ABSTRACT
Objective:To explore the efficacy of andrographolide sulfonate(ADS) nebulized inhalation on pediatric moderate to severe acute respiratory distress syndrome(ARDS) requiring invasive mechanical ventilation.Methods:We conducted a prospective randomized controlled single-blind study.Children with moderate-to-severe ARDS admitted to the PICU at Beijing Children′s Hospital of Capital Medical University from November 1, 2018 to December 31, 2019, aging from 29 days to 18 years, and requiring invasive mechanical ventilation therapy were collected.The experimental group received ADS, while the control group received normal saline.Bronchoalveolar lavage fluid was collected to detect cytokines before and after the experiment.The differences of demography, cytokines and management between two groups were analyzed.Results:Twenty children with a median age of 2.15(1.48, 8.01)years were included and 15(75.00%)cases were boys.Median score of pediatric index of mortality-2 was 12.25(4.53, 16.30). There was no significant differences in demography, basic clinical data and prognosis between two groups( P>0.05). Monocyte chemoattractant protein-1 decreased in the experimental group while increased in the control group with statistic difference[967.50(119.25, 5 206.00)pg/mL vs.-945.00(-3 935.50, 495.09)pg/mL, P=0.041]. Interleukin(IL)-8 decreased in the experimental group but increased in the control group[303.22(-452.00, 1 172.38)pg/mL vs.-490.14(-780.25, 240.52)pg/mL, P=0.151]; and the IL-6 increase of the experimental group was lower than that of the control group[-24.53(-501.76, 135.27)pg/mL vs.-325.85(-633.22, 133.75)pg/mL, P=0.364]; all with no statistic differences( P>0.05). The oxygenation index[11.35(6.00, 15.83) vs.20.65(6.23, 38.35), P=0.374] and the improvement rate of ARDS(80%vs.60%, P=0.628) of the experimental group was better than that of the control group, but with no statistic difference( P>0.05). There was no statistic difference of mortality and mechanical ventilation time between two groups( P>0.05). Conclusion:Inhalation of ADS might reduce the increase of IL-6 and the concentration of monocyte chemoattractant protein-1 and IL-8 in bronchoalveolar lavage fluid of children with ARDS, and might improve pulmonary oxygenation function.Further research is needed to verify the above conclusion.
ABSTRACT
OBJECTIVE: To establish a method for determination of the total content of andrographolide sulfonate, transport of two kinds of main components in the injection in Calu-3 and Caco-2 cell model, can be applied to the assessment of lung and oral administration to the safety and effectiveness of drugs. METHODS: Screening of safe concentration of drugs by cytotoxicity test. Injection of andrographolide total sulfonate in safe concentrationwere applied to Calu-3 and Caco-2 cell models. Samples were taken for a certain period of time to determine the influence of concentration and time on the transport, and the apparent osmotic coefficients of the principal components were calculated. RESULTS: When the concentration of the drug was less than 500 μg•mL-1, the survival rate of Calu-3 and Caco-2 cells was close to 100%. The established cell model showed excellent compactness and integrity. In the Calu-3 cell model, the apparent permeability coefficients of andrographolide sulfate C and 9-dehydro-17-hydro-andrographolide were 1 × 10 -5 orders of magnitude. In the Caco-2 cell model, both were 1 × 10-6 orders of magnitude. On two cell models, the efflux ratios were less than 2. CONCLUSION: The principal component of andrographolide total sulfonate injection is not the substrate for P glycoproteins, it has moderate absorption in the intestine, and has good absorption in the respiratory tract. Pulmonary administration is safer and more effective.
ABSTRACT
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.
ABSTRACT
Objective:To establish an UPLC method for the simultaneous determination of andrographolide sulfonate E and an-drographolide sulfonate F in andrographolide sulfonates. Methods: The sample was separated on a Shimadzu Shim-pack XR-ODSⅢcolumn (2. 0 m × 75 mm, 1. 6 μm) with acetonitrile( A) and potassium dihydrogen phosphate buffer solution( B:1. 361 g potassium dihydrogen phosphate and 1. 0g heptane-1-sodium sulfonate were dissolved in 1 000 ml water) as the mobile phase with gradient elu-tion, and the flow rate was 0. 4 ml·min-1 ,the column temperature was 30℃, and the detection wavelength was set at 225nm. Re-sults:The linear range of andrographolide sulfonate E was 4. 39-43. 88μg·ml-1(r=1. 000 0) and the average recovery was 98. 71%(RSD=1. 41%, n=6). The linear range of andrographolide sulfonate F was 4. 43-44. 32 g·ml-1(r=1. 000 0) and the average re-covery was 99. 29%(RSD=0. 76%, n=6). Conclusion:The method is reproducible, sensitive and accurate, which can be used in the quality control of andrographolide sulfonates.