Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats
Abstract
:1. Introduction
2. Results
2.1. GC-MS Analysis of Primary Metabolites
2.2. UPLC-MS/MS Analysis of Secondary Metabolites
2.3. Quality Control Assesment of M. frivaldszkyana Herba
2.4. Acute Toxicity of Methanolic Extract of M. frivaldszkyana
2.5. Effect of M. frivaldszkyana Methanolic Extract on Carrageenan-Induced Rat Paw Edema
3. Discussion
4. Materials and Methods
4.1. Plant Material and Methanolic Extract Preparation
4.2. Metabolite Extraction and Metabolite Measurements
4.3. Compound Annotation
4.4. Quality Control Assesment of M. frivaldszkyana Tissue
4.4.1. Dry Matter Moisture Content
- TH%—humidity level;
- M0—initial mass before drying;
- M1—mass obtained after drying.
4.4.2. pH Determination
4.4.3. Ash and Organic Matter Content
- OM%—organic matter;
- W0—initial mass of the capsule before calcination;
- W1—mass of the capsule after calcination;
- WS—mass of the sample.
4.4.4. Determination of Mineral Contents
4.5. Data Analysis
4.6. Animals
4.7. Acute Toxicity
- M0—the highest dose leading to no mortality among treated animals;
- M1—the lowest dose at which mortality is detected among treated animals.
4.8. Carrageenan-Induced Paw Edema
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ekor, M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol. 2013, 4, 177. [Google Scholar] [CrossRef] [PubMed]
- Mladenova, T.; Stoyanov, P.; Denev, P.; Dimitrova, S.; Katsarova, M.; Teneva, D.; Todorov, K.; Bivolarska, A. Phytochemical Composition, Antioxidant and Antimicrobial Activity of the Balkan Endemic Micromeria frivaldszkyana (Degen) Velen. (Lamiaceae). Plants 2021, 10, 710. [Google Scholar] [CrossRef] [PubMed]
- Biological Diversity Act; Promulgated, State Gazette No 77/9.08.2002; Republic of Bulgaria, National Assembly: Sofia, Bulgaria, 2002.
- Peev, D. Red Data Book of the Republic of Bulgaria; Plants and Fungi; BAS & MoEW: Sofia, Bulgaria, 2015; Volume 1, p. 550. [Google Scholar]
- Petrova, A. Atlas of Bulgarian Endemic Plants; Gea Libris: Sofia, Bulgaria, 2006; p. 399. [Google Scholar]
- Vukelić, D. Phytochemical Characterization of Polyphenols from Micromeria frivaldszkyana (Deg.) Vel. (Lamiaceae). Master’s Thesis, University of Zagreb, Zagreb, Croatia, 2015. [Google Scholar]
- Nikolova, M.; Aneva, I.; Zhelev, P.; Dimitrova, M. Flavonoid compounds and antioxidant activity of Bulgarian species of Micromeria. Annu. L’université De Sofia “St. Kliment Ohridski” Fac. Biol. 2017, 102, 7–13. [Google Scholar]
- Tabanca, N.; Kirimer, N.; Demirci, B.; Demirci, F.; Başer, K.H. Composition and antimicrobial activity of the essential oils of Micromeria cristata subsp. Phrygia and the enantiomeric distribution of borneol. J. Agric. Food Chem. 2001, 49, 4300–4303. [Google Scholar] [CrossRef] [PubMed]
- Duru, M.E.; Oztürk, M.; Uğur, A.; Ceylan, O. The constituents of essential oil and in vitro antimicrobial activity of Micromeria cilicica from Turkey. J. Ethnopharmacol. 2004, 94, 43–48. [Google Scholar] [CrossRef] [PubMed]
- Stojanović, G.; Palić, I. Antimicrobial and antioxidant activity of Micromeria Bentham species. Curr. Pharm. Des. 2008, 14, 3196–3202. [Google Scholar] [CrossRef] [PubMed]
- Abu-Gharbieh, E.; Shehab, N.G.; Khan, S.A. Anti-inflammatory and gastroprotective activities of the aqueous extract of Micromeria fruticosa (L.) Druce ssp Serpyllifolia in mice. Pak. J. Pharm. Sci. 2013, 26, 799–803. [Google Scholar] [PubMed]
- Shehab, N.G.; Abu-Gharbieh, E.; Almasri, I.M. Chemical composition, docking simulations and burn wound healing effect of Micromeria fruticosa extract and its isolated flavonoidal compound. Pak. J. Pharm. Sci. 2022, 35, 507–517. [Google Scholar] [PubMed]
