Phytotoxic phenols from the needles of Cedrus deodara.

During the course of screening for anti-seed germination phytochemicals, the methanol fraction of the Cedrus deodara fresh needles showed potent activity. Bioactivity-guided fractionation led to the isolation of thirty-eight phenolic compounds. Four ones were identified as previously undescribed including (7S,8S)-3-methoxy-9'-acetoxy-3',7-epoxy-8,4'-oxyneoligna-4,9-diol (7), (7S,8R)-dihydro-3'-hydroxy-8-acetoxymethyl-7-(4-hydroxy-3-methoxy-phenyl)-1'-benzofuranpropanol (10), (8S)-4,9,9'-trihydroxy-3,3'-dimethoxy-8,4'-oxyneolignan (11) and (7S,8S)-4,7,9'-trihydroxy-3,3'-dimethoxy-9-acetoxy-8,4'-oxyneolignan (16), respectively. The potential phytotoxic effects of these compounds on the seed germination and root elongation of Arabidopsis thaliana were evaluated by the filter paper assay developed in our laboratory. Bioassay results indicated that caffeic acid (36) displayed most significant inhibitory activities against the seed germination and root elongation of A. thaliana, stronger than those of the commercial herbicides acetochlor and glyphosate at the same concentration of 200 µg/mL. Ditetrahydrofuran lignan (1), dihydrochalcone (25), and eight simple phenols (28, 29, 31, 33-35, 37 and 38) completely inhibited the seed germination of A. thaliana at the concentration of 400 µg/mL, which were as active as acetochlor. Dihydroflavone (21) and the simple phenols 32-34 displayed stronger inhibitory effects on the root elongation of A. thaliana than that of glyphosate. The inhibitory effects of these active compounds on the seed germination and root elongation of Amaranthus tricolor and Lactuca sativa were evaluated as well. The phytotoxic activity of 11, 16, 22, 25, 31, 34, 37 and 38 were detected for the first time. In addition, the structure-activity relationships of the same class of these phytochemicals were discussed.

Cedrus deodara (Roxb. ex D.Don) G.Don bark fraction ameliorates metabolic, endocrine and ovarian dynamics in rats experiencing polycystic ovarian syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Ayurvedic system of medicine, Cedrus deodara bark has been utilized as a folk medicine to remove ovarian cysts and treat infertility in females. AIM: The present study is the first to investigate ameliorating potential of C. deodara bark on testosterone propionate and high-fat diet-induced polycystic ovarian syndrome in experimental rats. MATERIALS AND METHODS: LC-MS analysis of the fraction selected through bioassay-guided approach employing uterine relaxant activity was performed to determine the bioactive constituents present in it. Further, the identified compounds were docked on the catalytic site of the androgen receptor and insulin receptor substrate-1. Later, the fraction was investigated against testosterone propionate and high-fat diet-induced PCOS in rats. RESULTS: Chloroform fraction (F1) of the plant bark was found most active in uterine smooth muscle relaxant activity. LC-MS analysis of F1 indicated the presence of key flavonoids namely deodarin, cedrin, deodardione, and cedrusinin. Afterward, a molecular docking study of these compounds revealed impressive binding interactions with androgen receptor and insulin receptor substrate-1. Besides, in vivo studies, treatment with F1 significantly restored the estrous cycle in rats from the diestrus phase in a dose-dependent manner. Also, the disturbed metabolic and endocrine profile was markedly improved in rats. Later, histopathological analysis revealed the presence of a large number of mature follicles and corpora lutea in F1-treated rats. CONCLUSION: In a nutshell, F1 exhibited promising beneficial effects in PCOS and associated conditions via amelioration of metabolic, endocrine, and ovarian dynamics in experimental rats.

Effect of Cedrus deodara extract on the physiochemical and sensory properties of salted meat and its action mechanism.

