Norditerpenoid alkaloids from Aconitum refractum var. circinatum as autophagy inducers.

A total of twenty-two diterpenoid alkaloids, including ten unprecedented ones, namely refractines C-L, were isolated from the roots of Aconitum refractum (Finet et Gagnep.) Hand.-Mazz. Refractine C was the first example of a natural diterpenoid alkaloid wherein C-19 is linked to N position by an oxaziridine ring. Refractine L was a rare glycosidic diterpenoid alkaloid with fructofuranoside. Most of the isolated compounds obtained from a previous study were screened for their anti-inflammatory and myocardial protective activities. The autophagy-inducing effects of some of these compounds on RAW 264.7 cells were evaluated by assessing the expression of microtubule-associated protein 1 light chain 3 (LC3-II/LC3-I). Results revealed that some compounds exerted varying levels of inhibitory effects on the proliferative activity of RAW 264.7 cells.

Liver-boosting potential: chicory compound-mediated silver nanoparticles for hepatoprotection-biochemical and histopathological insights.

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20 mg/kg of body weight), fourth group (CCl4+chicory) (1.75 mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35 mg/kg), sixth group (CCl4 + chicory of 3.25 mg/kg), seventh group (CCl4 +AgNPs 1.75 mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35 mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25 mg/kg of b. wt.). Blood samples were taken 24 h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25 mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

Bioactive neolignan, iridoid and flavonoid glycosides from the leaves of Vaccinium bracteatum.

Two neolignan glycosides including a new one (1), along with seven iridoid glycosides (3 - 9) and nine flavonoid glycosides (10 - 18), were isolated from the leaves of Vaccinium bracteatum. Their structures were established mainly on the basis of 1D/2D NMR and ESIMS analyses, as well as comparison to known compounds in the literature. The structure of 1 with absolute stereochemistry was also confirmed by chemical degradation and ECD calculation. Selective compounds showed antiradical activity against ABTS and/or DPPH. Moreover, several isolates also suppressed the production of ROS in RAW264.7 cells and exerted neuroprotective effect toward PC12 cells.

Six New Compounds from the Herbaceous Stems of Ephedra intermedia Schrenket C. A. Meyer and Their Lung-Protective Activity.

Six new compounds, (7R,8S,8'R)-balanophorone (1), (7'S,8'R,8R)-yunnanensin A (2), (3S)-thunberginol C (3), (8R,8'R)-maninsigin B (4), (7S,8R)-4,7,8-dihydroxy-9,9-dimethyl-chroman (5), and 4-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butan-1-one (6), along with eight known compounds (7-14), were isolated from the herbaceous stems of Ephedra intermedia Schrenket C. A. Meyer. Their structures were elucidated based on their spectroscopic (MS, NMR, IR, and UV) data, and their absolute configurations were determined by comparing their calculated and experimental electronic circular dichroic (ECD) spectra. Moreover, compounds 1 and 3-6 were evaluated for their ability to protect human pulmonary epithelial cells (BEAS-2B) from injury induced by lipopolysaccharide (LPS) in vitro. The results showed that compound 6 exhibited a significant protective effect against LPS-induced injury in BEAS-2B, and compound 5 exhibited a slightly protective effect at the concentration of 10 µM.

Isolation, characterization, trypsin inhibition, liver protective and antioxidant activities of arabinoxylan from Massa Medicata Fermentata and its processed products.

Massa Medicata Fermentata (MMF) is a traditional Chinese medicine widely used in feed additives and human medicine. In this study, two neutral polysaccharides (SMMFP-1 and CMMFP-1) were isolated from two forms of MMF (sheng and chao MMF), and their structural characteristics and bioactivities were studied. The results showed that CMMFP-1 had higher average Mw compared with that of SMMFP-1. SMMFP-1 had a lower proportion of Ara, Xyl, GalA, and GlcA, but higher levels of Fuc, Gal, Man, and GulA. Compared with CMMFP-1, SMMFP-1 had a triple helix structure. SMMFP-1 had a layered structure, whereas CMMFP-1 had a curly layered structure. More glycosidic linkage types were found in SMMFP-1 than in CMMFP-1, and SMMFP-1 had a greater number of side chains. More importantly, SMMFP-1 showed better trypsin inhibition activity in vitro, liver-protective activity in vivo, and stronger antioxidant activity in vivo than CMMFP-1. Thus, arabinoxylans may be one of the active substances for different efficacies between MMF and its processed product. The results of this study facilitate the exploration of the correlation between the structural characteristics and biological functionalities of MMF arabinoxylans. Moreover, a theoretical basis is established for further study of the unique properties of arabinoxylans and their applications.

