Abstract
Cistus laurifolius L., Cistaceae, has long been used for traditional treatments against various skin diseases in Turkey. The study was designed to observe an antiviral effect against anti-HSV-1 activity and to develop an antiviral herbal lip balm. The cytotoxic activities of C. laurifolius extracts and their ability to inhibit cytopathic effect were evaluated by colorimetric XTT test on Vero cells. In the first experiments, crude extracts did not show antiviral activity due to high toxicity. The solid phase extraction, purification, and polyphenolic enrichment methods were applied for EtOH, MeOH, and H2O extracts to reduce the toxicity of the extracts and in this way, high antiviral results were obtained. Polyphenol-enriched fractions of MeOH (SI 431.17) and H2O (SI > 455.37), purified with solid phase extraction, showed high antiviral effects against HSV-1. In vitro, cytotoxicity for polyphenol-enriched of EtOH, MeOH, and H2O from C. laurifolius was investigated on human dermal fibroblast cells to develop herbal lip balm formulations. All fractions had no cytotoxic effect on human dermal fibroblast cells. Herbal lip balm formulations were also developed, and evaluation tests were performed on the herbal lip balm in this study. Twenty-one different phenolic contents in the extracts were dereplicated by HPLC–DAD. The hyperoside (49.37 ± 0.53 mg/g extract), isoquercitrin (48.05 ± 0.74 mg/g extract), rutin (45.84 ± 1.02 mg/g extract), epicatechin (14.83 ± 1.00 mg/g extract), quercetin-3-O-glucopyranoside (13.35 ± 0.16 mg/g extract), catechin (12.80 ± 0.1 mg/g extract), caffeic acid (3.15 ± 0.18 mg/g extract), and apigenin (6.30 ± 0.10 mg/g extract) were determined as the major components present in the polyphenol-enriched fractions of C. laurifolius H2O extract. The results show that the polyphenol-enriched fractions of C. laurifolius extracts have good anti-Herpes simplex virus type-1 activity, and the herbal formulation with antiviral activity has a better option with minimum side effects.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahmed S, Jubair A, Hossain MA, Hossain MM, Azam MS, Biswas M (2021) Free radical-scavenging capacity and HPLC-DAD screening of phenolic compounds from pulp and seed of Syzygiumclaviflorum fruit. J Agr Food Res 6:100203. https://doi.org/10.1016/j.jafr.2021.100203
Amale SS, Kamble RR, Wamane VB, Rode AR (2023) A research on herbal lip balm. Tıjer Int Res J 10:142–160
Ark M, Ustun O, Yesilada E (2004) Analgesic activity of Cistus laurifolius in mice. Pharm Biol 42:176–178. https://doi.org/10.1080/13880200490512250
Barrajon-Catalan E, Fernandez-Arroyo S, Roldan C, Guillen E, Saura D, Segura-Carretero A, Micol V (2011) A systematic study of the polyphenolic composition of aqueous extracts deriving from several Cistus genus species. Evolutionary Relationship Phytochem Anal 22:303–312. https://doi.org/10.1002/pca.1281
Barros L, Dueñas M, Aloes CT, Silvac S, Henriques M, Santos-Buelga C, Ferreiraa CFRI (2013) Antifungal activity and detailed chemical characterization of Cistus ladanifer phenolic extracts. Ind Crops Prod 41:41–45. https://doi.org/10.1016/j.indcrop.2012.03.038
Benali T, Bouyahya A, Habbadi K, Zengin G, Khabbach A, Achbani H, Hammani K (2020) Chemical composition and antibacterial activity of the essential oil and extracts of Cistus ladaniferus subsp. ladanifer and Menthasuaveolens against phytopathogenic bacteria and their ecofriendly management of phytopathogenic bacteria. Biocatal Agric Biotechnol 28:101696. https://doi.org/10.1016/j.bcab.2020.101696
Čanadanović-Brunet JM, Djilas SM, Ćetković GS, Tumbas VT, Mandić AI, Čanadanović VM (2006) Antioxidant activities of different Teucriummontanum L. extracts. Int J Food Sci Technol 41:667–673. https://doi.org/10.1111/j.1365-2621.2006.01133.x
