Exploring the Traditional Uses of Thymbra capitata Infusion in Algarve (Portugal): Anti-Inflammatory, Wound Healing, and Anti-Aging

Inflammation plays a pivotal role in the resolution of infection or tissue damage. In addition, inflammation is considered a hallmark of aging, which in turn compromises wound healing. Thymbra capitata is an aromatic plant, whose infusion is traditionally used as an anti-inflammatory and wound-healing agent. In this study, a T. capitata infusion was prepared and characterized by HPLC-PDA-ESI-MSn and its safety profile determined by the resazurin metabolic assay. The anti-inflammatory potential was revealed in lipopolysaccharide (LPS)-stimulated macrophages by assessing nitric oxide (NO) release and levels of inducible nitric oxide synthase (iNOS) and the interleukin-1β pro-form (pro-IL-1β). Wound-healing capacity was determined using the scratch assay. The activity of senescence-associated β-galactosidase was used to unveil the anti-senescent potential, along with the nuclear accumulation of yH2AX and p21 levels. The antiradical potential was assessed by DPPH and ABTS scavenging assays. The infusion contains predominantly rosmarinic acid and salvianolic acids. The extract decreased NO, iNOS, and pro-IL-1β levels. Interestingly, the extract promoted wound healing and decreased β-galactosidase activity, as well as yH2AX and p21 levels. The present work highlights strong antiradical, anti-inflammatory, and wound healing capacities, corroborating the traditional uses ascribed to this plant. We have described, for the first time for this extract, anti-senescent properties.

[1]  M. Cruz,et al.  Effect of Thymbra capitata (L.) Cav. on Inflammation, Senescence and Cell Migration , 2023, Nutrients.

[2]  M. Donato,et al.  Exploiting the Crithmum maritimum L. Aqueous Extracts and Essential Oil as Potential Preservatives in Food, Feed, Pharmaceutical and Cosmetic Industries , 2023, Antioxidants.

[3]  G. Zengin,et al.  New Biological and Chemical Evidences of Two Lamiaceae Species (Thymbra capitata and Thymus sipyleus subsp. rosulans): In Vitro, In Silico and Ex Vivo Approaches , 2022, Molecules.

[4]  Fei Yang,et al.  Sodium Danshensu Cream Promotes the Healing of Pressure Ulcers in Mice through the Nrf2/HO-1 and NF-κB Pathways , 2022, Pharmaceuticals.

[5]  M. Jordán,et al.  Polyphenolic Profile of Tunisian Thyme (Thymbra capitata L.) Post-Distilled Residues: Evaluation of Total Phenolic Content and Phenolic Compounds and Their Contribution to Antioxidant Activity , 2022, Molecules.

[6]  L. Lerman,et al.  Cellular senescence: the good, the bad and the unknown , 2022, Nature Reviews Nephrology.

[7]  Zhanyong Guo,et al.  Preparation of chitosan-rosmarinic acid derivatives with enhanced antioxidant and anti-inflammatory activities. , 2022, Carbohydrate polymers.

[8]  Bin Ning,et al.  Apigenin inhibits fibrous scar formation after acute spinal cord injury through TGFβ/SMADs signaling pathway , 2022, CNS neuroscience & therapeutics.

[9]  N. Lall,et al.  Targeting Acne Bacteria and Wound Healing In Vitro Using Plectranthus aliciae, Rosmarinic Acid, and Tetracycline Gold Nanoparticles , 2022, Pharmaceuticals.

[10]  N. Galeotti,et al.  Rosmarinic Acid Reduces Microglia Senescence: A Novel Therapeutic Approach for the Management of Neuropathic Pain Symptoms , 2022, Biomedicines.

[11]  Mingqiu Shan,et al.  A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight , 2022, Molecules.

[12]  M. Cruz,et al.  Chemical Composition and Effect against Skin Alterations of Bioactive Extracts Obtained by the Hydrodistillation of Eucalyptus globulus Leaves , 2022, Pharmaceutics.

[13]  C. A. Stamerra,et al.  The role of nutrition in inflammaging , 2022, Ageing Research Reviews.