Phytochemical Estimation and Therapeutic Amelioration of Aesculus hippocastanum L. Seeds Ethanolic Extract in Gastric Ulcer in Rats Possibly by Inhibiting Prostaglandin Synthesis.

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE2), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE2 and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS: LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE2 biosynthesis.

Indoloquinazoline alkaloids with cardiomyocyte protective activity against cold ischemic injury from Aspergillus clavatonanicus.

The arthropod-associated fungi have been demonstrated to be a remarkable producer of structurally captivating and bioactive secondary metabolites for drug discovery. In this study, eleven new indoloquinazoline alkaloids, namely aspergilloids A-K (1-11), along with five known congeners (12-16), were obtained from fungus Aspergillus clavatonanicus, which was isolated from the gut of a centipede collected in our Tongji campus. All these compounds were rarely defined by a 6/5/5 indolone ring system in conjugation with a five-membered spiral ring (1-5 and 10-16) or an opening five-membered spiral ring (6-9). Their structures were elucidated by widespread spectroscopic analyses, mainly including HRESIMS and 1D and 2D NMR data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) data analyses. The cardiomyocyte protective activity assay revealed that compounds 1, 2, 5, 12-14, and 16 ameliorated cold ischemic injury at 48 h post cold ischemia (CI), and compounds 1, 5, and 14 prevented cold ischemia induced Ser9 dephosphorylation of GSK3ß at 12 h post CI. Our current study highlights indoloquinazoline alkaloids as the first class of natural cardiomyocyte protective agents against cold ischemic injury, which furnishes promising lead molecules for the development of new cardioprotectants in heart transplantation medicine.

New chemical structures and liver-protective activity of the diterpenoids from Callicarpa rubella.

Callicarpa rubella is a characteristic folk herb in the genus Callicarpa, and has abundant ethnobotanical usage as indigenous medicine in Lingnan area of P. R. China. However, the phytochemical and pharmacological properties of C. rubella was rarely investigated. Now, three new diterpenoids, named rubellapene A-C (1-3), along with five known analogues (4-8), were isolated from C. rubella. Their structures were determined by spectroscopic methods, quantum chemical electronic circular dichroism calculations and single-crystal X-ray diffraction analysis. Notably, the norditerpenoids C18 of clerodane type (rubellapene B) was rarely found in the genus Callicarpa. The liver protective effects of all of the isolates (1-8) were evaluated by the changes of cell viability and transaminase content of AST and ALT in H2O2-induced BRL cells. Compound 1, 3-8 exhibited that potent liver protective effects at different levels.

Isolation and Identification of Antioxidative Peptide from Goose Liver Hydrolysate to Ameliorate Alcohol-Mediated Oxidative Stress Damage in HHL-5 Hepatocytes.

The aim of this study was to isolate and identify antioxidative peptide from goose liver hydrolysate (GLHP) for ameliorating oxidative stress damage by alcohol in HHL-5 hepatocytes. In this research, the target antioxidative peptides in GLHP were separated, purified, and identified via a tangential flow ultrafiltration system combined with size exclusion chromatography (SEC), ion exchange chromatography (IEC), reversed-phase liquid chromatography (RP-LC), and LC-MS/MS. The results suggested that the amino acid sequence of the target antioxidative peptide for ameliorating alcohol-mediated oxidative stress damage in HHL-5 hepatocytes was Leu-Pro-Leu-Pro-Phe-Pro (LPLPFP), which had a molecular weight of 683.41 Da, and was derived from NADH-ubiquinone oxidoreductase chain 1 in goose liver. In addition, LPLPFP was confirmed to have a satisfactory stability and maintained high hepatic protective activity in a simulated gastrointestinal digestion. Moreover, the mechanism of LPLPFP prevented against oxidative stress damage in HHL-5 hepatocytes was attributed to inhibiting the production of reactive oxide species (ROS) by upregulating genes expression in the Ahr-NQO1 signal pathway. In conclusion, these results indicated that dietary GLHP supplementation could ameliorate alcohol-mediated oxidative stress damage and provide an affordable dietary intervention strategy to prevent alcohol-mediated hepatocyte damage.

