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Introduction: Evidence declared lipopolysaccharide (LPS) initiates inflammatory responses by stimulating the abandon of cytokines, which may perturb organ function. On the other side, it has been suggested Cedrol has potential properties, including anti-inflammatory and anti-oxidative activities. Herein, this study was done to assess the protective effect of Cedrol against LPS-associated heart damage. Methods: Thirty-five rats (200-250 g) were sorted into five groups, including control, LPS, LPS-Cedrol 7.5 mg/kg, LPS-Cedrol 15 mg/kg, and LPS-Cedrol 30 mg/kg groups. Cedrol was administrated through injected intra-peritoneally for two weeks. The heart tissues were removed and malondialdehyde (MDA) as a lipid peroxidation marker, superoxide dismutase (SOD), and catalase (CAT) as antioxidant markers were assessed. Furthermore, the interleukin (IL)-6 level in cardiac tissue was measured and Masson's trichrome methods were employed to appraise cardiac inflammation and fibrosis, respectively. Results: Inflammation induced by LPS was significantly accompanied by myocardial fibrosis which was shown by Masson's trichrome staining (P<0.001). In addition, LPS administration enhanced the MDA level while it diminished the activity of anti-oxidant markers such as CAT and SOD (P<0.001 for all cases). In the histological results, Cedrol improved LPS-induced inflammation and cardiac fibrosis (P<0.01 to P<0.001). Cedrol also enhanced CAT and SOD activities, whereas declined MDA level in the cardiac tissue (P<0.01 to P<0.001). Conclusion: The current findings proposed that the administration of Cedrol exerted a protective role in LPS-associated heart damage by reducing inflammation, cardiac fibrosis, and oxidative stress.

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The JAK-STAT signalling pathway is considered to be a significant role involved in the regulation of inflammatory diseases and immune responses, which indicate that specific inhibition of JAK-STAT pathway would be a potential key strategy for RA (Rheumatoid arthritis) treatment. Cedrol (CE), found from ginger by our group earlier, has been proven to play an excellent role in ameliorating RA via acting on JAK3. In this study, 27 new (1, 3-28), along with one known (2) derivatives of CE were synthesized by using chloroacetic acid and acryloyl chloride as intermediate ligands. In vitro, the inhibition effect on JAK kinases were performed using HTRF (Homogenous Time-Resolved Fluorescence) detection technology, which is more convenient and stable than traditional methods. The results compared with the secretion of LPS-induced p-JAK3 can better reflect the true kinase-selective effect of the compounds. Compound 22 was identified as a potent inhibitor to reduce the secretion of LPS-induced p-JAK3 with a dose-dependent manner. Given these results, compound 22 could serve as a favourable inhibitor of JAK3 for further research.

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Background: Cedrol (CRL) is a sesquiterpene alcohol present in the essential oils of coniferous trees including Cupressus and Juniperus genera. CRL has shown potent anticancer activity by virtue of apoptosis. Red blood cells (RBCs), although devoid of mitochondria and nucleus, can undergo hemolysis and eryptosis which contribute to chemotherapy-induced anemia (CIA). In this work, we explored the hemolytic and eryptotic potential of CRL in human RBCs as a safety assessment of the sesquiterpene as an anticancer agent. Methods: RBCs from healthy donors were treated with anticancer concentrations of CRL for 24 h at 37°C with varying experimental manipulations. Hemolysis was photometrically assessed by measuring hemoglobin release whereas flow cytometry was employed to detect phosphatidylserine (PS) exposure by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, cell volume by forward scatter (FSC), and oxidative stress by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA). Results: Significant, concentration-responsive hemolysis was noted upon CRL exposure with concomitant K+, LDH, and AST leakage. CRL also significantly increased annexin-V-positive cells and Fluo4 fluorescence and reduced FSC. Moreover, the cytotoxicity of CRL was significantly ameliorated in the presence of L-NAME, D4476, and PEG 8,000 but was aggravated by urea and sucrose. Conclusion: CRL stimulates hemolysis and eryptosis characterized by PS exposure, Ca2+ overload, and cell shrinkage. The hemolytic activity of CRL was mediated through nitric oxide synthase and casein kinase 1α. Blocking either enzyme may attenuate the toxicity of CRL to RBCs and prevent undesirable side effects associated with its anticancer applications.

