AMP-activated protein kinase α (AMPKα) signaling pathway - Syringin attenuates cardiac hypertrophy by inhibiting the activation (phosphorylation) of AMPKα [2]
.
- Autophagy-related signaling pathway - Syringin alleviates cardiac autophagy by downregulating autophagy-related proteins including ATG5, ATG7, beclin 1, and LC3 A/B [2]
.
- Hypertrophic markers - Syringin decreases the expression of ANP, BNP, and β-MHC, while increasing α-MHC expression [2]
.

Cell Model: H9c2 rat cardiomyocytes were stimulated with angiotensin II (Ang II, 2 μM) for 24 hours to induce hypertrophy. Cells were treated with syringin (15 μM) alone or in combination with rapamycin (100 nM, an autophagy agonist) [2]
.
- Hypertrophy Reduction: Syringin treatment significantly reduced Ang II-induced cardiomyocyte enlargement as assessed by immunocytochemistry for cardiac α-actin. Quantification of cell cross-sectional area showed that syringin significantly decreased the enlarged cell surface area induced by Ang II. Rapamycin partially reversed this protective effect [2]
.
- Hypertrophic Marker Reduction: RT-qPCR analysis showed that syringin significantly decreased Ang II-induced upregulation of ANP, BNP, and β-MHC mRNA levels, while increasing α-MHC mRNA levels. Rapamycin attenuated these effects [2]
.
- Autophagy Inhibition: Immunofluorescence staining for LC3 showed that syringin decreased Ang II-induced LC3 expression. Western blot analysis confirmed that syringin reduced Ang II-induced upregulation of ATG7 and beclin 1 protein levels, while increasing p62 levels. Rapamycin reversed these effects [2]
.
- AMPKα Inhibition: Western blot analysis showed that syringin decreased Ang II-induced phosphorylation of AMPKα (p-AMPKα) in H9c2 cells [2]
.

Animal Model: Male C57BL/6 mice (8-10 weeks old, 23.5-27.5 g) were subjected to aortic banding (AB) to induce pressure overload-induced cardiac hypertrophy. Mice were randomly divided into 5 groups (n=20/group): sham + vehicle, sham + syringin, AB + vehicle, AB + low-dose syringin (50 mg/kg/day), and AB + high-dose syringin (100 mg/kg/day). Syringin was administered by gavage for 7 weeks starting 7 days after surgery. At 8 weeks post-surgery, mice were sacrificed for analysis [2]
.
- Cardiac Hypertrophy Attenuation: Syringin treatment significantly decreased heart weight/body weight (HW/BW) ratio, heart weight/tibia length (HW/TL) ratio, and cardiomyocyte cross-sectional area (CSA) compared to AB + vehicle group. Hematoxylin and eosin (H&E) staining and wheat germ agglutinin (WGA) staining confirmed reduced cardiac mass and myocyte size [2]
.
- Cardiac Function Improvement: Echocardiography showed that syringin treatment attenuated AB-induced increases in left ventricular end-diastolic diameter (LVEDd) and interventricular septum depth (IVSD), and prevented decreases in fractional shortening (FS%) and ejection fraction (EF%). Hemodynamic measurements showed that syringin improved dP/dt max and dP/dt min, indicating improved systolic and diastolic function [2]
.
- Hypertrophic Marker Reduction: RT-qPCR analysis of heart tissue showed that syringin significantly decreased AB-induced upregulation of ANP, BNP, and β-MHC mRNA levels, while increasing α-MHC mRNA levels [2]
.
- Autophagy Inhibition: RT-qPCR and Western blot analysis showed that syringin treatment significantly decreased AB-induced upregulation of autophagy-related genes and proteins including ATG5, ATG7, beclin 1, and LC3 A/B. The LC3-II/LC3-I ratio was decreased, while p62 levels were increased, indicating reduced autophagic flux [2]
.
- AMPKα Inhibition: Western blot analysis revealed that syringin treatment significantly decreased the phosphorylation levels of AMPKα (p-AMPKα) in heart tissue compared to AB + vehicle group, indicating inhibition of AMPKα activation [2]
.