Cationic Perylene Antivirals with Aqueous Solubility for Studies In Vivo.

Perylene-based compounds are attracting significant attention due to their high broad-spectrum antiviral activity against enveloped viruses. Despite unambiguous results of in vitro studies and high selectivity index, the poor water solubility of these compounds prevented in vivo evaluation of their antiviral properties. In this work, we synthesized a series of compounds with a perylene pharmacophore bearing positively charged substituents to improve the aqueous solubility of this unique type of antivirals. Three types of charged groups were introduced: (1) quaternary morpholinium salts (3a-b); (2) a 2'-O-l-valinyl-uridine hydrochloride residue (8), and (3) a 3-methylbenzothiazolium cation (10). The synthesized compounds were evaluated based both on antiviral properties in vitro (CHIKV, SARS-CoV-2, and IAV) and on solubility in aqueous media. Compound 10 has the greatest aqueous solubility, making it preferable for pre-evaluation by intragastrical administration in a mouse model of lethal influenza pneumonia. The results indicate that the introduction of a positively charged group is a viable strategy for the design of drug candidates with a perylene scaffold for in vivo studies.

Chemical Constituents from the Flowers of Carthamus tinctorius L. and Their Lung Protective Activity.

A new flavonoid, saffloflavanside (1), a new sesquiterpene, safflomegastigside (2), and a new amide, saffloamide (3), together with twenty-two known compounds (4-25), were isolated from the flowers of Carthamus tinctorius L. Their structures were determined based on interpretation of their spectroscopic data and comparison with those reported in the literature. The protective effects against lipopolysaccharide (LPS)-stimulated damage on human normal lung epithelial (BEAS-2B) cells of the compounds were evaluated using MTT assay and cellular immunofluorescence assay. The results showed that compounds 2-3, 8-11, and 15-19 exhibited protective effects against LPS-induced damage to BEAS-2B cells. Moreover, compounds 2-3, 8-11, and 15-19 can significantly downregulate the level of nuclear translocation of NF-κB p-p65. In summary, this study revealed chemical constituents with lung protective activity from C. tinctorius, which may be developed as a drug for the treatment of lung injury.

A novel exopolysaccharide produced by Zygosaccharomyces rouxii with cryoprotective and freeze-drying protective activities.

In the present work, a novel exopolysaccharide EPS-3791 was extracted and purified from a salt-tolerant yeast, Zygosaccharomyces rouxii. Structural analyses showed that EPS-3791 was composed of galactose, glucose and mannose in a molar ration of 1.00: 4.25: 13.30 with a molecular weight of 64.412 kDa. Fourier transform infrared spectroscopy manifested the main functional groups, α- and ß- configurations. Methylated analysis indicated T-Manp-(1→, →2)-Glcp-(1 â†’ and â†’ 2,6)-Manp-(1 â†’ were the main linkages. 800 MHz nuclear magnetic resonance spectroscopy demonstrated the EPS-3791 structure of a novel main chain and branched chain. Atomic force microscope and scanning electron microscope revealed a homogeneous and uniform porous structure. In addition, EPS-3791 was proven to have cryoprotective and freeze-drying protective effects on Lactococcus lactis, and exhibited better protective performance than that of trelahose during freeze-drying of L. lactis, suggesting that EPS-3791 could be developed into cryoprotectant or lyoprotectant applied in food industry.

Synthesis of new coumarin[1,3]oxazine derivatives of 7-hydroxy-6-isobornyl-4-methylcoumarin and their antioxidant activity.

In this work, we synthesized a series of new 9,10-dihydro-2H,8H-chromeno[8,7e][1,3]oxazine-2-on derivatives which incorporate isobornylcoumarin and 1,3-oxazine moieties. A structure-antioxidant activity relationship was analyzed. A comparative evaluation of their radical scavenging activity, antioxidant and membrane-protective properties was carried out in test with DPPH, as well as on the models of Fe2+ /ascorbate-initiated lipid peroxidation and oxidative hemolysis of mammalian red blood cells. The results suggest that all the obtained coumarin[1,3]oxazine derivatives of 7-hydroxy-6-isobornyl-4-methylcoumarin are capable of exhibiting antioxidant activity in various model systems. Compound 7 with a phenyl fragment, combining high radical scavenging activity and the ability to inhibit Fe2+ /ascorbate-initiated peroxidation of animal lipids in a heterogeneous environment, also proved to be the most effective membrane protector and antioxidant in the model of H2 O2 -induced erythrocyte hemolysis.

