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Terpenoids of Salvia hydrangea: two new, rearranged 20-norabietanes and the effect of oleanolic acid on erythrocyte membranes.

Four abietane-type terpenoids, including two known royleanones and two new, rearranged 20-norabietanes, were isolated from the roots of the Iranian medicinal plant Salvia hydrangea DC. ex Bentham (Lamiaceae), which is used as an anthelmintic and antileishmanial remedy. Their structures were established using COSY, NOESY, HSQC, and HMBC spectral data. The possible identity of one of the 20-norabietanes with demethylmulticauline, previously reported from a different Salvia species, is discussed. A moderate in vitro antiplasmodial effect of the extract of S. hydrangea flowers was found to be associated with the presence of large amounts of pentacyclic triterpenes, mainly oleanolic acid. The observed antiplasmodial activity of oleanolic acid is apparently due to its incorporation into the erythrocyte membrane, which adversely affects the growth of Plasmodium falciparum parasites. Thus, oleanolic acid caused transformation of erythrocytes into stomatocytes in the concentration range where the in vitro antiplasmodial activity was observed.

Abietanes↗

Tri-nordammarane triterpenoids and neoclerodane diterpenoids from Salvia aspera (Labiatae).

From the aerial parts of Salvia aspera one new tri-nordammarane named amblyol (1) was isolated besides amblyone (2). An X-ray analysis was performed on compound 1. In addition, three known neoclerodane diterpenoids were also isolated. The structures of these compounds were established by spectral and chemical methods. The presence of dammarane triterpenoids in a Mexican Salvia is described for the first time.

Chromatography, Thin Layer↗

Simultaneous determination and pharmacokinetic studies on (3,4-Dihydroxyphenyl)-lactic acid and protocatechuic aldehyde in rat serum after oral administration of Radix Salviae miltiorrhizae extract.

A simple and sensitive high-performance liquid chromatography method is developed for the simultaneous determination of (3,4-dihydroxyphenyl)-lactic acid (Dhpl) and protocatechuic aldehyde (Pal) in rat serum after oral administration of Radix Salviae miltiorrhizae extract. Serum samples are acidified with hydrochloric acid and extracted with ethyl acetate. Analysis of the extract is performed on a reversed-phase column and a mobile phase of 0.02% phosphoric acid-acetonitrile (91:9, v/v) with UV detection at 280 nm. Standard curves are linear in the range of 1.47-456.96 microg/mL for Dhpl and 0.124-7.936 microg/mL for Pal. For both regression coefficients, r(2) is greater than 0.993. Mean recovery is determined to be 75.23% and 84.06%, respectively, by analyzing serum standard containing 7.14, 57.12, and 228.48 microg/mL of Dhpl and 0.124, 0.992, and 3.968 microg/mL of Pal. The intraday precision (relative standard deviation) ranges from 3.91% to 12.03% at concentrations of 1.43, 57.12, and 228.48 microg/mL for Dhpl and 3.79% to 8.12% at concentrations of 0.124, 0.992, and 3.968 microg/mL for Pal. The interday precision (relative standard deviation) ranges from 5.06% to 9.93% for Dhpl and 3.05% to 10.00% for Pal, respectively, at the same three concentrations. This validated assay is applied to the determination of Dhpl and Pal concentrations and used to take a limited view of the pharmacokinetic profile in rat serum after oral administration of Radix Salviae miltiorrhizae extract.

Administration, Oral↗

Evaluation of pressurized liquid extraction and pressurized hot water extraction for tanshinone I and IIA in Salvia miltiorrhiza using LC and LC-ESI-MS.

Pressurized liquid extraction (PLE) and pressurized hot water extraction (PHWE) using a laboratory-made system are applied for the extraction of thermally labile components such as tanshinone I and IIA in Salvia miltiorrhiza. PLE and PHWE are carried out dynamically at a flow of 1 mL/min, temperature between 95-140 degrees C, applied pressure of 10-20 bars, and extraction times of 20 and 40 min, respectively. Effects of ethanol added into the water used in PHWE are explored. PLE is found to give comparable or higher extraction efficiencies compared with PHWE with reference to Soxhlet extraction for tanshinone I and IIA in Salvia miltiorrhiza. The tanshinone I and IIA present in the various medicinal plant extracts are determined by liquid chromatography and liquid chromatography-mass spectrometry.

Abietanes↗

Aqueous extract of Salvia miltiorrhoza regulates adhesion molecule expression of tumor necrosis factor alpha-induced endothelial cells by blocking activation of nuclear factor kappaB.