- Chandra, M.; Prakash, O.; Bachheti, R.K.; Kumar, M.; Pant, A.K. Essential oilcomposition and pharmacological activitiesof Micromeria biflora (Buch.-Ham. Ex D.Don) Benth. collected from Uttarakhandregion of India. J. Med. Plant Res. 2013, 4, 2538–2544. [Google Scholar]
- Ivanova, S.; Pashova, S.; Dyankov, S.; Georgieva, Y.; Ivanov, K.; Benbassat, N.; Koleva, N.; Bozhkova, M.; Karcheva-Bahchevanska, D. Chemical composition and future perspectives of essential oil obtained from a wild population of Stachys germanica L. distributed in the Balkan Mountains in Bulgaria. Int. J. Anal. Chem. 2023, 2023, 4275213. [Google Scholar] [CrossRef]
- Hanafy, A.; Aldawsari, H.M.; Badr, J.M.; Ibrahim, A.K.; Abdel-Hady, S.E.-S. Evaluation of Hepatoprotective Activity of Adansonia digitata Extract on Acetaminophen-Induced Hepatotoxicity in Rats. Evid. Based Complement. Altern. Med. 2016, 2016, 4579149. [Google Scholar] [CrossRef] [PubMed]
- Guerriero, G.; Berni, R.; Muñoz-Sanchez, J.A.; Apone, F.; Abdel-Salam, E.M.; Qahtan, A.A.; Alatar, A.A.; Cantini, C.; Cai, G.; Hausman, J.F.; et al. Production of Plant Secondary Metabolites: Examples, Tips and Suggestions for Biotechnologists. Genes 2018, 9, 309. [Google Scholar] [CrossRef] [PubMed]
- Zheljazkov, V.D.; Micalizzi, G.; Semerdjieva, I.; Mondello, L. Chemical Composition of the Essential Oil of the Endemic Species Micromeria frivaldszkyana (Degen) Velen. Molecules 2019, 24, 440. [Google Scholar] [CrossRef] [PubMed]
- Beale, D.J.; Pinu, F.R.; Kouremenos, K.A.; Poojary, M.M.; Narayana, V.K.; Boughton, B.A.; Komal Kanojia, K.; Dayalan, S.; Jones, O.A.H.; Dias, D.A. Review of recent developments in GC-MS approaches to metabolomics-based research. Metabolomics 2018, 14, 152. [Google Scholar] [CrossRef] [PubMed]
- Osorio, S.; Do, P.T.; Fernie, A. Profiling primary metabolites of tomato fruit with gas chromatography mass spectrometry. Methods Mol. Biol. 2012, 860, 101–109. [Google Scholar] [CrossRef] [PubMed]
- Hussein, R.A.; El-Anssary, A.A. Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants. In Herbal Medicine; Builders, P., Ed.; IntechOpen: London, UK, 2017; Chapter 2; pp. 11–28. [Google Scholar]
- Petkova-Gueorguieva, E.S.; Getov, I.N.; Ivanov, K.V.; Ivanova, S.D.; Gueorguiev, S.R.; Getova, V.I.; Mihaylova, A.A.; Madzharov, V.G.; Staynova, R.A. Regulatory Requirements for Food Supplements in the European Union and Bulgaria. Folia Medica 2019, 60, 41–48. [Google Scholar] [CrossRef] [PubMed]
- Kremer, D.; Müller, I.D.; Stabentheiner, E.; Vitali, D.; Kopricanec, M.; Ruscić, M.; Kosalec, I.; Bezić, N.; Dunkić, V. Phytochemical and micromorphological traits of endemic Micromeria pseudocroatica (Lamiaceae). Nat. Prod. Commun. 2012, 7, 1667–1670. [Google Scholar] [CrossRef]
- Kremer, D.; Stabentheiner, E.; Dunkić, V.; Dragojević, M.I.; Vujić, L.; Kosalec, I.; Ballian, D.; Bogunić, F.; Bezić, N. Micromorphological and chemotaxonomical traits of Micromeria croatica (Pers.) Schott. Chem. Biodivers. 2012, 9, 755–768. [Google Scholar] [CrossRef]
- Yang, B.; Liu, H.; Yang, J.; Gupta, V.K.; Jiang, Y. New insights on bioactivities and biosynthesis of flavonoid glycosides. Trends Food Sci. Technol. 2018, 79, 116–124. [Google Scholar] [CrossRef]
- Halici, Z.; Dengiz, G.O.; Odabasoglu, F.; Suleyman, H.; Cadirci, E.; Halici, M. Amiodarone has anti-inflammatory and anti-oxidative properties: An experimental study in rats with carrageenan-induced paw edema. Eur. J. Pharmacol. 2007, 566, 215–221. [Google Scholar] [CrossRef]
