查找使用阿拉丁产品的科研文献

Involvement of the dopamine D1 receptor system in the anxiolytic effect of cedrol in the elevated plus maze and light–dark box tests

Kai Zhang,Jing Lu,Lei Yao

Cedrol, mainly derived from Juniperus virginiana L. essential oil, has been demonstrated the anxiolytic effect, although its mechanism of action is still not fully established. In the present study, male ICR mice were submitted to the elevated plus maze (EPM) and light–dark box (LDB) tests to investigate the putative mechanism of anxiolytic effect. WAY100635 (5-HT 1A receptor antagonist), flumazenil (benzodiazepine receptor antagonist), SCH23390 (dopamine D 1 receptor antagonist) or sulpiride (dopamine D 2 /D 3 receptor antagonist) were used in the behavioral experiment to determine the mechanism of action of cedrol. Subsequently, the monoamine neurotransmitter levels were evaluated after behavioral tests. The data suggest that no significant effect in behavioral parameters were observed after sole intraperitoneal (i.p.) injection of antagonists compared to saline group. The anxiolytic effect of cedrol in behavioral procedures was blocked by either WAY100635 or flumazenil. The anxiolytic effect of cedrol (1200 mg/kg) was effectively antagonized by SCH23390 (0.125 mg/kg). Furthermore, cedrol decreased the DA and NE levels in hippocampus, striatum and hypothalamus. The present findings suggest that the dopaminergic system (D 1 receptor) rather than serotoninergic or GABAergic system may potentially be involved in the modulation of cedrol-induced anxiolytic-like behaviors in mice.

Essential Oils of Cedrus deodara Leaves Exerting Anti-inflammation on TPA-induced Ear Edema by Inhibiting COX-2/TNF-α/NF-κB Activation

Yu Chen,Lejing Chi,Xiaoxin Liang,Yaohui Shi,Tongyun Wu,Mao Ye,Ping Han,Li Lin,Lanyue Zhang,Peng Xu,Zhiyun Du

Cedrus deodara is a cedar plant from the Pinaceae family. Because Cedrus is widely used in health care products, cosmetics, medicine, and insecticides, the essential oils of Cedrus deodara (CDEOs) are gaining increasing levels of attention. However, there have only been a few studies on the anti-inflammatory effects of CDEOs. This study aimed to systematically study the composition and biological effects of CDEOs, in line with this, the study assessed the chemical composition of CDEOs and evaluated their anti-inflammatory mechanisms in mice. Gas chromatography-mass spectrometry (GC-MS) was used to determine and analyze a total of 41 compounds from CDEOs. It was found that the major components of CDEOs are thujopsene (28.23%), α-cedrene (17.01%), and cedrol (15.55%); moreover, our results showed that the active ingredients in CDEOs have anti-inflammatory and antioxidant effects and that the active ingredients in CDEOs can be used as an antioxidant, as an important biological resource in functional food, and as ingredients in cosmetics and pharmaceuticals. Taken together, these CDEOs serve as ideal additives for anti-inflammatory drugs.

Cedrol from ginger alleviates rheumatoid arthritis through dynamic regulation of intestinal microenvironment

Yumeng Zhang,Yang Liu,Fei Peng,Xinrui Wei,Huiqin Hao,Wei Li,Yuqing Zhao

The imbalance of intestinal flora would induce immune inflammation. Cedrol (CE), found from ginger by our group earlier, has been proven to play an excellent role in ameliorating rheumatoid arthritis (RA) via acting on JAK3, MAPK, and NF-κB. However, there have been no studies on CE ameliorating RA through the regulation of the micro-environment. In this study, the adjuvant arthritis model (AIA) is established to evaluate the weight, arthritis score, paw swelling, bone destruction, immune organ index, inflammatory cell infiltration, cartilage erosion, and metabolic enzymes of kidneys in AIA rats after CE intervention. The results indicated CE could alleviate paw swelling, reduce arthritis score, decrease the secretion of TNF-α, IL-6, and IL-1β in serum in a dose-dependent manner, and inhibit the immune organ index of the spleen while having no significant effect on metabolic enzymes of the kidney. In addition, pathological sections of ankle and knee joints suggested CE might significantly prevent inflammatory cell infiltration, synovial hyperplasia, and joint degeneration and protect articular cartilage. Then, for the first time, 16S rRNA gene was applied to analyze the regulatory effect of CE on intestinal flora. CE could effectively improve the uniformity, diversity, and richness of intestinal flora, reduce the number of pathogenic bacteria, and increase the proportion of beneficial bacteria, and it significantly inhibited the abundance of Prevotella in RA rats, which was 12.43 times smaller than that in methotrexate. The distribution and excretion of CE in vivo were detected by GC-MS. It was found that CE would massively accumulate in the gastrointestinal tract after oral administration, which is then mainly excreted through feces. Interestingly, the research suggested that CE, which plays a role in the dynamic regulation of the intestinal micro-environment, could be used as a potential component to prevent RA.

