Adbiotech (South Korea)

Diosgenin is a key starting material for the synthesis of steroidal drugs, such as corticosteroids and sex hormones. While the primary commercial source of diosgenin is the tubers of Dioscorea spp., identifying alternative plant hosts capable of diosgenin biosynthesis could enhance its production. In this study, we present Solanum nigrum, a widely distributed species of the Solanum genus, as a novel platform for diosgenin production. S. nigrum naturally accumulates high concentrations of steroidal glycoalkaloids (SGAs) with a closed F-ring (spirostanol type) in green fruits and steroidal saponins (STSs) with an open F-ring (furostanol type) in leaves. Both classes originate from cholesterol and share the early oxidation steps, followed by specific reactions that redirect distinct metabolic fluxes. In SGAs, the CYP450 enzyme SnGAME4 oxidises C26-OH to an aldehyde, enabling subsequent transamination. In STSs, SnGAME25, a 3β-hydroxysteroid dehydrogenase/isomerase, initiates the reduction reactions at the C5 double bond. Disruption of these two genes shifted the metabolic profiles from the native SGAs and STSs toward furostanol-type proto-diosgenin glycosides. However, these open F-ring structures yield low diosgenin levels during acid hydrolysis. To overcome this limitation, we identified endogenous furostanol glycoside 26-O-β-glucosidases and employed spontaneous fermentation to convert the furostanol structure to the spirostanol structure. Altogether, S. nigrum green fruits yielded diosgenin up to 1% of dry weight. In addition, we engineered S. nigrum to increase fruit number in combination with the SnGAME4 mutation. These results establish S. nigrum as a promising and scalable host for diosgenin production.

Abstract This study was conducted to investigate Angelica gigas Nakai leaf extract (ALE) as an antidiabetic. The inhibitory activity of ALE on α-glucosidase inhibition and rat intestinal disaccharidase were measured. Also, its effect on glucose uptake in 3T3-L1 cells was analyzed. Supplementation of ALE up to 150µg/mL showed cell viability higher than 90% in 3T3-L1 cells. The 60% and 80% of ethanol ALE revealed the highest α-glucosidase inhibitory activity. Further, the 60% ethanol ALE extracts were freeze-dried (FD60) and spray-dried (SD60) to evaluate their antidiabetic effects. The α-glucosidase inhibitory assay revealed that the IC50 of SD60 and FD60 were 4.08 mg/mL and 2.93 mg/mL, respectively. A Lineweaver-Burk plot showed that ALE demonstrates mixed-type inhibition. FD60 and SD60 showed no significant difference in inhibiting maltase, sucrase, and glucoamylase of rat intestinal disaccharidase. FD60 and SD60 significantly (p < 0.05) increased insulin-stimulated glucose uptake in 3T3-L1 cells compared to D-pinitol. Moreover, ALE could increase the expression of pAkt Thr308 in Vero 76 cells via western blot analysis. These findings suggest that ALE has potential antidiabetic properties.

IL-32 exists as seven mRNA transcripts that can translate into distinct individual IL-32 variants with specific protein domains. These translated protein domains of IL-32 variants code for specific functions that allow for interaction with different molecules intracellularly or extracellularly. The longest variant is IL-32γ possessing 234 amino acid residues with all 11 protein domains, while the shortest variant is IL-32α possessing 131 amino acid residues with three of the protein domains. The first domain exists in 6 variants except IL-32δ variant, which has a distinct translation initiation codon due to mRNA splicing. The last eleventh domain is common domain for all seven IL-32 variants. Numerous studies in different fields, such as inflammation, autoimmunity, pathogen infection, and cancer biology, have claimed the specific biological activity of individual IL-32 variant despite the absence of sufficient data. There are 4 additional IL-32 variants without proper transcripts. In this review, the structural characteristics of seven IL-32 transcripts are described based on the specific protein domains.

It has been reported that fatty acid binding proteins (FABPs) do not act only as intracellular mediators of lipid responses but also have extracellular functions. This study aimed to investigate whether extracellular liver type (L)-FABP has a biological activity and to determined serum L-FABP levels in patients with end-stage renal disease (ESRD). We isolated L-FABP complementary deoxyribonucleic acid (cDNA) from the Huh7 human hepatocarcinoma cell line and expressed the recombinant L-FABP protein in Escherichia coli. A549 lung carcinoma and THP-1 monocytic cells were stimulated with the human recombinant L-FABP. Human whole blood cells were also treated with the human recombinant L-FABP or interleukin (IL)-1α. IL-6 levels were measured in cell culture supernatants using IL-6 enzyme-linked immunosorbent assay (ELISA). Human recombinant L-FABP induced IL-6 in a dose-dependent manner in A549, THP-1 cells, and whole blood cells. The blood samples of healthy volunteers and patients with ESRD were taken after an overnight fast. The serum levels of L-FABP in healthy volunteers and ESRD patients were quantified with L-FABP ELISA. The values of L-FABP in patients with ESRD were significantly lower than those in the control group. Our results demonstrated the biological activity of L-FABP in human cells suggesting L-FABP can be a mediator of inflammation.

The Wnt signaling pathway is mediated by a family of secreted glycoproteins through canonical and noncanonical mechanism. The signaling pathways are regulated by various modulators, which are classified into two classes on the basis of their interaction with either Wnt or its receptors. Secreted frizzled-related proteins (sFRPs) are the member of class that binds to Wnt protein and antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK) proteins family that binds to Wnt receptor complex. The present review discusses the disease related association of various polymorphisms in Wnt signaling modulators. Furthermore, this review also highlights that some of the sFRPs and DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their function needs to be explored more extensively.