The effect of pine needle extract from Cedrus deodara (PNE) on the quality of salted meat was reported, and its action mechanism was further investigated. With the treatment of PNE, the physicochemical properties of salted meat were improved. The peroxide value decreased from 16.18 to 6.78 mmol O2 /kg, while the thiobarbituric acid value decreased from 0.79 to 0.40 mg MDA/kg. Moreover, the salted meat with PNE also had the better texture, color, and volatile compositions. The 0.2% PNE group showed the highest ΔE value (63.16 ± 0.56), hardness (813.5 ± 48.7 g), and volatility (45.86 ± 0.39), while the control group showed the lowest ΔE value (43.92 ± 2.13), hardness (515.8 ± 17.3 g) and volatility (29.97 ± 0.56). In addition, with the analysis of fluorescence and circular dichroism spectroscopy, the spatial structures of myofibrillar protein (MP) in salted meat were obviously changed by PNE. Meanwhile, methylconiferin, 1-O-feruloyl-ß-D-glucose, nortrachelogenin, secoxyloganin, 1-O-(4-coumaroyl)-ß-D-glucose and pelargonidin-3-O-glucoside were identified from PNE. Furthermore, according to the analysis of molecular docking, hydrogen bond, hydrophobic force, and electrostatic force were obtained as the main molecular forces between MP and the phenolic compounds of PNE, while arginine, glutamic acid, and glycine residues were the main binding sites. All results suggested that PNE might be a potential candidate to improve the quality of salted meat in the food industry. PRACTICAL APPLICATION: The quality deterioration of meat may not only affect its further processing and consumption but also may lead to some food safety problems. In present study, PNE exhibited the fine capability to inhibit the oxidation of meat, while it could ameliorate the texture, color, and physicochemical properties of meat due to its tightly interaction with myofibrillar protein. All result suggested that PNE could be potentially utilized to improve the quality of meat in food industry.

Cedrus deodara (Roxb. ex D.Don) G.Don: A review of traditional use, phytochemical composition and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus deodara (Roxb. ex D.Don) G.Don (Family: Pinaceae) is a medicinal tree traditionally important and well mentioned in traditional system of medicine of India, Pakistan, China, Korea etc. for its use in the management of skin diseases, microbial infections, joint disorders, asthma, kidney stones, ulcer, brain disorders and immunological disorders. AIM AND OBJECTIVES: This review provides an insight into the information available regarding traditional uses, ethnobotany, phytochemistry and, pharmacological profiling of C. deodara crude extract, its isolated compounds and, fractions, to explore its potential for the development of novel therapeutic agents. MATERIAL AND METHODS: Various databases including Scopus, Google Scholar, Science Direct, ACS, Wiley, Web of Science, Springer Link and, PubMed were used to collect all the appropriate information available in previously published literature related to this plant. Besides, other official electronic sources viz. Encyclopedia Britannica and Northern Regional Center, Botanical Survey of India, theplantlist.org. and relevant book chapters and books were also explored. RESULTS: C. deodara is a popular medicinally active tree, traditionally used in the form of decoction, syrup, oil, powder, and extract alone or in combination with other herbs for the management of different ailments viz. asthma, ulcers, bone fractures, sprains rheumatism, boils, leprosy, etc. Phytochemical studies reported 105 chemical constituents from different parts of the plant, most of them belong to a class of terpenoids and flavonoids. Crude extracts, essential oils, fractions, and isolated compounds of C. deodara exhibited some important pharmacological activities including anticancer, antimicrobial, antifungal, analgesic, anti-inflammatory, neuroprotective, antidiabetic, antiurolithiatic, antiarthritic and, antiasthmatic. CONCLUSION: Present article delivers in-depth information on botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology. C. deodara has been in practice among indigenous people of India, Pakistan, Nepal, Korea, China, Nigeria and Russia and 28 different ethnicities for the management of approximately 40 diseases. Bioactive compounds particularly cedrin, himachalol, himachalene and atlantone are recognized as key constituents for observed pharmacological activities of C. deodara. However, further in-depth studies involving bio-guided fractionation, isolation, identification using advanced techniques to afford some new therapeutically active phytoconstituents in the management of different diseases. Preliminary pharmacological investigations on different extracts and fractions of C. deodara partially validated its traditional claims in different ailments such as skin diseases, asthma, neurological disorders, arthritis, microbial infections, gastric disturbances, and inflammation. However, immediate attempts are required to establish its mechanism of action, efficacy, dosage range, and safety in combating different pathological states.