Cell Culture: H9c2 rat cardiomyocytes were cultured in DMEM supplemented with 10% calf serum, 100 U/mL penicillin, and 100 mg/mL streptomycin at 37°C with 5% CO₂ [2]
.
- Hypertrophy Induction: Cells were stimulated with angiotensin II (Ang II, 2 μM) for 24 hours to induce hypertrophy. Syringin (15 μM) was added to the medium simultaneously. For mechanism studies, rapamycin (100 nM, autophagy agonist) was added to investigate the role of autophagy [2]
.
- Immunocytochemistry: Cells were stained with primary antibody to cardiac α-actin to assess cardiomyocyte hypertrophy. Cell cross-sectional area was quantified by measuring 100 random cells per group using image analysis software [2]
.
- Immunofluorescence: Cells were stained with primary antibody to LC3 A/B to assess autophagy. Fluorescence microscopy was used to visualize LC3 expression [2]
.
- RT-qPCR: Total RNA was extracted using TRIzol reagent. mRNA was reverse transcribed into cDNA. Real-time quantitative PCR was performed using SYBR-Green I Master Mix with specific primers for ANP, BNP, α-MHC, β-MHC, ATG5, ATG7, beclin 1, LC3 A/B, and GAPDH (housekeeping). Results were normalized to GAPDH [2]
.
- Western Blot: Protein was extracted using RIPA buffer and quantified by BCA assay. Proteins were separated by SDS-PAGE, transferred to PVDF membranes, and incubated with primary antibodies against p-AMPKα, AMPKα, ATG7, beclin 1, p62, LC3 A/B, and GAPDH. Blots were scanned using a two-color infrared imaging system [2]
.

Animals:** Male C57BL/6 mice (8-10 weeks old, 23.5-27.5 g) were housed under controlled temperature and humidity [2]
.
- **Surgical Procedure (Aortic Banding):** Mice were anesthetized, and the aortic arch branch was exposed through an incision at the second and third intercostals. The vessel was ligated using a 26G/27G syringe needle placed parallel above the vessel. After needle withdrawal to achieve aortic constriction, the chest was closed. Sham-operated mice underwent the same procedure without vessel ligation. Post-operative pain was managed with 0.1 mL 0.5% bupivacaine injected subcutaneously [2]
.
- **Drug Administration:** Syringin was dissolved and administered by gavage at doses of 50 mg/kg/day (low-dose) or 100 mg/kg/day (high-dose) for 7 weeks, starting 7 days after surgery. Control groups received equal volumes of normal saline (vehicle) [2]
.
- **Experimental Groups:** Five groups (n=20 each): sham + vehicle, sham + syringin (100 mg/kg), AB + vehicle, AB + low-dose syringin (50 mg/kg), and AB + high-dose syringin (100 mg/kg) [2]
.
- **Echocardiography:** At 8 weeks post-surgery, mice were anesthetized with 1.5% isoflurane. Echocardiography was performed using a MyLabTM 30CV cardiovascular ultrasound system with a 10 MHz linear array transducer. LVEDd, IVSD, FS%, and EF% were measured [2]
.
- **Hemodynamic Measurements:** A microtip catheter transducer was inserted into the right carotid artery and advanced into the left ventricle. dP/dt max and dP/dt min were recorded using a Millar Pressure-Volume System and analyzed by PVAN software [2]
.
- **Tissue Collection:** Mice were sacrificed by cervical dislocation at 8 weeks post-surgery. Hearts were rapidly excised, weighed, and processed for histological analysis (H&E staining, WGA staining) or frozen for molecular analysis [2]
.
- **Histological Analysis:** Heart sections were stained with H&E for morphological evaluation. For myocyte cross-sectional area measurement, sections were stained with fluorescein isothiocyanate-conjugated WGA to visualize membranes and DAPI to visualize nuclei. CSA was calculated using Image Pro-Plus 6.0 software [2]
.

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Animals: Male C57BL/6 mice (8-10 weeks old, 23.5-27.5 g) were housed under controlled temperature and humidity [2]
.
- Surgical Procedure (Aortic Banding): Mice were anesthetized, and the aortic arch branch was exposed through an incision at the second and third intercostals. The vessel was ligated using a 26G/27G syringe needle placed parallel above the vessel. After needle withdrawal to achieve aortic constriction, the chest was closed. Sham-operated mice underwent the same procedure without vessel ligation. Post-operative pain was managed with 0.1 mL 0.5% bupivacaine injected subcutaneously [2]
.
- Drug Administration: Syringin was dissolved and administered by gavage at doses of 50 mg/kg/day (low-dose) or 100 mg/kg/day (high-dose) for 7 weeks, starting 7 days after surgery. Control groups received equal volumes of normal saline (vehicle) [2]
.
- Experimental Groups: Five groups (n=20 each): sham + vehicle, sham + syringin (100 mg/kg), AB + vehicle, AB + low-dose syringin (50 mg/kg), and AB + high-dose syringin (100 mg/kg) [2]
.
- Echocardiography: At 8 weeks post-surgery, mice were anesthetized with 1.5% isoflurane. Echocardiography was performed using a MyLabTM 30CV cardiovascular ultrasound system with a 10 MHz linear array transducer. LVEDd, IVSD, FS%, and EF% were measured [2]
.
- Hemodynamic Measurements: A microtip catheter transducer was inserted into the right carotid artery and advanced into the left ventricle. dP/dt max and dP/dt min were recorded using a Millar Pressure-Volume System and analyzed by PVAN software [2]
.
- Tissue Collection: Mice were sacrificed by cervical dislocation at 8 weeks post-surgery. Hearts were rapidly excised, weighed, and processed for histological analysis (H&E staining, WGA staining) or frozen for molecular analysis [2]
.
- Histological Analysis: Heart sections were stained with H&E for morphological evaluation. For myocyte cross-sectional area measurement, sections were stained with fluorescein isothiocyanate-conjugated WGA to visualize membranes and DAPI to visualize nuclei. CSA was calculated using Image Pro-Plus 6.0 software [2]
.