Chattopadhyay D, Chawla-Sarkar M, Chatterjee T, Dey RS, Bag P, Chakraborti S, Khan MTH (2009) Recent advancements for the evaluation of antiviral activities of natural products. N Biotechnol 25:347–368. https://doi.org/10.1016/j.nbt.2009.03.007
Comandini O, Contu M, Rinaldi AC (2006) An overview of Cistus ectomycorrhizal fungi. Mycorrhiza 16:381–395. https://doi.org/10.1007/s00572-006-0047-8
Cruz-Filho IJC, Barros BRS, Aguiar LMS, Navarro CDC, Lorena PVMB, Rocha GJM, Vercesi AE, Maior AMS (2019) Lignins isolated from prickly pear cladodes of the species Opuntiafícus-indica (Linnaeus) Miller and Opuntiacochenillifera (Linnaeus) Miller induces mice splenocytes activation, proliferation and cytokines production. Int J Biol Macromol 123:1331–1339. https://doi.org/10.1016/j.ijbiomac.2018.09.120
Demetzos D, Dimas K, Hatziantoniou S, Anastasaki T, Angelopoulou D (2001) Cytotoxic and anti-inflammatory activity of labdane and cis-clerodane type diterpenes. Planta Med 67:614–618. https://doi.org/10.1055/s-2001-17362
Demirci T, Haskoylu ME, Eroğlu MS, Hemberger J, ToksoyOner E (2020) Levan-based hydrogels for controlled release of amphotericin b for dermal local antifungal therapy of candidiasis. Eur J Pharm Sci 145:105–255. https://doi.org/10.1016/j.ejps.2020.105255
Dimas K, Demetzos C, Angelopoulou D, Kolokouris A, Mavromoustakos T (2000) Biological activity of myricetin and its derivatives against human leukemic cell lines in vitro. Pharmacol Res 42:475–478. https://doi.org/10.1006/phrs.2000.0716
Dinda M, Dasgupta U, Singh N, Bhattacharyya D (2015) Pı3k-mediated proliferation of fibroblasts by Calendula officinalis tincture: ımplication in wound healing. PTR 29:607–616. https://doi.org/10.1002/ptr.5293
Dolar N, Serdaroglu S, Yilmaz G, Ergin S (2006) Seroprevalence of herpes simplex virus type 1 and type 2 in Turkey. JEADV 20:1232–1236. https://doi.org/10.1111/j.1468-3083.2006.01766.x
Duman R, Dogan HH, Karakıs H (2019) Antiviral activity of Spartiumjunceum against Herpes simplex virus type-1: an in vitro study. Int J Pharm Sci 10:3274–3282. https://doi.org/10.13040/IJPSR.0975-8232.10(7).3274-82
Ehrhardt C, Hrincius ER, Korte V, Mazur I, Droebner K, Poetter A, Dreschers S, Schmolke M, Planz O, Ludwig S (2007) A polyphenol-rich plant extract, CYSTUS052, exerts anti-influenza virus activity in cell culture without toxic side effects or the tendency to induce viral resistance. Antivir Res 76:38–47. https://doi.org/10.1016/j.antiviral.2007.05.002
Fatahzadeh M, Schwartz RA (2007) Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol 57:737–763. https://doi.org/10.1016/j.jaad.2007.06.027
Ghildiyal R, Prakash V, Chaudhary VK, Gupta V, Gabrani R (2020) Phytochemicals as antiviral agents: recent updates. Nature 12:279–295. https://doi.org/10.1007/978-981-15-1761-7_12
Hayati F, Chabib L (2016) Formulation and evaluation of herbal lipsticks from carrot (Daucuscarota L.) extract. Int J Pharm 8:403–405
İğde FA, Yazıcı Z, İğde M (2011) Seroepidemiological study of herpes simplex virus type 1 in the black sea region of Turkey Balkan. Med J 28:37–42. https://doi.org/10.5174/tutfd.2009.02681.2
Kadu M, Vishwasrao S, Singh S (2015) Review on natural lip balm. Int J Cosmet Sci 5:1–7
Kaerber G (1964) Diagnostic procedures for virus and ricketsial disease. J Am Public Health Assoc 3:48–50
Kasparaviciene G, Savickas A, Kalveniene Z, Velziene S, Kubiliene L, Bernatoniene J (2016) Evaluation of beeswax influence on physical properties of lip balm using instrumental and sensory methods. Evid Based Compl Altern Med 2016:3816460. https://doi.org/10.1155/2016/3816460
Kumar P, Nagarajan A, Pradeep DU (2018) Analysis of cell viability by the MTT assay. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/pdb.prot095505
KupeliAkkol E, Erdogan OI, Yesilada E (2012) Anticholinesterase and antioxidant effects of the ethanol extract, ethanol fractions and isolated flavonoids from Cistus laurifolius L. leaves. Food Chem 131:626–631. https://doi.org/10.1016/j.foodchem.2011.09.041