Salvia miltiorrhoza Bunge is a traditional herb medicine often used in China for the treatment of cardiovascular disorders, such as atherosclerosis. The purpose of this study was to examine the effect of aqueous extract of Salvia miltiorrhoza Bunge (ESM) on expression of adhesion molecules in tumor necrosis factor (TNF)alpha-induced endothelial cells. When preincubated with ESM (100, 200, 400 microg/mL) for 18 hours, the adhesion of HL-60 cells to TNFalpha-induced endothelial cells was significantly decreased in a concentration-dependent manner, and down-regulation of adhesion molecules, intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), was also observed. The inhibitory effect of ESM on TNFalpha-induced VCAM-1 expression was attenuated by inhibition of intracellular glutathione (GSH) synthesis. In addition, ESM also significantly inhibited TNFalpha-induced translocation of nuclear factor kappaB (NF-kappaB) from cytoplasm to nuclei in endothelial cells. These results demonstrated that inhibition of ESM on the expression of adhesion molecules may result from its blocking activation on NF-kappaB. It may imply one of the mechanisms by which ESM exerts its beneficial effect preventing the progress of atherosclerosis.

Cell Adhesion Molecules↗

Biosynthesis and regulatory mechanism of tanshinones and phenolic acids in Salvia miltiorrhiza.

Salvia miltiorrhiza, a perennial plant of the genus Salvia in the family Lamiaceae, is one of the most important traditional Chinese medicinal herbs, renowned for its significant economic and medicinal value. Its application in China dates back to 200 BC, where it has been utilized clinically either as a monotherapy or in combination with other herbal medicines for treating cardiovascular and cerebrovascular diseases, as well as various other ailments. The bioactive constituents of S. miltiorrhiza primarily include lipophilic tanshinones and hydrophilic phenolic acids. Over the past decades, the biosynthetic pathways of tanshinones and phenolic acids have been elucidated. Coupled with the sequencing of its genome, substantial progress has been made in deciphering the biosynthesis and regulatory mechanisms of bioactive compounds in S. miltiorrhiza, including tanshinones, phenolic acids, flavonoids, and prenylated quinones. This review summarizes recent advances in the regulatory mechanisms underlying the biosynthesis of phenolic acids and tanshinones in S. miltiorrhiza, focusing on transcriptional regulation, post-translational modifications, and epigenetic regulation. These insights provide a foundation for enhancing the production of bioactive compounds through biotechnological approaches and advancing pharmacological applications.

Salvia miltiorrhiza↗

Quinone derivatives by chemical transformations of 16-hydroxycarnosol from Salvia species.

The known diterpenes 12,16-epoxycarnosol (2), isotanshinone II (6), and (+)-neocryptotanshinone (8) were obtained by partial synthesis from 16-hydroxycarnosol (1), a C-16 hydroxylated abietatriene diterpene isolated in relative abundance from the aerial part of Salvia mellifera GREENE. The physical and spectroscopic data of these semisynthetic diterpenes were identical to those given for the natural ones in the literature. These abietane diterpenes have very interesting biological activities and the semisynthetic approach described here represents an alternative to obtain them from other major diterpenes isolated from Salvia species. Additionally, seven new semisynthetic diterpene analogues, 11,14-dioxo-12,16-epoxy-8,12-abietadien-20,7beta-olide (3), 11,14-dioxo-12,16-epoxy-8,12,15(16)-abietatrien-20,7beta-olide (4), 15,16-didehydro-12,16-epoxycarnosol (5), 1-oxoisotanshinone II (7), 16-hydroxycolumbaridione (9), 12,16-diacetoxycolumbaridione (10), and 14-methoxy-12,16-epoxycarnosol (13), were obtained from 1. The structures of the new compounds were established based on their spectroscopic data.

Abietanes↗

Multi-component HPLC fingerprinting of Radix Salviae Miltiorrhizae and its LC-MS-MS identification.

The multi-component fingerprinting method of Radix Salviae Miltiorrhizae (Root of Salvia miltiorrhiza BGE.), an important and popular medicinal herb in traditional Chinese medicine, was studied using reverse-phase HPLC and LC-MS-MS. Extract containing both the water-soluble phenolic compounds and nonpolar diterpenoid compounds known to be the herb's main bioactive components was prepared by a two-step extractive procedure. An HPLC fingerprinting method which can simultaneously separate these two types of compounds was established with gradient elution mode and photodiode array detection at 280 nm. Eighteen peaks in this HPLC fingerprint were structurally identified by employing LC-MS-MS techniques. The electrospray ionization (ESI) MS-MS spectra of most salvianolic acids displayed a characteristic behavior of loss of danshensu and caffeic acid moieties, while those of tanshinones showed a particular behavior of loss of H2O which is quite different from the fragmentation pattern in electron ionization mass spectrometry (EI-MS). The HPLC fingerprints of 7 batches of crude drugs showed similar separation pattern and provided much chemical information of the pharmacologically-active compounds in the crude drugs, which is useful for the authentication and quality evaluation of this medicinal herb.

