Rosmarinic acid: insights into analytical, pharmacological & pharmaceutical aspects
DOI:
https://doi.org/10.1590/s2175-97902025e24575Keywords:
Rosmarinic acid, Structure activity relationship, Pharmacological activity, Formulation, ExtractionAbstract
Rosmarinic acid is an indigenous antioxidant molecule derived from a variety of widely available herbal plants. This molecule exhibits a diverse array of pharmacological properties. Recently, there has been an increasing interest in the importance of its effects and its possible use as a natural antioxidant in processed foods. It is a naturally-occurring hydroxylated compound that is commonly found in species. The escalating emergence of antimicrobial resistance and the detrimental repercussions resulting from the excessive utilization of antibiotics are generating a need for novel antimicrobial therapies. Researchers are currently investigating natural compounds as a promising option in this context. Medicinal plants possess a substantial quantity of rosmarinic acid. It is widely used as a spice in various cuisines and is highly regarded in traditional medicine for its healing properties. Rosemary contains significant amounts of powerful antioxidant chemicals, such as phenolic diterpenes, flavonoids, and phenolic. This review aims to analyze the relationship between the structure and activity of Rosmarinic acid, as well as its chemistry, sources, biotechnological production, and neuroprotective effect. Additionally, it will focus on the nano formulation and commercialized formulations of Rosmarinic acid.
Downloads
References
Abbas M, Saeed F, Anjum FM, Afzaal M, Tufail T, Bashir MS et al. Natural polyphenols: An overview. nt. J Food Prop. 2017 Aug 3;20(8):1689-99
Akhtar J, Khan AA, Ali Z, Haider R, Yar MS. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities. Eur J Med Chem. 2017 Jan 5;125:143-89.
Alagawany M, Abd El-Hack ME, Farag MR, Gopi M, Karthik K, Malik YS, et al. Rosmarinic acid: modes of action, medicinal values and health benefits. Anim. Health Res Rev. 2017 Dec;18(2):167-76.
Aldoghachi FE, UM NA, Shari FH. Antioxidant activity of rosmarinic acid extracted and purified from Mentha piperita.Arch. Razi Inst. 2021 Nov;76(5):1279.
Ali M, Zahid S. The neurogenic effects of rosmarinic acid in a mouse model of type 2 diabetes mellitus. Braz J Pharm Sci. 2020 Jun 21;56:e18772.
Alsanad S, Aboushanab T, Khalil M, Alkhamees OA. A descriptive review of the prevalence and usage of traditional and complementary medicine among Saudi diabetic patients. Scientifica (Cairo). 2018;2018(1):6303190.
Amoah SK, Sandjo LP, Kratz JM, Biavatti MW. Rosmarinic acid–pharmaceutical and clinical aspects. Planta Med. 2016 Mar;82(05):388-406.
Anwar S, Shamsi A, Shahbaaz M, Queen A, Khan P, Hasan GM, et al. Rosmarinic acid exhibits anticancer effects via MARK4 inhibition. Sci Rep. 2020 Jun 25;10(1):10300.
Arome D, Sunday AI, Onalike EI, Amarachi A. Pain and inflammation: Management by conventional and herbal therapy. IJPN. 2014 Jan 1;28(1):5-12.
Babaei M, Borja Zamfir GM, Chen X, Christensen HB, Kristensen M, Nielsen J, et al. Metabolic Engineering of Saccharomyces cerevisiae for Rosmarinic Acid Production. ACS Synth Biol. 2020;9(8):1978–88.
Belščak-Cvitanović A, Durgo K, Huđek A, Bačun-Družina V, Komes D. Overview of polyphenols and their properties. InPolyphenols: Properties, recovery, and app. 2018 Jan 1 (pp. 3-44).
Bernatoniene J, Cizauskaite U, Ivanauskas L, Jakstas V, Kalveniene Z, Kopustinskiene DM. Novel approaches to optimize extraction processes of ursolic, oleanolic and rosmarinic acids from Rosmarinus officinalis leaves. Ind Crops Prod. 2016 Jun 1;84:72-9.
Boonyarikpunchai W, Sukrong S, Towiwat P. Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl. PBBHAU. 2014 Sep 1;124:67-73.