- Zhang, H.; Shang, C.; Tian, Z.; Amin, H.K.; Kassab, R.B.; Abdel Moneim, A.E.; Zhang, Y. Diallyl disulfide suppresses inflammatory and oxidative machineries following carrageenan injection-induced paw edema in mice. Mediat. Inflamm. 2020, 2020, 8508906. [Google Scholar] [CrossRef] [PubMed]
- Tian, D.; Yang, Y.; Yu, M.; Han, Z.Z.; Wei, M.; Zhang, H.W.; Jia, H.M.; Zou, Z.M. Anti-inflammatory chemical constituents of Flos Chrysanthemi indici determined by UPLC-MS/MS integrated with network pharmacology. Food Funct. 2020, 11, 6340–6351. [Google Scholar] [CrossRef] [PubMed]
- Ye, Y.; Chen, Z.; Wu, Y.; Gao, M.; Zhu, A.; Kuai, X.; Luo, D.; Chen, Y.; Li, K. Purification Process and In Vitro and In Vivo Bioactivity Evaluation of Pectolinarin and Linarin from Cirsium japonicum. Molecules 2022, 27, 8695. [Google Scholar] [CrossRef] [PubMed]
- Mottaghipisheh, J.; Taghrir, H.; Boveiri Dehsheikh, A.; Zomorodian, K.; Irajie, C.; Mahmoodi Sourestani, M.; Iraji, A. Linarin, a Glycosylated Flavonoid, with Potential Therapeutic Attributes: A Comprehensive Review. Pharmaceuticals 2021, 14, 1104. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Guang, C.; Zhao, N.; Feng, X.; Qiu, F. LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin. Molecules 2019, 24, 3342. [Google Scholar] [CrossRef] [PubMed]
- Hwang, S.J.; Kim, Y.W.; Park, Y.; Lee, H.J.; Kim, K.W. Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm. Res. 2014, 63, 81–90. [Google Scholar] [CrossRef]
- Hussein, R.M.; Sawy, D.M.; Kandeil, M.A.; Farghaly, H.S. Chlorogenic acid, quercetin, coenzyme Q10 and silymarin modulate Keap1-Nrf2/heme oxygenase-1 signaling in thioacetamide-induced acute liver toxicity. Life Sci. 2021, 277, 119460. [Google Scholar] [CrossRef]
- Magaña, A.A.; Kamimura, N.; Soumyanath, A.; Stevens, J.F.; Maier, C.S. Caffeoylquinic acids: Chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity. Plant J. 2021, 107, 1299–1319. [Google Scholar] [CrossRef] [PubMed]
- Chen, D.; Pan, D.; Tang, S.; Tan, Z.; Zhang, Y.; Fu, Y.; Lü, G.; Huang, Q. Administration of chlorogenic acid alleviates spinal cord injury via TLR4/NF-kappaB and p38 signaling pathway antiinflammatory activity. Mol. Med. Rep. 2018, 17, 1340–1346. [Google Scholar] [CrossRef]
- Murai, T.; Matsuda, S. The Chemopreventive Effects of Chlorogenic Acids, Phenolic Compounds in Coffee, against Inflammation, Cancer, and Neurological Diseases. Molecules 2023, 28, 2381. [Google Scholar] [CrossRef]
- Choi, S.S.; Park, H.R.; Lee, K.A. A Comparative Study of Rutin and Rutin Glycoside: Antioxidant Activity, Anti-Inflammatory Effect, Effect on Platelet Aggregation and Blood Coagulation. Antioxidants 2021, 10, 1696. [Google Scholar] [CrossRef] [PubMed]
- Muvhulawa, N.; Dludla, P.V.; Ziqubu, K.; Mthembu, S.X.H.; Mthiyane, F.; Nkambule, B.B.; Mazibuko-Mbeje, S.E. Rutin ameliorates inflammation and improves metabolic function: A comprehensive analysis of scientific literature. Pharmacol. Res. 2022, 178, 106163. [Google Scholar] [CrossRef] [PubMed]
- Selloum, L.; Bouriche, H.; Tigrine, C.; Boudoukha, C. Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. Exp. Toxicol. Pathol. 2003, 54, 313–318. [Google Scholar] [CrossRef] [PubMed]
- Chriscensia, E.; Arham, A.A.; Wibowo, E.C.; Gracius, L.; Nathanael, J.; Hartrianti, P. Eupatorin from Orthosiphon aristatus: A Review of The Botanical Origin, Pharmacological Effects and Isolation Methods. Curr. Bioact. Compd. 2023, 19, e310323215364. [Google Scholar] [CrossRef]
- Laavola, M.; Nieminen, R.; Yam, M.; Sadikun, A.; Asmawi, M.; Basir, R.; Welling, J.; Vapaatalo, H.; Korhonen, R.; Moilanen, E. Flavonoids eupatorin and sinensetin present in Orthosiphon stamineus leaves inhibit inflammatory gene expression and STAT1 activation. Planta Medica 2012, 78, 779–786. [Google Scholar] [CrossRef] [PubMed]