A computational approach for rational discovery of inhibitors for non-structural protein 1 of SARS-CoV-2.

BACKGROUND: Non-structural protein 1 (Nsp1), a virulence agent of SARS-CoV-2, has emerged as an important target for drug discovery. Nsp1 shuts down the host gene function by associating with the 40S ribosomal subunit. METHODS: Molecular interactions, drug-likeness, physiochemical property predictions, and robust molecular dynamics (MD) simulations were employed to discover novel Nsp1 inhibitors. In this study, we evaluated a series of molecules based on the plant (Cedrus deodara) derived α,ß,γ-Himachalenes scaffolds. RESULTS: The results obtained from estimated affinity and ligand efficiency suggested that BCH10, BCH15, BCH16, and BCH17 could act as potential inhibitors of Nsp1. Moreover, MD simulations comprising various MD driven time-dependent analyses and thermodynamic free energy calculations also suggested stable protein-ligand complexes and strong interactions with the binding site. Furthermore, the selected molecules passed drug likeliness parameters and the physiochemical property analysis showed acceptable bioactivity scores. CONCLUSION: The structural parameters of dynamic simulations revealed that the reported molecules could act as lead compounds against SARS-CoV-2 Nsp1 protein.

Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies.

Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G0/G1 phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future.

Benzosuberene-sulfone analogues synthesis from Cedrus deodara oil and their therapeutic evaluation by computational analysis to treat type 2 diabetes.

Benzosuberene-sulfone (BSS) analogues have been semi-synthesized following green approaches from himachalenes, which has been extracted from essential oil of Cedrus deodara. In this process, benzosuberene in presence of different aryl or alkyl sodium sulfinates, I2 and potassium persulfate (K2S2O8) in acetonitrile-water solvent conditions gave BSS-analogues at room temperature. Under this reaction, a facile endocyclic ß-H elimination has been noticed for BSS-analogues synthesis instead of vinyl sulfones and the reason may be due to its specific structure and electronic environment. The BSS-compounds were obtained with moderate to excellent yields under mild conditions. All the compounds were computationally subjected to drug likeliness and toxicity prediction studies. Further, the synthesized molecules were evaluated under in-silico studies for their binding affinity towards the native Peroxisome Proliferator-Activated Receptor Gamma (PPARG), and two PPARG mutants (R357A and V290M). Both the mutant forms of PPARG are deficient in eliciting a response to treatment with full and partial agonists. Our computational studies suggested that the molecule 3q performed better than the standard drug (Rosiglitazone) in all three protein structures. This implies that our suggested molecule could act as a more potent antagonist to native PPARG and could also be developed to treat type-2 diabetes patients with R357A and V290M mutations, which didn't elicit any response to currently available drugs in the market.

Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis.

This study investigated the anti-leukemic effects of Cedrus atlantica extract (CAt extract) on cell cycle distribution and apoptosis in human acute myeloid leukemia (AML) cells. AML often occurs in older adults, accounting for 60% of the cases, and is likely to be resistant to chemotherapy due to multidrug resistance, resulting in early death during cancer treatment. With the increasing focus on prevention medicine, natural plant components are being used as a major source for the development of therapeutic drugs or functional foods to cure or alleviate the disease. Cedrus species are known to have anti-inflammatory, antimicrobial, antiviral, and anticancer effects; however, the anticancer effects of CAt extract have not been elucidated. In this study, CAt extract demonstrated an inhibitory effect on human leukemia cells in a concentration-dependent manner; CAt extract induced G0/G1 phase arrest via restrained protein levels of p-Rb and cell cycle-related proteins. After CAt extract exposure, the extrinsic and intrinsic apoptotic pathways were activated through caspase-8, -9, and -3 cleavage. Additionally, CAt extract suppressed VEGF, MMP-2, and MMP-9 expression. This study demonstrated that CAt extract treatment significantly reduced cell growth, cell cycle arrest in the G0/G1 phase, and induction of apoptosis, leading to leukemia cell death.

Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo.

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.

Cedrol, a Sesquiterpene Alcohol, Enhances the Anticancer Efficacy of Temozolomide in Attenuating Drug Resistance via Regulation of the DNA Damage Response and MGMT Expression.

Glioblastoma (GBM) is a common and aggressive brain tumor with a median survival of 12-15 months. Temozolomide (TMZ) is a first-line chemotherapeutic agent used in GBM therapy, but the occurrence of drug resistance limits its antitumor activity. The natural compound cedrol has remarkable antitumor activity and is derived from Cedrus atlantica. In this study, we investigated the combined effect of TMZ and cedrol in GBM cells in vitro and in vivo. The TMZ and cedrol combination treatment resulted in consistently higher suppression of cell proliferation via regulation of the AKT and MAPK signaling pathways in GBM cells. The combination treatment induced cell cycle arrest, cell apoptosis, and DNA damage better than either drug alone. Furthermore, cedrol reduced the expression of proteins associated with drug resistance, including O6-methlyguanine-DNA-methyltransferase (MGMT), multidrug resistance protein 1 (MDR1), and CD133 in TMZ-treated GBM cells. In the animal study, the combination treatment significantly suppressed tumor growth through the induction of cell apoptosis and decreased TMZ drug resistance. Moreover, cedrol-treated mice exhibited no significant differences in body weight and improved TMZ-induced liver damage. These results imply that cedrol may be a potential novel agent for combination treatment with TMZ for GBM therapy that deserves further investigation.

Impregnation of pectin-cedarwood essential oil nanocapsules onto mini cotton bag improves larvicidal performances.

The use pesticide is one of the indispensable means to combat mosquito borne diseases. However, the repeated use of synthetic pesticides has induced resistance in the vector pest along with undesirable impact on the environment. The biodegradability, non-persistent and user's safety are the root cause to prefer plant-derived pesticides to synthetic ones. The botanical based pesticides tend to degrade rapidly under the influence of several environmental factors. For the feasible application as pesticides, the plant products are formulated either as liquid or as purely solid. Despite well-established formulation technology in pesticide delivery, their handling trouble is being ignored. There is difficulty in liquid formulation of pesticide products, as they are prone to splashing and spillage, resulting in contamination, wastage and direct exposure to skin; whereas a solid formulation tends to produce dust. In the present work, cedarwood (Cedrus deodara) essential oil embedded pectin nanocapsules were produced. The nanocapsules were characterized according to their morphology, size, encapsulation efficiency and thermal stability. Furthermore, the nanocapsules were impregnated onto mini cotton tea bags to be employed as RTU (ready to use) formulation for treating the breeding sites of mosquitoes. The larvicidal activity of the bags treated with pectin-cedar wood nanocapsules was assessed against malaria vector, Anopheles culicifacies and 98% mortality was recorded till 4 weeks, this suggests its potential and hassle free applications in controlling mosquito vector.

Cedrus deodara (Bark) Essential Oil Induces Apoptosis in Human Colon Cancer Cells by Inhibiting Nuclear Factor kappa B.

