Efficacy and safety of the traditional herbal medication Chai-Ling-Tang (in China), Siryung-tang (in Republic of Korea) or Sairei-To (in Japan)

Ethnopharmacological relevance: The herbal medicine designated Chai-Ling-Tang in China, Siryung-tang in South Korea, and Sairei-To (or Tsumura Saireito extract granules, TJ-114) in Japan is a complex polyherbal formulations with 12 plant components. It is used historically to treat Shaoyang syndrome, recorded in an ancient Chinese medical text "Treatise on Cold Damage Disorder" (Shanghan Lun). Chai-Ling-Tang formula combines two traditional Chinese herbal medicine prescriptions: Xiao-Chai-Hu-Tang and Wu-Ling-San (known as Sho-Saiko-To and Goreisan in Japan, and So Shi Ho Tang and Oreonsang in Korea, respectively). These traditional Chinese/Korean medicines and Kampo medicine have been used for more than 2000 years in East Asia, notably as regulators of body fluid homeostasis. Aim of the study: This study aims to evaluate clinical uses, pharmacological effects and unwanted effects of Sairei-To through a narrative literature survey. The main active phytoconstituents and their mechanism of actions are also collated based on the literature. Methods: Several databases including SciFinder and PubMed were searched in sourcing information using keywords corresponding to the medicinal treatment names and the corresponding plants and phytochemicals. Relevant textbooks, reviews, and digital documents (mostly in English) were consulted to collate all available scientific literature and to provide a complete science-based survey of the topic. Results: Sairei-To derives from ten plants and two fungi. The three major components are Bupleuri radix (Saiko), Pinelliae rhizoma (Hange), and Alismatis rhizoma (Takusha). The rest includes the species Scutellariae radix, Zizyphi fructus, Ginseng radix, Glycyrrhizae radix, Zingiberis rhizoma, Cinnamomi cortex, Atractylodis lanceae rhizoma, Poria sclerotium, and Polyporus sclerotium. The therapeutic uses of Sairei-To are very diversified, ranging from the treatment of autoimmune diseases, intestinal inflammatory disorders, edema, intestinal and kidney diseases, cancers, inflammatory skin pathologies, and other conditions such as reproductive failure. Sairei-To is considered as a safe and efficient medication, with potential rare unwanted side effects, notably lung injuries (pneumonitis essentially). Marked anti-inflammatory and immune-modulatory effects of Sairei-To have been reported, generally associated to the action of saponins (saikosaponins, glycyrrhizin), terpe-noids (alisols) and flavonoids (baicalin, oroxylin A). Conclusion: Sairei-To is commonly used to treat inflammatory diseases and appears efficient to decrease the side effects of corticosteroids. Its immune-regulatory action is well recognized and exploited to treat certain skin lesions and chemotherapy-related toxic effects. The activity of the Sairei-To product relies on the synergistic action of its individual ingredients. Further studies are warranted to quantify the synergy of action inherent to this interesting botanical medication.