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.

Ectomycorrhizas of Rhizopogon himalayensis on Cedrus deodara.

The ectomycorrhizal (EcM) roots of Cedrus deodara associated with a unique hypogeous EcM fungus-Rhizopogon himalayensis is meticulously characterized and comprehensively described based on well-established standard morphological and anatomical features. The mycobiont-R. himalayensis was found organically associated with the roots of C. deodara. The EcM morphotypes are distinguished by differences in the shape and color of the roots, type of ramification, surface texture, type of mantle, as well as different chemical reactions. All the examined morphotypes were having similar mycorrhizal system and anatomically (Mantle and Hartig net) no disparities were seen, that is, nonsignificant (p > 0.05) variations were observed. The majority of mycorrhizal systems were irregularly pinnate, dichotomous type with 0-1 order of ramification and occasional coralloid type. Mantle surface was densely cottony to loosely wooly. The outer and inner mantles were H & Q type. Hartig net was a complex net-like structure with uniseriate to mutiseriate type of hyphal cell arrangement. Rhizomorph were smooth and round, consistently growing along roots. Moreover, extraradical hyphae were hyaline, septate, and without clamp connections. Sclerotia and cystidia were absent. Our findings will contribute to the biology of ectomycorrhizae associated with primitive and economically valuable conifers, thriving in the face of shifting environmental conditions in the northwestern Himalayas.

Exploring the Larvicidal and Repellent Potential of Taurus Cedar (Cedrus libani) Tar against the Brown Dog Tick (Rhipicephalus sanguineus sensu lato).

This study investigated the potential acaricidal and repellent effects of tar obtained from the Lebanon cedar (Cedrus libani A. Rich.) against the brown dog tick species Rhipicephalus sanguineus sensu lato Latreille (Acari: Ixodidae). The goal was to find an alternative, safe, and effective way to eliminate ticks. Tar is traditionally extracted from cedar trees in the Antalya region of Türkiye. The composition of the tar is primarily characterized by a diverse mixture of terpenes, with ß-himachalene (29.16%), α-atlantone (28.7%), ar-turmerone (8.82%), longifolene-(V4) (6.66%), α-himachalene (5.28%), and ß-turmerone (5.12%) emerging as the predominant constituents. The toxic effects of tar on tick larvae were studied through larval immersion tests (LIT), and its repellent activity was evaluated using a new larval repellent activity test (LRAT). The results revealed significant acaricidal effects, with mortality rates of 77.7% and 82.2% for the Konyaalti and Kepez strains of the brown dog tick, respectively, in response to a 1% concentration of tar. LC50 and LC90 values were determined as 0.47% and 1.52% for the Kepez strain and 0.58% and 1.63% for the Konyaalti strain, respectively. When comparing the repellent effect of tar to the widely used synthetic repellent DEET, repellency rates of up to 100% were observed. As a result, this study establishes, for the first time, the larvicidal and repellent effects of C. libani tar on ticks.

Optimization and antifungal efficacy against brown rot fungi of combined Salvia rosmarinus and Cedrus atlantica essential oils encapsulated in Gum Arabic.

The stability, sensitivity, and volatility of essential oils are some of their most serious limitations, and nanoencapsulation has been considered one of the most effective techniques for solving these problems. This research aimed to investigate the incorporation of Salvia rosmarinus Speen and Cedrus atlantica Manetti (MEO) essential oil mixture in Gum Arabic (GA) and to evaluate nanoencapsulation's ability to promote antifungal activity against two brown rot fungi responsible for wood decay Gloeophyllum trabeum and Poria placenta. The optimization of encapsulation efficiency was performed using response surface methodology (RSM) with two parameters: solid-to-solid (MEO/GA ratio) and solid-to-liquid (MEO/ethanol). The recovered powder characterization was followed by various techniques using a scanning electron microscope (SEM), X-ray diffractometry (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and thermo-gravimetric analysis (TGA). The optimal nanoencapsulating conditions obtained from RSM were ratios of MEO/GA of 1:10 (w/w) and MEO/ethanol of 10% (v/v), which provided the greatest encapsulation efficiency (87%). The results of SEM, XRD, DLS, FTIR, and TGA showed that the encapsulation of MEO using GA modified particle form and molecular structure and increased thermal stability. An antifungal activity assay indicated that an effective concentration of MEO had an inhibitory effect on brown rot fungi. It had 50% of the maximal effect (EC50) value of 5.15 ± 0.88 µg/mL and 12.63 ± 0.65 µg/mL for G. trabeum and P. placenta, respectively. Therefore, this product has a great potential as a natural wood preservative for sustainable construction and green building.