[14]  L. Mondello,et al.  Phenolic Compounds, Antioxidant and Antibacterial Activities of Extracts from Aerial Parts of Thymus zygis subsp. gracilis, Mentha suaveolens and Sideritis incana from Morocco , 2022, Chemistry & biodiversity.

[15]  Xiaolei Zhang,et al.  Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells , 2022, Frontiers in Cell and Developmental Biology.

[16]  M. Vinciguerra,et al.  The costs and benefits of senotherapeutics for human health. , 2022, The Lancet. Healthy longevity.

[17]  M. Cruz,et al.  Chemical composition and biological activity of essential oil of Teucrium scordium L. subsp. scordioides (Schreb.) Arcang. (Lamiaceae) from Sardinia Island (Italy) , 2021, Natural product research.

[18]  B. Vázquez-Lasa,et al.  Chitosan - Rosmarinic acid conjugates with antioxidant, anti-inflammatory and photoprotective properties. , 2021, Carbohydrate polymers.

[19]  D. Gupta,et al.  Rosmarinic Acid: A Naturally Occurring Plant Based Agent Prevents Impaired Mitochondrial Dynamics and Apoptosis in Ultraviolet‐B‐Irradiated Human Skin Cells , 2021, Photochemistry and photobiology.

[20]  Chuanbo Ding,et al.  Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota , 2021, Scientific Reports.

[21]  Jia-Ning Dai,et al.  Sodium Danshensu promotes the healing of stage 2 pressure injury wounds in ischemia/reperfusion injury rat models: possible regulation of apoptosis and inflammatory response. , 2021, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan.

[22]  P. Mecocci,et al.  Senotherapeutics: Targeting senescent cells for the main age-related diseases , 2021, Mechanisms of Ageing and Development.

[23]  S. Melov,et al.  Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging. , 2021, American journal of physiology. Heart and circulatory physiology.

[24]  Minho Lee,et al.  Rosmarinic acid represses colitis-associated colon cancer: A pivotal involvement of the TLR4-mediated NF-κB-STAT3 axis , 2021, Neoplasia.

[25]  Byung-Min Choi,et al.  Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD[Formula: see text]-CD38 Axis. , 2021, The American journal of Chinese medicine.

[26]  T. Ma,et al.  Rosmarinic acid prevents refractory bacterial pneumonia through regulating Keap1/Nrf2-mediated autophagic pathway and mitochondrial oxidative stress. , 2021, Free radical biology & medicine.

[27]  A. Moslehi,et al.  SIRT1/NFκB pathway mediates anti-inflammatory and anti-apoptotic effects of rosmarinic acid on in a mouse model of nonalcoholic steatohepatitis (NASH) , 2021, Journal of receptor and signal transduction research.

[28]  Jinfang Zhang,et al.  Apigenin promotes osteogenic differentiation of mesenchymal stem cells and accelerates bone fracture healing via activating Wnt/β-catenin signaling. , 2021, American journal of physiology. Endocrinology and metabolism.

[29]  K. Shaari,et al.  UHPLC-UV/PDA Method Validation for Simultaneous Quantification of Luteolin and Apigenin Derivatives from Elaeis guineensis Leaf Extracts: An Application for Antioxidant Herbal Preparation , 2021, Molecules.

[30]  E. Talero,et al.  Anti-Inflammatory Effects of Rosmarinic Acid-Loaded Nanovesicles in Acute Colitis through Modulation of NLRP3 Inflammasome , 2021, Biomolecules.

[31]  M. Kampa,et al.  The Therapeutic Potential of the Essential Oil of Thymbra capitata (L.) Cav., Origanum dictamnus L. and Salvia fruticosa Mill. And a Case of Plant-Based Pharmaceutical Development , 2020, Frontiers in Pharmacology.

[32]  Dongtao Wang,et al.  Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice , 2020, The journals of gerontology. Series A, Biological sciences and medical sciences.

[33]  A. Türkoğlu,et al.  Comparison of local rosmarinic acid and topical dexpanthenol applications on wound healing in a rat experimental wound model. , 2020, Folia morphologica.

[34]  E. Schapoval,et al.  Anti-inflammatory effect of rosmarinic acid isolated from Blechnum brasiliense in adult zebrafish brain. , 2020, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[35]  Xuan Cao,et al.  A novel salvianolic acid A analog with resveratrol structure and its antioxidant activities in vitro and in vivo , 2020, Drug development research.

