Syringopicroside

Preparation, characterization, and in vivo evaluation of glycyrrhetinic acid-mediated nano-drug delivery system co-loaded with syringopicroside and hydroxytyrosol.[Pubmed:37625157]

J Biomater Appl. 2023 Sep;38(3):392-411.

This study aimed to create a glycyrrhetinic acid (GA)-mediated, multi-component, self-assembled nano-drug delivery system co-loaded with Syringopicroside (S) and hydroxytyrosol (H) obtained from Syringa Linn by synthesizing a GA-polyethylene glycol-poly (lactic acid-co-glycolic acid) (GPP) nanoparticle delivery carrier to actively target the liver. The nanoparticles were optimized using the central composite design. Nanoparticle characterization, cytotoxicity, pharmacodynamics, and tissue distribution study were performed. The optimized SH-GPP nanoparticle was a white solid powder, which was safe and non-toxic. The particle size and Zeta potential of the nanoparticles were 101.5 +/- 3.18 nm and -23.3 +/- 0.82 mV, respectively. The polydispersity index value (PDI) was 0.190 +/- 0.005; the particle size distribution was comparatively uniform. The average total encapsulation efficiency of the optimized SH-GPP nanoparticle was 50.26% +/- 1.29%, and drug loading was 15.47% +/- 0.39%. After S and H were arranged into nanoparticles, the proliferation inhibition of HepG2.2.15 cells was improved, and the aim of drug-loaded synergism between GPP and SH was achieved. The GA-mediated nanoparticles were better targeted, were retained longer in vivo, and had higher concentrations in the liver than the unmodified nanoparticles. These nanoparticles have the potential to be a new effective anti-hepatitis B treatment and have great research potential in clinical treatment.

A novel strategy against hepatitis B virus: Glycyrrhetnic acid conjugated multi-component synergistic nano-drug delivery system for targeted therapy.[Pubmed:36373787]

J Biomater Appl. 2023 Mar;37(8):1393-1408.

It is well known that Glycyrrhetnic acid (GA) has significant liver-targeting and anti-inflammatory effects. Syringopicroside (SYR) and Hydroxytyrosol (HT), the active components of the Chinese herb Syringa oblata Lindl, have earned great reputation for their potential in preventing or treating viral hepatitis type B. Therefore, we loaded SYR and HT into GA-conjugated PEG-PLGA, so that they could target the liver in additional to exerting their own pharmacological effects in a synergistic. However, the in vivo targeting and the low bioavailability of SYR and HT pose a huge challenge. Therefore, we synthesized GA-conjugated multi-component nano-drug delivery system (SH-GPP). SH-GPP had a regular spherical shape with a uniform size distribution of 110.5 +/- 3.18 nm. We further evaluated the effects of SH-GPP in vitro and in vivo. In the in vivo experiment, we evaluated the following parameters: the serum ALT and AST values; liver tissue homogenate MDA and SOD; HE staining of the pathological liver sections; and the liver coefficient. In the in vitro studies, the following parameters were evaluated: cellular uptake of SH-GPP; wound healing/scratch assay; cellular apoptosis; cell cycle; HBsAg; and HBeAg content. SH-GPP had better anti-hepatitis B effect than Syringopicroside and hydroxytyrosol (SH) and NPP alone. The targeting ability of GA enabled HT and SYR in GPP to reach the liver accurately, and played a synergistic role to maximize their therapeutic effects. This study provides a novel strategy against hepatitis B virus, and also provides a feasible scheme for improving the low bioavailability of the active components of traditional Chinese medicine.

Effect of Hepatocyte Targeting Nanopreparation Syringopicroside on Duck Hepatitis B Virus and Evaluation of Its Safety.[Pubmed:35352245]

Bull Exp Biol Med. 2022 Mar;172(5):573-578.

Syringopicroside is a kind of iridoid monomer compound isolated from Syringa oblata exhibiting a potent effect against hepatitis B virus (HBV). The therapeutic effect and safety of Syringopicroside-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SYR-NP) were studied on the model of HBV-infected ducklings and on cultured HepG2.2.15 cells. HBV DNA in ducklings was assessed by fluorescence quantitative PCR. In HepG2.2.15 cells, the content of HBsAg and HBeAg were assayed. Acute toxicity of SYR-NP was studied in ICR mice in 12 h and 7 days after SYR-NP administration. The serum levels of HBV DNA in ducklings treated with SYR-NP in a high dose was significantly lower than in the control. In HepG2.2.15 cells treated with different doses of SYR-NP, the concentrations of HBsAg and HBeAg were significantly below the control. Acute toxicity test showed high safety of SYR-NP. Thus, SYR-NP can inhibit replication of HBV DNA and protect the liver tissue.