Chromatography, High Pressure Liquid↗

Quantitative determination of four diterpenoids in Radix Salviae Miltiorrhizae using LC-MS-MS.

An HPLC-ESI-MS-MS method has been developed for the quantitative determination of four diterpenoids, dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA in Radix Salviae Miltiorrhizae (RSM, the root of Salvia miltiorrhiza BGE.). The diterpenoids were chromatographically separated on a C18 HPLC column, and the quantification of these diterpenoids was based on the fragments of [M+H]+ under collision-activated conditions and in Selected Reaction Monitoring (SRM) mode. The quantitative method was validated, and the mean recovery rates from fortified samples (n=5) of dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA were 95.0%, 97.2%, 93.1%, and 95.9% with variation coefficient of 6.0%, 4.3%, 3.7%, and 4.2%, respectively. The established method was successfully applied to the quality assessment of seven batches of RSM samples collected from different regions of China.

Chromatography, Liquid↗

Interaction between warfarin and danshen (Salvia miltiorrhiza).

OBJECTIVE: To discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhiza Bge, and warfarin. DATA SOURCES: A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. All articles written in English or with an English extract were considered for review. STUDY SELECTION AND DATA EXTRACTION: All studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed. DATA SYNTHESIS: Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III-like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen. CONCLUSIONS: Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.

Animals↗

Antimicrobial activity of six constituents of essential oil from Salvia.

The antimicrobial activity of three Salvia species, i.e. S. santolinifolia, S. hydrangea and S. mirzayanii, essential oils were investigated. The essential oils were obtained from the aerial parts of plants and analyzed by GC-MS. The main constituents of aforementioned species were alpha-pinene (72.4%), beta-pinene (6.6%) and limonene (5.3%); beta-caryophyllene (25.1%), 1,8-cineol (15.2%) and caryophyllene oxide (11.5%); alpha-terpinenyl acetate (22.6%), 1,8-cineol (21.2%) and linalool (8.9%), respectively. Bioassays exhibited that the property of the oil of S. myrzayanii was superior to others. The antimicrobial activity of essential oil from Salvia species may well be due to the presence of synergy between six tested compounds (linalool, 1,8-cineol, alpha-pinene, beta-pinene, beta-caryophyllene and limonene) and other constituents of the oils with various degrees of antimicrobial activity. Among these, linalool and 1,8-cineol had the highest antimicrobial activity.

Anti-Bacterial Agents↗

Establishment of Salvia officinalis L. hairy root cultures for the production of rosmarinic acid.

Shoots of Salvia officinalis, a medicinally important plant, were infected with Agrobacterium rhizogenes strains ATCC 15834 and A4 which led to the induction of hairy roots in 57% and 37% of the explants, respectively. Seven lines of hairy roots were established in WP liquid medium under light and dark conditions. The transformed nature of the root lines was confirmed by polymerase chain reaction using rolB and rolC specific primers. Transformed root cultures of Salvia officinalis showed variations in biomass and rosmarinic acid production depending on the bacterial strain used for transformation and the root line analyzed. Both parameters (growth and rosmarinic acid content) of ATCC 15834-induced lines were significantly higher than the A4-induced lines. The maximum accumulation of rosmarinic acid (about 45 mg g(-1) of dry weight) was achieved by hairy root line 1 (HR-1) at the end of the culture period (45-50 days). The level was significantly higher than that found in untransformed root culture (19 mg g(-10 of dry wt).

Antifungal Agents↗

[Production of allochtonic formations in callus cells of Salvia miltiorrhiza Bge].

OBJECTIVE: To study the effect of hormones content in the medium on of allochtonic formations in the callus from Salvia miltiorrhiza. METHOD: Study the development of allochtonic formations in the callus from explants of Salvia miltiorrhiza cultured on hormones of different content ratios in the medium. RESULT AND CONCLUSION: 2,4-D inhibits the production of water-soluble active principles and KT promotes the production of total tanshinone.

Abietanes↗

[Biomechanical experimental study on effective fraction of radix salviae miltiorrhizae on healing of bone fracture].