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Ginger is an important cooking spice and herb worldwide, and scientific research has gradually confirmed the effect of ginger on preventing hair loss. Cedrol (CE) is a small sesquiterpene molecule in ginger and its external administration (EA) has shown hope in promoting hair growth, and alternative administration mode has become a potential treatment scheme to improve the efficacy of CE. The purpose of this study is to evaluate the effects of oral administration (OA) and EA of CE on hair regeneration of C57BL/6 alopecia areata (AA) mice induced by cyclophosphamide (CP) and to clarify the potential hair growth mechanism of CE in AA model in vitro and in vivo. The results showed that CE-OA has a shorter hair-turning black time and faster hair growth rate, and can lessen hair follicle damage induced by CP and promote hair follicle cell proliferation. Its effect is superior to CE-EA. At the same time, CE can increase the cytokines IFN-γ, IL-2, and IL-7 in the serum of mice, and decrease the expression of adhesion factors ICAM-1 and ELAM-1, thus alleviating the immunosuppression induced by CP. Mechanism research shows that CE regulates the JAK3/STAT3 signaling pathway, activates the Wnt3α/ß-catenin germinal center, and ameliorates oxidative stress induced by CP, thus promoting the proliferation of hair follicle cells and reversing AA. These results provide a theoretical basis for understanding the anti-AA mechanism of CE-OA, indicating that CE can be used as raw material for developing oral hair growth drugs.

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Background: Cedrol, a sesquiterpene alcohol, is found in a high amount in several conifers. It possess several beneficial health effects, including antioxidant and anti-inflammatory properties. Objective: This study evaluates the neuroprotective role of cedrol against lipopolysaccharide (LPS)-induced neuroinflammation and memory loss in rats. Methods: Wistar rats were treated with cedrol (7.5, 15, and 30 mg/kg, oral, two weeks). During the last week, the rats (except for the control group) were treated with LPS (intraperitoneal injection, 1 mg/kg) to induce memory impairment. After that, the animals were subjected to behavioral studies (Morris water maze and passive avoidance) and biochemical assessments. Results: Our results showed a significant decrease in learning and memory function-in LPS-induced rats which were reversed by cedrol. Also, there was a significant increase in the cerebral levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and malondialdehyde (MDA) as well as acetylcholinesterase (AChE) activity in LPS-treated rats. Besides, a significant reduction in total thiol and superoxide dismutase levels was observed in LPS-treated rats. However, cedrol significantly decreased the brain level of AChE, TNF-α, and IL-1ß. Administration of cedrol also restored the oxidative stress markers. Conclusion: the beneficial effects of cedrol against LPS-induced memory impairment could be due to antioxidant activities and modulation of neuro-inflammatory mediators.

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Passiflora foetida is a climbing herb employed in ethno-medicine for the treatment of various ailments. The essential oil from flowers of P. foetida was obtained by hydrodistillation. The ethanol extract of the leaves was dissolved in water, then partitioned with n-hexane and n-butanol to obtain the various fractions; the fractions and isolated compound were subjected to in vitro antioxidant activity. Gas chromatography-mass spectrometry afforded the identification of forty-two constituents in the floral oil, dominated by ß-caryophyllene (17.2%), cedrol (11.5%), and α-humulene (11.5%). The n-butanol fraction was the most active (70% inhibition and absorbance 0.401; 100 µg/mL) in the 2,2-diphenyl-1-picrylhydrazyl radicals and ferric reducing power assays, respectively. Chromatographic analysis facilitated the isolation of 8-C-ß-d-glucosylapigenin (vitexin) from the butanol fraction of P. foetida. Vitexin demonstrated good antioxidant activities (75% inhibition and absorbance 0.424; 100 µg/mL) compared with ascorbic acid. The volatile metabolites of P. foetida flowers are reported for the first time.

