Water Soluble Active Components of Salvia miltiorrhiza and Related Plants

Chemical studies on nine Salvia species yielded various polyphenolic acids. Eleven of them were depsides of R (+) β (3,4 dihydroxyphenyl) lactic acid and a caffeic acid derivative or caffeic acid dimer. Except the two known depsides, rosmarinic acid and lithospermic acid, this type of depsides has not been isolated from other plant materials before, so they were named salvianolic acid A, B, C, D, E, H, I, J and isosalvianolic acid C. Salvianolic acid F, G and przewalskinic acid A were new polyphenolic acids. Pharmacological studies of these polyphenolic acids showed potent antioxidant activities. The effects of these components in protecting against brain and heart damage have been studied.

SALVIANOLIC ACID H,A NEW DEPSIDE FROM SALVIA CAVALERIEI VAR.SIMPLICIFOLIA

A new depside named salvianolic acid H was isolated from the aqueous extract of Salvia cavaleriei vat.simplicifolia,along with salvianolic acid A,B,C,isosalvianolic acid C,lithospermic acid, rosmarinic acid,R-(+)-β-(3,4-dihydroxyphenyl)lacticacid and protocatechualdehyde.Rosmarinic acid was obtained as the major component.

Lethaclado acid A and B from Lethariella cladonioides

Two new compounds, lethaclado acid A （1） and B （2）, were isolated from the acetone extract ofLethariella cladonioides. Their structures were elucidated on the basis of 1D and 2D NMR as well as ESI-MS spectral data.

Characterization of the depsidone gene cluster reveals etherification,decarboxylation and multiple halogenations as tailoring steps in depsidone assembly

Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity.Previous structure-activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity.However,the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin(3)remain enigmatic.In this study,we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption,heterologous expression and in vitro biochemical experiments.We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and nonreducing polyketide synthase,which is distinct from the common depside skeleton biosynthesis.This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation,respectively.In addition,the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates.Finally,and interestingly,we discovered a halogenase encoded remotely from the biosynthetic gene cluster,which catalyzes triple-halogenation to produce the active end product nornidulin(3).These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.

Postmarketing safety evaluation: depside salt injection made from Danshen(Radix Salviae Miltiorrhizae)

OBJECTIVE: To systematically examine the postmarketing safety of depside salt injection made from Danshen(Radix Salviae Miltiorrhizae),identifythe potential risk factors, and ensure its clinical safety.METHODS: We examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen(Radix Salviae Miltiorrhizae). Data from Ⅰ-Ⅳ clinical drug trials, hospital information systems(HIS), and spontaneous reporting systems(SRS) were also analyzed.RESULTS: The effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached morethan 80%. The median lethal dose(LD50) calculated by the Bliss method was 1.49 g/kg, with 95%confidence intervals of 1.29-1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions(ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen(Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.CONCLUSION: This study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen(Radix Salviae Miltiorrhizae),and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.