Glycosides from Buddleja officinalis with their protective effects on photoreceptor cells in light-damaged mouse retinas.

A new phenylethanoid, hebitol IV (1), along with fifteen known glycosides (2-16), were isolated from water extract of the flower buds of Buddleja officinalis. Their structures were elucidated on the basis of 1 D-NMR, 2 D-NMR and MS data. Molecular docking showed the potential activities of the natural products against VEGFR-2. Bioassay results revealed that the compounds 10 and 14 exhibited strong inhibitory activity against VEGFR-2 with IC50 values of 0.51 and 0.32 µM, respectively. Moreover, the potential retinal protective effects of 10 and 14 were then investigated in the mouse model featuring bright light-induced retinal degeneration. The results demonstrated remarkable photoreceptor protective activities of 10 and 14 in vivo.

Preventive Vaccination with Mesenchymal Stem Cells Protects Mice from Lethal Infection Caused by Herpes Simplex Virus 1.

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect almost all organs and tissues, cause genital herpes-the most common sexually transmitted disease-disorders of the central nervous system (CNS), and lead to severe complications in children. Despite the available drugs, the incidence of HSV-1/2 continues to rise. None of the prophylactic vaccine candidates have shown a protective effect in trials nor approval for use in clinical practice. We have investigated the protective properties of mesenchymal stem cells (MSC) isolated from the bone marrow of mice. A comparative analysis of the protective response to the introduction of primary and modified MSCs (mMSC) was carried out using the plasmid containing gene of the HSV and an inactivated virus in a model of lethal HSV-1 infection in mice. mMSCs were obtained by transfection of the Us6 gene encoding glycoprotein D (gD) of the HSV, the plasmid contained the same gene. After twofold immunization with primary MSCs, the formation of antibodies interacting with the viral antigen (according to enzyme immunoassay data) and neutralizing the infectious activity of HSV-1 in the reaction of biological neutralization was observed in the peripheral blood of mice. In addition, the introduction of primary MSCs induced the production of interferon gamma (INF-γ) which is detected in the peripheral blood of mice. After infection with HSV-1, the immunized mice showed significantly increased titers of virus-specific antibodies, an increased level of IFNγ, and were completely protected from lethal HSV-1 infection. The protective effect of the other three immunogens was lower and did not exceed 50-65%. Considering the wide availability of MSCs, the proven safety of intravenous administration, and the results obtained in this work on the ability to induce innate, adaptive and protective immunity to HSV-1, MSCs can be considered a promising basis for the development of new cellular vaccines for the prevention of herpesvirus and other viral infections.

Discovery of a Fungicide Candidate Targeting Succinate Dehydrogenase via Computational Substitution Optimization.

Succinate dehydrogenase (SDH, EC 1.3.5.1) has proven to be an important fungicidal target, and the inhibition of SDH is useful in the treatment of plant pathogens. The discovery of a novel active SDH inhibitor is of high value. Herein, we disclose the discovery of a potent, highly active inhibitor as a fungicide candidate by using a computational substitution optimization method, a fast drug design method developed in our laboratory. The greenhouse experiments showed that compound 17c exhibited high protective activity against south corn rust, soybean rust (SBR), and rice sheath blight at a very low dosage of 0.781 mg/L. Moreover, the field trials indicated that compound 17c is comparable to and even better than commercial fungicides against SBR and cucumber powdery mildew at 50 mg/L concentration. Most surprisingly, compound 17c resulted to be strictly better in curative activity than the commercial fungicide benzovindiflupyr. The computation results indicated that 17c could form another hydrogen bond with C_S42 and then lead to strong van der Waals and electronic interactions with SDH. Our results suggested that 17c is a potential fungicide candidate for SDH.

Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach.

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ 721 (fillers); Plasdone S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carrs index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ 721), copovidone (Plasdone S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.

[Preventive Vaccination with Mesenchymal Stem Cells Protects Mice from Lethal Infection Caused by Herpes Simplex Virus 1].

