Novel MeON-glycosides of ursolic acid: Synthesis, antitumor evaluation, and mechanism studies.

Ursolic acid (UA) is a pentacyclic triterpenoid widely found in in medicinal plants, edible plants, fruits, and flowers. The great interest in this bioactive compound is related to the positive effects in human health. However, its limited solubility, moderate biological activity and poor bioavailability limit the potential and further applications of UA. Here, we explored the efficacy of MeON-Glycosides of UA in inhibiting tumor cell proliferation. A number of compounds showed significant antitumor activity against tested five cancer cell lines. Among them, compound 2a exhibited the most potent activity against HepG2 cells with IC50 values of 3.1 ± 0.5 µM. Especially, compound 2a could induce HepG2 cells apoptosis and reduce mitochondrial membrane potential. Western blot analysis showed that compound 2a up-regulated Bax, cleaved caspase-3/9, cleaved PARP levels and down-regulated Bcl-2 level of HepG2 cells. These results indicated that compound 2a could obviously induce the apoptosis of HepG2 cells. At the same time, compound 2a significantly decreased the expression of p-AKT and p-mTOR, which indicated that compound 2a might exert its cytotoxic effect by targeting PI3K/AKT/mTOR signaling pathway. Moreover, the in silico ADME predictions showed that compound 2a has improved water solubility and other properties. Thus, compound 2a may be a promising antitumor candidate, which may be potentially used to prevent or treat cancers.

Performance of wetland applied to ecological remediation of abandoned fish ponds: A case study in Gonghu Bay, Tai lake.

To restore the abandoned fish ponds to "near natural" state, the wetland restoration was carried out in Gonghu Bay lakeside, and its long-term performance of controlling external load was studied for 5 years. The findings showed that water quality and biodiversity had been improved dramatically after the preliminary transformation. The concentrations of permanganate index (CODMn), total nitrogen (TN), and total phosphorus (TP) obviously decreased from 12.91 mg L-1 to 4.32 mg L-1, from 3.46 mg L-1 to 1.42 mg L-1, and from 0.27 mg L-1 to 0.04 mg L-1, respectively. The proportion of Cyanophyta was effectively reduced from 31.82% to 18.89%, and favored the growth of diatoms (31.82%-37.78%) to be the dominant algae species. Aquatic plant species and coverage gradually increased from 16 to 56 and from 5% to 60%, respectively. An in-deep monitoring done for 5 years (2013-2017) showed that the wetland achieved a satisfactory removal efficiency of 58.95% for TN, 64.60% for TP, and up to 77.83% for chlorophyll-a. Besides, three pollution scenarios, such as stormwater runoff, algal bloom, and continuous water transfer, were selected to explore the tolerance of the wetland to the suddenly increased pollution loads. The results dedicated that even if the inlet load was up to 1.0 × 105 m3 d-1, the removal rate coefficients of wetland for chlorophyll-a, TP, and TN were 0.135-0.239 d-1, 0.041-0.112 d-1, and 0.030-0.109 d-1, respectively, which were equivalent to the well-running wetlands. This study confirmed that the wetland was not only a promising ecological remediation technique to contaminated abandoned fish ponds, but also could withstand high pollution load, which had the prospect of sustainable utilization.

Derivatization of Soyasapogenol A through Microbial Transformation for Potential Anti-inflammatory Food Supplements.

For the optimum use of soyasaponins isolated from soybean cake and to explore the potential anti-inflammatory agents from pentacyclic triterpenes as natural food supplements, microbial transformation of soyasapogenol A was carried out. Four strains of microbes, including Bacillus megaterium CGMCC 1.1741, Penicillium griseofulvum CICC 40293, Bacillus subtilis ATCC 6633, and Streptomyces griseus ATCC 13273, showed robust catalytic capacity to the substrate. Preparative biotransformation and column chromatographic purification led to the isolation of 10 novel and 1 reported metabolites. The structure elucidation was performed using 1D/2D NMR and HR-ESI-MS analytical method. Several novel tailoring reactions, such as allyl oxidation, C-C double bond rearrangement, hydroxylation, dehydrogenation, and glycosylation, were observed in the biotransformation. In the follow-up bioassay, most of the metabolites exhibited low cytotoxicity and potent inhibitory activity against the production of nitric oxide (NO) in RAW 264.7 cells stimulated by lipopolysaccharide. Especially compound 6 (3-oxo-11α,21ß,22ß,24-tetrahydroxy-olean-12-ene) showed comparable activity to the positive control of quercetin with an IC50 value of 16.70 µM. These findings provided an experimental approach to achieve the derivatization of natural aglycons in soybeans through microbial transformation for developing potent anti-inflammatory food supplements.

Biotransformation of Erythrodiol for New Food Supplements with Anti-Inflammatory Properties.

Erythrodiol, a typical pentacyclic triterpenic diol in olive oil and its byproduct, olive pomace, frequently appears in food additives for the prevention of cardiovascular diseases because of its antioxidation, anti-inflammatory, and antitumor activities. To develop new derivatives of erythrodiol (1), preparative biotransformations were investigated through Streptomyces griseus ATCC 13273, Penicilium griseofulvum CICC 40293, and Bacillus subtilis ATCC 6633, and ten new (1a-1j) and one known metabolites were isolated. Their structures were elucidated by high resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Furthermore, relative to 1, most metabolites exhibited lower toxicity and more potent inhibitory activities against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In particular, the glycosylated metabolite 1k showed a dramatically increased inhibitory effect with an IC50 value of 2.40 µM, which is even lower than that of quercetin. Thus, biotransformation of erythrodiol is a viable strategy for discovering new triterpenes as food supplements with anti-inflammatory properties.