Caleja C, Barros L, Prieto MA, Barreiro MF, Oliveira MB, Ferreira IC. Extraction of rosmarinic acid from Melissa officinalis L. by heat-, microwave- and ultrasound-assisted extraction techniques: A comparative study through response surface analysis. Sep Purif Technol. 2017 Oct 2;186:297-308.
Cardullo N, Catinella G, Floresta G, Muccilli V, Rosselli S, Rescifina A, et al. Synthesis of rosmarinic acid amides as antioxidative and hypoglycemic agents. J Nat Prod. 2019 Feb 20;82(3):573-82.
Ceylan Z, Kilinc YB, Yılmaz A, Ünal K, Özdenir B. Production of Rosmarinic Acid Nanoparticles, and Investigation of Anti-Oxidation Effects on Salmon Fish Meat. JOTCSA. 2022;9(2):311-20.
Chaitanya MV, Ramanunny AK, Babu MR, Gulati M, Vishwas S, Singh TG, et al. Journey of Rosmarinic acid as biomedicine to nano-biomedicine for treating cancer: Current strategies and future perspectives. Pharmaceutics. 2022 Nov 7;14(11):2401.
Chandra A. Overview of cancer and medicinal herbs used for cancer therapy. AJP. 2018 May 13;12(01).
Chen X, Su HZ. Detailed studies on the anticancer action of rosmarinic acid in human Hep-G2 liver carcinoma cells: evaluating its effects on cellular apoptosis, caspase activation and suppression of cell migration and invasion. JBUON. 2020 Jul 1;25(4):2011-6.
Chhabra P, Chauhan G, Kumar A. Augmented healing of full thickness chronic excision wound by rosmarinic acid loaded chitosan encapsulated graphene nanopockets. Drug Dev Ind Pharm. 2020 Jun 2;46(6):878-88.
Christopoulos A, Changeux JP, Catterall WA, Fabbro D, Burris TP, Cidlowski JA, et al. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands. Pharmacol Rev. 2014 Oct 1;66(4):918-47.
Chung CH, Jung W, Keum H, Kim TW, Jon S. Nanoparticles derived from the natural antioxidant rosmarinic acid ameliorate acute inflammatory bowel disease. Acs Nano. 2020 May 25;14(6):6887-96.
Coelho VR, Vieira CG, de Souza LP, Moysés F, Basso C, Papke DK, et al. Antiepileptogenic, antioxidant and genotoxic evaluation of rosmarinic acid and its metabolite caffeic acid in mice. Life Sci. 2015 Feb 1;122:65-71.
Colica C, Di Renzo L, Aiello V, De Lorenzo A, Abenavoli L. Rosmarinic acid as potential anti-inflammatory agent. Rev Recent Clin Trials. 2018 Oct 1;13(4):240-2.
Cutrim CS, Cortez MA. A review on polyphenols: Classification, beneficial effects and their application in dairy products. Int J Dairy Technol. 2018 Aug;71(3):564-78.
da Silva SB, Amorim M, Fonte P, Madureira R, Ferreira D, Pintado M, et al. Natural extracts into chitosan nanocarriers for rosmarinic acid drug delivery. Pharm Biol. 2015 May 4;53(5):642-52.
Dewanjee S, Chakraborty P, Mukherjee B, De Feo V. Plant-based antidiabetic nanoformulations: the emerging paradigm for effective therapy. Int J Mol Sci. 2020 Mar 23;21(6):2217.
Elansary HO, Szopa A, Kubica P, Ekiert H, El-Ansary DO, Al-Mana FA, et al. Saudi Rosmarinus officinalis and Ocimum basilicum L. polyphenols and biological activities. Processes. 2020 Apr 10;8(4):446.
Ellithy MM, Aly RM, Tarek HE. Nanoformulated rosemary extract impact on oral cancer: in vitro study. Bulletin of the National Research Centre. 2022 Jul 7;46(1):195.
Elufioye TO, Habtemariam S. Hepatoprotective effects of rosmarinic acid: Insight into its mechanisms of action. Biomed Pharmacother. 2019 Apr 1;112:108600.
