Deconstructing the traditional Japanese medicine “Kampo”: compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms

Abstract

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism.

Exploration of serum biomarkers for predicting the response to Inchinkoto (ICKT), a Japanese traditional herbal medicine

“…A clinical study reported that glychyrrhetinic acid can be detected 3 h or more after administration of licorice root containing the Kampo medicine, rikkunshito (Kitagawa et al 2015 ). Additionally, we have evaluated some herbal medicines in mice and rats using plasma metabolome analysis (Ohbuchi et al 2015 ; Nishi et al 2017 ). In these studies, a number of metabolites significantly changed at 2–4 h after administration.…”

Secondary Metabolite Differences between Naturally Grown and Conventional Coarse Green Tea

“…Similarly, our results suggest that there exists a metabolite-level property that is particularly based on the in natura state of culture condition, which has been generally treated as the irreplaceable support of the whole food quality that cannot be produced with synthetic nutritional supplements. Generally, the health effects of plant products cannot be totally evaluated with a single component, but should be considered within the whole diet composed of many compounds acting synergistically on human health [52,53]. The intrinsic distribution of compounds particular to in natura metabolite should further be considered when evaluating the sustainability of food systems toward the resolution of the health-diet-environment trilemma [3].…”

In Vivo Pharmacokinetic Analysis Utilizing Non-Targeted and Targeted Mass Spectrometry and In Vitro Assay against Transient Receptor Potential Channels of Maobushisaishinto and Its Constituent Asiasari Radix

“…One animal (n = 1) at a time was sacrificed 1 h post-drug administration under anesthesia with isoflurane by collecting whole blood from the abdominal inferior vena cava using an EDTA-2K treated syringe. According to previous pharmacokinetic studies of herbal medicines [ 33 , 58 ], many of the components were quickly absorbed into the bloodstream, thereby providing the rationale for a sampling time at 1 h. Blood was centrifuged at 1200× g at 4 °C for 30 min to obtain plasma; then, the sample was stored at −80 °C until LC-HRMS analysis.…”

“…Occasionally, in vitro pharmacological experiments involving herbal medicine are conducted by direct exposure to rodent or human cell lines. However, this method might be unsuitable for understanding the precise action of medicines, as many ingredients within herbal medicines are not absorbed as their intact form [ 33 ]. Therefore, we performed a pharmacokinetic study utilizing the non-targeted analysis to explore the bioavailable ingredients of AR using rats, prior to performing the pharmacological study.…”