Cedrol-loaded dissolvable microneedles based on flexible backing for promoting hair growth

Yanjun Zhou,Luan Jia,Guangshuai Zhang,Gang Chen,Di Zhou,Xianbao Shi,Qiang Fu,Ning Li

Cedrol, a Major Component of Cedarwood Oil, Ameliorates High-Fat Diet-Induced Obesity in Mice

Yuhan Zhao,Mengjie Li,Jingya Guo,Jingjing Fang,Ruixuan Geng,Yanan Wang,Tingting Liu,Seong-Gook Kang,Kunlun Huang,Tao Tong

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.

Cedrol alleviates postmenopausal osteoporosis in rats through inhibiting the activation of the NF-κB signaling pathway

Zheng Zhen,Fan Ying,Zhang Jingyun,Wang Jian,Li Zhenyu

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.

Cedrol impedes lung cancer metastasis by reducing tumor-associated macrophage polarization mediated by MYC-driven aerobic glycolysis

Li Qingsheng,Liu Yuxi,Zhang Lin,Zheng Yi,Feng Xiaofan,Wang Yanjie

The occurrence of tumor metastasis is associated with the phenotype of tumor-associated macrophages (TAMs). Within the tumor microenvironment, TAMs undergo metabolic reprogramming. Aerobic glycolysis contributes to TAM polarization into an M2-like phenotype. Cedrol is a component extracted from herbal medicines. Anti-cancer activities of cedrol have been reported, however, its effect on the metabolic reprogramming and pro-metastatic ability of TAMs remains unclear. Here, we found that cedrol reduced THP-1-derived macrophage polarization into M2-like phenotypes. Cedrol impaired the promoting effects of TAMs on the migration and invasion of lung cancer cells. Tumor metastasis in C57BL/6 mice was reduced following cedrol treatment, accompanied by decreases in M2-like TAMs in the lung tissues. Cedrol treatment decreased glucose consumption and lactate production and downregulated glycolysis-associated gene expression. A glycolytic inhibitor (2-DG) was utilized to confirm that suppression of glycolysis in TAMs limited the metastasis of lung cancer cells. MYC was identified as a downregulated gene in cedrol-treated TAMs based on the mRNA sequencing analysis. MYC overexpression could reverse the effects of cedrol on TAMs. Cedrol treatment reduced MYC expression at least partly via the PI3K-Akt pathway. These findings suggest that cedrol exerts anti-tumor effects by inhibiting TAM polarization into an M2-like phenotype by modulating MYC-mediated aerobic glycolysis, indicating cedrol as a potential drug for lung cancer treatment.

Cedrol attenuates acute ischemic injury through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways

Yu Bi,Ziyi Xie,Xiang Cao,Huanyu Ni,Shengnan Xia,Xinyu Bao,Qinyue Huang,Yun Xu,Qingxiu Zhang

Microglia-associated neuroinflammation plays essential roles in pathology of acute stroke. Cedrol, a natural compound extracted from ginger, has been shown to confer inhibitory effects on inflammation in various diseases. However, whether Cedrol suppresses neuroinflammation and protects brains from acute ischemic injury still remains unclear. In this study, we found that Cedrol inhibited microglia activation and the production of inflammatory factors in LPS-challenged microglia and the penumbra region of middle cerebral artery occlusion (MCAO) mice. We also found that Cedrol reduced the infarct size and mNSS scores and improved acute cerebral ischemia-induced behavioral outcomes, suggesting remarked neuroprotection of Cedrol. Molecular docking analysis showed that Cedrol bound to estrogen receptor β (ERβ) with moderate-strong affinity. Intriguingly, treatment with fulvestrant, an ER blocker, abolished the anti-inflammatory effects of Cedrol. Cedrol significantly reversed the LPS- and MCAO-induced increases in phosphorylation levels of IκB and NF-κB P65 in primary microglia and MCAO mice, respectively. Additionally, Cedrol was observed to rescue LPS-induced shuttling of NF-κB P65 from cytoplasm to nuclei in primary microglia, indicating inhibitory effects of Cedrol on NF-κB signaling. These results suggest microglia associated neuroinflammation may be mediated by ERβ-NF-κB signaling pathway. Together, our study reveals that Cedrol protected brain function from acute cerebral ischemia through inhibition of microglia-associated neuroinflammation via ERβ-NF-κB signaling pathways, and Cedrol may serve as an alternative option for treatment of acute stroke injury.