Erkan N, Ayranci G, Ayranci E. Antioxidant activities of rosemary (Rosmarinus Officinalis L.) extract, blackseed (Nigella sativa L.) essential oil, carnosic acid, rosmarinic acid and sesamol. Food Chem. 2008 Sep 1;110(1):76-82.
Ertas A, Boga M, Yilmaz MA, Yesil Y, Tel G, Temel H, et al. A detailed study on the chemical and biological profiles of essential oil and methanol extract of Thymus nummularius (Anzer tea): Rosmarinic acid. Ind Crops Prod. 2015 May 1;67:336-45.
Farghali H, Kemelo MK, Wojnarová L, Canová NK. In vitro and in vivo experimental hepatotoxic models in liver research: applications to the assessment of potential hepatoprotective drugs. Physiol Res. 2016 Jul 5;65.
Fonmboh DJ, Abah ER, Fokunang TE, Herve B, Teke GN, Rose NM, et al. An overview of methods of extraction, isolation and characterization of natural medicinal plant products in improved traditional medicine research. Asian J Res Med Pharm Sci. 2020 Aug;9(2):31-57.
Fuster MG, Carissimi G, Montalbán MG, Víllora G. Antitumor activity of rosmarinic acid-loaded silk fibroin nanoparticles on HeLa and MCF-7 cells. Polymers. 2021 Sep 18;13(18):3169.
Govindaraj J, Sorimuthu Pillai S. Rosmarinic acid modulates the antioxidant status and protects pancreatic tissues from glucolipotoxicity mediated oxidative stress in high-fat diet: streptozotocin-induced diabetic rats. MCBI. 2015 Jun;404:143-59.
Han S, Yang S, Cai Z, Pan D, Li Z, Huang Z, et al. Anti-Warburg effect of rosmarinic acid via miR-155 in gastric cancer cells. Drug Des Devel Ther. 2015 May 19:2695-703.
Hasanein P, Mohammad Zaheri L. Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats. Pharm Biol. 2014 Nov 1;52(11):1398-402.
Hassan AHE, Bayoumi WA, El-Sayed SM, Phan TN, Oh T, Ham G, et al. Design, Synthesis, and Repurposing of Rosmarinic Acid-β-Amino-α-Ketoamide Hybrids as Antileishmanial Agents. Pharmaceuticals. 2023;16(11).
Hitl M, Kladar N, Gavarić N, Božin B. Rosmarinic acid–human pharmacokinetics and health benefits. Planta Med. 2021 Apr;87(04):273-82.
Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V, Akbani R. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell. 2018 Apr 5;173(2):291-304.
Ijaz S, Iqbal J, Abbasi BA, Ullah Z, Yaseen T, Kanwal S, et al. Rosmarinic acid and its derivatives: Current insights on anticancer potential and other biomedical applications. Biomed Pharmacother. 2023 Jun 1;162:114687.
Jafarpour S, Hirsch LJ, Gaínza-Lein M, Kellinghaus C, Detyniecki K. Seizure cluster: definition, prevalence, consequences, and management. Seizure. 2019 May 1;68:9-15.
Jayanthy G, Subramanian S. Rosmarinic acid, a polyphenol, ameliorates hyperglycemia by regulating the key enzymes of carbohydrate metabolism in high fat diet–STZ induced experimental diabetes mellitus. BPN. 2014 Jul 1;4(3):431-7.
Khojasteh A, Mirjalili MH, Alcalde MA, Cusido RM, Eibl R, Palazon J. Powerful plant antioxidants: A new biosustainable approach to the production of rosmarinic acid. Antioxidants. 2020 Dec 14;9(12):1273.
Kim D, Maharjan P, Jin M, Park T, Maharjan A, Amatya R, et al. Potential albumin-based antioxidant nanoformulations for ocular protection against oxidative stress. Pharmaceutics. 2019 Jun 26;11(7):297.
Kim GD, Park YS, Jin YH, Park CS. Production and applications of rosmarinic acid and structurally related compounds. Appl Microbiol Biotechnol. 2015 Mar;99:2083-92.
Lawag IL, Sostaric T, Lim LY, Hammer K, Locher C. The development and application of a HPTLC-derived database for the identification of phenolics in honey. Molecules. 2022 Oct 6;27(19):6651.