AIMS: The aim of this study is to explore essential oil from the bark of Cedrus deodara (CDEO) as an potential anticancer agent. BACKGROUND: The frontline drugs against cancer in clinical settings are posing challenges of resistance and other detrimental side-effects. This has led to the exploration of new anticancer chemical entities from natural sources, particularly plant-based products such as essential oils that serve as vast repositories of pharmacologically active substances for combating cancer. OBJECTIVE: The objective is to isolate and characterize the essential oil from the bark of Cedrus deodara (CDEO) and evaluate its potential as an anticancer agent and delineate the possible underlying mechanism of action. METHODS: Cedrus deodara essential oil from bark (CDEO) was obtained by hydro-distillation and analyzed by GC/MS for vital constituents. Further, in vitro cytotoxic potential was measured by MTT assay against a panel of cancer cell lines. The apoptosis-inducing potential of CDEO was analyzed by mitochondrial membrane potential loss (ΔΨm) and nuclear fragmentation assay. Besides, wound healing assay and colonogenic assay were employed to check the anti-metastatic potential of CDEO. Molecular docking approaches were employed for target identification, while immuno-blotting was carried out for target validation. RESULTS AND DISCUSSION: The major components identified were 2-(tert-Buyl)-6-methyl-3-(2- (trifluoromethyl) benzyl)imidazo [1,2-a]pyridine (26.32 %);9- Octadecenoic acid (8.015 %); Copaene (5.181 %);2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H- benzo[g]indazole(4.36 %) and 9(E),11(E)- Conjugated linoleic acid (4.299 %). Further, potent in vitro cytotoxic activity with IC50 values of 11.88 µg/ ml and 14.63 µg/ ml in colon cancer cell lines of HCT-116 and SW-620, respectively. Further, a significant and dose-dependent decrease in colony formation, cell migration, induction of ROS formation and loss in ΔΨm was observed. Additionally, major compounds identified were chosen for ligandprotein binding interaction studies to predict the molecular targets in colon cancer. It was observed that compounds such as 9-Octadecenoic acid;4H-1- Benzopyran-4-one, 3-(3,4-dimethoxyphenyl)-6,7- dimethoxy; 2-(4-Methoxy-2,6-dimethylphenyl) -3-methyl-2H-benzo [g]indazole and 2-Bornanol,5-(2,4- dinitro phenyl) hydrazono have a prominent binding affinity with NF-κB. This was also further validated by immuno-blotting results wherein CDEO treatment in colon cancer cells led to the abrogation of NFκB, and the Bcl-2-associated X protein (Bax): B-cell lymphoma (Bcl)-2 ratio was up-regulated leading to enhanced cleaved caspase 3 formation and subsequent apoptosis. CONCLUSION: These results unveil CDEO inhibits cell proliferation and induces apoptosis in colon cancer cells, which can be attributed to the abrogation of the NFκB signaling pathway.

Utilization of the extract of Cedrus deodara (Roxb. ex D.Don) G. Don against the biofilm formation and the expression of virulence genes of cariogenic bacterium Streptococcus mutans.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus deodara (Roxb. ex D.Don) G. Don is applied as anti-inflammatory and anti-infection agents in folklore medicine. AIM OF THE STUDY: The present study aimed to assess the antimicrobial activity of Cedrus deodara (Roxb. ex D.Don) G. Don extract (CDE) against Streptococcus mutans biofilm formation and its biocompatibility, as well as to identify its chemical components. MATERIALS AND METHODS: Confocal laser scanning microscopy (CLSM), crystal violet staining, and CFU counting assay were applied to investigate the effect of CDE on S. mutans biofilm formation and extracellular polysaccharides (EPS) synthesis. The microstructure of S. mutans biofilms formed on glass coverslips and bovine enamel treated with CDE was observed by scanning electron microscopy (SEM). qRT-PCR was used to measure the expression of virulence genes gtfB, gtfC, and gtfD, and zymogram assay was performed to investigate the enzymatic activity of Gtfs. Moreover, HPLC-MS and NMR were applied to identify its chemical components. CCK-8 assay was also performed on human oral cells to evaluate its biocompatibility. RESULTS: Under the treatment of CDE, S. mutans formed less biofilm on both coverslips and enamel surfaces and synthesized less EPS. Moreover, CDE downregulated the expression of gtf genes and inhibited the enzymatic activity of Gtfs. According to HPLC-MS and NMR results, molecular structures of six main compounds in CDE were identified. CDE also has a good biocompatibility. CONCLUSIONS: CDE exhibits inhibitory activity against S. mutans and a good biocompatibility. It has the potential to be developed as anti-caries agents for clinical use.

Effect of geographical origin on yield and composition of cone essential oils of Cedrus libani A. Rich. growing in Lebanese protected areas and variability assessment in comparison with literature survey.