Effect of Syringopicroside Extracted from Syringa oblata Lindl on the Biofilm Formation of Streptococcus suis.[Pubmed:33673668]

Molecules. 2021 Feb 27;26(5):1295.

Syringopicroside is a natural drug with antibacterial activity, which is the main ingredient of Syringa oblata Lindl (S. oblata). In order to further develop the application of S. oblata and evaluate the ability of Syringopicroside against Streptococcus suis (S. suis), this investigation first applied an ultrasonic-assisted method to extract Syringopicroside, and then response surface methodology (RSM) was performed to get the optimum condition. Based on RSM analysis, a second-order polynomial equation about the Syringopicroside yield and four variables, including ultrasonic power, time, temperature, and liquid-to-solid ratio, was purposed. Through RSM prediction and model verification experiments, the optimum conditions were determined, as follows: ultrasonic time was 63 min, temperature was 60 degrees C, a liquid-to-solid ratio was set to 63 mL/g, and ultrasonic power was 835 W. Under this condition, a high Syringopicroside yield was obtained (3.07 +/- 0.13 mg/g), which was not significantly different with a predicated value. After separation and purification by HPD 500 microporous resin, then mass spectrum was applied to identify the main ingredient in aqueous extract. A minimal inhibitory concentration (MIC) assay revealed the value against S. suis of Syringopicroside was 2.56 microg/microL and Syringopicroside with sub-inhibitory concentrations that could effectively inhibit biofilm formation of S. suis. Besides, scanning electron microscopy analysis indicated Syringopicroside could destroy the multi-layered aggregation structure of S. suis. Finally, molecular docking analysis confirmed that Syringopicroside was combined with Orfy protein of S. suis through hydrogen bonds, hydrophobic interaction, and pi-pi stacking.

The antibacterial activity of syringopicroside, its metabolites and natural analogues from Syringae Folium.[Pubmed:26912454]

Fitoterapia. 2016 Apr;110:20-5.

In the present study, the in vitro antibacterial activity of an effective fraction (ESF) from Syringae Folium (SF) on Methicillin-resistant Staphylococcus aureus (MRSA) was evaluated and then its in vivo activity was evaluated by using the MRSA-infected mouse peritonitis model. The ESF showed a significant in vitro and in vivo activity on decreasing the Minimum Inhibitory Concentrations (MICs) and increasing the survival rate of mouse from 42.8% to 100%. Six iridoid glucosides (IGs) of ESF were characterized by UPLC-TOF-MS method and also isolated by column chromatography. Most of them showed in vitro anti MRSA activity. Syringopicroside (Sy), the major compound of IGs, was found to increase the survival rate from 42.8% to 92.8% of the MRSA-infected mouse, which revealed Sy is also the main active components of ESF. In order to know why the effect of oral administration of SF is better than its injections in clinic and the metabolites of Sy, seven metabolites of Sy were isolated from rat urine and identified on the basis of NMR and MS spectra. Most of metabolites possessed stronger in vitro anti-MRSA activity than that of Sy, which furtherly proved the clinical result.

Preparation, in vitro and in vivo evaluation of mPEG-PLGA nanoparticles co-loaded with syringopicroside and hydroxytyrosol.[Pubmed:26704541]

J Mater Sci Mater Med. 2016 Feb;27(2):24.

This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with Syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with Syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 +/- 2.76 %. Total drug loading was 12.01 +/- 0.42 %, particle size was 91.70 +/- 2.11 nm, polydispersity index was 0.22 +/- 0.01, and zeta potential was -24.5 +/- 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with Syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that Syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.

[Study on intestinal absorption kinetics of syringopicroside in rats].[Pubmed:22860467]

Zhongguo Zhong Yao Za Zhi. 2012 May;37(10):1487-90.

OBJECTIVE: To study the intestinal absorption mechanism of traditional Chinese medicine monomer Syringopicroside in rats. METHOD: The in situ rat single-pass intestinal perfusion model was established to detect the concentration of Syringopicroside by HPLC. The absorption at different intestine segments in rat and the influence of concentration, pH and P-glycoprotein inhibitors of the drug solution on the absorption of Syringopicroside were also observed. RESULT: The absorption rate constant (K,) of Syringopicroside at duodenum, jejunum, ileum, and colon were 0.00255, 0.00630, 0.00900, 0.00799 min- , respectively; Ka from intestine at Syringopicroside concentration of 0.090, 0.180, 0.360 g x L(-1) were 0.00370, 0.00708, 0.00694 min(-1), respectively; and Ka at pH of 7.4, 6.8 and 5.0 were 0.00733, 0.00747, 0.00362 min(-1), respectively. P-glycoprotein inhibitor on the intestinal absorption of Syringopicroside showed significant influence (P < 0.05). CONCLUSION: Syringopicroside is well absorbed at the lower small intestine. When the drug concentration is low, the absorption rate constant is low, where as Ka increases at medium and high concentrations; the Ka is low at pH 5.0 and increases at pH 6.8 and pH 7.4. Syringopicroside is proved to be a substrate of P-glycoprotein.

