Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP) on HFD/STZ-Induced Nephropathy in Mice.

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-ß 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-ß 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-ß1 signaling pathway in diabetic nephropathy mice.

The augmented anti-tumor effects of Antrodia camphorata co-fermented with Chinese medicinal herb in human hepatoma cells.

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).