Fucoidan extracted from brown algae has multiple beneficial functions. In this study, we investigated the effects of low-molecular-weight fucoidan (oligo-FO) on renal fibrosis under in vitro and in vivo diabetic conditions, and its molecular mechanisms. Advanced glycation product (AGE)-stimulated rat renal proximal tubular epithelial cells (NRK-52E) and diabetic mice induced by high-fat diet and intraperitoneal injection of streptozotocin and nicotinamide were used. Oligo-FO treatment significantly inhibited anti-high mobility group box 1 (HMGB1)/RAGE/ anti-nuclear factor-kappa B (NF-κB)/transforming growth factor-β1 (TGF-β1)/TGF-β1R/Smad 2/3/fibronectin signaling pathway and HIF-1α activation in AGE-stimulated NRK-52E cells. Conversely, the expression and activity of Sirt-1; the levels of ubiquitin-specific peptidase 22 (USP22), p-AMPK, glucagon-like peptide-1 receptor (GLP-1R), and heme oxygenase-1 (HO-1); and Nrf2 activation were remarkably increased by oligo-FO in AGE-stimulated cells. However, the above effects of oligo-FO were greatly diminished by inhibiting Sirt-1, HO-1, or GLP-1R activity. Similar changes of these pro-fibrotic genes in the kidney and a marked attenuation of renal injury and dysfunction were observed in oligo-FO-treated diabetic mice. These findings indicated that the inhibitory effects of the oligo-FO on diabetes-evoked renal fibrosis are mediated by suppressing TGF-β1-activated pro-fibrogenic processes via Sirt-1, HO-1, and GLP-1R dependence. Collectively, fucoidan-containing foods or supplements may be potential agents for ameliorating renal diseases due to excessive fibrosis.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM). Inonotus obliquus (IO) is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs) have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ)-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP), from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD) plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10-100 kDa, LIOP (300 mg/kg) had progressively increased their sensitivity to glucose (less insulin tolerance), reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR) compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 µg/mL) incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1), while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF-κB/TGF-β1 signaling pathway in diabetic nephropathy mice.

The use of an electrospun polycaprolactone (PCL) nonwoven mat that is coated with a layer of chitosan (CS) containing active ingredient [tea tree oil (TTO)] represents an effective strategy for producing functional dressings. CS-coated porous PCL nonwoven mat (CS3/PCLNM) with various concentrations of active ingredients were produced and investigated. In vitro, active ingredient-containing CS3/PCLNM is effective in inhibiting the formation of nitrite and the growth of Staphylococcus aureus. Both active ingredient TTO and CS have been proven to reach their maximum amount of releases within 24 h of contact with water-based environment. In vivo, full-thickness skin removal (1.2 cm × 1.2 cm) was performed on the back of the C57BL6/J mice in noninfected and infected animal models. Four groups of functional dressings were tested in this work including Tegderm™, PCLNM, CS3/PCLNM, and 100 μL TTO-CS3/PCLNM. After 7 days post-treatment, the bacterial levels were found to be significantly lower in both CS3/PCLNM and 100 μL TTO-CS3/PCLNM-treated groups than in the control group (81.6 ± 18.1% and 93.7 ± 9.57% of reductions in the bacterial load in the pus relative to the control group, respectively). Additionally, based on the histological analyses, the 100 μL TTO-CS3/PCLNM-treated group outperformed all other groups in wound healing.

Silk fibroin protein, gastrodia elata, and tea tree oil are naturally derived and have been used throughout human history. This work develops an all-natural and highly porous foam-containing silk fibroin protein and above herbal extract, as a dressing for wound management. Scanning electron microscopic analyses and measurements of porosity by Archimedes method revealed a highly porous structure with porosity ranging from 40%–80%, depending on the preparation condition. In vitro, cytotoxicity test of a series of gastrodia elata–containing silk fibroin protein and tea tree oil–containing silk fibroin protein foam dressings on 3T3 fibroblast cells showed 90%–100% cell viability, which indicated that the produced all-natural dressings have no significant cytotoxicity toward skin cells. In another anti-inflammatory assay using the lipopolysaccharide-induced inflammatory Raw 264.7 macrophages model, the produced two dressings exhibited up to 70% and 90.1% of reduction in the formation of nitrite, in comparison with the untreated group. In vivo studies showed that all herbal extract–containing foam dressings accelerated wound recovery and achieved full closure of the wound within 21 days, and the histological analysis of regenerative skin tissues indicated that the produced foam dressings enhance the generation of thicker, denser, and more abundant collagen fibers in the dermis layer in comparison with the positive and negative control groups.

Antrodia camphorata, unique fungal specie, has been used as a folk medicine in Taiwan for many years. The purpose of this study was to compare the extracts from the solid-state culture of A. camphorata co-fermented with Chinese medicinal herb (AC-CF) with two other extracts from fruiting bodies (AC-FB) or solid-state culture (AC-SS), for their anti-tumor effects in human hepatoma HepG2 cells. We measured in vitro cell proliferation, percentage of apoptosis, population distribution of cell cycles, Western blot analysis of multiple drugs resistance-1 (MDR-1), and apoptosis-related proteins in HepG2 cells treated with three different preparations of A. camphorate extracts. Our results showed that AC-CF had better anti-proliferation effect on human hepatoma HepG2 cells than AC-FB or AC-SS dose-dependently. In addition, AC-CF in combination with anti-tumor agents (mitomycin C or methotrexate) showed better adjuvant anti-tumor effects than AC-FB or AC-SS. We further demonstrated the augmented adjuvant anti-tumor effects of AC-CF not only through down regulation of MDR-1 expression but also through a COX-2 dependent apoptosis pathway, involving down-regulation of COX-2 and p-AKT and up-regulation of PARP-1. In conclusion, in this study, we have demonstrated a novel strategy of fermenting A. camphorata with Chinese medicinal herb (AC-CF), which augmented their anti-tumor effects in human hepatoma HepG2 cells as compared to the traditional ones (AC-FB or AC-SS).