Curcumol metabolized by rat liver S9 fraction and orally administered in mouse suppressed the proliferation of colon cancer in vitro and in vivo.

Following 3R (reduction, refinement, and replacement) principles, we employed the rat liver S9 fraction to mimic liver metabolism of curcumol having high in vitro IC50 on cancer cells. In HCT116 and HT29 colon cancer cells, the metabolites of curcumol by S9 fraction exerted more enhanced activity in inducing cell cycle arrest and apoptosis via regulating the expression of cyclin D1, CDK1, p21, PARP and Bcl-2 than curcumol. In addition, oral administration of curcumol at 4 mg/kg BW significantly suppressed the development of colon tumor induced by azoxymethane/dextran sulfate sodium, and induced cell cycle arrest and apoptosis in tumor tissues. In mass analysis, curcumenol and curzerene were identified as the metabolites of curcumol by S9 fraction metabolism. Taken together, curcumol metabolites showed the enhanced suppressive effect on colon cancer, suggesting that S9 fraction can be considered as simple, fast, and bio-mimicking platform for the screening of chemical libraries on different chronic diseases.

Cycloastragenol inhibits adipogenesis and fat accumulation in vitro and in vivo through activating Hedgehog signaling.

In this study, we investigated the effect of cycloastragenol (CAG), a triterpenoid isolated from Astragalus membranaceus roots, on regulating the adipogenesis and fat accumulation in vitro and in vivo. During the adipogenesis of 3T3-L1 cells, CAG inhibited lipid accumulation and the expression of key adipogenic factors, proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding protein α (C/EBPα) and increased the expression of Gli1, a key mediator in Hedgehog (Hh) signaling. In HFD-induced animal experiment, CAG significantly reduced body weight gain without affecting brown fat weight. In addition, CAG regulated the expression of PPARγ, C/EBPα, and Gli1 in visceral white adipose tissue (vWAT). We also confirmed the inhibitory effect of CAG on specifically targeting white adipose tissue (WAT) formation in stromal vascular fraction (SVF) cell differentiation. Taken together, these results suggest that CAG may be a potent phytochemical preventing adipogenesis and obesity via Hh signaling. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01403-0.

Correction to: 1,3,5,8­Tetrahydroxyxanthone suppressed adipogenesis via activating Hedgehog signaling in 3T3­L1 adipocytes.

[This corrects the article DOI: 10.1007/s10068-022-01130-y.].

Perilla oil and α-linolenic acid ameliorated thrombosis in rats induced by collagen and epinephrine.

Perilla frutescens is an annual herbaceous plant widely cultivated for oil production in China, Japan, and Korea. In this study, we investigated the effect of perilla oil (PO) on thrombosis induced by collagen and epinephrine (CE) in rats. The oral administration of PO significantly increased prothrombin time (PT) and activated partial thromboplastin time (aPTT) in the blood plasma and inhibited the expression of cells adhesion markers (CAMs) such as intercellular CAM-1 (ICAM-1), vascular CAM (VCAM-1), E-selectin and P-selectin in the aorta tissue. Furthermore, pulmonary occlusion induced by CE in rats was suppressed by PO. α-Linolenic acid (ALA) was quantified at 60.14 ± 2.50 g/100 g of PO, and its oral administration at the same concentration with that in PO exerted the similar effect on PT, aPTT, ICAM-1, VCAM-1, E-selectin and P-selectin in CE-induced thrombosis rats. Taken together, PO and ALA significantly ameliorated thrombosis by regulating CAMs.

Garcinone C Suppresses Tumorsphere Formation and Invasiveness by Hedgehog/Gli1 Signaling in Colorectal Cancer Stem-like Cells.

Hyperactivation of hedgehog signaling occurs in colorectal cancer stem-like cells (CSCs), a rare subpopulation, potentially involved in metastasis, chemotherapy resistance, and cancer relapse. Garcinone C, a xanthone isolated from mangosteen (Garcinia mangostana), suppresses colorectal cancer in vivo and in vitro by inhibiting Gli1-dependent noncanonical hedgehog signaling. Herein, we investigated the effect of garcinone C on cancer stemness and invasiveness in colorectal cancer; Gli1 was noted as pivotal in maintaining stemness and invasiveness in HCT116 and HT29 CSCs. Garcinone C inhibited the proliferation and self-renewal of HCT116 and HT29 CSCs. Colon cancer stemness markers such as CD44, CD133, ALDH1, and Nanog were significantly decreased by garcinone C. Computational studies showed that garcinone C showed a high affinity with the Gli1 protein ZF domain by forming hydrogen bonds with amino acid residues of ASP244, ARG223, and ASP216. Besides, MG132 blocked the effects of garcinone C on Gli1. Thus, garcinone C suppressed colorectal CSCs by binding to Gli1 and enhancing its degradation. MMP2 and MMP9 levels, invasive-related markers, were increased in HCT116 CSCs but decreased by garcinone C. E-cadherin level was reduced in HCT116 CSCs, while the presence of garcinone C was restored. Garcinone C inhibited the proliferation and invasiveness of colorectal CSCs by targeting Gli1-dependent Hh signaling. Garcinone C may be a potent natural agent against colorectal cancer relapse.