Assessment of in vivo estrogenic and anti-inflammatory activities of the hydro-ethanolic extract and polyphenolic fraction of parsley (Petroselinum sativum Hoffm.)

Ethnopharmacological relevance: Since the dawn of time, medicinal and aromatic plants (AMPs) represent a
precious heritage for humanity, especially in developing countries, who exploit their virtues in traditional
pharmacopoeia to cope with health problems such as diabetes, kidney stones, ulcer, and digestive disorders.
Petroselinum sativum Hoffm. belongs to Apiaceae family. It is traditionally used to treat arterial hypertension,
diabetes, cardiac disease, renal disease, and recently reported as a plant endowed with a female anti-infertility
effect.
Aim of the study: This study aims to evaluate the in vivo effect of hydro-ethanolic extract and polyphenols of
Petroselinum sativum Hoffm. on cholesterol, protein and estrogen levels, and characterize the chemical composition of polyphenolic fraction. In addition, acute toxicity and anti-inflammatory activity of tested extract was
also investigated.
Materials and methods: Chemical composition of polyphenolic fraction was determined using High-Performance
Liquid Chromatography with Diode-Array Detection (HPLC-DAD). First, toxicological investigations including
sub-acute toxicity were performed by measuring animals weights daily for four weeks. Afterwards, histopathological examination of livers and kidneys, and serum assay of ASAT and ALAT were also checked. Next, the
acute in vivo anti-inflammatory study of the hydro-ethanolic extract and polyphenols of Petroselinum sativum
Hoffm. versus Indomethacin was conducted. Furthermore, we evaluated the estrogenic effect of its hydroethanolic extract and the polyphenolic fraction following biochemical assays for the determination of proteins, cholesterol and estrogen levels.
Results: The results revealed the presence of some phenolic compounds mainly ferulic acid, gallic acid and
quercetin. Petroselinum sativum Hoffm. extracts also showed no evidence of hepatotoxicity nor nephrotoxicity,
with remarkable anti-inflammatory activity, as well as a significant estrogenic effect compared to negative
control.
Conclusion: This study provides a scope of the potential use of Petroselinum sativum Hoffm. extracts in counteracting female infertility issues.
Bibliografia:
- Agyare, C., Appiah, T., Boakye, Y.D., Apenteng, J.A., 2017. Chapter 25 - Petroselinum
crispum: a review. In: Kuete, V. (Ed.), Medicinal Spices and Vegetables from Africa.
Academic Press, pp. 527–547. https://doi.org/10.1016/B978-0-12-809286-
6.00025-X.
- Alhowiriny, T., Al-Sohaibani, M.O., El-Tahir, K.H., Rafatullah, S., 2003. Preliminary
evaluation of the anti-inflammatory and anti-hepatotoxic activities of “Parsley”
Petroselinum crispum in rats. J. Nat. Remedies 3, 54–62.
- Andrews, P., Freyberger, A., Hartmann, E., Eiben, R., Loof, I., Schmidt, U.,
Temerowski, M., Becka, M., 2001. Feasibility and potential gains of enhancing the
subacute rat study protocol (OECD test guideline no. 407) by additional parameters
selected to determine endocrine modulation. A pre-validation study to determine
endocrine-mediated effects of the antiandrogenic drug flutamide. Arch. Toxicol. 75,
65–73. https://doi.org/10.1007/s002040100214.
- Awe, E., Banjoko, S., 2013. Biochemical and Haematological Assessment of Toxic Effects
of the Leaf Ethanol Extract of Petroselinum crispum (Mill) Nyman Ex A.W. Hill
(Parsley) in Rats. https://doi.org/10.1186/1472-6882-13-75.
- Balandrin, M.F., Klocke, J.A., Wurtele, E.S., Bollinger, W.H., 1985. Natural Plant
Chemicals: Source of Industrial and Medicinal Materials, vol. 228. Sci. Wash. DC U.
S. https://doi.org/10.1126/science.3890182
- Bayala, B., Tamboura, H.H., Pellicer, M.R., Zongo, D., Traor´e, A., Ou´edraogo, L.,
Malpaux, B., 2006. Effets ø estrog´eniques du mac´er´e aqueux des feuilles de
Holarrhena floribunda (G. Don) Dur & Schinz chez la rate ovariectomis´ee.
