ABSTRACT
Alkannin/shikonin (A/S) and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants. They are integral constituents of traditional Chinese medicine Zicao (roots of Lithospermum erythrorhizon). In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders. This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs. Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.
ABSTRACT
Objective: To investigate and characterize the O-glucuronidation pathways of the S-stereoisomer of shikonin (alkannin). Methods: Liquid chromatography and mass spectrometry were employed for the detection of akannin and its glucuronide. The incubation of alkannin in human liver microsomes (HLM), human kidney microsomes (HKM) and recombinant human UDP-glucuronyltransferases (UGT) were employed for the study of metabolism profile, the involved UGT isoforms and kinetic analysis. Recombinant human UGT screening, correlation study and chemical inhibition experiments were used for elucidation the selectivity of UGT isoform towards alkannin. Results: In the incubation of alkannin in HLM with the presence of UDPGA, a single UGT metabolite was detected. The screening of the recombinant human UGTs found that UGT1A9 high selectively catalyzed the glucuronidation of alkannin. Kinetic analysis revealed the kinetic of alkannin in HLM, HKM and recombinant UGT1A9 all followed substrate inhibition model and the Km values were 3.75-4.50 μmol/L. The glucuronidation of alkannin and propofol, a probe substrate of UGT1A9, in 12 individual HLM showed really good correlation, the correlation coefficient R2 was 0.88. Chemical inhibition experiments indicated that HLM magnolol and niflumic acid showed obvious inhibition to alkannin glucuronidation; Testerone, celastrol, and nilotinib did not inhibit alkannin glucuronidation. Conclusion: This study finds that UGT metabolism is an important metabolism pathway of alkannin in human, and alkannin is a highly selective probe substrate of human UGT1A9.
ABSTRACT
Objective Optimizing the preparation technology of Red buttock ointment,by exploring the best extraction conditions of the alkannin,radix arnebiae seu lithospermi polysaccharides and so on.Methods Selecting radix arnebiae seu lithospermi 1kg and using orthogonal experiment to explore the best extraction conditions.Naphtho-quinone pigment chemicals were extracted by reflux extraction method;ethanol and paraffin wax were chosen as the composite solvent.Radix arnebiae seu lithospermi polysaccharide was extracted by water decocting,which to observe the rationality of process.Results The best extraction condition is A3 B2 C1 D1 , including section A:ethanol was 20 times the quality of medicinal materials (select radix arnebiae seu lithospermi 1kg and ethanol 20kg),section B:the amount of paraffin was 5% of ethanol(select radix arnebiae seu lithospermi 1kg and paraffin 1 kg),section C:Boiling water was 20 times the quality of medicinal materials,section D:the boiling time was 2h.Conclusion The more practical production process conditions:Ethanol was 10 times the quality of medicinal materials,and the amount of paraffin was 5%of ethanol.Boiling water was 10 times the quality of medicinal materials,and the boiling time was 1 h.This method is economic, simple, reasonable, stable, reproducible and easy to operation.Red buttock ointment obtained by this method possesses of excellent quality,good performance and superior effect.