Saponins, consisting of sapogenins as their aglycones and carbohydrate chains, are widely found in plants and some marine organisms. Due to the complexity of the structure of saponins, involving different types of sapogenins and sugar moieties, investigation of their absorption and metabolism is limited, which further hinders the explanation of their bioactivities. Large molecular weight and complex structures limit the direct absorption of saponins rendering their low bioavailability. As such, their major modes of action may be due to interaction with the gastrointestinal environment, such as enzymes and nutrients, and interaction with the gut microbiota. Many studies have reported the interaction between saponins and gut microbiota, that is, the effects of saponins on changing the composition of gut microbiota, and gut microbiota playing an indispensable role in the biotransformation of saponins into sapogenins. However, the metabolic routes of saponins by gut microbiota and their mutual interactions are still sparse. Thus, this review summarizes the chemistry, absorption, and metabolic pathways of saponins, as well as their interactions with gut microbiota and impacts on gut health, to better understand how saponins exert their health-promoting functions.

Purpose: Pancreatic cancer is the worst prognosis among all human cancers, and novel effective treatments are urgently needed. Signal transducer and activator of transcription 3 (STAT3) has been demonstrated as a promising target for pancreatic cancer. Meanwhile, selectively targeted STAT3 with small molecule remains been challenging. Experimental Design: To specifically identify STAT3 inhibitors, more than 1.3 million compounds were screened by structure-based virtual screening and confirmed with the direct binding assay. The amino acid residues that WB436B bound to were verified by induced-fit molecular docking simulation, RosettaLigand computations, and site-directed mutagenesis. On-target effects of WB436B were examined by microscale thermophoresis, surface plasmon resonance, in vitro kinase assay, RNA sequencing, and selective cell growth inhibition assessment. In vivo studies were performed in four animal models to evaluate effects of WB436B on tumor growth and metastasis. Kaplan–Meier analyses were used to assess survival. Results: WB436B selectively bound to STAT3 over other STAT families protein, and in vitro antitumor activities were improved by 10 to 1,000 fold than the representative STAT3 inhibitors. WB436B selectively inhibits STAT3-Tyr705 phosphorylation, STAT3 target gene expression, and the viability of STAT3-dependent pancreatic cancer cells. WB436B significantly suppresses tumor growth and metastasis in vivo and prolongs survival of tumor-bearing mice. Mechanistic studies showed that WB436B have unique binding sites located in STAT3 Src homology 2 domain. Conclusions: Our work presents the first-in-class selective STAT3 inhibitor WB436B as a potential therapeutic candidate for the treatment of pancreatic cancer.

In this research, oat resistant starch (ORS) was prepared by autoclaving-retrogradation cycle (ORS-A), enzymatic hydrolysis (ORS-B), and ultrasound combined enzymatic hydrolysis (ORS-C). Differences in their structural features, physicochemical properties and digestive properties were studied. Results of particle size distribution, XRD, DSC, FTIR, SEM and in vitro digestion showed that ORS-C was a B + C-crystal, and ORS-C had a larger particle size, the smallest span value, the highest relative crystallinity, the most ordered and stable double helix structure, the roughest surface shape and strongest digestion resistance compared to ORS-A and ORS-B. Correlation analysis revealed that the digestion resistance of ORS-C was strongly positively correlated with RS content, amylose content, relative crystallinity and absorption peak intensity ratio of 1047/1022 cm⁻¹ (R_1047/1022), and weakly positively correlated with average particle size. These results provided theoretical support for the application of ORS-C with strong digestion resistance prepared by ultrasound combined enzymatic hydrolysis in the low GI food application.