Usability of biomonitors in monitoring the change of tin concentration in the air.

Air pollution, a pressing global issue, encompasses various harmful elements, with heavy metals being particularly significant pollutants affecting all forms of life. Effective monitoring and regulation of heavy metal concentrations, especially in the atmosphere, is pivotal. Employing trees as biomonitors emerges as a potent tool, particularly in retrospectively assessing long-term heavy metal contamination trends. This study aims to furnish insights into both tin (Sn) pollutants and the most suitable species for monitoring and mitigating such pollution. Within this study's ambit, samples were collected from Pinus pinaster, Cupressus arizonica, Picea orientalis, Cedrus atlantica, and Pseudotsuga menziesii species in Duzce Province. This area, ranked as the fourth-most air-polluted in Europe according to the World Air Pollution Report, was examined to discern changes in Sn concentration across species, organs, orientations, and age groups over the last four decades. The findings revealed varying potentials for Sn accumulation among the species. Specifically, Pinus pinaster and Picea orientalis were identified as suitable species for monitoring Sn pollution, while Cupressus arizonica, Cedrus atlantica, and Pseudotsuga menziesii exhibited potential for reducing Sn pollution.

Antioxidant, Volatile Compounds; Antimicrobial, Anti-Inflammatory, and Dermatoprotective Properties of Cedrus atlantica (Endl.) Manetti Ex Carriere Essential Oil: In Vitro and In Silico Investigations.

Cedrus atlantica (Endl.) Manetti ex Carriere is an endemic tree possessing valuable health benefits which has been widely used since time immemorial in international traditional pharmacopoeia. The aim of this exploratory investigation is to determine the volatile compounds of C. atlantica essential oils (CAEOs) and to examine their in vitro antimicrobial, antioxidant, anti-inflammatory, and dermatoprotective properties. In silico simulations, including molecular docking and pharmacokinetics absorption, distribution, metabolism, excretion, and toxicity (ADMET), and drug-likeness prediction were used to reveal the processes underlying in vitro biological properties. Gas chromatography-mass spectrophotometry (GC-MS) was used for the chemical screening of CAEO. The antioxidant activity of CAEO was investigated using four in vitro complementary techniques, including ABTS and DPPH radicals scavenging activity, ferric reductive power, and inhibition of lipid peroxidation (ß-carotene test). Lipoxygenase (5-LOX) inhibition and tyrosinase inhibitory assays were used for testing the anti-inflammatory and dermatoprotective properties. GC-MS analysis indicated that the main components of CAEO are ß-himachalene (28.99%), α-himachalene (14.43%), and longifolene (12.2%). An in vitro antimicrobial activity of CAEO was examined against eleven strains of Gram-positive bacteria (three strains), Gram-negative bacteria (four strains), and fungi (four strains). The results demonstrated high antibacterial and antifungal activity against ten of them (>15 mm zone of inhibition) using the disc-diffusion assay. The microdilution test showed that the lowest values of MIC and MBC were recorded with the Gram-positive bacteria in particular, which ranged from 0.0625 to 0.25 % v/v for MIC and from 0.5 to 0.125 % v/v for MBC. The MIC and MFC of the fungal strains ranged from 0.5 to 4.0% (MIC) and 0.5 to 8.0% v/v (MFC). According to the MBC/MIC and MFC/MIC ratios, CAEO has bactericidal and fungicidal activity. The results of the in vitro antioxidant assays revealed that CAEO possesses remarkable antioxidant activity. The inhibitory effects on 5-LOX and tyrosinase enzymes was also significant (p < 0.05). ADMET investigation suggests that the main compounds of CAEO possess favorable pharmacokinetic properties. These findings provide scientific validation of the traditional uses of this plant and suggest its potential application as natural drugs.