- González-Cortazar, M.; Salinas-Sánchez, D.O.; Herrera-Ruiz, M.; Román-Ramos, D.C.; Zamilpa, A.; Jiménez-Ferrer, E.; Ble-González, E.A.; Álvarez-Fitz, P.; Castrejón-Salgado, R.; Pérez-García, M.D. Eupatorin and Salviandulin-A, with Antimicrobial and Anti-Inflammatory Effects from Salvia lavanduloides Kunth Leaves. Plants 2022, 11, 1739. [Google Scholar] [CrossRef]
- Alam, W.; Khan, H.; Shah, M.A.; Cauli, O.; Saso, L. Kaempferol as a Dietary Anti-Inflammatory Agent: Current Therapeutic Standing. Molecules 2020, 25, 4073. [Google Scholar] [CrossRef] [PubMed]
- Ali, F.; Rahul; Naz, F.; Jyoti, S.; Siddique, Y.H. Health functionality of apigenin: A review. Int. J. Food Prop. 2017, 20, 1197–1238. [Google Scholar] [CrossRef]
- Ginwala, R.; Bhavsar, R.; Chigbu, D.I.; Jain, P.; Khan, Z.K. Potential Role of Flavonoids in Treating Chronic Inflammatory Diseases with a Special Focus on the Anti-Inflammatory Activity of Apigenin. Antioxidants 2019, 8, 35. [Google Scholar] [CrossRef]
- Yoon, J.H.; Kim, M.Y.; Cho, J.Y. Apigenin: A Therapeutic Agent for Treatment of Skin Inflammatory Diseases and Cancer. Int. J. Mol. Sci. 2023, 24, 1498. [Google Scholar] [CrossRef]
- Boonyarikpunchai, W.; Sukrong, S.; Towiwat, P. Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl. Pharmacol. Biochem. Behav. 2014, 124, 67–73. [Google Scholar] [CrossRef] [PubMed]
- Lucarini, R.; Bernardes, W.A.; Ferreira, D.S.; Tozatti, M.G.; Furtado, R.; Bastos, J.K.; Pauletti, P.M.; Januário, A.H.; Silva, M.L.; Cunha, W.R. In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts, Rosmarinic acid and its acetyl ester derivative. Pharm. Biol. 2013, 51, 1087–1090. [Google Scholar] [CrossRef] [PubMed]
- Usha, T.; Middha, S.K.; Bhattacharya, M.; Lokesh, P.; Goyal, A.K. Rosmarinic Acid, a New Polyphenol from Baccaurea ramiflora Lour. Leaf: A Probable Compound for Its Anti-Inflammatory Activity. Antioxidants 2014, 3, 830–842. [Google Scholar] [CrossRef] [PubMed]
- Giavalisco, P.; Li, Y.; Matthes, A.; Eckhardt, A.; Hubberten, H.M.; Hesse, H.; Segu, S.; Hummel, J.; Köhl, K.; Willmitzer, L. Elemental formula annotation of polar and lipophilic metabolites using 13C, 15N and 34S isotope labelling, in combination with high-resolution mass spectrometry. Plant J. 2011, 68, 364–376. [Google Scholar] [CrossRef] [PubMed]
- Salem, M.A.; Yoshida, T.; Perez de Souza, L.; Alseekh, S.; Bajdzienko, K.; Fernie, A.R.; Giavalisco, P. An improved extraction method enables the comprehensive analysis of lipids, proteins, metabolites and phytohormones from a single sample of leaf tissue under water-deficit stress. Plant J. 2020, 103, 1614–1632. [Google Scholar] [CrossRef] [PubMed]
- Lisec, J.; Schauer, N.; Kopka, J.; Willmitzer, L.; Fernie, A.R. Gas chromatography mass spectrometry–based metabolite profiling in plants. Nat. Protoc. 2006, 1, 387–396. [Google Scholar] [CrossRef] [PubMed]
- Kopka, J.; Schauer, N.; Krueger, S.; Birkemeyer, C.; Usadel, B.; Bergmüller, E.; Dörmann, P.; Weckwerth, W.; Gibon, Y.; Stitt, M.; et al. [email protected]: The Golm Metabolome Database. Bioinformatics 2005, 21, 1635–1638. [Google Scholar] [CrossRef] [PubMed]
- Hummel, C.S.; Lu, C.; Loo, D.D.F.; Hirayama, B.A.; Voss, A.A.; Wright, E.M. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am. J. Physiol. Cell Physiol. 2011, 300, 14–21. [Google Scholar] [CrossRef] [PubMed]
- NF V03-402; Spices and HERBS—Determination of Water Content—Entrainment Method. Spices and Aromatics—Determination of Water Content—Entrainment Method. AFNOR Editions: La Plaine Saint-Denis, France, 1985.