[36]  Wafaa H. B. Hassan,et al.  Phytochemical profile, antioxidant and cytotoxic potential of Parkinsonia aculeata L. growing in Saudi Arabia , 2020, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[37]  M. Don,et al.  Detection of polyphenols and tanshinones in commercial Danshen by liquid chromatography with UV and mass spectrometry , 2020 .

[38]  M. Cruz,et al.  Chemical composition of Crithmum maritimum L. essential oil and hydrodistillation residual water by GC-MS and HPLC-DAD-MS/MS, and their biological activities , 2020 .

[39]  A. Eid,et al.  Herbal Medicine for Slowing Aging and Aging-Associated Conditions: Efficacy, Mechanisms, and Safety. , 2020, Current vascular pharmacology.

[40]  Shuang Feng,et al.  Salvianolic Acid A Exhibits Anti-Inflammatory and Antiarthritic Effects via Inhibiting NF-κB and p38/MAPK Pathways , 2020, Drug design, development and therapy.

[41]  A. Doustimotlagh,et al.  The effects of rosmarinic acid on oxidative stress parameters and inflammatory cytokines in lipopolysaccharide-induced peripheral blood mononuclear cells , 2020, Molecular Biology Reports.

[42]  P. Amin,et al.  Correlation of two validated methods for the quantification of naringenin in its solid dispersion: HPLC and UV spectrophotometric methods , 2020, SN Applied Sciences.

[43]  F. Lamari,et al.  Ethnopharmacological survey of medicinal plants traded in herbal markets in the Peloponnisos, Greece , 2020 .

[44]  Yue Liu,et al.  New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach , 2019, Oxidative medicine and cellular longevity.

[45]  Alejandro Lucia,et al.  Chronic inflammation in the etiology of disease across the life span , 2019, Nature Medicine.

[46]  M. Cruz,et al.  Unveiling the bioactive potential of the essential oil of a Portuguese endemism, Santolina impressa. , 2019, Journal of ethnopharmacology.

[47]  Artur M. S. Silva,et al.  Differentiation of Phenolic Composition Among Tunisian Thymus algeriensis Boiss. et Reut. (Lamiaceae) Populations: Correlation to Bioactive Activities , 2019, Antioxidants.

[48]  Antonio J. Pérez-Pulido,et al.  NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice , 2019, Aging cell.

[49]  Jie Xiao,et al.  Rosmarinic acid improved antioxidant properties and healthspan via the IIS and MAPK pathways in Caenorhabditis elegans. , 2019, BioFactors.

[50]  E. Ranzato,et al.  Scratch Wound Healing Assay. , 2019, Methods in molecular biology.

[51]  H. Oliveira,et al.  Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes , 2019, Marine drugs.

[52]  Chia-Fang Tsai,et al.  Protective Effects of Rosmarinic Acid against Selenite-Induced Cataract and Oxidative Damage in Rats , 2019, International journal of medical sciences.

[53]  K. Siems,et al.  Phytochemicals Rosmarinic Acid, Ampelopsin, and Amorfrutin-A Can Modulate Age-Related Phenotype of Serially Passaged Human Skin Fibroblasts in vitro , 2019, Front. Genet..

[54]  K. Bacharı,et al.  Phenolic compounds characterization by LC-DAD- ESI/MSn and bioactive properties of Thymus algeriensis Boiss. & Reut. and Ephedra alata Decne. , 2019, Food research international.

[55]  H. Kestler,et al.  Cohesin-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation , 2018, The Journal of experimental medicine.

[56]  C. Ferri,et al.  Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives , 2018, International journal of molecular sciences.

[57]  M. Cruz,et al.  New insights on the anti-inflammatory potential and safety profile of Thymus carnosus and Thymus camphoratus essential oils and their main compounds. , 2018, Journal of ethnopharmacology.

[58]  L. Cui,et al.  Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice. , 2018, Nanomedicine : nanotechnology, biology, and medicine.

[59]  L. Ferrucci,et al.  Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty , 2018, Nature Reviews Cardiology.

[60]  Zhenzhong Wang,et al.  Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol , 2018, PloS one.