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Pharmacological studies have shown that Cedrol (CE) exhibits extensive biological activities, including anti-inflammatory and analgesic. Moreover, it can inhibit the NF-κB pathway and the expression of various associated proteins. This study aimed to investigate the role of CE in postmenopausal osteoporosis. The results showed that intragastric administration of CE (10 and 20 mg/kg) significantly improved the bone microstructure damage and increased bone mineral density, trabecular bone volume, and bone trabecular thickness in ovariectomized (OVX) rats (p < 0.05). CE treatment additionally made a well-organized arrangement of bone trabeculae and improved its thickness and density. Compared with the OVX group, the levels of tartrate-resistant acid phosphatase from 5b and C-terminal telopeptide of type I collagen were significantly reduced by 42.75% and 49.27% in the OVX + CE rats (p < 0.05). TRAP staining visually showed that the number of osteoclasts in the femur tissue of CE-treated rats was less than that of the OVX group. The expressions of nuclear factor of activated T-cells, cytoplasmic 1, acid phosphatase 5, and cathepsin K in OVX + CE rats were significantly decreased by 51.61%, 46.07%, and 50.34% compared to the OVX group (p < 0.01). In addition, CE intervention effectively reduced the phosphorylation levels of P65 and IκBα and inhibited the NF-κB signaling pathway. Meanwhile, CE diminished the number of multinucleated osteoclasts induced by receptor activator for nuclear factor-κB ligand and hindered cell fusion as well as nuclear translocation of osteoclast precursor cells P65. In conclusion, CE inhibits osteoclastogenesis by suppressing the activation of the NF-κB signaling pathway, thereby alleviating postmenopausal osteoporosis.

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Cedrol is a major bioactive compound present in the Cedrus atlantica with numerous biological properties. In this study, we elucidated the neuroprotective properties of cedrol against ischemic infarction in animal and in vitro studies. A cerebral ischemic/reperfusion model was induced in adult Wistar rats, and oxygen-glucose deprivation/reperfusion was induced in SH-SY5Y neuronal cells and treated with different concentrations of cedrol. The percentage of water content, cerebral  infarct, and neurological deficit score was assessed in experimental rats. The acetylcholinesterase activity and inflammatory cytokines were quantified to analyze the anti-inflammatory potency of cedrol. Oxidative stress marker malondialdehyde and antioxidants were quantified to evaluate the antioxidant potency of cedrol in an ischemic condition. The neuroprotective potency of cedrol was confirmed by histopathological analysis of the brain tissue of cedrol-treated I/R-induced rats. In in vitro studies, the MTT and LDH assays were performed in cedrol-treated OGD/R SH-SY5Y cells to analyze the cytoprotective effect of cedrol. The anti-inflammatory property of cedrol was confirmed by quantifying the pro-inflammatory cytokine levels in OGD/R-induced cedrol-treated SH-SY5Y cells. The results obtained prove that cedrol significantly prevents brain edema, neurological deficits, acetylcholinesterase activity, and oxidative damage in ischemic-induced rats. It inhibited neuroinflammation in ischemic-induced rats and also in in vitro models. The neuroprotective effect of cedrol during an ischemic condition was authentically established with histological analysis in an animal model and cell survival assays in an in vitro model. Overall, our results confirm that cedrol is a potent alternative drug to treat cerebral ischemia in the future.

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Androgenetic alopecia seriously affects the physical and mental health of patients. The main clinical therapeutic agent, minoxidil tincture, is challenged by solvent irritation and dose-dependent side effects. Our recent work has identified a biosafety natural product, cedrol, that is synergistic in combination with minoxidil, thereby improving medication safety by substantially reducing the clinical dose of minoxidil. In addition, ccross-linked CD-MOF were designed as carriers for hair follicle delivery, and γ-CD in the carriers was cross-linked by diphenyl carbonate with covalent bonds to protect the CD-MOF from rapid disintegration in an aqueous environment. This improved nanocarrier has a drug loading of 25%, whereas nanocarriers increased drug delivery to the hair follicles through ratchet effect, and increased human dermal papilla cells uptake of drugs via endocytosis pathways mainly mediated by lattice proteins, energy-dependent active transport, and lipid raft-dependent, thus improved cell viability, proliferation, and migration, followed by significantly enhancing the anti-androgenetic alopecia effect, with cedrol focusing on inhibiting 5α-reductase and activating Shh/Gli pathway, and minoxidil, which up-regulated VEGF, down-regulated TGF-ß, and activated ERK/AKT pathway. This drug combination provides a new therapeutic strategy for androgenetic alopecia, while the newly developed cross-linked CD-MOF has been shown to serve as a promising follicular delivery vehicle.