Impact of climatic conditions on radial growth of non-native Cedrus libani compared to native conifers in Central Europe.

Ongoing climate change increasingly affects growth conditions of native conifers such as Picea abies (Norway spruce) and Pinus sylvestris (Scots pine) in Central Europe. These conifers are primarily cultivated for wood production. To obtain ecologically and economically stable forests, forestry seeks alternative species that might be less prone to novel climatic conditions, such as Cedrus libani (Lebanon cedar). We aim at investigating growth responses to climatic factors of C. libani compared to native P. abies and P. sylvestris in Central Europe for 25 years (1994-2019). Growth responses were used as a proxy for tolerance towards climatic stress events, such as heat and drought. Height, diameter at breast height (DBH) and radial increment were measured for 40-year-old tree stands of C. libani and native conifers. Radial growth responses to selected climate parameters were analysed using bootstrapped correlations with detrended growth index chronologies and growth response indices for drought years (2003, 2012, 2015, 2018). For C. libani, radial growth was positively correlated with high water availability in late winter and spring, while for P. abies, February and summer and for P. sylvestris, July showed such a relationship. Cedrus libani exhibited the highest resistance, recovery, and resilience in response to climatic extremes. Against the background of climate change, C. libani could serve as an alternative conifer species to establish climate-resistant viable forests in Central Europe.

Chemical Composition, Antioxidant and Antibacterial Activities and Acute Toxicity of Cedrus atlantica, Chenopodium ambrosioides and Eucalyptus camaldulensis Essential Oils.

The essential oils yield of Cedrus atlantica, Chenopodium ambrosioides and Eucalyptus camaldulensis was different. C. ambrosioides gave a relatively higher yield (2.1 ± 0.1%), while that of C. atlantica was low (1.0 ± 0.1%) and that of E. camaldulensis was lower (0.75 ± 0.1% of dry matter). The active ingredients of the essential oils and some of their biological effects were also determined. The characterization of their chemical compositions showed that the three essences have different chemical profiles: C. atlantica was richer in sesquiterpenes (ß-Himachalene (54.21%) and γ -Himachalene (15.54%)), C. ambrosioides was very rich in monoterpene peroxides and monoterpenes (α-Terpinene (53.4%), ascaridole (17.7%) and ρ-Cymene (12.1%)) and E. camaldulensis was very rich in monoterpene compounds and monoterpenols (p-cymene (35.11%), γ-Eudesmol (11.9%), L-linalool (11.51%) and piperitone (10.28%)). The in vitro measurement of antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) reduction assay showed a significant performance of the eucalyptus oil and average performance of the other two (C. atlantica and C. ambrosioides). The in vitro bio-test for their antimicrobial effects showed that the antibacterial activity differed depending on the essential oil and the concentration used, and that their bactericidal efficacy was similar or superior to that of synthetic antibiotics. The toxicity test on rats revealed that the LD50 of the three essential oils was 500 mg/kg body weight, which classifies them as category four cytotoxic natural products at high doses.

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.

Cedrus libani tar prompts reactive oxygen species toxicity and DNA damage in colon cancer cells.