[61]  J. Grillari,et al.  Cellular Senescence and Inflammaging in Age-Related Diseases , 2018, Mediators of inflammation.

[62]  Artur M. S. Silva,et al.  Variation of phenolic constituents of Tunisian Thymus capitatus (L.) Hoff. et Link. populations , 2018 .

[63]  Wei Gao,et al.  Metabolic profile of danshen in rats by HPLC-LTQ-Orbitrap mass spectrometry , 2018, Journal of Zhejiang University-SCIENCE B.

[64]  Tao Zhang,et al.  Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced Mastitis in Mice , 2018, Inflammation.

[65]  H. Hosseinzadeh,et al.  Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain: An evidence of anti-oxidative and anti-inflammatory effects. , 2018, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[66]  K. Ahn,et al.  Protective effects of rosmarinic acid against hydrogen peroxide‑induced cellular senescence and the inflammatory response in normal human dermal fibroblasts. , 2017 .

[67]  M. Bronze,et al.  Characterization of phenolic compounds in chia (Salvia hispanica L.) seeds, fiber flour and oil. , 2017, Food chemistry.

[68]  Shao-Cong Sun,et al.  NF-κB signaling in inflammation , 2017, Signal Transduction and Targeted Therapy.

[69]  Judith Campisi,et al.  Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells , 2017, GeroScience.

[70]  Mosotho J. George,et al.  Highlighting mass spectrometric fragmentation differences and similarities between hydroxycinnamoyl-quinic acids and hydroxycinnamoyl-isocitric acids , 2017, Chemistry Central Journal.

[71]  Wenyi Liang,et al.  Quality Evaluation and Chemical Markers Screening of Salvia miltiorrhiza Bge. (Danshen) Based on HPLC Fingerprints and HPLC-MSn Coupled with Chemometrics , 2017, Molecules.

[72]  T. Stafilov,et al.  LC/DAD/MS n and ICP-AES Assay and Correlations between Phenolic Compounds and Toxic Metals in Endemic Thymus alsarensis from the Thallium Enriched Allchar Locality , 2017, Natural product communications.

[73]  H. Hosseinzadeh,et al.  Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[74]  F. Bucar,et al.  LC-PDA-ESI-MSn analysis of phenolic and iridoid compounds from Globularia spp. , 2016, Journal of mass spectrometry : JMS.

[75]  A. Jain,et al.  Fabrication of Apigenin loaded gellan gum-chitosan hydrogels (GGCH-HGs) for effective diabetic wound healing. , 2016, International journal of biological macromolecules.

[76]  S. An,et al.  Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo. , 2016, International journal of molecular medicine.

[77]  K. Kang,et al.  Rosmarinic Acid Attenuates Cell Damage against UVB Radiation-Induced Oxidative Stress via Enhancing Antioxidant Effects in Human HaCaT Cells , 2016, Biomolecules & therapeutics.

[78]  K. Peru,et al.  The application of HPLC ESI MS in the investigation of the flavonoids and flavonoid glycosides of a Caribbean Lamiaceae plant with potential for bioaccumulation , 2015, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

[79]  Ling Zhao,et al.  Inflammatory responses and inflammation-associated diseases in organs , 2015, Oncotarget.

[80]  E. Llorent-Martínez,et al.  HPLC-ESI-MSn characterization of phenolic compounds, terpenoid saponins, and other minor compounds in Bituminaria bituminosa , 2015 .

[81]  E. Fernandes,et al.  Anti‐inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation , 2015, Basic & clinical pharmacology & toxicology.

[82]  Q. Li,et al.  Apigenin Induces Dermal Collagen Synthesis Via smad2/3 Signaling Pathway , 2015, European journal of histochemistry : EJH.

[83]  Y. Zu,et al.  Effects of rosmarinic acid on liver and kidney antioxidant enzymes, lipid peroxidation and tissue ultrastructure in aging mice. , 2015, Food & function.

[84]  M. Materska.  Flavone C-glycosides from Capsicum annuum L.: relationships between antioxidant activity and lipophilicity , 2015, European Food Research and Technology.

[85]  E. Llorent-Martínez,et al.  Analysis of phenolic compounds in leaves from endemic trees from Madeira Island. A contribution to the chemotaxonomy of Laurisilva forest species , 2015 .