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Cedrol-like compounds are of pharmacological interest due to their diverse range of medicinal effects and are used globally in traditional medicines and cosmetics. Many cedrol tautomers are known from molecular studies but few have been studied in crystalline form by X-ray diffraction. Acicular white crystals collected from the wood of eastern red cedar (Juniperus virginiana) are determined to be (+)-cedrol hemihydrate, namely, (1S,2R,5S,7R,8R)-2,6,6,8-tetramethyltricyclo[5.3.1.01,5]undecan-8-ol hemihydrate, C15H26O·0.5H2O, a novel packing of two unique cedrol molecules (Z' = 2) with a single water molecule [space group P212121; a = 6.1956 (1), b = 14.5363 (1), and c = 30.9294 (4) Å]. The hydrogen bonding forms a one-dimensional spiral chain running along the a axis, following the chirality of the cedrol molecule, through hydrogen-bonding interactions with a right-handed helical configuration in graph-set notation Δ-C33(6) > a > c > b. The crystal packing and symmetry are different from crystalline isocedrol due to the different hydrogen-bonding geometry.

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Phellinus noxius is a highly destructive fungus that causes brown root disease in trees, leading to decay and death. In Taiwan, five prized woods-Taiwania cryptomerioides, Calocedrus macrolepis var. formosana, Cunninghamia lanceolata var. konishii, Chamaecyparis formosensis, and Chamaecyparis obtusa var. formosana-are known for their fragrance and durability. This study aims to explore the anti-brown-root-rot-fungus activity of Cunninghamia lanceolata var. konishii (CL) essential oil (CLOL) and its primary components, while also delving into their mechanisms of action and inhibition pathways. The essential oil (CLOL) from CL wood demonstrated significant efficacy against P. noxius, with an inhibitory concentration (IC50) of 37.5 µg/mL. Cedrol, the major component (78.48%) in CLOL, emerged as a potent antifungal agent, surpassing the reference drug triflumizole. Further assays with cedrol revealed a stronger anti-brown-root-disease activity (IC50 = 15.7 µg/mL) than triflumizole (IC50 = 32.1 µg/mL). Scanning electron microscopy showed deformation and rupture of fungal hyphae treated with CLOL and cedrol, indicating damage to the fungal cell membrane. Cedrol-induced oxidative stress in P. noxius was evidenced by increased reactive oxygen species (ROS) levels, leading to DNA fragmentation, mitochondrial membrane potential reduction, and fungal apoptosis through the mitochondrial pathway. Gel electrophoresis confirmed cedrol-induced DNA fragmentation, whereas TUNEL staining demonstrated increased apoptosis with rising cedrol concentrations. Moreover, protein expression analysis revealed cedrol-triggered release of cytochrome c, activation of caspase-9, and subsequent caspase-3 activation, initiating a caspase cascade reaction. This groundbreaking study establishes cedrol as the first compound to induce apoptosis in P. noxius while inhibiting its growth through oxidative stress, an increase in mitochondrial membrane permeability, and activation of the mitochondrial pathway. The findings offer compelling evidence for cedrol's potential as an effective antifungal agent against the destructive brown root disease caused by P. noxius.

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OBJECTIVES: The dissolvable microneedles loaded with cedrol based on flexible backing were developed to deliver cedrol directly and continuously to the dermis, where the drug concentration in the hair follicle can be increased locally. METHODS: The tip-layer matrix solution was prepared by mixing cedrol and polyvinylpyrrolidone K25 (PVP K25), and the pedestal matrix solution was prepared with aqueous hyaluronic acid. The cedrol-loaded dissolvable microneedles (cedrol-DMNs) were prepared under vacuum conditions. The mechanical properties, pig skin penetration efficiency, in vitro cutaneous permeation test, and the amount of drug in the skin and receptor chamber were evaluated. Pharmacodynamical studies were performed with C57BL/6 mice. RESULTS: The mechanical properties of cedrol-DMNs were good. In vitro cutaneous permeation tests and pharmacodynamical studies demonstrated that cedrol-DMN could efficiently deliver the drug to the deep dermis and effectively promote hair growth. CONCLUSIONS: The cedrol-DMNs offer a promising strategy for treating patients suffering from hair loss.