BACKGROUND: Many chemotherapeutic drugs used in cancer treatment have anticancer properties by inducing reactive oxygen species (ROS). However, the same effect occurs in normal cells, limiting the availability of these drugs. Therefore, studies on the detection of new herbal anticancer agents that have selective effects on cancer cells are of great importance. The aim of this study is to investigate the metabolite profile of Cedrus libani tar and its mechanism of anticancer effect on colon cancer cells. METHODS AND RESULTS: Effect of cedar tar on cells (12 cancers and 5 normal cell lines) viability was determined by MTT, apoptosis induction was determined by Annexin-V, ROS and MMP determined by flow cytometry assay. Cleaved caspase-8, 9 and Ɣ-H2AX expression determined by western blot. Apoptotic and antioxidant genes expression level determined by qPCR. Metabolite profiling was performed with LC-MS/MS and GC-MS. Cedar tar showed the highest cytotoxic effect among cancer cells in colon cancer (HCT-116, IC50: 30.4 µg/mL) and its toxic effect on normal cells (HUVEC, IC50: 74.07 µg/mL) was less than cancer cell. Cedar tar increases ROS production in colon cancer cells. The metabolite profile of the cedar tar contains high amounts of metabolites such as fatty acids mainly (Duprezianene, Himachalene and Chamigrene), phenolic compounds (mostly Coumarin, p-coumaric acid, Vanillic acid and tr-Ferulic acid etc.) and organic acids (mainly 3-oh propanoic acid, 2-oh butyric acid and 3-oh isovaleric acid etc.). CONCLUSION: As a result, it has been found that cedar tar has the potential to be used in the treatment of colon cancer.

Chemical Characterization, Antioxidant and Antimicrobial Properties of Different Types of Tissue of Cedrus brevifolia Henry Extracts.

This study aimed to determine the chemical composition of different types of tissue of Cedrus brevifolia Henry (Pinaceae) methanolic extracts, namely needles, twigs, branches, and bark. Cedrus brevifolia is a narrow endemic coniferous tree species of Cyprus, growing in a sole population in the mountainous area of Paphos Forest. Chemical analysis of the extracts was performed using liquid chromatography combined with time-of-flight high-resolution mass spectrometry (LC/Q-TOF/HRMS). The majority of the 36 compounds tentatively identified belonged to the flavonoids family. The extract of needles was the richest extract in terms of secondary metabolites. The extracts were studied for their antioxidant activity using the DPPH free radical scavenging assay. Additionally, the antibacterial activity was evaluated by determining both the minimum inhibitory concentration and the minimum bactericidal concentration against Staphylococcus aureus and Escherichia coli. All extracts demonstrated antioxidant property, while bark gave the highest antioxidant capacity (IC50 value of 0.011 mg/mL) compared to the other tissues. Antibacterial activity was observed against both types of bacteria, with the extract of branches presenting the strongest activity against S. aureus (MIC, 0.097 mg/mL and MBC, 0.195 mg/mL). This is the first time that extracts of needles, twigs, branches, and bark of C. brevifolia are compared regarding their chemical composition as well as their antimicrobial and antioxidant properties.

Chemical Modification of Biomarkers through Accelerated Degradation: Implications for Ancient Plant Identification in Archaeo-Organic Residues.

Biochemical and biomolecular archaeology is increasingly used to elucidate the consumption, use, origin, and trade of plants in the past. However, it can be challenging to use biomarkers to identify the taxonomic origin of archaeological plants due to limited knowledge of molecular survival and degradation for many key plant compounds in archaeological contexts. To gain a fundamental understanding of the chemical alterations associated with chemical degradation processes in ancient samples, we conducted accelerated degradation experiments with essential oil derived from cedar (Cedrus atlantica) exposed to materials commonly found in the archaeological record. Using GC-MS and multivariate analysis, we detected a total of 102 compounds across 19 treatments that were classified into three groups. The first group comprised compounds that were abundant in fresh cedar oil but would be unlikely to remain in ancient residues due to rapid degradation. The second group consisted of compounds that remained relatively stable or increased over time, which could be potential biomarkers for identifying cedar in archaeological residues. Compounds in the third group were absent in fresh cedar oil but were formed during specific experiments that could be indicative for certain storage conditions. These results show that caution is warranted for applying biomolecular profiles of fresh plants to ancient samples and that carefully designed accelerated degradation experiments can, at least in part, overcome this limitation.

Attenuation of cisplatin induced myelosuppression by methanol extract of Cedrus deodara in Wistar rats.