- ISO 928:1997; Spices and Condiments—Determination of Total Ash. International Organization for Standardization: Geneva, Switzerland, 1997.
- Miller, O. Microwave Digestion of Plant Tissue in Closed Vessels. In Handbook of Reference Methods for Plant Analysis, 1st ed.; Kalra, Y.P., Ed.; CRC Press: Boca Raton, FL, USA, 1998; pp. 69–73. ISBN 978-1-57444-124-6. [Google Scholar]
- Kassambra, A. Ggpubr: ‘ggplot2’ Based Publication Ready Plots. R Package Version 0.4.0. 2020. Available online: https://CRAN.R-project.org/package=ggpubr (accessed on 11 September 2022).
- Zheleva-Dimitrova, D.; Simeonova, R.; Gevrenova, R.; Savov, Y.; Balabanova, V.; Nasar-Eddin, G.; Bardarov, K.; Danchev, N. In vivo toxicity assessment of Clinopodium vulgare L. water extract characterized by UHPLC-HRMS. Food Chem. Toxicol. 2019, 134, 110841. [Google Scholar] [CrossRef]
- Lukova, P.; Apostolova, E.; Baldzhieva, A.; Murdjeva, M.; Kokova, V. Fucoidan from Ericaria crinita Alleviates Inflammation in Rat Paw Edema, Downregulates Pro-Inflammatory Cytokine Levels, and Shows Antioxidant Activity. Biomedicines 2023, 11, 2511. [Google Scholar] [CrossRef]
TH (%) | pH | Ashes (%) | OM (%) |
---|---|---|---|
19.4 ± 0.92 | 5.853 ± 0.032 | 88.28 ± 0.25 | 11.72 ± 0.043 |
Ca | K | Mg | Na | B | Al |
283.7 (3.2) | 8734.6 (4.4) | 2094.3 (3.5) | 11.5 (4.4) | 5.4 (3.5) | 28.5 (2.7) |
Mn | Fe | Cu | Zn | Sr | Ba |
17.6 (3.0) | 67.1 (4.0) | 2.5 (1.8) | 534.6 (0.3) | 6.1 (2.7) | 6.0 (1.2) |
Dose (mg/kg bw) | 200 | 400 | 600 | 800 | 1000 | 1500 | 2000 | 5000 |
---|---|---|---|---|---|---|---|---|
Mortality | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 |
Toxic effects | None observed | None observed | None observed | None observed | None observed | None observed | None observed | None observed |
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Stavrakeva, K.; Metodieva, K.; Benina, M.; Bivolarska, A.; Dimov, I.; Choneva, M.; Kokova, V.; Alseekh, S.; Ivanova, V.; Vatov, E.; et al. Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats. Int. J. Mol. Sci. 2024, 25, 5396. https://doi.org/10.3390/ijms25105396
Stavrakeva K, Metodieva K, Benina M, Bivolarska A, Dimov I, Choneva M, Kokova V, Alseekh S, Ivanova V, Vatov E, et al. Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats. International Journal of Molecular Sciences. 2024; 25(10):5396. https://doi.org/10.3390/ijms25105396
Chicago/Turabian StyleStavrakeva, Kristina, Kalina Metodieva, Maria Benina, Anelia Bivolarska, Ivica Dimov, Mariya Choneva, Vesela Kokova, Saleh Alseekh, Valentina Ivanova, Emil Vatov, and et al. 2024. "Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats" International Journal of Molecular Sciences 25, no. 10: 5396. https://doi.org/10.3390/ijms25105396