LC-MS Method for Determination and Pharmacokinetic Study of Chimaphilin in Rat Plasma after Oral Administration of the Traditional Chinese Medicinal Preparation Lu Xian Cao Decoction

Abstract

Lu xian cao (Hebra pyrolae) is a traditional Chinese medicine used for the treatment of several major diseases. Chimaphilin has been demonstrated one of the major active components in Lu xian cao by modern pharmacological studies. In this study, a liquid chromatography-mass spectrometry method for the determination of chimaphilin in rat plasma was developed and validated. The separation was carried out on a C 18 column using methanol and water as mobile phase after the plasma sample was extracted with diethyl ether. Atmospheric pressure chemical ionization in negative ion mode and selected ion monitoring method were developed to determine [M] ؊ at 186 and 210 for chimaphilin and benzil (internal standard), respectively. The lower limit of quantitation was 10 ng/ml and the calibration curve was linear (rϾ0.9964) over the concentration range 10-1000 ng/ml. The method was demonstrated reproducible and reliable with intra-day precision Ͻ11.5%, inter-day precision Ͻ7.6%, accuracy in the range of 88.4-113.0%, and mean extraction recovery excess of 83.0%, which were all calculated from the quality control samples at concentrations of 20, 100, and 500 ng/ml. The method was successfully applied to pharmacokinetic study of chimaphilin in rat plasma following oral administration of a 30-mg/kg dose of chimaphilin in Lu xian cao decoction to male Wistar rats.

Homogenate-assisted negative pressure cavitation extraction of active compounds from Pyrola incarnata Fisch. and the extraction kinetics study

“…Chimaphilin is a kind of naphthoquinones. It possesses anti-inflammatory and analgesic properties (Babula et al, 2006;Ribeiro et al, 2009;Zang et al, 2006). Efficient extraction of main active compounds from P. incarnata is a rational strategy to increase the economic value of this plant.…”

1,4-Naphthoquinones: Some Biological Properties and Application

“…45) Additionally, this compound showed the ability to improve the functioning of the muscular system and lipid and protein metabolism in first-and secondtype diabetic patients. 46) 2.4. Anti-inflammatory and Analgesic Properties Anti-inflammatory and analgesic properties of a number of naphthoquinones have been discovered.…”

“…In subsequent studies, the biologically active nucleus of natural quinones was modified by organic synthesis 63,64) and the newly obtained biologically active derivatives of these 1,4-naphthoquinones were patented. 65) The efficacy of a series of 2-hydroxy-3-phenylsulfanylmethyl- [ (46) (Fig. 11) showed higher susceptibility to bloodstream trypomastigotes and exhibited a greater efficacy against trypomastigotes from different T. cruzi of Brazil and CL strains through the induction of intracellular autophagy and elevation of ROS level, leading to parasite death.…”

“…Methyl-1,3-benzothiazol-2-yl)amino]naphthalene-1,4-dione and their Ni(II) complexes(46) 2-Hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones Are effective against T. cruzi, induction of intracellular autophagy and elevation of ROS level Cytotoxic and anticancer activity (52) (4-(((3-Chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)methyl)-N-(pyridin-3-yl)benzamide Inhibits cell proliferation; strongly inhibits Itch (astrophin-1 interacting protein-4)Naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone Inducts cell apoptosis via ROS-mediated regulation of MAPK, Akt and STAT3 signaling pathways 78) 79) (56-59) Sulfanyl-phenylamino-1,4-naphthoquinone derivatives Induct apoptosis and arrest of cell cycle at the G1 phase via up-regulation of caspase-3 and caspase-Naphthoquinines and quinoline-5,8-dione Induct oxidative stress and caspase 3/7 activity 80) (61) 1,4-Naphthoquinone-2,3-bis-sulfide Inducts apoptosis, caspase 3/7 activation, up-regulation of p53, Mdm-2 and Bcl-2, down-regulation of Bax gene expression 81) (62-63) N-2,3-Bis(6-substituted-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)naphthalene-1,4-diones Inhibit ETS-1 phosphorylation by ERK2 82) (64-65) 1,4-Naphthoquinones, bearing various cyclic and aliphatic amines at 2-position Bind G protein-coupled receptor 55 (GPR55) and exert its pronounced anti-prolifamount, uncoupled mitochondrial oxidation from phosphorylation impairing energy production and cause cell death by -1,4-naphthoquinone (juglone) Inhibit β-secretase activity, reduce β-amyloid formation and aggregation 85…”

Anti-arthritic activity of Fu-Fang-Lu-Jiao-Shuang on collagen-induced arthritis in Balb/c mice and its underlying mechanisms

“…[ 15 16 ] Moreover, the dried whole plant of Pyrola decorata H. Andres has been used as tonics, sedatives, hemostatics, anti-inflammatory, and analgesics against RA in China since the antiquity. [ 17 ] Cinnamomum cassia Presl is used as an analgesic and anti-pyretic against influenza and rheumatic pain. [ 18 ] Lonmicera japonica Thunb and Morus alba L were also investigated in various inflammatory models.…”