Biotechnol. Agron. Soc. Environ. 10, 173–180.
- Bend, E.F., Oundoum, P.C.O., Njila, M.I.N., Koloko, B.L., Nyonseu, C.D., Mandengue, S.
H., Moundipa, P., Dimo, T., Lemb`e, D.M., 2018. Effect of the aqueous extract of
schumanniophyton magnificum harms on sexual maturation and fertility of
immature (K. Schum) female rat. Pharmacol. Amp Pharm. 9, 415–427. https://doi.
org/10.4236/pp.2018.910031.
- Black, L.J., Sato, M., Rowley, E.R., Magee, D.E., Bekele, A., Williams, D.C., Cullinan, G.J.,
Bendele, R., Kauffman, R.F., Bensch, W.R., 1994. Raloxifene (LY139481 HCI)
prevents bone loss and reduces serum cholesterol without causing uterine
hypertrophy in ovariectomized rats. J. Clin. Invest. 93, 63–69. https://doi.org/
10.1172/JCI116985.
- Chaves, D.S.A., Frattani, F.S., Assafim, M., de Almeida, A.P., de Zingali, R.B., Costa, S.S.,
2011. Phenolic chemical composition of Petroselinum crispum extract and its effect
on haemostasis. Nat. Prod. Commun. 6, 961–964.
- Condrata, D., Cris¸anb, F., Harjaa, F., 2011. Quantitative analysis of gallic acid from
apium graveolens, equisetum arvense l. and petroselinum crispum using high
performance liquid chromatography - ProQuest. Annals of west university of
timisoara, Chemistry 5.
- Della Loggia, R., Tubaro, A., Dri, P., Del Negro, P., 1986. The role of flavonoids in the
anti-inflammatory activity of Chamomilla recutita, 213, 481–484.
Evers, J.L., 2002. Female subfertility. Lancet 360, 151–159. https://doi.org/10.1016/
S0140-6736(02)09417-5.
- Farzaei, M.H., Abbasabadi, Z., Ardekani, M.R.S., Rahimi, R., Farzaei, F., 2013. Parsley: a
review of ethnopharmacology, phytochemistry and biological activities. J. Tradit.
Chin. Med. 33, 815–826. https://doi.org/10.1016/S0254-6272(14)60018-2.
- Fata, S., Tokat, M.A., Bagardi, N., Yilmaz, B., 2019. The traditional practices used by
couples with fertility problems, affecting factors, expected benefits, and learning
paths: the Turkey Sample. Niger. J. Clin. Pract. 22, 806. https://doi.org/10.4103/
njcp.njcp_383_18.
- Ferrandiz, ´ M.L., Alcaraz, M.J., 1991. Anti-inflammatory activity and inhibition of
arachidonic acid metabolism by flavonoids. Agents Actions 32, 283–288.
- Fongod, A.G.N., Veranso, M.C., Libalah, M.N., 2013. Identification and use OF plants IN
treating infertility IN human females IN fako division, Cameroon - ProQuest. Glob. J.
Res. Med. Plants Indig. Med. 2, 724–737.
- Guzick, D.S., Silliman, N.P., Adamson, G.D., Buttram, V.C., Canis, M., Malinak, L.R.,
Schenken, R.S., 1997. Prediction of pregnancy in infertile women based on the
American Society for Reproductive Medicine’s revised classification of
endometriosis. Fertil. Steril. 67, 822–829. https://doi.org/10.1016/S0015-0282(97)
81392-1.
- Ho, C.T., 1992. Antioxidative effect of polyphenol extract prepared from various Chinese
teas. Prev. Med. 21, 520–525.
- Jassim, A.M., 2013. Protective Effect of Petroselinum crispum(parsley)extract on
histopathological changes in liver ,kidney and pancreas induced by Sodium
Valproate- in male Rats. Kufa J. Vet. Med. Sci. 4, 20–27.
- Jensen, E.V., DeSombre, E.R., 1972. Mechanism of action of the female sex hormones.
Annu. Rev. Biochem. 41, 203–230. https://doi.org/10.1146/annurev.
bi.41.070172.001223.