[1]. Syringin prevents bone loss in ovariectomized mice via TRAF6 mediated inhibition of NF-κB and stimulation of PI3K/AKT. Phytomedicine. 2018 Mar 15;42:43-50.

[2]. Syringin prevents cardiac hypertrophy induced by pressure overload through the attenuation of autophagy. Int J Mol Med. 2017 Jan;39(1):199-207.

Syringin is a monosaccharide derivative composed of trans-sinopeptidyl alcohol linked to the 1-position of a β-D-glucanose residue via a glycosidic bond. It possesses hepatoprotective, plant metabolic, apoptosis-inducing, autophagy-inducing, anti-inflammatory, neuroprotective, and antidepressant effects. Syringin is a β-D-glucosinolate, a monosaccharide derivative, a primary alcohol, and a dimethoxybenzene. Functionally, it is related to trans-sinopeptidyl alcohol. Syringin has been found in Acanthus ebracteatus, Jasminum mesnyi, and other organisms with relevant data. See also: Codonopsis pilosula root (part).

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Source and Chemical Identity: Syringin (C₁₇H₂₄O₉, molecular weight 372.37), also known as eleutheroside B, is a major biologically active component extracted from Eleutherococcus senticosus, a Chinese herb. Purity was confirmed as 98% by HPLC [2]
.
- Background Pharmacological Properties: Previous studies have demonstrated that syringin possesses multiple pharmacological properties including anti-inflammatory effects, antioxidant effects, immunomodulatory properties, sleep-potentiating effects, and plasma glucose lowering effects. This study is the first to investigate its effects on cardiac hypertrophy [2]
.
- Mechanism of Action in Cardiac Hypertrophy: Syringin attenuates pressure overload-induced cardiac hypertrophy through inhibition of the AMPKα signaling pathway and suppression of excessive autophagy. By inhibiting AMPKα phosphorylation and reducing autophagy-related protein expression (ATG5, ATG7, beclin 1, LC3), syringin decreases hypertrophic marker expression (ANP, BNP, β-MHC) and improves cardiac function [2]
.
- Autophagy Regulation: The study demonstrates that syringin alleviates excessive autophagy in hypertrophic hearts, which is considered a maladaptive response. The protective effects of syringin were partially reversed by rapamycin, an autophagy agonist, confirming that autophagy inhibition is involved in its mechanism of action [2]
.
- Dual Role of AMPK in Cardiac Hypertrophy: The authors discuss that AMPK activation may play dual roles in cardiac hypertrophy - protective in early stages but potentially detrimental in pathological hypertrophy by promoting fatty acid oxidation. Syringin-mediated inhibition of AMPKα phosphorylation may help restore metabolic balance [2]
.
- Therapeutic Potential: The study suggests that syringin possesses therapeutic potential to attenuate the progression of cardiac hypertrophy and may represent a novel pharmacotherapeutic strategy for preventing heart failure induced by pressure overload [2]
.

C17H24O9

372.37

372.142

118-34-3

5316860

White to off-white solid powder

1.4±0.1 g/cm3

642.6±55.0 °C at 760 mmHg

192°C

342.4±31.5 °C

0.0±2.0 mmHg at 25°C

1.623

-1.94

5

9

7

26

432

5

COC1=CC(=CC(=C1O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)OC)/C=C/CO

QJVXKWHHAMZTBY-GCPOEHJPSA-N

InChI=1S/C17H24O9/c1-23-10-6-9(4-3-5-18)7-11(24-2)16(10)26-17-15(22)14(21)13(20)12(8-19)25-17/h3-4,6-7,12-15,17-22H,5,8H2,1-2H3/b4-3+/t12-,13-,14+,15-,17+/m1/s1

(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[4-[(E)-3-hydroxyprop-1-enyl]-2,6-dimethoxyphenoxy]oxane-3,4,5-triol

NSC287441 Eleutheroside B NSC 287441Syringin NSC-287441

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~268.55 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)