Kupeli E, Yesilada E (2007) Flavonoids with anti-inflammatory and antinociceptive activity from Cistus laurifolius L. leaves through bioassay-guided procedures. J Ethnopharmacol 112:524–530. https://doi.org/10.15584/ejcem.2018.2.8
Latiff NA, Ong PY, Abd Rashid SNA, Abdullah LC, Mohd Amin NA, Fauzi NAM (2021) Enhancing recovery of bioactive compounds from Cosmos caudatus leaves via ultrasonic extraction. Sci Rep 11:17297. https://doi.org/10.1038/s41598-021-96623-x
Liu L, Jiang X, Wenhui Y (2019) Dracohodin perochlorate stimulates fibroblast proliferation via EGFR activation and downstream ERK/CREB and PI3K/Akt/ mTOR pathways in vitro. Evid Based Compl Altern Med 2019:6027186. https://doi.org/10.1155/2019/6027186
Lyu SY, Rhim JY, Park WB (2005) Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. Arch Pharm Res 28:1293–1301. https://doi.org/10.1007/BF02978215
Madavaraju K, Koganti R, Volety I, Yadavalli T, Shukla D (2021) Herpes simplex virus cell entry mechanisms: an update. Front Cell Infect Microbiol 10:617578. https://doi.org/10.3389/fcimb.2020.617578
Magalhães PJ, Vieira JS, Gonçalves LM, Pacheco JG, Guido LF, Barros AA (2010) Isolation of phenolic compounds from hop extracts using polyvinylpolypyrrolidone: characterization by high-performance liquid chromatography–diode array detection–electrospray tandem mass spectrometry. J Chromatogr A 1217:3258–3268. https://doi.org/10.1016/j.chroma.2009.10.068
Rebensburg S, Helfer M, Schneider M, Koppensteiner H, Eberle J, Schindler M, Koppensteiner H, Eberle J, Schindler M, Gurtler L, Brack Werner R (2016) Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins. Sci Rep 6:20394. https://doi.org/10.1038/srep20394
Sayah K, Chemlal L, Marmouzi M, El-Jemli Y, Abbes CME, F, (2017) In vivo anti-inflammatory and analgesic activities of Cistus salviifolius L. and Cistus monspeliensis L. aqueous extracts. S Afr J Bot 113:160–163. https://doi.org/10.1016/j.sajb.2017.08.015
Skendi A, Irakli M, Chatzopoulou P (2017) Analysis of phenolic compounds in Greek plants of Lamiaceae family by HPLC. J Appl Res Med Arom Plant 6:62–69. https://doi.org/10.1016/j.jarmap.2017.02.001
Stepien A, Aebisher D, BartusikAebisher D (2018) Biological properties of Cistus species. Eur J Clin Exp Med 16:127–132. https://doi.org/10.15584/ejcem.2018.2.8
Ustun O, Ozçelik B, Baykal T (2016) Bioactivities of ethanolic extract and its fractions of Cistus laurifolius L. (Cistaceae) and Salvia wiedemannii Boiss. (Lamiaceae) species. Pharmacogn Mag 12:S82–S85. https://doi.org/10.4103/0973-1296.176125
Xiang YF, Pei Y, Wang YF (2008) Current status of natural products from plants as anti-herpes simplex virus-1 agents. Virol Sin 23:305–314. https://doi.org/10.1007/s12250-008-2962-7
Yadav A, Karmokar K, Gop R, Mudartha D, Maheshwari V (2020) Formulation and evaluation of herbal lip balm from amaranth leaf colour pigment. Int J Appl Sci 8:653–662. https://doi.org/10.22214/ijraset.2020.6107
Funding
This study was supported by a project of the Afyonkarahisar Health Sciences University Research Foundation, Project No. 19. TIP.001.
Author information
Authors and Affiliations
Contributions
NO, SFE, SÇ, and ÖEA contributed to the study design, data collection, performing of field experiments, statistical analysis, and writing-original draft preparation of the manuscript. HHD, RD, and ÜÜ contributed to the implementation of antiviral experiments, HPLC, and statistical analysis, reviewing and editing the manuscript. All authors read and approved the final manuscript.
Corresponding author
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Okumuş, N., Erdoğmuş, S.F., Doğan, H.H. et al. Anti HSV-1 Activity of Cistus laurifolius and Development of Antiviral Herbal Lip Balm. Rev. Bras. Farmacogn. 34, 625–636 (2024). https://doi.org/10.1007/s43450-024-00513-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43450-024-00513-y