Apium graveolens Prevents Intrauterine Growth Restriction via Suppression of Antiangiogenic Factor Production

https://doi.org/10.22146/mot.36112

Exma Mu'tatal Hikmah(1*), Paulus Liben(2), Widjiati Widjiati(3)

(1) Master Student in Basic Medical Science of Physiology, Faculty of Medicine, Airlangga University, Indonesia
(2) Physiology Department, Faculty of Medicine, Airlangga University, Indonesia
(3) Embryology Department, Faculty of Veterinary Medicine, Airlangga University, Indonesia
(*) Corresponding Author

Abstract


Preeclampsia is the worldwide leading cause of fetomaternal morbidity and mortality which involves the placental dysfunction. A poor placentation and formed of non-dilated spiral artery caused utero-placental circulation insufficiency, resulted in inadequate supply of nutrients and oxygen to support normal aerobic growth of the fetus. Apium graveolens or celery has been widely known as antioxidant, antiinflammation and antihypertensive with flavonoid-apigenin as main active compound. Apigenin can inhibit TNF-α, HIF-1α and nitric oxide blocking as major pathophysiological pathway of preeclampsia. This study was aimed to find how the Apium graveolens can improve intrauterine growth and its correlation with suppression of anti-angiogenic factor sFlt-1 in anti-Qa2 preeclampsia animal model. Twenty female BALB/c Mus musculus were divided into 4 groups: control, anti-Qa2 and anti-Qa2 with 500 and 1000 mg/kgBW celery herbs extract. The fetal weights and lengths, placental weights and serum sFlt-1 levels were measured and analyzed with One Way ANOVA and further tested with Least Significance Difference in 95% confidence interval. The result showed a difference between control and treatments group (p≤0.05) with 1000 mg/kgBW significantly increase intrauterine growth and decrease sFlt-1, then there is a negative correlation between intrauterine weight and serum sFlt-1. This study suggests that celery herbs extract (CHE) has an apigenin-flavonoid compound which can prevent intrauterine growth restriction (IUGR) via suppression of antiangiogenic factor production in preeclampsia mice model.


Keywords


Apium graveolens; preeclampsia; IUGR; sFlt-1

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References

Ahmed, A. & Perkins, J., 2000, ‘Angiogenesis and intrauterine growth restriction’, Best Pract. Res. Clin. Obstet. Gynaecol. 14, 981–998

Ahmed, A. & Ramma, W., 2015, ‘Unravelling the theories of pre-eclampsia: Are the protective pathways the new paradigm?’, Br. J. Pharmacol. 172, 1574–1586

Cunningham, F. G., Leveno, K. J., Bloom, S. L., Spong, C. Y., Dashe, J. S., Hoffman, B. L., Sheffield, J. S., 2014, Williams obstetrics (24th edition). New York: McGraw-Hill Education

Da Silva, I. L. et al., 2017, ‘Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells’, Sci. Rep. 7, 1–11

Djurisic, S. & Hviid, T. V. F., 2014, ‘HLA class Ib molecules and immune cells in pregnancy and preeclampsia’, Front. Immunol. 5, 1–17

Durmanova, V., Homolova, M., Drobny, J., Shawkatova, I. & Buc, M., 2013, ‘Role of HLA-G and other immune mechanisms in pregnancy’, Open Life Sci. 8

Herraiz, I. et al., 2015, ‘Angiogenesis-related biomarkers (sFlt-1/PLGF) in the prediction and diagnosis of placental dysfunction: An approach for clinical integration’ Int. J. Mol. Sci. 16, 19009–19026

Herse, F. & LaMarca, B., 2013, ‘Angiotensin II type 1-Receptor Autoantibody (AT1-AA)-mediated pregnancy hypertension’, Am J Reprod Immunol 76, 211–220

Hidayati, R. & Kalim, H., 2015, ‘Mangosteen Peel Extracts Decreased Nfκ-B, sFlt-1, TNF-α, Blood Pressure and Proteinurine in Mouse Model of Preeclampsia’, J. Appl. Environ. Biol. Sci. 5, 1–8

Jin, B. et al, 2009, ‘Apigenin protects endothelium-dependent relaxation of rat aorta against oxidative stress’. Eur. J. Pharmacol. 616, 200–205

Jorge, V. G., 2013, ‘Vasorelaxant activity of extracts obtained Possible source for vasorelaxant molecules antihypertensive effect from Apium graveolens : isolation with potential antihypertensive effect’ Asian Pac. J. Trop. Biomed. 3, 776–779

Kalkunte, S. et al., 2010, ‘Sera from preeclampsia patients elicit symptoms of human disease in mice and provide a basis for an in vitro predictive assay’, Am. J. Pathol. 177, 2387–2398

Kooti, W. & Daraei, N., 2017, ‘A Review of the Antioxidant Activity of Celery (Apium graveolens L.)’, J. Evid. Based. Complementary Altern. Med. 1–6