Gas chromatography-mass spectrometry analysis together with principal component analysis revealed that geographical origin influenced the yield and composition of the essential oils (EOs) extracted by hydrodistillation performed for 3 h using a Clevenger-type apparatus, from the cones of Cedrus libani A. Rich., growing wild at four Lebanese natural reserves and protected areas: Bsharri, Chouf, Ehden, and Tannourine, and from a cultivated cedar growing in Qartaba. Essential oil chemical variability established between the different studied provenances suggested the involvement of abiotic factors such as geographical conditions, cultivation conditions, soil composition, and environmental factors in the chemical polymorphism of C. libani cones EOs. α-Pinene/ß-pinene characterized Ehden (ß-pinene 35.6%/α-pinene 27.7%), Chouf (α-pinene 37.3%/ß-pinene 26.1%), Bsharri (α-pinene 27.7%/ß-pinene 21.4%), and Tannourine (α-pinene 25.1%/ß-pinene 16.0%) samples, whereas Qartaba EO was distinguished by the dominance of myrcene (30.6%), α-pinene(26%), and limonene (14.1%). Comparison with the existing literature reinforced the chemical variability of C. libani EOs. This current study helped the estimation of a best harvest location for a good EO quality production, resource optimization, and pharmacological properties evaluation, according to the market demand.

A novel water-in-oil emulsion with a lecithin-modified bentonite prevents skin damage from urban dust and cedar pollen.

OBJECTIVE: Particulate matter (PM), such as air pollutants and pollens, are known to cause skin ageing through skin inflammation. It is important to develop formulations which protect the skin from PM. We previously developed a conventional water-in-oil emulsion with a synthetic surfactant, distearyldimonium chloride, modified bentonite (C-W/O), which protects skin from allergens. In the present study, we developed a novel water-in-oil emulsion with a natural surfactant, lecithin, modified bentonite (N-W/O). METHODS: The microarray analysis was performed using total RNA extracted from a reconstructed human epidermis (RHE) stimulated with urban aerosols or cedar pollen for 6 h in order to develop an epidermal inflammation model by PM for the evaluation of topical formulations. We then compared the efficacy of N-W/O and C-W/O to prevent epidermal degradation. Tissues and culture media were collected 24 h after the urban aerosol or cedar pollen stimulation for a histological assay, and the quantification of MMP1 and IL-8 secretion. RESULTS: The expression levels of proinflammatory cytokines and chemokines, such as IL1A and CXCL8, and matrix metalloproteinases, including MMP1, MMP3 and MMP9, were significantly up-regulated by the PM stimulation. As a result of ranking based on the pathway enrichment analysis, oxidative stress-related pathways, such as MAPK-mediated signalling, HIF-1 signalling, IL-1 signalling and ROS-induced cellular signalling, were ranked high in the urban dust- and cedar pollen-treated groups. A thickened stratum corneum, thinned vital layer and cleaved E-cadherin were observed by haematoxylin and eosin staining and immunohistochemical staining of E-cadherin in the PM treated groups. The secretion of MMP1 and IL-8 into the media was significantly increased by the PM stimulation. N-W/O prevented the degradation of epidermal integrity and secretion of inflammatory proteins more effectively than C-W/O. CONCLUSION: The present results showed that N-W/O made using natural surfactant is useful at protecting skin from PM, such as urban aerosols and cedar pollen.