OBJECTIVE: The present study was performed to evaluate the protective effects of methanol extract of Cedrus deodara against cisplatin induced. METHODS: Myelosuppression in albino Wistar rats. All experimental animals were administered with cisplatin on 1st, 3rd, 5th and 7th day to induce bone marrow toxicity and rats were treated with methanol extract of C. deodara for 21 days. Blood samples were collected from all the animals on day 1st, 7th, 14th and 21st after 1 h before the administration of the drugs and hematological parameters like RBC, WBC, platelets, hemoglobin, hematocrit, eosinophils, basophils, neutrophils, lymphocytes, bleeding time and clotting time were determined were determined. At 21st, all rats were sacrificed and bone marrow samples were collected. The part of bone marrow samples was used for the determination of antioxidant enzymes and remaining were subjected to histopathological examination. RESULTS: The animals of therapeutic groups administered with extract of C. deodara have exhibited significant rise in hematological parameters and shorten bleeding time and clotting time when compare to toxic control animals on the day 14 and day 21. The histopathological examination revealed the regeneration of bone marrow cells in the extract treated animals. There was significant reduction in lipid peroxidation and increase in antioxidant enzymes was found in extract treated animals. CONCLUSIONS: The methanol extract of C. deodara of have shown significant protective effects against cisplatin induced myelosuppression in albino Wistar 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.

The potential of using Cedrus atlantica as a biomonitor in the concentrations of Cr and Mn.

Air pollution is becoming increasingly dangerous which is quite a significant issue of today's world, especially air pollution from heavy metal, whose emission increases with industrial and traffic activities. This is of great importance in terms of environmental pollution and human health. Heavy metals do not deteriorate and disappear easily on earth. They are liable to bioaccumulate within cells in organisms. Most of them demonstrate harmful effects in addition as a result of advanced accumulation, and thus they emerge as toxic and carcinogenic. Therefore, it is of great importance to observe the changes in heavy metal concentrations in the air. One of the most effective techniques for monitoring the change of heavy metal concentrations in the atmosphere is the use of annual rings of trees as biomonitors. In this study, in the annual rings of the Cedrus atlantica Manetti tree cut at the Kastamonu province at the end of 2019, the variation of the concentrations of some of the heavy metals most associated with traffic density was tried to be determined. Within the scope of the study, Cr and Mn concentration in the outer bark and the inner bark was compared with the direction and wood for the variation of heavy metal concentrations. Also, variance analysis and Duncan test were applied and evaluated. As a result of the study, while the highest values in many heavy metals are generally obtained in the outer bark, the transfer of metals in the wood is limited, and some heavy metal concentrations change significantly depending on the direction, especially in the wood. This change is related to the traffic density, so Cedrus atlantica Manetti annual rings are very suitable as biomonitors for air pollution control.

Influence of temperature on the development and reproduction of Cinara cedri (Hemiptera: Aphidoidea: Lachninae).

Temperature is one of the main factors affecting insect growth, development and reproduction. The effects of temperatures (10, 15, 20, 25 and 30°C) on the development and reproduction of Cinara cedri Mimeur (Hemiptera: Aphidoidea: Lachnidae) fed on Cedrus deodara (Roxb.) G. Don were evaluated in this study. With the increase of temperature from 10 to 30°C, the development duration at different development stages gradually shortened. There was a significant positive correlation between the developmental rates and temperature, following a quadratic regression model. The lower developmental threshold temperature (C) and effective accumulated temperatures (K) for completing a generation were 4.13°C and 263.4 degree-days, respectively. The highest fecundity was observed at 20°C with 25.74 first-instar nymphs/female. Both the highest intrinsic rate of increase (r, 0.11 ± 0.03) and net reproduction rate (R0, 19.06 ± 2.05) were observed at 20°C, whereas the lowest values of r (0.05 ± 0.01) at 10°C and R0 (5.78 ± 0.88) at 30°C were observed. The results suggest that temperature significantly affects the biology of C. cedri and the optimal temperature for its development is 20°C.

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.