The 1H-NMR, LC-MS, and HPLC guided isolation of n-hexane and ethyl acetate fractions led to the purification of one new sesterterpene cheilanthenetetraol (1) together with thirteen known compounds (2-14) for the first time from Aleuritopteris bicolor Roxb. The structure of the isolated compounds were established by extensive analysis of spectroscopic data, 1D and 2D NMR, HR-ESI-MS, and IR. The isolated compounds (2, 3, 6, and 9-14), as well as the n-hexane, ethyl acetate fractions, and aqueous methanol extract, were evaluated for cytotoxic activity against the HepG2 cancer cell line. All the tested compounds exhibited significant cytotoxic activity with an IC50 ranging from 10.08 µM to 14.04 µM. The extracts exhibited moderate activity with an IC50 value of 315.68, 391.55, and 274.89µg/mL, respectively. The anti-inflammatory activity of compounds 6, 9, and 10 were assessed, and the results demonstrated that these compounds exhibited significant activity at 10 and 30 µM concentrations in LPS-stimulated macrophages.

High levels of UV radiation in Okinawa contribute to skin damage, photoaging, and inflammation. Calophyllum inophyllum L. (Tamanu) trees are frequently cultivated along roadways in Okinawa. The oil isolated from Tamanu nuts is renowned for antioxidants, antibacterial, and anti-inflammatory properties. However, the specific UV-absorbing compounds responsible for its anti-inflammatory activity remain unidentified. This study aimed to isolate, characterize, and evaluate the anti-inflammatory activity of UV-absorbing components from Okinawan Tamanu oil. Clinical tests confirmed the UV-protective effects of Tamanu oil, with SPF and PA values of 6.3 ± 0.4 and 2.9 ± 0.6, respectively. UV-absorbing compounds were isolated based on absorbance at 300nm and structurally characterized by mass spectrometry and NMR. The anti-inflammatory effects of calophyllolide (CAL), inocalophyllin A (ICA), and inocalophyllin B (ICB) were evaluated in LPS-stimulated RAW 264 macrophages and UVB-induced HaCaT keratinocytes. The specific absorbance at 300nm of CAL, ICA, and ICB isolated from Tamanu oil (300nm specific absorbance = 28) were = 695, 285, and 378, respectively. All three compounds significantly inhibited nitric oxide production in LPS-induced RAW 264 cells. CAL downregulated TNF-α, IL-1β, IL-6, and IL-1α, while ICA and ICB suppressed IL-1β, IL-6, and IL-1α. In UVB-stimulated HaCaT cells, all compounds reduced IL-1α production. ICA also suppressed TNF-α, HMGB1, and HDAC2, while ICB downregulated CASP1, BAX, NLRP3, HDAC1, and HDAC2 significantly. These findings suggest that CAL, ICA, and ICB have strong anti-inflammatory properties, with ICA and ICB providing additional protection against UVB-induced skin damage via inhibition of necroptosis and inflammatory signaling.

Carbazoles exhibit various pharmacological activities, including antitumor activity. Eustifoline-B is a carbazole from Murraya (Rutaceae) plants that exhibited strong antiproliferative activity against cancer stem cells (CSCs) that were established from a human glioblastoma (GBM) cell line (U-251 MG). This activity was stronger than that against GBM cells (non-CSCs), indicating that the activity was CSCs-selective. In this study, the efficacy of carbazole derivatives against GBM was evaluated, their structure-activity relationships were examined, and their blood-brain-barrier (BBB) permeability was investigated in vitro. First, 26 carbazole derivatives, two indole derivatives, and two quinoline derivatives were synthesized, including 12 new compounds. Next, 34 compounds, including the synthesized carbazole derivatives, were evaluated for their antiproliferative activities against U-251 MG CSCs and non-CSCs. Carbazoles with prenyl groups, including eustifoline-B, showed concentration-dependent antiproliferative activity against U-251 MG CSCs (IC50 = 3.5-19.8µM). Among the prenyl groups, carbazole derivatives with geranyl groups, such as eustifoline-B and eustifoline-C, tended to have stronger activity against CSCs (IC50 = 6.2µM and 3.5µM) than that against non-CSCs (IC50 > 25µM and IC50 = 6.6µM), indicating that they are CSCs-selective. Finally, in vitro BBB permeability studies were performed using six carbazoles; most carbazoles, including eustifoline-C, exhibited BBB permeability. These results suggest the promising potential of carbazoles as new pharmaceutical agents for the treatment of GBM.

Three novel triterpenoids, yatiaroic acids A-C (1-3) with an unprecedented seco-serratane skeleton were isolated from branches of Myrica gale var. tomentosa. The relative and absolute stereochemistry of 1-3 were determined on the basis of the 2D NMR data, chemical transformation, and CD calculation.

The human gastrointestinal tract harbors over a thousand coexisting bacterial species that together constitute a highly complex intestinal microbiome. Dysbiosis of this microbial ecosystem has been implicated in the pathogenesis of disorders such as ulcerative colitis and obesity and has driven the development of microbiota-targeted prevention and treatment strategies. Traditional Kampo medicines are used with the aim of restoring the balance of the whole body, having been developed and established uniquely in Japan based on traditional Chinese medicine with a history of over two millennia. Recent evidence has revealed that the gut microbiota plays critical roles in the pharmacological effects of traditional Kampo medicines. For example, the anti-obesity activity of Bofutsushosan has been linked to an increase in Akkermansia muciniphila. The laxative effect of Daiokanzoto is related to rheinanthrone, which is produced from sennoside A through the gut microbiota, and drugs and foods that can alter the gut microbiota change the laxative activity of Daiokanzoto. In recent years, clinical trials have been conducted to examine the relationship between changes in the gut microbiota and the pharmacological effects of Kampo medicines, and this relationship has come to the forefront. This review discusses the findings of basic and clinical research on the role of the gut microbiota in the pharmacological action of traditional Kampo medicines, focusing on Bofutsushosan, Daiokanzoto, Daikenchuto, and Hangeshashinto, and discusses future issues and prospects for research into these interactions.