Antitumor Effects of Delta (9)-Tetrahydrocannabinol and Cannabinol on Cholangiocarcinoma Cells and Xenograft Mouse Models.

Cholangiocarcinoma (CCA) is a very aggressive tumor. The development of a new therapeutic drug for CCA is required. This study aims to evaluate the antitumor effect of ∆9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), and cannabinol (CBN), a minor, low-psychoactive cannabinoid, on CCA cells and xenograft mice. THC and CBN were isolated, and their identities were confirmed by comparing 1H- and 13C-NMR spectra and mass spectra with a database. Cell proliferation, cell migration, and cell apoptosis assays were performed in HuCCT1 human CCA cells treated with THC or CBN. The phosphorylation of signaling molecules in HuCCT1 cells was detected. To determine the effects of THC and CBN in an animal model, HuCCT1 cells were inoculated subcutaneously into nude mice. After the tumors reached an appropriate size, the mice were treated with THC or CBN for 21 days. Tumor volumes were monitored and calculated. The 1H- and 13C-NMR data of THC and CBN were almost identical to those reported in the literature. THC and CBN significantly inhibited cell proliferation and migration and induced apoptosis in HuCCT1 cells. The phosphorylation of AKT, GSK-3α/ß, and ERK1/2 decreased in HuCCT1 cells treated with THC or CBN. CCA xenograft mice treated with THC showed significantly slower tumor progression and smaller tumor volumes than control mice. THC and CBN induced apoptosis in CCA by inhibiting the AKT and MAPK pathways. These findings provide a strong rationale for THC and CBN as therapeutic options for CCA.

Correction: Wu et al. Secondary Metabolites with Antimicrobial Activities from Chamaecyparisobtusa var. formosana. Molecules 2022, 27, 429.

The authors wish to make the following changes to their paper [...].

Secondary Metabolites with Antimicrobial Activities from Chamaecyparis obtusa var. formosana.

Seven new compounds, including one dimer novel skeleton, chamaecyformosanin A (1); three diterpenes, chamaecyformosanins B-D (2-4); one sesquiterpene, chamaecyformosanin E (5); and two monoterpenes, chamaecyformosanins F and G (6 and 7) were isolated from the methanol extract of the bark of Chamaecyparis obtusa var. formosana. Their structures were established by the mean of spectroscopic analysis and the comparison of NMR data with those of known analogues. Their structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry. Furthermore, the isolated compounds were subjected to an evaluation of their antimicrobial activity. Metabolites 1, 3, and 4 present antibacterial activities. It is worth mentioning that the chemical composition of the bark of C. obtusa var. formosana has never been studied in the past. This is the first time the barks from C. obtusa var. formosana were studied and two new skeleton compounds, 1 and 7, were obtained.

Dimeric γ-lactone derivatives from the soil-derived fungus Lasiodiplodia theobromae NSTRU-PN1.4.

Investigation of the soil-derived fungus Lasiodiplodia theobromae NSTRU-PN1.4 resulted in the isolation of five dimeric γ-lactones including two new botryosphaerilactones D and E (4 and 5) and three known structurally related analogoues (1-3) along with seven known compounds. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 1-5 was determined by comparison of the ECD data with those of the structurally related monomeric γ-lactones. For biological evaluation, this is the first report on antifungal activity of the known (3 R,4R)-4-acetyl-3-methyl-2(3H)-dihydrofuranone which displayed weak antifungal activity against Cryptococcus neoformans with an MIC value of 200 µg/mL.

Phytoconstituents and Biological Activities of Garcinia dulcis (Clusiaceae): A Review.

Garcinia dulcis (Roxb.) Kurz is a tropical fruit tree native to Southeast Asia where it has a long history of use as a traditional medicine for the treatment of ailments such as lymphatitis, parotitis, struma, scurvy, cough, and sore throat. Despite its medicinal values, this plant is not well known and rarely found nowadays. Research on the phytochemical constituents and biological activities of G. dulcis have demonstrated that various parts of the plant contain an. abundance of bioactive compounds mainly xanthones and flavonoids, with significant pharmacological properties such as anti-atherosclerosis, anti-bacterial, anti-cancer, anti-hypertension, and anti-malarial. In the present review, current knowledge of the phytochemistry of G. dulcis and biological activities of its active constituents based on the available literature are summarized in order to explore application potentials and prospective research works on this plant.

Tetrahydroanthraquinone and xanthone derivatives from the marine-derived fungus Trichoderma aureoviride PSU-F95.

Trichodermaquinone (1) and trichodermaxanthone (2) were isolated from the marine-derived fungus Trichoderma aureoviride PSU-F95 together with eleven known compounds. The structures were interpreted by spectroscopic methods. Known coniothranthraquinone 1 and emodin displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with the MIC values of 8 and 4 µg/mL, respectively.

Anthraquinone, cyclopentanone, and naphthoquinone derivatives from the sea fan-derived fungi Fusarium spp. PSU-F14 and PSU-F135.

Five new metabolites, fusaranthraquinone (1), fusarnaphthoquinones A-C (2-4), and fusarone (5), were isolated from the sea fan-derived fungi Fusarium spp. PSU-F14 and PSU-F135 along with 18 known compounds. The structures were elucidated on the basis of spectroscopic evidence. Their antibacterial, antifungal, antimycobacterial, antimalarial, and cytotoxic activities were examined.

Cyclohexene, diketopiperazine, lactone and phenol derivatives from the sea fan-derived fungi Nigrospora sp. PSU-F11 and PSU-F12.

Nigrosporanenes A (1) and B (2), two new cylohexene derivatives, and tyrosol (3) were isolated from the sea fan-derived fungus Nigrospora sp. PSU-F11, whereas five known compounds: 4-hydroxybenzoic acid (4), aplysiopsene D (5), 3-isochromanone (6), (-)-drimenin (7) and diketopiperazine derivative (8), were obtained from the fungus Nigrospora sp. PSU-F12. Their structures were established by spectroscopic evidence. We also tested their cytotoxic (on African green monkey kidney fibroblast and breast cancer cells), antioxidant (in the DPPH assay), and antibacterial (against the standard Staphylococcus aureus ATCC 25923 and methicillinresistant S. aureus) activities.

An [11]cytochalasin derivative from the marine-derived fungus Xylaria sp. PSU-F100.

A new [11]cytochalasin derivative, xylarisin (1), was isolated from the marine-derived fungus Xylaria sp. PSU-F100 along with six known metabolites: three mellein derivatives (2-4), one pyrone derivative (5) and two carboxylic acids (6,7). The structure and stereochemistry of 1 were determined by NMR and X-ray diffraction analyses. All isolated compounds showed mild antibacterial activity against standard Staphylococcus aureus ATCC 25923 and methicillin-resistant strain.