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As drug-resistant strains of Eimeria have emerged and concerns about drug residues in poultry have grown, there is renewed interest in identifying natural alternatives to control coccidiosis. Cedrol, a natural sesquiterpene alcohol, was used in this study to test anticoccidial efficacy in chicks. Both the control and treatment groups were orally challenged with 2 × 104 oocysts per chicken. Chicks administered with cedrol had reduced oocyst count, an increase in the relative weight gain rate of chicks, and a decrease in severe swelling of the cecum. Based on the above, ACI was calculated and the cedrol group reached moderate anti-coccidial activity (169.34). In chickens treated with cedrol, there were no changes in serum biochemical parameters, but oxidative stress biomarkers and cytokine levels associated with anticoccidial response were altered. These changes suggest that the administered concentration of cedrol did not have any adverse effects on the chickens while enhancing their antioxidant capacity and immunity, leading to an improved anticoccidial ability. In conclusion, this study shows that the addition of cedrol in poultry production has an anticoccidial effect and successfully improves growth performance during the growth period.

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Cedrol is a sesquiterpene alcohol isolated from Cedrus atlantica, which has been traditionally used in aromatherapy and has anticancer, antibacterial and antihyperalgesic effects. One characteristic of glioblastoma (GB) is the overexpression of vascular endothelial growth factor (VEGF), which induces a high degree of angiogenesis. Although previous studies have reported that cedrol inhibits GB growth by inducing DNA damage, cell cycle arrest and apoptosis, its role in angiogenesis remains unclear. The aim of the present study was to investigate the effects of cedrol on VEGF-induced angiogenesis of human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 0-112 µM cedrol and 20 ng/ml VEGF for 0-24 h, and then anti-angiogenic activation of cedrol was determined by MTT assay, wound healing assay, Boyden chamber assay, tube formation assay, semi-quantitative reverse transcription-PCR and western blotting. These results demonstrated that cedrol treatment inhibited VEGF-induced cell proliferation, migration and invasion in HUVECs. Furthermore, cedrol prevented VEGF and DBTRG-05MG GB cells from inducing capillary-like tube formation in HUVECs and decreased the number of branch points formed. Moreover, cedrol downregulated the phosphorylation of VEGF receptor 2 (VEGFR2) and the expression levels of its downstream mediators AKT, ERK, VCAM-1, ICAM-1 and MMP-9 in HUVECs and DBTRG-05MG cells. Taken together, these results demonstrated that cedrol exerts anti-angiogenic effects by blocking VEGFR2 signaling, and thus could be developed into health products or therapeutic agents for the prevention or treatment of cancer and angiogenesis-related diseases in the future.

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Fu brick tea (FBT) is popular for its unique 'fungal flower' aroma, however, its key odor-active compounds are essentially unknown. In this study, the odor-active compounds of "stale-fungal" aroma (CJX), "fresh-fungal" aroma (QJX), and "fermentation-fungal" aroma (FJX) types FBT were extracted and examined by headspace solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) and gas chromatographyolfactometry (GC-O). A total of 43 volatile and 38 odor-active compounds were identified by these methods. Among them, the content of dihydroactindiolide (4596-13189 µg/L), (E)-linalool oxide (2863-6627 µg/L), and benzyl alcohol (4992-6859 µg/L) were highest. Aroma recombination experiments further verified that these odor-active compounds could be simulated the overall aroma profile of FBT successfully. Furthermore, omission experiments confirmed that 15, 20, and 15 key odor-active compounds in CJX, QJX, and FJX FBT, respectively. This study will provide a theoretical basis for comprehensively understanding the formation of characteristic aromas in FBT.

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SCOPE: Excellent health-promoting effects of cedrol (CED), including anti-inflammatory, anti-arthritic, and antinociceptive effects, have been reported. The present study aims to investigate the preventive effects of CED on high-fat diet (HFD)-induced obesity and the related metabolic syndrome, and to delineate the underlying mechanism. METHODS AND RESULTS: Ten-week-old C57BL/6J mice are fed chow, HFD, or HFD supplemented with CED (0.2% w/w) for 19 weeks. Results demonstrate that CED effectively reduces HFD-induced body weight gain, decreases visceral fat pad weight, and significantly prevents adipocyte hypertrophy in mice. HFD-induced hepatic steatosis, glucose intolerance, insulin resistance, and gluconeogenesis are ameliorated by CED supplementation. 16S rRNA analysis reveals that CED does not change gut microbiota composition at the phylum and genus levels, indicating that CED may have limited effects on gut microbiota in HFD-fed mice. Further transcriptome analysis of epididymal white adipose tissue reveals reprogrammed RNA profiles by CED. CONCLUSION: These results demonstrate that incorporating CED in the diet can prevent HFD-induced obesity and related metabolic syndrome, and highlight that CED can be a promising dietary component for obesity therapeutic intervention.

