Novel and safe debranched starch-zinc complexes with endoconcave structure as zinc supplements.

Zinc deficiency is a serious risk to human health and growth, especially in children. The development of zinc supplements can effectively reduce this harm. Here, a series of debranched starch­zinc complexes (DS-Zn) were prepared, whose zinc complexation was inversely proportional to the amylopectin content in the debranched starch (DS). The physicochemical properties of DS-Zn were characterized using the conductivity, XRD, iodine staining and thermogravimetry. Combined with XPS, solid-state 13C NMR and IR, it was elucidated that the structure of DS-Zn is endoconcave structure with 2-O and 3-O of DS on the inner side and 6-O of DS on the outer side, where zinc is located. The DS-Zn exhibits good biosafety including blood, cellular and mutagenicity. In vitro simulations of digestion and zinc-deficient cellular models showed that DS-Zn was more tolerant to the gastrointestinal environment and more effective in zinc supplementation (increased by 33 %) than inorganic zinc supplements. Utilizing the compressibility of starch, DS-Zn was prepared as a more palatable oral cartoon tablet for children. This study will provide important support to advance the development and application of novel starch-based zinc nutritional supplements.

Ecliptasaponin A attenuates renal fibrosis by regulating the extracellular matrix of renal tubular cells.

Renal fibrosis is the most common manifestation of end-stage renal disease (ESRD), including diabetic kidney disease (DKD), but there is no effective treatment in renal fibrosis. Natural products are a rich source of clinical drug research and have been used in the clinical research of various diseases. In this study, we searched for traditional Chinese medicine monomers that attenuate fibrosis and assessed their effect on the fibrosis marker connective tissue growth factor (CTGF) in cells which we found ecliptasaponin A. Subsequently, we evaluated the effect of ecliptasaponin A on renal fibrosis in the classic renal fibrosis unilateral ureteral obstruction (UUO) mouse model and found that ecliptasaponin A could reduce the renal collagen fiber deposition and renal extracellular matrix (ECM) protein expression in UUO mice. In vitro, ecliptasaponin A can inhibit ECM protein expression in human kidney-2 (HK-2) cells induced by transforming growth factor-beta1 (TGFß1). To further clarify the mechanism of ecliptasaponin A in attenuating renal fibrosis, we performed transcriptome sequencing of HK-2 cells treated with TGFß1 and ecliptasaponin A. The functions and pathways were mainly enriched in the extracellular matrix and TGFß signalling pathway. Matrix metalloproteinase 10 (MMP10) and matrix metalloproteinase 13 (MMP13) are the main differentially expressed genes in extracellular matrix regulation. Then, we measured MMP10 and MMP13 in the cells and found that ecliptasaponin A had a significant inhibitory effect on MMP13 expression but not on MMP10 expression. Furthermore, we overexpressed MMP13 in HK-2 cells treated with TGFß1 and found that MMP13 promoted HK-2 cell injury. Our findings suggest that ecliptasaponin A can attenuate renal fibrosis, which may provide a new method for treating renal fibrosis clinically.

Ophiopogonin B induces reactive oxygen species­dependent apoptosis through the Hippo pathway in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China and is characterized by a high death rate. Ophiopogonin B (OP­B) is a bioactive component of Radix Ophiopogon japonicus, which is frequently used in traditional Chinese medicine to treat cancer. The present study aimed to examine the anti­cancer properties of OP­B on NPC cells. Cell viability and cell proliferation were measured using MTT and EdU assays. Flow cytometry was used to measure cell apoptosis, reactive oxygen species and mitochondrial membrane potential. Western blotting was used to investigate the expression of apoptosis and Hippo signaling pathway proteins. OP­B inhibited the proliferation of NPC cells by inducing apoptosis and disturbing the mitochondrial integrity. OP­B enhanced ROS accumulation. In addition, OP­B promoted the expression of mammalian STE20­like kinase 1, large tumor suppressor 1 and phosphorylated yes­associated protein (YAP) and suppressed the expression of YAP and transcriptional enhanced associate domain in NPC cells. OP­B increased the expression of forkhead box transcription factor O1 in the nuclear fraction. In conclusion, OP­B has therapeutic potential and feasibility in the development of novel YAP inhibitors for NPC.