[86]  J. Hoeijmakers,et al.  An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. , 2014, Developmental cell.

[87]  M. Simirgiotis,et al.  HPLC-UV-MS Profiles of Phenolic Compounds and Antioxidant Activity of Fruits from Three Citrus Species Consumed in Northern Chile , 2014, Molecules.

[88]  A. Serafin,et al.  Effects of potassium apigenin and verbena extract on the wound healing process of SKH‐1 mouse skin , 2014, International wound journal.

[89]  S. Sukrong,et al.  Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl. , 2014, Pharmacology Biochemistry and Behavior.

[90]  Ana Maria Carvalho,et al.  Pterospartum tridentatum, Gomphrena globosa and Cymbopogon citratus: A phytochemical study focused on antioxidant compounds , 2014 .

[91]  Manuel Serrano,et al.  Cellular senescence: from physiology to pathology , 2014, Nature Reviews Molecular Cell Biology.

[92]  Rahul,et al.  Protective effect of apigenin against N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in albino rats. , 2014, Mutation research. Genetic toxicology and environmental mutagenesis.

[93]  C. Franceschi,et al.  Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[94]  Ying-Ju Lin,et al.  Effects of Danshensu and Salvianolic Acid B from Salvia miltiorrhiza Bunge (Lamiaceae) on Cell Proliferation and Collagen and Melanin Production , 2014, Molecules.

[95]  A. Khaki,et al.  Effect of rosmarinic acid on sertoli cells apoptosis and serum antioxidant levels in rats after exposure to electromagnetic fields. , 2013, African journal of traditional, complementary, and alternative medicines : AJTCAM.

[96]  S. Sarker,et al.  Exploration of the wound healing potential of Helichrysum graveolens (Bieb.) Sweet: isolation of apigenin as an active component. , 2013, Journal of ethnopharmacology.

[97]  Weidong Zhang,et al.  Structural Characterization and Identification of Major Constituents in Jitai Tablets by High-Performance Liquid Chromatography/Diode-Array Detection Coupled with Electrospray Ionization Tandem Mass Spectrometry , 2012, Molecules.

[98]  H. Seo,et al.  Salvianolic acid A suppress lipopolysaccharide-induced NF-κB signaling pathway by targeting IKKβ. , 2011, International immunopharmacology.

[99]  S. Gorzalczany,et al.  Vicenin-2, a potential anti-inflammatory constituent of Urtica circularis. , 2011, Journal of natural products.

[100]  T. Shirasawa,et al.  Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis , 2009, Journal of neuroscience research.

[101]  P. Beard,et al.  H2AX Is Required for Cell Cycle Arrest via the p53/p21 Pathway , 2009, Molecular and Cellular Biology.

[102]  De-an Guo,et al.  Analysis on the Stability of Total Phenolic Acids and Salvianolic Acid B from Salvia miltiorrhiza by HPLC and HPLC-MSn , 2008 .

[103]  Hongbin Xiao,et al.  Identification of phenolic constituents in Radix Salvia miltiorrhizae by liquid chromatography/electrospray ionization mass spectrometry. , 2006, Rapid communications in mass spectrometry : RCM.

[104]  L. Ng,et al.  Characterization of cigarette tobacco by direct electrospray ionization-ion trap mass spectrometry (ESI-ITMS) analysis of the aqueous extract--a novel and simple approach. , 2004, Journal of agricultural and food chemistry.

[105]  H. Azaizeh,et al.  Ethnopharmacological survey of medicinal herbs in Israel, the Golan Heights and the West Bank region. , 2002, Journal of ethnopharmacology.

[106]  C. Duarte,et al.  Granulocyte–macrophage colony‐stimulating factor activates the transcription of nuclear factor kappa B and induces the expression of nitric oxide synthase in a skin dendritic cell line , 2001, Immunology and cell biology.

[107]  L. Foo,et al.  Salvianolic acid L, a potent phenolic antioxidant from Salvia officinalis , 2001 .

[108]  M. Ali-Shtayeh,et al.  Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants. , 2000, Journal of ethnopharmacology.

[109]  S. Tannenbaum,et al.  Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. , 1982, Analytical biochemistry.