OBJECTIF: Les particules en suspensions (PM), telles que les polluants atmosphériques et les pollens, sont connues comme des causes de vieillissement de la peau par inflammation cutanée. Il est essentiel de mettre au point des formules qui protègent la peau contre ces particules. Par le passé, nous avons mis au point une émulsion eau-dans-huile classique composée d'un tensioactif synthétique, de distearyldimonium chloride et de bentonites modifiées (E/H-C), qui protège la peau contre les allergènes. Dans la présente étude, nous avons conçu une nouvelle émulsion eau-dans-huile composée d'un tensioactif naturel, de lécithine et de bentonites modifiées (N-E/H). MÉTHODES: L'analyse des microréseaux a été réalisée à l'aide de l'ARN total extrait d'un épiderme humain reconstitué (EHR) stimulé par les aérosols urbains ou le pollen de cèdre pendant 6 h afin de mettre au point un modèle d'inflammation de l'épiderme par les particules en suspensions en vue de l'évaluation des formulations topiques. Nous avons ensuite comparé l'efficacité de la N-E/H et de l'E/H-C dans le but d'éviter la dégradation de la peau. Les milieux de culture tissulaire ont été collectés 24 h après stimulation par l'aérosol urbain ou par du pollen de cèdre pour un dosage histologique et une quantification de MMP-1 et des sécrétions de l'IL-8. RÉSULTATS: Les niveaux d'expression des cytokines pro-inflammatoires et des chimiokines, à l'instar de l'IL1A et du CXCL8, ainsi que des métalloprotéinases matricielles, notamment les MMP1, les MMP3 et les MMP9, étaient essentiellement régulés positivement par la stimulation des particules en suspensions. En raison du classement basé sur l'analyse d'enrichissement des voies, le stress oxydatif, telles que la signalisation médiée par MAPK, la signalisation HIF-1, la signalisation IL-1 et la signalisation cellulaire induite par les ROS ont été classés en tête pour les groupes traités par la poussière urbaine et par le pollen-de cèdre. Un stratum corneum épaissie, une couche vitale fine et une clivée d'E-cadhérine ont été observées par coloration à l'hématoxyline-éosine et par coloration immunohistochimique de l'E-cadhérine dans les groupes traités aux particules en suspensions. La sécrétion de MMP1 et de l'IL-8 dans les milieux a augmenté de façon significative par stimulation des particules en suspensions. La N-E/H a permis d'éviter une dégradation de l'intégrité de la peau et la sécrétion de protéines inflammatoires de manière plus efficace que l'E/H-C. CONCLUSION: Les résultats actuels ont révélé que la N-E/H produite grâce à l'utilisation d'un tensioactif naturel est utile pour la protection de la peau contre les particules en suspensions telles que les aérosols urbains et le pollen de cèdre.

Himachalol induces apoptosis in B16-F10 murine melanoma cells and protects against skin carcinogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus libani A. Rich (C. libani) is majestic evergreen Mediterranean conifer growing in the mountains of Lebanon. The ethnobotanical and traditional uses of cedar wood oil traces back to ancient times for the treatment of various ailments including cancer. Previous work in our laboratories revealed that himachalol (7-HC), a major sesquiterpene isolated from C. libani, possesses potent cytotoxic activity against various human cancer cell lines as well as promising anti-inflammatory effect in isolated rat monocytes. AIM OF THE STUDY: The present study aims to elucidate the mechanism of action behind the cytotoxic activity of 7-HC against murine melanoma cells (B16F-10) and evaluates its chemopreventive effect against chemically-induced skin carcinogenesis in mice. MATERIALS AND METHODS: 7-HC was extracted and purified from Cedrus libani wood. Cell viability was evaluated using WST-1 kit. Cell cycle analysis and apoptosis were assessed by Flow cytometry using propidium iodide (PI) and fluorescein Isothiocyanate (FITC)-conjugated Annexin V/PI staining respectively. Apoptosis related protein were quantified using western blot. The chemopreventive activity of 7-HC was evaluated for 20 weeks using a DMBA/TPA induced skin carcinogenesis model in Balb/c mice. RESULTS: 7-HC displayed a potent anti-proliferative activity against the melanoma cells with an IC50 of 8.8 µg/ml and 7.3 µg/ml at 24 and 48 h, respectively. Co-treatment with Cisplatin did not show any synergistic or additive effect on cell viability. Flow cytometry analysis using PI revealed that 7-HC treatment (5 and 10 µg/ml) induces the accumulation of cells in the sub-G1 phase and causes a decline in cell populations in the S and G2/M phases. Annexin/PI staining also reveals that 7-HC treatment significantly increases the percentage of cells undergoing early and late apoptosis. Western blot analysis shows that 7-HC treatment decreases the level of the anti-apoptotic protein Bcl-2 and increases the level of the pro-apoptotic protein Bax. A reduction in the level of phosphorylated Erk and Akt was also observed. 7-HC via topical (2.5%), intraperitoneal (10, 25 and 50 mg/kg) or gavage (50 mg/kg) treatment revealed a significant decrease in papilloma volume with no adverse effect on liver and kidney function. CONCLUSIONS: The present study demonstrates that 7-HC treatment protects against chemically-induced skin carcinogenesis, promotes cell cycle arrest and induces apoptosis partially through an inhibition of both the MAPK/Erk and PI3K/Akt pathways.