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect almost all organs and tissues, cause genital herpes-the most common sexually transmitted disease-disorders of the central nervous system (CNS), and lead to severe complications in children. Despite the available drugs, the incidence of HSV-1/2 continues to rise. None of the prophylactic vaccine candidates have shown a protective effect in trials nor approval for use in clinical practice. We have investigated the protective properties of mesenchymal stem cells (MSC) isolated from the bone marrow of mice. A comparative analysis of the protective response to the introduction of primary and modified MSCs (mMSC) was carried out using the plasmid containing gene of the HSV and an inactivated virus in a model of lethal HSV-1 infection in mice. mMSCs were obtained by transfection of the Us6 gene encoding glycoprotein D (gD) of the HSV, the plasmid contained the same gene. After twofold immunization with primary MSCs, the formation of antibodies interacting with the viral antigen (according to enzyme immunoassay data) and neutralizing the infectious activity of HSV-1 in the reaction of biological neutralization was observed in the peripheral blood of mice. In addition, the introduction of primary MSCs induced the production of interferon gamma (INF-γ) which is detected in the peripheral blood of mice. After infection with HSV-1, the immunized mice showed significantly increased titers of virus-specific antibodies, an increased level of IFNγ, and were completely protected from lethal HSV-1 infection. The protective effect of the other three immunogens was lower and did not exceed 50-65%. Considering the wide availability of MSCs, the proven safety of intravenous administration, and the results obtained in this work on the ability to induce innate, adaptive and protective immunity to HSV-1, MSCs can be considered a promising basis for the development of new cellular vaccines for the prevention of herpesvirus and other viral infections.

Synthetic Analogs of Streptococcus pneumoniae Capsular Polysaccharides and Immunogenic Activities of Glycoconjugates.

Streptococcus pneumoniae is a Gram-positive bacterium (pneumococcus) that causes severe diseases in adults and children. It was established that some capsular polysaccharides of the clinically significant serotypes of S. pneumoniae in the composition of commercial pneumococcal polysaccharide or conjugate vaccines exhibit low immunogenicity. The review considers production methods and structural features of the synthetic oligosaccharides from the problematic pneumococcal serotypes that are characterized with low immunogenicity due to destruction or detrimental modification occurring in the process of their preparation and purification. Bacterial serotypes that cause severe pneumococcal diseases as well as serotypes not included in the composition of the pneumococcal conjugate vaccines are also discussed. It is demonstrated that the synthetic oligosaccharides corresponding to protective glycotopes of the capsular polysaccharides of various pneumococcal serotypes are capable of inducing formation of the protective opsonizing antibodies and immunological memory. Optimal constructs of oligosaccharides from the epidemiologically significant pneumococcal serotypes are presented that can be used for designing synthetic pneumococcal vaccines, as well as test systems for diagnosis of S. pneumoniae infections and monitoring of vaccination efficiency .

Oregano (Origanum vulgare L.) essential oil provides anti-inflammatory activity and facilitates wound healing in a human keratinocytes cell model.

Skin acts as a protective barrier between the body and the external environment. Skin wounds are a common inflammatory disorder for the solution of which plants and essential oils have been applied as a medical option for centuries. Origanum vulgare essential oil (OEO) is largely used in folk medicine, but its molecular mechanisms of action are not fully known. In this study, we evaluated the anti-inflammatory/antioxidant activity as well as wound healing capacity of a well-characterized OEO on human keratinocytes NCTC 2544 treated with interferon-gamma (IFN-γ) and histamine (H) or subjected to a scratch test. The expression of pro-inflammatory mediators such as reactive oxygen species (ROS), inter-cellular adhesion molecule (ICAM)-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2 were verified. The DNA damage was shown by the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) and activation of proliferating cell nuclear antigen (PCNA). Moreover, the abnormal modification of extracellular matrix components (ECM) was examined by determining matrix metalloproteinase (MMP)-1, and -12. Compared to untreated control, OEO showed efficacy in supporting and enhancing the cell motility. In IFN-γ and H treated cells, OEO displayed a significant reduction of ROS, ICAM-1, iNOS, COX-2, 8-OHdG, MMP-1, and MMP-12. OEO proved useful to treat inflammation and support cell motility during wound healing.