OBJECTIVE: To assess the effect of Danshen-9403 (DS-9403, an effective fraction of Radix Salviae Miltiorrhizae) on healing of bone fracture. METHODS: Standardized radial fracture was performed in 120 Wistar rats. The model animals were randomized into four groups: group A was fed with DS-9403, group B injected with Staphylococcus Aureus, group C with normal saline, and group D with Salviae injection. The treatment began at the first day of fracture. The rats were sacrificed on the 25th, 39th and 50th day separately in batches and their intact radii were removed by dissection for detecting load and stress of three-point bending test with autograph universal material testing machine (Shimazu, Japan). RESULTS: The parameters of load in DS-9403 treated groups on the 39th day and that of stress at 25th, 39th and 50th day were (6.20 +/- 1.32) N, (5.71 +/- 3.58) N/mm2, (8.27 +/- 2.42) N/mm2 and (66.25 +/- 26.21) N/mm2 respectively, which were significantly higher than those in other groups, P < 0.05. CONCLUSION: DS-9403 has the action of increasing the strength of fracture healing site.

Animals↗

[Medicinal resources of Salvia yunnanensis].

Salvia yunnanensis is a habitually used medicinal plant in Yunnan. It distributed widely over the southwest China, and its contents of tanshinone II-A and protocatechuic aldehyde are higher than those of Salvia miltiorrhiza. Therefore, S. yunnanensis is one of the best resources of the medicinal plant.

Abietanes↗

[Cultivation of fibroblasts derived from urethral scar and the effects of salviae miltiorrhizae and ligustrazine on its growth].

OBJECTIVE: To explore the possible effect and related mechanism of salviae miltiorrhizae (SM) and ligustrazine in the treatment of urethral scar. METHODS: In vitro cultivation of fibroblasts derived from urethral scar has been developed. The effects of these two medicines on its morphology and proliferation have been detected based on the in vitro culture system. RESULTS: The spindle cells were found to become elliptical in shape. The two medicines inhibited the proliferation of fibroblasts derived from urethral scar, and this may be resulted from their inhibitive effects on cell division rather than cell necrosis or degradation. CONCLUSION: Salviae multiorrhizae and ligustrazine as effective scar inhibitors may have application prospects in the treatment of urethral stricture.

Adult↗

[The intervention effects of Angelica sinensis, Salvia miltiorrhiza and ligustrazine on peritoneal macrophages during peritoneal dialysis].

OBJECTIVE: To study the effect of Angelica sinensis, Salvia miltiorrhiza and Ligustrazine on function of peritoneal macrophages during peritoneal dialysis. METHODS: Peritoneal macrophages of mice were cultured in culture medium (control), peritoneal dialysate (PD), drugs contained PD containing Angelica, Salvia and Ligustrazine combined (PD-ASL) or separated (PD-A, PD-S, PD-L) with concentration of 2 micrograms/ml, 10 micrograms/ml and 100 micrograms/ml, separately for 24 hrs. The nitric oxide (NO) content, methyl thiazolyl tetrazolium (MTT) reducing capacity (MTT-RC) and phagocytosis capacity of macrophages were determined and compared. RESULTS: NO content and MTT-RC of macrophages cultured in PD group were significantly lower than those of the control (P < 0.01), as compared with those in drug contained PD groups, the NO content in the PD-L group and the MTT-RC in the PD-ASL group were higher significantly (P < 0.01). The phagocytosis capacity and NO content in the PD-ASL group were raised along with the increased concentration of drug in PD. CONCLUSION: Administering Chinese herbal medicine during peritoneal dialysis has important significance in improving the defense function of peritoneal macrophages, reducing the incidence of peritonitis and enhancing the therapeutic effect of peritoneal dialysis.

Angelica sinensis↗

[Determination of salvianolic acid B in the radix of Salvia miltiorrhiza Bge. by HPLC].

OBJECTIVE: To develop an HPLC method for determining salvianolic acid B in radix of Salvia miltiorrhiza. METHOD: The sample was extracted with 75% methanol. ODS column was used with methanol-5% acetic acid solution (35:65) as mobile phase. Detection wavelength was 281 nm. RESULT: Salvianolic acid B was separated well. Good linearity of salvianolic acid B was obtained (r = 0.9997) within the range of 0.17-1.7 micrograms. The average recovery was 98.9%. Repeatability was good, and RSD was 1.82%. CONCLUSION: This method can be used for quality control of radix of Salvia miltiorrhiza.

Benzofurans↗