirmed, showing that this enzyme can perform the redox reaction independently. Regarding the metabolic pathway of THC, anti-THCA monoclonal antibody (MAb) having a wide range of affinities functioned to efficiently isolate metabolites, elucidate their structures, and clarify their metabolic pathways.

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Diosgenin is a steroidal sapogenin compound in several plants such as Dioscorea spp., fenugreek, Polygonatum spp., and Smilax spp. The rhizomes of Dioscorea batatas (Chinese yam) and Dioscorea japonica (Japanese yam) are known informally in Japanese as "nagaimo" and "yamanoimo", respectively, and are also listed in the Japanese Pharmacopoeia as the crude drug "sanyaku". Diosgenin has clear effects on a diverse range of diseases. Among them, improvement of cognitive function by diosgenin has been substantially studied. Administration of diosgenin to Alzheimer's disease model mice restored memory impairment. The receptor of diosgenin in neurons was identified as 1,25D3-membrane-associated rapid-response steroid binding protein (1,25D3-MARRS). By visualization of axon-growing neurons, the molecules responsible for axonal repairing were found to be SPARC and Galectin-1. Increases in SPARC and Galectin-1 were mediated by 1,25D3-MARRS stimulation. Diosgenin-high content Chinese yam extract was evaluated in humans for its effect on cognitive performance. The randomized, double blinded, crossover clinical study demonstrated upregulation of cognitive function by taking yam extract for 12 weeks. Interestingly, diosgenin has a variety of ameliorative effects on other diseases, such as cancer, obesity, non-alcoholic fatty liver disease, decreased bone density, hypertension, depression, ischemia, multiple sclerosis, diabetic peripheral neuropathy, and spinal cord injury, which are outlined in this review.

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Antimicrobial agents are used to treat bacterial diseases in Japanese aquaculture. Although the number of approved antimicrobial agents has varied over time, currently 13 drugs are used. While antimicrobial agents have been effective in treating bacterial diseases in cultured fish, many antimicrobial-resistant bacteria have been reported. The problem of drug-resistant bacteria is important not only as a disease control measure for farmed fish, but also because of its relationship to human pathogens. In Japan, the "National Action Plan on Antimicrobial Resistance (AMR)" has been formulated, and monitoring for antimicrobial resistance has been conducted as part of the plan. In antimicrobial susceptibility testing of Lactococcus garvieae conducted since 2004, resistance has emerged to only three drugs, erythromycin (EM), oxytetracycline (OTC), and lincomycin (LCM). In 2004, LCM resistance accounted for more than 90%, and the rate of EM and OTC resistance was approximately 50%. However, since 2013, EM and OTC resistance has almost disappeared, and the LCM resistance rate has decreased to approximately 60%. This is thought to be largely because of vaccines, but the importance of chemotherapy with antimicrobial agents has not changed, as antigenic variants have emerged that vaccines are ineffective against. It is theorized that antimicrobial-resistant bacteria and genes emerged through usage of antimicrobials in aquaculture that are associated with antimicrobial resistance in human pathogens. In the future, even more prudent use of antibacterial agents will be required.

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Countries in the South Asia are famous for spicy food. Use of a variety of spices for cooking is a common characteristic of the food culture in these countries. Rice with several varieties of curries is popular in most parts of the countries with tropical climate. This paper selects the food habits of India and Sri Lanka to analyze how and why such food cultures should spread in Japan. With the detailed analysis of the effects of several major spices used in these countries, this paper proposes that the meaning of the use of spices for food preparation is beyond just adding a flavor, color or an aroma. Expected health effects thanks to the systematic use of spices not only makes food tastier, but assists to spend a healthier life as well. Even though Japan does not use spices as in the South Asian countries, there are fair reasons to examine how the use of spices in Japanese cousins can spread.

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