Preparation, characterization and in vivo distribution of solid lipid nanoparticles loaded with syringopicroside.[Pubmed:21699077]

Pharmazie. 2011 Jun;66(6):404-7.

A solvent emulsification evaporation method was employed to prepare solid lipid nanoparticles (SLN) loaded with Syringopicroside. The conventional broad-spectrum antibacterial and antiviral drug Syringopicroside was incorporated into SLN to improve drug targeting. The SYR-SLNs were spherical and uniform in transmission electron microscopy (TEM). The mean particle size and potential were 180.31 +/- 10 nm, and -41.9 +/- 10.3 mV, respectively. Also, a sephadex column chromatography was adopted to investigate the encapsulation efficiency (EE %) of the SLN. This method is based on the principle of molecular sieve effect, and the EE% of the optimal formulation was 42.35 %. Drug-loading capacity was 5.33 %. The in vitro release profile revealed that Syringopicroside was released from SLN efficiently and completely in normal saline (NS) compared with other release media. A HPLC method was established for in vivo assay of Syringopicroside. A tissue distribution study was conducted in rats after iv administration of 15 mg/kg SYR-SLN and Syringopicroside NS, and it was found that SYR-SLN has improved delivery to the liver compared with any other organizations. These results indicated that solvent emulsification evaporation is a simple, easy, available and effective method for preparing SYR-SLN.

[Studies on the chemical constituents of Pharbitis purpurea].[Pubmed:21355193]

Zhong Yao Cai. 2010 Oct;33(10):1571-4.

OBJECTIVE: To study the chemical constituents of Pharbitis purpurea. METHODS: The constituents were isolated by silica gel column chromatography, HPLC and recrystallization and their structures were elucidated on the basis of spectral analysis. RESULTS: Fourteen compounds were isolated and identified as daucosterol (1), umbelliferone (2), ursolic acid (3), N-p-hydroxy-cis-coumaroyltyramine (4), N-p-hydroxy-trans-coumaroyltyramine (5), N-cis-feruloyltyramine (6), N-trans-feruloyltyramine (7), (3R, 5R, 6S, 7E, 9S)-megastigman-5,6-epoxy-7-ene-3,9-diol (8), (6S,9R)-vomifoliol (9), (+)-syringaresinol (10), isovitexin (11), Syringopicroside( 12), uricil (13), (6S,9R)-roseoside (14). CONCLUSION: Compounds 3, 8-2,14 are isolated from the genus for the first time.

Preparative separation and enrichment of syringopicroside from Folium syringae leaves with macroporous resins.[Pubmed:21234415]

J Biomed Biotechnol. 2010;2010:572570.

Syringopicroside is the major constituent in Folium syringae leaves with known pharmacological activities. In this study, a simple method for preparative separation of Syringopicroside from F. syringae leaves with macroporous resins was developed. Adsorption characteristics of Syringopicroside on six types of macroporous resins, including ADS-8, ADS-17, D141, NKA-9, HPD450, and HPD600, have been compared, among which D141 resin showed the best adsorption and desorption capacities for Syringopicroside. Adsorption isotherms were used to D141 resin at different temperatures and fitted well to Langmuir and Freundlich equations. Dynamic adsorption and desorption tests were performed on D141 resin-packed column to optimize the separation process of Syringopicroside. After one run with D141 resin, the content of Syringopicroside was increased 24-fold from 2.32% to 55.74% with a recovery yield of 92.16%. The chromatographic process optimized in this work avoids toxic organic solvent and, thus, is a promising basis for large-scale preparation of Syringopicroside.

Secoiridoid glucosides with free radical scavenging activity from the leaves of Syringa dilatata.[Pubmed:12722154]

Phytother Res. 2003 Apr;17(4):417-9.

Activity-guided fractionation of the EtOAc and MeOH extract of the leaves of Syringa dilatata NAKAI furnished one free radical scavenger, the secoiridoid glucoside oleuropein together with ligstroside and an iridoid glucoside, Syringopicroside. Oleuropein interacted with the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and showed an IC(50) value of 40.4 microM. L-Ascorbic acid as a positive control showed an IC(50) value of 50.3 microM.