Plant-microorganisms interaction promotes removal of air pollutants in Milan (Italy) urban area.

Plants and phyllosphere microorganisms may effectively contribute to reducing air pollution in cities through the adsorption and biodegradation of pollutants onto leaves. In this work, during all seasons, we sampled atmospheric particulate matter (PM10) and leaves of southern magnolia Magnolia grandiflora and deodar cedar Cedrus deodara, two evergreen plant species widespread in the urban area of Milan where the study was carried out. We then quantified Polycyclic Aromatic Hydrocarbons (PAHs) both in PM10 and on leaves and used sequencing of 16S rRNA gene, shotgun metagenomics and qPCR analyses to investigate the microbial communities hosted by the sampled leaves. Taxonomic and functional profiles of epiphytic bacterial communities differed between host plant species and seasons and the microbial communities on leaves harboured genes involved in the degradation of hydrocarbons. Evidence collected in this work also suggested that the abundance of hydrocarbon-degrading microorganisms on evergreen leaves increased with the concentration of hydrocarbons when atmospheric pollutants were deposited at high concentration on leaves, and that the biodegradation on the phyllosphere can contribute to the removal of PAHs from the urban air.

Histopathological effects on stomach, liver and kidney associated with Cedrus deodara root oil in ulcer induced rats (Wistar strain).

Cedrus deodara have been used traditionally in ayurvedic system against peptic ulcer. Present work is concerned with the determination of histopathological effects in ethanol induced ulcer on rats (Wistar Strain) treated with Cedrus deodara root oil at a dose of 200mg/kg and comparison of its antiulcer activity against control, positive control and standard anti-ulcer drug (Omeprazole). The aim was to find out the antiulcer effect of Cedrus deodara root oil and to observe histopathology of liver, kidney as well. 120 Albino rats were taken and divided into four groups i.e. A, B, C and D designated as control, positive control, standard and treated groups respectively. Normal and intact general architecture of mucosa and submucosa layers of stomach observed. No significant changes observed in thickness of epithelium, no inflammatory cells were present on the mucosa and submucosal layer and gastric glands were normal. Liver of albino rats, showed no dilation and congestion in central as well as portal vein. Kidney of albino rats exhibited no shrinkage in glomeruli, no congested and dilated renal corpuscles, neither hemolysis nor congested and dilated renal tubules were seen. It is concluded that C. deodara root oil has anti-ulcer properties without effecting kidney and liver tissues.

Analyzing of usability of tree-rings as biomonitors for monitoring heavy metal accumulation in the atmosphere in urban area: a case study of cedar tree (Cedrus sp.).

It is important to monitor the heavy metal pollution in order to identify risk zones and to determine the change in the heavy metal concentration of the atmosphere within the process. For this, it is necessary to carry out measurements for many years; however, this is not possible. Especially from past to present, one of the most effective methods to determine the changes of heavy metal concentrations in the atmosphere is to use the annual tree rings as biomonitors. Perennial plants growing in our country create annual rings, and it is possible to gain information regarding the changes of heavy metal concentrations in that region by determining the heavy metal concentrations in these rings. In this study, it was aimed to determine the annual changes of Pb, Co, and Fe elements' concentrations in these sections by determining the annual rings on the logs taken from the main stem of the cedar tree (Cedrus sp.), which was cut by the end of 2016, in December, 2016, in Kastamonu province. Within the scope of the study, the element concentrations were also determined in the inner and outer bark. As a result of the study, it was found that the heavy metal values in the organelles taken from the road-facing part, especially the heavy metal concentrations in the outer bark were higher than the metal concentrations in the inward-facing part, and that the concentrations changed significantly on organelle and year basis.

Evaluation of the anti-cancer potential of Cedrus deodara total lignans by inducing apoptosis of A549 cells.

BACKGROUND: Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. METHODS: We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. RESULTS: The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 µg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. CONCLUSION: At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.