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Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.

Here, we describe the identification of PARP1/2 as direct binding proteins of andrographolide (Andro) using protein microarray, surface plasmon resonance (SPR), and enzyme activity assays. We then evaluated the proliferation inhibition, apoptosis, and cell migration effects of Andro on the MDA-MB-436 cell line in vitro. The final biological evaluation confirmed that Andro was a highly effective single agent in the MDA-MB-436 xenograft model and had a low hERG-mediated cardiac toxicity. Therefore, Andro represents the first natural product, non-amide member of a novel nanomolar-potency PARP1/2 inhibitor family.

A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 μmol/L, 5.5 μmol/L and 6.6 μmol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells.

Aconitum species is an essential but toxic herb in Traditional Chinese Medicine (TCM). As a main and characteristic constituent in Aconitum species, hypaconitine (HA) was selected to illustrate the P-glycoprotein-mediated drug-HA interactions using Caco-2 cell monolayers. The HA absorption results revealed that HA was not only an inhibiter but also a substance of P-glycoprotein (P-gp). In TCM theory, it is acknowledged that Aconitum species are incompatible with Bulbus Fritillariae for the increase of the poisoning risk. Peimine and peiminine, which are the active components of Bulbus Fritillariae, increased the bioavailability of HA suggested this effect should be one of the reason to increase the poisoning risk when Bulbus Fritillariae combined with Aconitum species. However, no significant difference in absorption of peimine (PE) or peiminine (PEN) was observed when they combined with HA, respectively. Glycyrrhiza is a famous detoxifying herb in TCM, and the combined use of Glycyrrhiza and Aconitum spe...

The organic anion of the title compound, {[Na(C15H9O10S)(H2O)2]·H2O}n {systematic name: poly[[diaqua[μ-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4-oxo-4H-chromene-8-sulfonato]sodium] monohydrate]}, has a nearly planar structure. The Na atom is six-coordinated by O atoms, two from water molecules and four from the anion. The dihedral angle between the ring systems in the anion is 10.1 (1)°. Intramolecular O—H...S and O—H...O interactions occur. In the crystal structure, an extensive network of classical intermolecular O—H...S and O—H...O hydrogen bonds forms layers along the c axis.