Cedrol mitigates hepatic lipid accumulation and adipocyte hypertrophy induced by corticosteroids through the inhibition of glucocorticoid receptor activity

Shu Minghui,Wang Pan

Cedrol is a sesquiterpene alcohol derived from ginger and cedar oil. Cedrol has multiple pharmacological effects such as sedation, promoting hair growth, decreasing blood pressure and reducing obesity. But its pharmacological mechanisms are not fully understood and its direct targets remain unknown. Glucocorticoids, particularly dexamethasone, are stress hormones in the body and interact with glucocorticoid receptors (GRs) to regulate physiological functions such as metabolism. In this study, we find that cedrol effectively mitigates the lipid accumulation in liver and adipose tissues induced by dexamethasone in adult male mice. Cedrol treatment also inhibits the dexamethasone-induced expression of genes involved in lipid metabolism, including Cd36 , C/ebp β, Srebp1 , Fas and Scd1 in the liver. In addition, cedrol binds to GR in the cellular thermal shift assay and shows antagonistic activity in luciferase reporter assays. These results indicate that cedrol has GR antagonist activity, which may be responsible for its effect on lipid metabolism, and suggest that cedrol could also be potentially used in the treatment of lipid metabolism disorders induced by high glucocorticoids.

Cedrol ameliorates ulcerative colitis via myeloid differentiation factor 2-mediated inflammation suppression, with barrier restoration and microbiota modulation

Yi-Qing Zhao,Yu Zhang,Yan Qin,Rui-Ya Zhang,Jun-Ping Wang

BACKGROUND Ulcerative colitis (UC) is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe. Cedrol (CE) is a bioactive natural product present in many traditional Chinese medicines. It is known for its suppression of inflammation and mitigation of oxidative stress. Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized. AIM To investigate the therapeutic potential and mechanisms of CE in UC. METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model. Network pharmacology was employed to predict potential targets and pathways. Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. The anti-inflammatory mechanisms were further verified using in vitro assays. Additionally, the gut microbiota composition was analyzed via 16S rRNA gene sequencing. RESULTS CE significantly alleviated colitis symptoms, mitigated histopathological damage, and suppressed inflammation. Moreover, CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins (zonula occludens 1, occludin, claudin-1). Mechanistically, CE stably bound to MD2, inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells. This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, downregulating the expression of tumor necrosis factor-alpha, interleukin-1β, and interleukin-6. Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta . CONCLUSION CE acted on MD2 to suppress proinflammatory cascades, promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.

Characterization of a sesquiterpene cyclase from the glandular trichomes of Leucosceptrum canum for sole production of cedrol in Escherichia coli and Nicotiana benthamiana

Fei Luo,Yi Ling,De-Sen Li,Ting Tang,Yan-Chun Liu,Yan Liu,Sheng-Hong Li

Cedrol is an extremely versatile sesquiterpene alcohol that was approved by the Food and Drug Administration of the United States as a flavoring agent or adjuvant and has been commonly used as a flavoring ingredient in cosmetics, foods and medicine. Furthermore, cedrol possesses a wide range of pharmacological properties including sedative, anti-inflammatory and cytotoxic activities. Commercial production of cedrol relies on fractional distillation of cedar wood oils , followed by recrystallization, and little has been reported about its biosynthesis and aspects of synthetic biology . Here, we report the cloning and functional characterization of a cedrol synthase gene ( Lc-CedS ) from the transcriptome of the glandular trichomes of a woody Lamiaceae plant Leucosceptrum canum . The recombinant Lc-CedS protein catalyzed the in vitro conversion of farnesyl diphosphate into the single product cedrol, suggesting that Lc-CedS is a high-fidelity terpene synthase. Co-expression of Lc-CedS , a farnesyl diphosphate synthase gene and seven genes of the mevalonate (MVA) pathway responsible for converting acetyl-CoA into farnesyl diphosphate in Escherichia coli afforded 363 μg/L cedrol as the sole product under shaking flask conditions. Transient expression of Lc-CedS in Nicotiana benthamiana also resulted in a single product cedrol with a production level of 3.6 μg/g fresh weight. The sole production of cedrol by introducing of Lc-CedS in engineered E. coli and N. benthamiana suggests now alternative production systems using synthetic biology approaches that would better address sufficient supply of cedrol.