Natural product; microcirculation-related diseases

Salvianolic acid B (SA-B) 1 and 10 μmol/L downregulated procollagen α1(I) mRNA expression to 77.0% and51.8%, respectively, and decreased cell activity TGF-β1 secretion by 63.3% and 15.6%, respectively, in comparison to the control. (P<0.05). Additionally, SA-B 1 and 10 µmol/L reduced MAPK activity by one and two times, respectively. [3] Salvianolic acid B degrades in response to temperature. Stable for 30 hours at 4°C in an aqueous solution. On the other hand, the salvianolic acid B aqueous solution immediately breaks down at 25°C, and this breakdown is accelerated at 37, 65, and 100°C. Conversely, salvianolic acid B remained stable in total phenolic acids (TPA) for thirty hours at 4, 25, and 37 degrees Celsius. [4] Salvianolic acid B can withstand 30 hours at pH 1.5, 3.0, and 5.0 in buffered phosphate saline solutions. Sal B's stability declines when the pH rises from neutral.

Salvianolic acid B (SalB) (5 mg·kg-1·h-1) can effectively ameliorate LPS-induced pulmonary microcirculation problems, including increases in leukocyte adhesion and albumin leakage. In addition, LPS can increase the wet-to-dry weight ratio of lung tissue and the levels of tumor necrosis factor α and interleukin-8 in plasma and bronchoalveolar lavage fluid, and elevate E-selectin, intercellular adhesion molecule 1, and myeloperoxidase. , MMP-2, and MMP-9, whereas it lowers the expression of AQP-1 and AQP-5 in lung tissue, all of which are decreased by SalB pretreatment [1]. SalB treatment (10 mg/kg) significantly alleviated Aβ25-35 peptide-induced memory impairment in the passive avoidance task (P<0.05). SalB therapy also reduced the number of activated microglia and astrocytes detected during the inflammatory response after delivery of Aβ25-35 peptide. Furthermore, SalB dramatically reduced the expression levels of inducible nitric oxide synthase and cyclooxygenase-2 as well as thiobarbituric acid-reactive compounds, which were elevated by administration of Aβ25-35 peptide. In addition, SalB treatment effectively reduced the Aβ25-35 peptide-induced decrease in choline acetyltransferase and brain-derived neurotrophic factor protein levels [1].

Hepatic stellate cell (HSC) was isolated from normal rat through in situ perfusion of liver with pronase E and density-gradient centrifugation with 11 % nycondenz, then cells were subcultured. Cell proliferation was observed by [3H]TdR uptake. Cellular collagen deposition was measured with Ponceau S stain and semi-quantified with image analytic system. Type I collagen secretion in the supernatant was detected with ELISA. The gene expression of type I pro-collagen was analyzed by RT-PCR. The supernatant was acidified and active TGF-beta1 contents were assayed with ELISA. Mitogen-activated protein kinase (MAPK) activity was analyzed with immunoprecipitation and Western blot[2].

Salvianolic acid B (SalB) is a polyphenolic compound found in Salvia miltiorrhiza Bunge that has several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether SalB has neuroprotective effects in an amyloid β (Aβ) peptide-induced Alzheimer's disease mouse model. Mice were injected with Aβ25-35 peptide intracerebroventricularly and were subsequently administered SalB once daily for 7 days. Subchronic SalB administration (10mg/kg) significantly ameliorated the Aβ25-35 peptide-induced memory impairment in the passive avoidance task (P<0.05). SalB treatment also reduced the number of activated microglia and astrocytes that were observed during the inflammatory reaction after the administration of the Aβ25-35 peptide. Moreover, SalB markedly reduced inducible nitric oxide synthase and cyclooxygenase-2 expression levels and thiobarbituric acid reactive substances, which were increased by the administration of the Aβ25-35 peptide. Furthermore, SalB administration significantly rescued the Aβ25-35 peptide-induced decrease of choline acetyltransferase and brain-derived neurotrophic factor protein levels. These results suggest that SalB exerts neuroprotective activity via anti-inflammatory and anti-oxidative effects and that SalB may be a potential candidate for Alzheimer's disease therapy.[1]

