Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats

Author:

Stavrakeva Kristina1,Metodieva Kalina2ORCID,Benina Maria3,Bivolarska Anelia2ORCID,Dimov Ivica2,Choneva Mariya2ORCID,Kokova Vesela1ORCID,Alseekh Saleh34,Ivanova Valentina3ORCID,Vatov Emil3,Gechev Tsanko3ORCID,Mladenova Tsvetelina5,Mladenov Rumen56,Todorov Krasimir5ORCID,Stoyanov Plamen56ORCID,Gyuzeleva Donika5,Popova Mihaela7,Apostolova Elisaveta18ORCID

Affiliation:

1. Department of Pharmacology, Toxicology, and Pharmacotherapy, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria

2. Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria

3. Center of Plant Systems Biology and Biotechnology, 14, Sveti Knyaz Boris I Pokrastitel, Str., 4023 Plovdiv, Bulgaria

4. Max Planck Institute of Molecular Plant Physiology, 1 Am Muehlenberg, 14476 Potsdam, Germany

5. Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv “Paisii Hilendarski”, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria

6. Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria

7. Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria

8. Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria

Abstract

Extracts from medicinal plants are widely used in the treatment and prevention of different diseases. Micromeria frivaldszkyana is a Balkan endemic species with reported antioxidant and antimicrobial characteristics; however, its phytochemical composition is not well defined. Here, we examined the metabolome of M. frivaldszkyana by chromatography–mass spectrometry (GC-MS), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS-MS), and inductively coupled plasma mass spectrometry (ICP-MS). Amino acids, organic acids, sugars, and sugar alcohols were the primary metabolites with the highest levels in the plant extract. Detailed analysis of the sugar content identified high levels of sucrose, glucose, mannose, and fructose. Lipids are primary plant metabolites, and the analysis revealed triacylglycerols as the most abundant lipid group. Potassium (K), magnesium (Mg), zinc (Zn), and calcium (Ca) were the elements with the highest content. The results showed linarin, 3-caffeoil-quinic acid, and rosmarinic acid, as well as a number of polyphenols, as the most abundant secondary metabolites. Among the flavonoids and polyphenols with a high presence were eupatorin, kaempferol, and apigenin—compounds widely known for their bioactive properties. Further, the acute toxicity and potential anti-inflammatory activity of the methanolic extract were evaluated in Wistar rats. No toxic effects were registered after a single oral application of the extract in doses of between 200 and 5000 mg/kg bw. A fourteen-day pre-treatment with methanolic extract of M. frivaldszkyana in doses of 250, 400, and 500 mg/kg bw induced anti-inflammatory activity in the 1st, 2nd, and 3rd hours after carrageenan injection in a model of rat paw edema. This effect was also present in the 4th hour only in the group treated with a dose of 500 mg/kg. In conclusion, M. frivaldszkyana extract is particularly rich in linarin, rosmarinic acid, and flavonoids (eupatorin, kaempferol, and apigenin). Its methanolic extract induced no toxicity in male Wistar rats after oral application in doses of up to 5000 mg/kg bw. Additionally, treatment with the methanolic extract for 14 days revealed anti-inflammatory potential in a model of rat paw edema on the 1st, 2nd, and 3rd hours after the carrageenan injection. These results show the anti-inflammatory potential of the plant, which might be considered for further exploration and eventual application as a phytotherapeutic agent.

Funder

Medical University of Plovdiv through the Interuniversity

Medical University of Plovdiv

Publisher

MDPI AG

Reference59 articles.

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3. (2002). Biological Diversity Act, Republic of Bulgaria, National Assembly. Promulgated, State Gazette No 77/9.08.2002.

4. Peev, D. (2015). Red Data Book of the Republic of Bulgaria, BAS & MoEW. Plants and Fungi.

5. Petrova, A. (2006). Atlas of Bulgarian Endemic Plants, Gea Libris.

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