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Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Ginger, a food spice and traditional medicine with ancient history, exhibits the potential to alleviate osteoporosis in preclinical experiments, whereas its complex composition leads to ambiguous pharmacological mechanisms. The purpose of this study was to investigate the effect and mechanism of Ced in estrogen-deficient osteoporosis, a sesquiterpene alcohol recently discovered from Ginger with multiple pharmacological properties. RANKL was stimulated BMM (bone marrow macrophages) differentiation into osteoclasts in vitro. And the osteoclast activity and number were assessed by TRAcP and SEM. We found that Ced mitigated RANKL-induced osteoclastogenesis by descending the ROS content and obstructing NFATc1, NF-κB, and MAPK signaling. Also, Ced-mediated anti-osteolytic property was found in ovariectomized mice by Micro-CT scanning and histological staining. Summarily, our works demonstrated the anti-osteoporotic potential of Cedrol in Ginger for the first time, which also offered more pharmacological evidence for Ginger as food or medicine used for bone metabolic disease.

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Background: Cedrol is a natural sesquiterpene alcohol found in Cedrus atlantica, which has been proven to have a broad spectrum of biological activities, such as antimicrobial, anti-inflammatory, analgesic, anxiolytic, and anti-cancer effects. However, the underlying anticancer mechanisms and in vivo inhibitory effects of cedrol on colorectal cancer (CRC) have not been elucidated. In the present study, we investigated the anti-CRC potential of cedrol using in vitro and in vivo models. Methods: The effects of cedrol on cell viability, cell cycle progression, and apoptosis of HT-29 and CT-26 cells were detected by MTT, flow cytometry, and TUNEL assays. Western blotting was used to measure protein expression for molecular signaling analyses. Results: Cedrol inhibited HT-29 and CT-26 cell proliferation in a time- and dose-dependent manner, with IC50 values of 138.91 and 92.46 µM, respectively. Furthermore, cedrol induced cell cycle arrest at the G0/G1 phase by regulating the expression of cell cycle regulators, such as CDK4 and cyclin D1, and triggered apoptosis through extrinsic (FasL/caspase-8) and intrinsic (Bax/caspase-9) pathways. In addition, cedrol in combination with the clinical drug 5-fluorouracil exhibited synergistic inhibitory effects on CRC cell growth. Importantly, cedrol treatment suppressed the progression of CRC and improved the survival rate of animals at a well-tolerated dose. Conclusion: These results suggest that cedrol has an anti-cancer potential via induction of cell cycle arrest and apoptosis, and it could be considered as an effective agent for CRC therapy.

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The bHLH transcription factors play important roles in the regulation of plant growth, development, and secondary metabolism. ß-Caryophyllene, epi-cedrol, and ß-farnesene, three kinds of sesquiterpenes mainly found in plants, are widely used as spice in the food industry and biological pesticides in agricultural production. Furthermore, they also have a significant value in the pharmaceutical industry. However, there is currently a lack of knowledge on the function of bHLH family TFs in ß-caryophyllene, epi-cedrol, and ß-farnesene biosynthesis. Here, we found that AabHLH112 transcription factor had a novel function to positively regulate ß-carophyllene, epi-cedrol, and ß-farnesene biosynthesis in Artemisia annua. Exogenous MeJA enhanced the expression of AabHLH112 and genes of ß-caryophyllene synthase (CPS), epi-cedrol synthase (ECS), and ß-farnesene synthase (BFS), as well as sesquiterpenes content. Dual-LUC assay showed the activation of AaCPS, AaECS, and AaBFS promoters were enhanced by AabHLH112. Yeast one-hybrid assay showed AabHLH112 could bind to the G-box (CANNTG) cis-element in promoters of both AaCPS and AaECS. In addition, overexpression of AabHLH112 in A. annua significantly elevated the expression levels of AaCPS, AaECS, and AaBFS as well as the contents of ß-caryophyllene, epi-cedrol, and ß-farnesene, while suppressing AabHLH112 expression by RNAi reduced the expression of the three genes and the contents of the three sesquiterpenes. These results suggested that AabHLH112 is a positive regulator of ß-caryophyllene, epi-cedrol, and ß-farnesene biosynthesis in A. annua.

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Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.

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