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The aim of the present study was to examine the effect and possible mechanism of salvianolic acid B (SalB) on pulmonary microcirculation disturbance induced by lipopolysaccharide (LPS) in rat. Male Sprague-Dawley rats were subjected to thoracotomy under continuous anesthesia and mechanical ventilation. Albumin leakage from pulmonary capillary and the numbers of leukocytes adherent to the pulmonary capillary wall were determined for 60 min by an upright microscope upon LPS (2 mg · kg(-1) · h(-1)) infusion with or without administration of SalB (5 mg · kg(-1) · h(-1)). Pulmonary tissue wet-to-dry weight ratio, tumor necrosis factor α, and interleukin 8 in plasma and bronchoalveolar lavage fluid were measured. In addition, the expressions of E-selectin, intercellular adhesion molecule 1, and myeloperoxidase in pulmonary tissue were assessed by immunohistochemistry. The expressions of aquaporin 1 (AQP-1), AQP-5, metalloproteinase 2 (MMP-2), and MMP-9 were assessed by Western blot assay. Pretreatment with SalB significantly attenuated LPS-induced pulmonary microcirculatory disturbance, including the increase in leukocyte adhesion and albumin leakage. In addition, LPS increased pulmonary tissue wet-to-dry weight ratio and tumor necrosis factor α and interleukin 8 levels in plasma and bronchoalveolar lavage fluid enhanced the expression of E-selectin, intercellular adhesion molecule 1, myeloperoxidase, MMP-2, and MMP-9, whereas it decreased the expression of AQP-1 and AQP-5 in pulmonary tissue, all of which were attenuated by SalB pretreatment. Salvianolic acid B pretreatment improves pulmonary microcirculation disturbance and lung injury on LPS exposure. More studies are required to evaluate the potential of SalB as an option for protecting lung from endotoxemia.[2]

[1]. Neuroprotective effects of salvianolic acid B on an Aβ25-35 peptide-induced mouse model of Alzheimer's disease. Eur J Pharmacol. 2013 Mar 15;704(1-3):70-7.
[2]. Effect of salvianolic acid B on collagen production and mitogen-activated protein kinase activity in rat hepatic stellate cells. Acta Pharmacol Sin. 2002 Aug;23(8):733-8.
[3]. Salvianolic acid B protects from pulmonary microcirculation disturbance induced by lipopolysaccharide in rat. Shock. 2013 Mar;39(3):317-25.

Salvianolic acid B is a member of the class of 1-benzofurans that is an antioxidant and free radical scavenging compound extracted from S. miltiorrhiza It has a role as a plant metabolite, an anti-inflammatory agent, an antioxidant, a hypoglycemic agent, an osteogenesis regulator, an apoptosis inducer, a hepatoprotective agent, a neuroprotective agent, a cardioprotective agent, an autophagy inhibitor, an antidepressant and an antineoplastic agent. It is a polyphenol, a member of 1-benzofurans, an enoate ester, a dicarboxylic acid and a member of catechols.
Lithospermic acid B has been reported in Salvia miltiorrhiza, Celastrus hindsii, and other organisms with data available.
See also: Salvia Miltiorrhiza Root (part of).

C36H30O16

718.62

718.153

C, 60.17; H, 4.21; O, 35.62

121521-90-2

Danshensu;76822-21-4

6451084

Off-white to yellow solid powder

1.6±0.1 g/cm3

1020.3±65.0 °C at 760 mmHg

98-110ºC

322.1±27.8 °C

0.0±0.3 mmHg at 25°C

1.739

2.14

9

16

14

52

1290

4

C1=CC(=C(C=C1C[C@H](C(=O)O)OC(=O)/C=C/C2=C3[C@@H]([C@H](OC3=C(C=C2)O)C4=CC(=C(C=C4)O)O)C(=O)O[C@H](CC5=CC(=C(C=C5)O)O)C(=O)O)O)O

SNKFFCBZYFGCQN-QUYNTYMASA-N

InChI=1S/C36H30O16/c37-20-6-1-16(11-24(20)41)13-27(34(45)46)50-29(44)10-5-18-3-9-23(40)33-30(18)31(32(52-33)19-4-8-22(39)26(43)15-19)36(49)51-28(35(47)48)14-17-2-7-21(38)25(42)12-17/h1-12,15,27-28,31-32,37-43H,13-14H2,(H,45,46)(H,47,48)/b10-5+/t27?,28?,31-,32+/m0/s1

2-(((2S,3S)-4-((E)-3-(1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy)-3-oxoprop-1-en-1-yl)-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carbonyl)oxy)-3-(3,4-dihydroxyphenyl)propanoic acid

Lithospermic acid B; 121521-90-2; Dan Shen Suan B; Danfensuan B; Monardic acid B; 115939-25-8; UNII-C1GQ844199; Dan Shen Suan B; Danfensuan B Salvianolic acid B; Salvianolic acid B; Dan Shen Suan B; Salvianolic acid B

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 is not stable in solution, please use freshly prepared working solution for optimal results.

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

H2O : ~50 mg/mL (~69.58 mM)
DMSO : ~25 mg/mL (~34.79 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.48 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 (3.48 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 (3.48 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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Solubility in Formulation 4: 50 mg/mL (69.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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