Identification of narciclasine from Lycoris radiata (L'Her.) Herb. and its inhibitory effect on LPS-induced inflammatory responses in macrophages.

Lycoris radiata (L'Her.) Herb. (L. radiata) was traditionally used as a folk medicine in China for treatment of Alzheimer's disease. However, the specific component responsible for its considerable toxicity remained unclear thus restricting its clinical trials. Narciclasine (NCS) was isolated from L. radiata and treatment of NCS for 72 h exhibited significant antiproliferative effects against L02, Hep G2, HT-29 and RAW264.7 cells. However, what needs to be emphasized is that at safe working concentrations of 0.001-0.016 µM, administration of NCS for 24 h inhibited the mRNA expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-ɑ), interleukin-1beta (IL-1ß) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced macrophages thereby suppressing production of nitric oxide (NO), IL-6, TNF-ɑ and IL-1ß. NCS supplementation also inhibited nuclear factor-kappa B (NF-κB) activation by suppressing NF-κB P65 phosphorylation and nuclear translocation, IκBɑ degradation and phosphorylation, and IκKɑ/ß phosphorylation. The phosphorylation of c-Jun N-terminal kinase (JNK) and P38, and expression of COX-2 was also attenuated by NCS. These results suggested that NCS might exert anti-inflammatory effects through inhibiting NF-κB and mitogen-activated protein kinase (MAPK) pathways even at very low doses.

Renal toxic ingredients and their toxicology from traditional Chinese medicine.

INTRODUCTION: There have been increasing concerns regarding adverse reactions and toxicity incidents caused by traditional Chinese medicines (TCMs), among which the nephrotoxicity is particularly worrying. AREAS COVERED: This review summarizes the ingredients with renal toxicity from some TCMs through searching the relevant literature published over the past two decades. Renal toxicity components from TCMs include aristolochic acids (AAS), alkaloids, anthraquinones and others. TCM renal toxicity is most commonly caused by AAS and some alkaloids. AAS mainly come from Aristolochia contorta Bunge, Aristolochia manshuriensis Kom, Clematis Chinensis Osbeck, Aristolochia cathcartii Hook. Some renal toxic alkaloids are derived from Tripterygium regelii Sprague et Takeda, Stephania tetrandra S. Moore, Strychnos nux-vomica Linn. and Aconitum carmichaeli Debx. A few kinds of anthraquinones, flavonoids, and glycosides from TCMs also cause renal toxicity. All of these renal toxicity components and their associated renal toxicity, structures and toxic mechanism are introduced in detail in this review. EXPERT OPINION: Given the complexity of the toxic components, a lot of work needs to be done to analyze the specific modes of action of toxic components in vivo and in vitro, in particular, to elucidate the molecular mechanism of toxicity, in order to reduce the occurrence of renal toxicity of TCM.