Lockwood, C. J. et al., 2008, ‘Preeclampsia-Related Inflammatory Cytokines Regulate Interleukin-6 Expression in Human Decidual Cells’, Am. J. Pathol. 172, 1571–1579

Manolescu, B., Oprea, E., Busu, C. & Cercasov, C., 2009, ‘Natural compounds and the hypoxia-inducible factor (HIF) signalling pathway’, Biochimie 91, 1347–1358

Maynard, S. E. & Karumanchi, S. A., 2011, ‘Angiogenic Factors and Preeclampsia’, Semin. Nephrol. 31, 33–46

Olszanecki, R., Gebska, A., Kozlovski, V. I. & Gryglewski, R. J., 2002, ‘Flavonoids and nitric oxide synthase’, J. Physiol. Pharmacol. 53, 571–584

Powe, C. E., Levine, R. J. & Karumanchi, S. A., 2011, ‘Preeclampsia, a disease of the maternal endothelium: The role of antiangiogenic factors and implications for later cardiovascular disease’, Circulation 123, 2856–2869

Rahma, H., Indrawan, I. W. A., Nooryanto, M., Rahajeng & Keman, K., 2017, ‘Effect of a black cumin (Nigella sativa) ethanol extract on placental angiotensin II type 1-receptor autoantibody (AT1-AA) serum levels and endothelin-1 (ET-1) expression in a preeclampsia mouse model’. J. Taibah Univ. Med. Sci. 1

Saito, S., 2010, ‘Th17 cells and regulatory T cells: new light on pathophysiology of preeclampsia’. Immunol. Cell Biol. 88, 615–617

Santner-Nanan, B. et al., 2009, ‘Systemic Increase in the Ratio between Foxp3+ and IL-17-Producing CD4+ T Cells in Healthy Pregnancy but Not in Preeclampsia’, J. Immunol. 183, 7023–7030

Sharma, D., Shastri, S., Farahbakhsh, N. & Sharma, P., 2016, ‘Intrauterine growth restriction – part 1’, J Matern Fetal Neonatal Med. 29(24): 3977–3987

Soetrisno, Sulistyowati, S., & Wibowo, A.S., 2017, ‘L-arginine improves uterine spiral arterial wall thickness in mouse models of preeclampsia’, Univ Med, 36:131-7

Sones, J. L. & Davisson, R. L., 2016, ‘Preeclampsia, of mice and women’, Physiol. Genomics 48, 565–572

Steegers, E. A. P., Von Dadelszen, P., Duvekot, J. J. & Pijnenborg, R., 2010, ‘Pre-eclampsia’, Lancet 376, 631–644

Sulistyowati, S., Abadi, A. & Wijiati, 2010, ‘Low Class Ib (HLA-G/Qa-2) MHC Protein Expression against Hsp-70 and VCAM-1 Profile on Preeclampsia. An observation on experimental animal Mus Musculus with Endothelial Dysfunction model’, Indones J Obs. Gynecol 34, 103–107

Sulistyowati, S. et al., 2017, ‘Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model’, J. Perinat. Med. 45, 245–251

Tang, Y. et al., 2015, ‘Hypermethylation of the HLA-G promoter is associated with preeclampsia’ Mol. Hum. Reprod. 21, 736–744

The Practice Committee of the American Society for Reproductive Medicine, 2008, ‘Gonadotropin preparations: past, present, and future perspectives’, Fertil. Steril. 90, 13–20

Turner, P. V, Brabb, T., Pekow, C. & Vasbinder, M., 2011, ‘Administration of substances to laboratory animals: routes of administration and factors to consider’, J Am Assoc Lab Anim Sci 50, 600–613

Wicaksono, B. A., Candra, S., Baktiyani, W. & Fitri, L. E., 2015, ‘Intraperitoneal Injection of High Tumor Necrosis Factor (TNF- α) Serum Increase Soluble Fms-like Tyrosine Kinase 1 (sFlt-1) and Blood Pressure of Pregnant Mice’, J. Trop. Life. Sci. 5, 8–13

Yamagata, K., Miyashita, A., Chino, M. & Matsufuji, H., 2011, ‘Apigenin inhibits tumor necrosis factor alpha plus high glucose-induced LOX-1 expression in human endothelial cells’, Microvasc. Res. 81, 60–67

Yao, Y., Sang, W., Zhou, M. & Ren, G., 2011, ‘Phenolic composition and antioxidant activities of 11 celery cultivars’, J. Food Sci. 75, 9–13

Zhang, Y., Park, Y., Kim, T., Fang, L. & Ahn, H., 2002, ‘Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin’, Gen. Pharmacol. 35, 341–347

Zygmunt, M., Herr, F., Münstedt, K., Lang, U., Liang, O.D., 2003, ‘Angiogenesis and vasculogenesis in pregnancy’, Eur J Obstet Gynecol Reprod Biol. 22;110 Suppl 1:S10-8.




DOI: https://doi.org/10.22146/mot.36112

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