ABSTRACT
OBJECTIVE To study the nephrotoxicity induced by bakuchiol alone and bakuchiol combined with psoralen and to explore its mechanism. METHODS The cytotoxicities of bakuchiol and bakuchiol combined with psoralen were investigated using human renal tubular epithelial cell lines (HK-2), in presence or absence of hepatic S9 mixture. The HK-2 cells were exposed to culture medium alone (blank control), 0.5% DMSO (vehicle control), aristolochic acid Ⅰ (AAⅠ;positive control), psoralen 5 μmol·L~(-1) group, bakuchiol 5,10,20,30 and 40 μmol·L~(-1) groups, and bakuchiol+psoralen (20+5), (30+5) and (40+5)μmol·L~(-1) groups, respectively. The cell viabilities were examined by MTT assay; cell membrane injuries were examined by detecting lactate dehydrogenase (LDH) release rate; and the morphological changes in HK-2 cells were observed with contrast microscope. The rate of cell apoptosis was detected by AnnexinⅤ/PI staining, and cell cycle was detected by PI staining with flow cytometry. RESULTS No cytotoxicity was found in psoralen 5 μmol·L~(-1) group. The HK-2 cell viabilities were significantly reduced after 4, 24, 48 and 72 h of exposure to either bakuchiol 20, 30 and 40 μmol·L~(-1)groups or bakuchiol+psoralen (20+5), (30+5) and (40+5)μmol·L~(-1) groups in a time- and concentration-dependent manner. The IC_(50) values of bakuchiol were (26.4±4.8), (21.8±0.6) and (24.1±0.8)μmol·L~(-1) for 24, 48 and 72 h exposure, respectively. The cytotoxicity of bakuchiol was significantly decreased in presence of hepatic S9 mixture. The LDH release rate of HK-2 cell increased significantly after 24 h of exposure to bakuchiol 20,30 and 40 μmol·L~(-1) or bakuchiol+psoralen groups. With the concentration and time increasing, the HK-2 cells became more and more contracted and rounded. In bakuchiol 40 μmol·L~(-1) or bakuchiol+psoralen (20+5), (30+5) and (40+5)μmol·L~(-1) groups, HK-2 cells showed apoptotic characters. In bakuchiol or bakuchiol+psoralen groups, apoptotic cells significantly increased and cells in G2 phase markedly decreased. CONCLUSION Bakuchiol has a significant cytotoxicity in HK-2 cells, and combined with psoralen can not decrease its toxicity. The cytotoxicity of bakuchiol is significantly reduced in the presence of hepatic S9 mixture. The possible mechanisms of the renal cytorotoxicity of bakuchiol are as follows: ① direct damage to the cell membrane; ② inducing cell apoptosis; ③ inhibiting intracellular DNA synthesis and block cell mitosis and proliferation.
ABSTRACT
Cinnabar has been an important traditional Chinese medicine as a sedative and soporific agent for more than 2000 years. It is a naturally occurring mercuric sulfide and containing more than 96% mercuric sulfide (HgS). There are about 10% -30% Chinese patent medicines containing cinnabar according to the Pharmacopoeia of China (2005). It's hard to deny that cinnabar has therapeutic effect in clinic practice. However, cinnabar's extraordinary high containing mercury makes people hesitate to use. Furthermore, the abuse of cinnabar, which caused intoxication cases, has been reported occasionally. The safety and toxicity of cinnabar has been debated for centuries. The exact mechanism of cinnabar is still largely unknown. The present review focused on researches about cinnabar's mechanisms of pharmacological and toxicological effects since 2000.
Subject(s)
Animals , Humans , Drug Therapy , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal , Pharmacology , Toxicity , Mercury Compounds , Pharmacology , ToxicityABSTRACT
<p><b>OBJECTIVE</b>To develop a new quality control method for cinnabar, in order to ensure the safety application of cinnabar.</p><p><b>METHOD</b>Three inorganic mercury compounds (HgS, HgO, and HgCl2) and cinnabar samples were analyzed by laser Raman spectroscopy. The cinnabar samples were identified by comparing the Raman band in the Raman spectrum with pure HgS.</p><p><b>RESULT</b>Different Raman bands were observed among three inorganic mercury compounds. The Raman spectroscopic results indicated that cinnabar samples showed the same Raman band as pure HgS, consisting with the HgS contents by XRF analysis.</p><p><b>CONCLUSION</b>The Raman spectroscopic method is simple, rapid, and reliable. It can be applied as an alternative quality control method for cinnabar.</p>