Li P, Liu A, Li Y, Yuan B, Xiao W, Liu Z, et al. Development and validation of an analytical method based on HPLC-ELSD for the simultaneous determination of rosmarinic acid, carnosol, carnosic acid, oleanolic acid and ursolic acid in rosemary. Molecules. 2019 Jan 17;24(2):323.
Lin SY, Wang YY, Chen WY, Liao SL, Chou ST, Yang CP, et al. Hepatoprotective activities of rosmarinic acid against extrahepatic cholestasis in rats. Food Chem Toxicol. 2017 Oct 1;108:214-23.
Lu YH, Hong Y, Zhang TY, Chen YX, Wei ZJ, Gao CY. Rosmarinic acid exerts anti-inflammatory effect and relieves oxidative stress via Nrf2 activation in carbon tetrachloride-induced liver damage. Food Nutr Res. 2022;66.
Lucarini R, Bernardes WA, Ferreira DS, Tozatti MG, Furtado R, Bastos JK, et al. In vivo analgesic and anti-inflammatory activities of Rosmarinus officinalis aqueous extracts, rosmarinic acid and its acetyl ester derivative. Pharm Biol. 2013 Sep 1;51(9):1087-90.
Luo C, Zou L, Sun H, Peng J, Gao C, Bao L, et al. A review of the anti-inflammatory effects of rosmarinic acid on inflammatory diseases. Front Pharmacol. 2020a Feb 28;11:153.
Luo Y, Ma Z, Xu X, Qi H, Cheng Z, Chen L. Anticancer effects of rosmarinic acid in human oral cancer cells is mediated via endoplasmic reticulum stress, apoptosis, G2/M cell cycle arrest and inhibition of cell migration. J BUON. 2020b Mar 1;25(2):1245-50.
Madureira AR, Nunes S, Campos DA, Fernandes JC, Marques C, Zuzarte M, et al. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: In vitro and animal approaches. Int J Nanomed. 2016 Aug 4:3621-40.
Mahmoud MA, Okda TM, Omran GA, Abd-Alhaseeb MM. Rosmarinic acid suppresses inflammation, angiogenesis, and improves paclitaxel induced apoptosis in a breast cancer model via NF3 κB-p53-caspase-3 pathways modulation. J Appl Biomed. 2021 Oct 1;19(4).
Marchev AS, Vasileva LV, Amirova KM, Savova MS, Koycheva IK, Balcheva-Sivenova ZP, et al. Rosmarinic acid-From bench to valuable applications in food industry. Trends Food Sci Technol. 2021 Nov 1;117:182-93.
Muñoz-Muñoz JL, Garcia-Molina F, Ros E, Tudela J, García-Canovas F, Rodriguez-Lopez JN. Prooxidant and antioxidant activities of rosmarinic acid. J Food Biochem. 2013 Aug;37(4):396-408.
Mushtaq N, Schmatz R, Ahmed M, Pereira LB, da Costa P, Reichert KP, et al. Protective effect of rosmarinic acid against oxidative stress biomarkers in liver and kidney of strepotozotocin-induced diabetic rats. J Physiol Biochem. 2015 Dec;71:743-51.
Mushtaq N, Schmatz R, Pereira LB, Ahmad M, Stefanello N, Vieira JM, et al. Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats. Cell Biochem Funct. 2014 Apr;32(3):287-93.
Ngo YL, Lau CH, Chua LS. Review on rosmarinic acid extraction, fractionation and its anti-diabetic potential. Food Chem Toxicol. 2018 Nov 1;121:687-700.
Öztürk N, Tunçel M, Uysal UD, Oncu-Kaya EM, Koyuncu O. Determination of rosmarinic acid by high-performance liquid chromatography and its application to certain Salvia species and rosemary. Food Anal Methods. 2011 Sep;4:300-6.
Pérez-Tortosa V, López-Orenes A, Martínez-Pérez A, Ferrer MA, Calderón AA. Antioxidant activity and rosmarinic acid changes in salicylic acid-treated Thymus membranaceus shoots. Food Chem. 2012 Jan 15;130(2):362-9.
Petersen M. Rosmarinic acid: new aspects. Phytochem Rev. 2013 Mar;12:207-27.