- Jha, U., Asad, M., Asdaq, S.M.B., Das, A.K., Prasad, V.S., 2010. Fertility inducing effect of
aerial parts of Coccinia cordifolia L. in female rats. J. Ethnopharmacol. 127,
561–564. https://doi.org/10.1016/j.jep.2009.10.021.
- Kim, H.P., Son, K.H., Chang, H.W., Kang, S.S., 2004. Anti-inflammatory plant flavonoids
and cellular action mechanisms. J. Pharmacol. Sci. 96, 229–245.
- Kreuzaler, F., Hahlbrock, K., 1973. Flavonoid glycosides from illuminated cell suspension
cultures of Petroselinum hortense. Phytochemistry 12, 1149–1152. https://doi.org/
10.1016/0031-9422(73)85031-9.
- Kreydiyyeh, S.I., Usta, J., 2002. Diuretic effect and mechanism of action of parsley.
J. Ethnopharmacol. 79, 353–357. https://doi.org/10.1016/s0378-8741(01)00408-1.
- Larrey, D., 2002. Epidemiology and individual susceptibility to adverse drug reactions
affecting the liver. Semin. Liver Dis. 22, 145–156. https://doi.org/10.1055/s-2002-
30105.
- Latitudeto. GPS coordinates of taounate, Morocco. Latitude: 34.5366 longitude: -4.6401
[WWW document]. Latitudeto maps geolocated artic. Latit. Longit. Coord. Convers.
n.d URL. https://latitude.to/map/ma/morocco/cities/taounate. accessed 6.8.20.
Lee, P.-C., Lee, W., 1996. In vivo estrogenic action of nonylphenol in immature female
rats. Bull. Environ. Contam. Toxicol. 57, 341–348. https://doi.org/10.1007/
s001289900196.
- Lienou, L.L., Telefo, P.B., Njimou, J.R., Nangue, C., Bayala, B.R., Goka, S.C., Biapa, P.,
Yemele, M.D., Donfack, N.J., Mbemya, J.T., Tagne, S.R., Rodrigues, A.P.R., 2015.
Effect of the aqueous extract of Senecio biafrae (Oliv. & Hiern) J. Moore on some
fertility parameters in immature female rat. J. Ethnopharmacol. 161, 156–162.
https://doi.org/10.1016/j.jep.2014.12.014.
- Limer, J.L., Speirs, V., 2004. Phyto-oestrogens and breast cancer chemoprevention.
Breast Cancer Res. 6, 119. https://doi.org/10.1186/bcr781.
- Mahmood, S., Hussain, S., Malik, F., 2014. Critique of medicinal conspicuousness of
Parsley(Petroselinum crispum): a culinary herb of Mediterranean region. Pak. J.
Pharm. Sci. 27, 193–202. A.O. of the U. Nations, F., 1997. Medicinal plants for forest conservation and health care
Food & Agriculture Org 92, 158, 11.
- Nazik, E., Apay, S., Ozdemir, ¨ F., Nazik, H., 2015. Traditional Practices of Turkish infertile
women: an example from a rural county. Coll. Antropol. 39, 21–25.
- Ogbuewu, I.P., Unamba-Oparah, I.C., Odoemenam, V.U., Etuk, I.F., Okoli, I.C., 2011. The
potentiality of medicinal plants as the source of new contraceptive principles in
males. N. Am. J. Med. Sci. 3, 255–263. https://doi.org/10.4297/najms.2011.3250.
- Parrilla, M.C.G., Heredia, F.J., Troncoso, A.M., 1999. Sherry wine vinegars: phenolic
composition changes during aging. Food Res. Int. 32, 433–440. https://doi.org/
10.1016/S0963-9969(99)00105-2.
- Plazoni´c, A., Bucar, F., Maleˇs, Z., ˇ Mornar, A., Nigovi´c, B., Kujundˇzi´c, N., 2009.
Identification and quantification of flavonoids and phenolic acids in burr parsley
(caucalis platycarpos L.), using high-performance liquid chromatography with Diode
array detection and electrospray ionization mass spectrometry. Molecules 14,
2466–2490. https://doi.org/10.3390/molecules14072466.