Prabhu S, Molath A, Choksi H, Kumar S, Mehra R. Classifications of polyphenols and their potential application in human health and diseases. Int J Physiol Nutr Phys Educ. 2021 Jan 1;6(1):293-301.
Qi Y, Zhao X, Liu H, Wang Y, Zhao C, Zhao T, et al. Identification of a quality marker (Q-Marker) of Danhong injection by the zebrafish thrombosis model. Molecules. 2017 Aug 31;22(9):1443.
Rahbardar MG, Amin B, Mehri S, Mirnajafi-Zadeh SJ, Hosseinzadeh H. Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain. Biomed Pharmacother. 2017 Feb 1;86:441-9.
Ramalingam S, Karuppiah M, Thiruppathi M. Antihyperglycaemic potential of rosmarinic acid attenuates glycoprotein moiety in high-fat diet and streptozotocin-induced diabetic rats. All Life. 2020 Jan 1;13(1):120-30.
Razboršek MI. Stability studies on trans-rosmarinic acid and GC–MS analysis of its degradation product. J Pharm Biomed Anal. 2011 Jul 15;55(5):1010-6.
Runtuwene J, Cheng KC, Asakawa A, Amitani H, Amitani M, Morinaga A, et al. Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4. Drug Des Devel Ther. 2016 Jul 7:2193-202.
Shalabalija D, Mihailova L, Crcarevska MS, Karanfilova IC, Ivanovski V, Nestorovska AK, et al. Formulation and optimization of bioinspired rosemary extract loaded PEGylated nanoliposomes for potential treatment of Alzheimer's disease using design of experiments. J Drug Delivery Sci Technol. 2021 Jun 1;63:102434.
Shekarchi M, Hajimehdipoor H, Saeidnia S, Gohari AR, Hamedani MP. Comparative study of rosmarinic acid content in some plants of Labiatae family. Pharmacogn Mag. 2012 Jan;8(29):37.
Sik B, Hanczné Lakatos E, Kapcsándi V, Székelyhidi R, Ajtony Z. Investigation of the long-term stability of various tinctures belonging to the lamiaceae family by HPLC and spectrophotometry method. Chem Pap. 2021 Nov;75(11):5781-91.
Sotnikova R, Okruhlicova L, Vlkovicova J, Navarova J, Gajdacova B, Pivackova L, et al. Rosmarinic acid administration attenuates diabetes-induced vascular dysfunction of the rat aorta. J Pharm Pharmacol. 2013 May;65(5):713-23.
Stansbury J, Saunders P, Winston D, Zampieron E. Rosmarinic acid as a novel agent in the treatment of autoimmune disease. J Restor Med. 2012 Sep 1;1(1):112-6.
Swisłocka R, Regulska E, Karpinska J, Swiderski G, Lewandowski W. Molecular structure and antioxidant properties of alkali metal salts of rosmarinic acid. Experimental and DFT studies. Molecules. 2019;24(14)
Tawfeeq AA, Mahdi MF, Abaas IS, Alwan AH. Isolation, quantification, and identification of rosmarinic acid, gas chromatography-mass spectrometry analysis of essential oil, cytotoxic effect, and antimicrobial investigation of rosmarinus officinalis leaves. Asian J Pharm Clin Res. 2018 Jun 7;11(6):126-32.
Wang CC, Hsieh PW, Kuo JR, Wang SJ. Rosmarinic acid, a bioactive phenolic compound, inhibits glutamate release from rat cerebrocortical synaptosomes through GABAA receptor activation. Biomolecules. 2021 Jul 15;11(7):1029.
Yilmaz MA. Simultaneous quantitative screening of 53 phytochemicals in 33 species of medicinal and aromatic plants: A detailed, robust and comprehensive LC–MS/MS method validation. Ind Crops Prod. 2020 Jul 1;149:112347.
Yücel Ç, Şeker Karatoprak G, Değim İT. Anti-aging formulation of rosmarinic acid- loaded ethosomes and liposomes. J Microencapsul. 2019 Feb 17;36(2):180-91.
Downloads
Published
Data Availability Statement
Not informed.
Issue
Section
License
Copyright (c) 2025 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.