- Rao, M.R., Palada, M.C., Becker, B.N., 2004. Medicinal and aromatic plants in
agroforestry systems. In: Nair, P.K.R., Rao, M.R., Buck, L.E. (Eds.), New Vistas in
Agroforestry: A Compendium for 1st World Congress of Agroforestry, 2004,
Advances in Agroforestry. Springer Netherlands, Dordrecht, pp. 107–122. https://
doi.org/10.1007/978-94-017-2424-1_8.
- Slighoua, M., Mahdi, I., Amrati, F.E., Boukhira, S., Youbi, A.E.H.E., Bari, A., Bousta, D.,
2019. Ethnopharmacological survey of medicinal plants used in the traditional
treatment of female infertility in Fez region, Morocco. Phytoth´erapie 1–19. https://
doi.org/10.3166/phyto-2019-0194.
- Sofowora, A., 1996. Medicinal plants and traditional medicine in Africa. Med. Plants
Tradit. Med. Afr. 2, 365–372. https://doi.org/10.1089/acm.1996.2.365, 3.
Strauss, J.F., Schuler, L.A., Rosenblum, M.F., Tanaka, T., 1981. Cholesterol metabolism
by ovarian tissue. In: Paoletti, R., Kritchevsky, D. (Eds.), Advances in Lipid Research.
Elsevier, pp. 99–157. https://doi.org/10.1016/B978-0-12-024918-3.50009-5.
- Suman, Pundir, C.S., 2003. Co-immobilization of cholesterol esterase, cholesterol oxidase
and peroxidase onto alkylamine glass beads for measurement of total cholesterol in
serum. Curr. Appl. Phys., India-Japan Workshop on New Advanced Materials in
Molecular Electronics 3, 129–133. https://doi.org/10.1016/S1567-1739(02)00178-
5.
- Telefo, B.P., Tagne, S.R., Koona, O.E.S., Yemele, D.M., Tchouanguep, F.M., 2011. Effect
of the aqueous extract of justicia insularis t. Anders (acanthaceae) on ovarian
folliculogenesis and fertility of female rats. Afr. J. Tradit. Complement. Altern. Med.
AJTCAM 9, 197–203. of the E Union, P.O., 1986. Council Directive 86/609/EEC of 24 November 1986 on the
approximation of laws, regulations and administrative provisions of the Member
States regarding the protection of animals used for experimental and other scientific
purposes, CELEX1 [WWW Document]. URL. https://op.europa.eu:443/en/publica
tion-detail/-/publication/cc3a8ccb-5a30-4b6e-8da8-b13348caeb0c/language-en.
accessed 12.21.19.
- Wafa, G., Amadou, D., Larbi, K.M., H´ela, E.F.O., 2014. Larvicidal activity, phytochemical
composition, and antioxidant properties of different parts of five populations of
Ricinus communis L. Ind. Crop. Prod. 56, 43–51. https://doi.org/10.1016/j.
indcrop.2014.02.036.
- Wiesenfeld, H.C., Hillier, S.L., Meyn, L.A., Amortegui, A.J., Sweet, R.L., 2012. Subclinical
pelvic inflammatory disease and infertility. Obstet. Gynecol. 120, 37–43. https://doi.
org/10.1097/AOG.0b013e31825a6bc9.
- Wilkinson, A.P., Wah¨ al a, K., Williamson, G., 2002. Identification and quantification of
polyphenol phytoestrogens in foods and human biological fluids. J. Chromatogr. B,
Analytical and Biomedical Aspects of Natural Compounds with Estrogenic Activity
777, 93–109. https://doi.org/10.1016/S1570-0232(02)00095-8.
- Winter, C.A., Risley, E.A., Nuss, G.W., 1962. Carrageenin-induced edema in hind paw of
the rat as an assay for antiinflammatory drugs. Proc. Soc. Exp. Biol. Med. 111,
544–547. https://doi.org/10.3181/00379727-111-27849.
- Yıldız, L., Bas¸kan, K.S., Tütem, E., Apak, R., 2008. Combined HPLC-CUPRAC (cupric ion
reducing antioxidant capacity) assay of parsley, celery leaves, and nettle. Talanta 77,
304–313. https://doi.org/10.1016/j.talanta.2008.06.028.