Comparison of the pharmacokinetics of Crocin-I in normoxic and hypoxic rats

Wang, Peng; Mao-xing, L.I.; GUO, Zi-liang; WANG, Wei-gang; Xiao-lin, L.I.; Yan, Na; LIU, Tian-long

doi:10.1016/j.taap.2022.116088

Cited by 4 publications

(2 citation statements)

References 11 publications

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“…Crocin is the primary constituent of Crocus sativus L. extract, which can be absorbed into the blood, and most of it will be converted into Crocetin for absorption, scholars have reported that the biological half‐life of Crocin is 2.67 h t1/2(α) and 81.53 h t1/2(β), indicating rapid distribution but relatively slow elimination (Ruiming, 1988 ; Wang et al., 2022 ). Mounting evidence has suggested that Crocin is effective in managing multiple diseases, including neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway

Su,

Wang,

Shao

et al. 2024

Brain and Behavior

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BackgroundCrocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD.MethodsAD mice were set up by injecting Aβ25‐35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open‐field test, Y‐maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL‐1β, IL‐6, and TNF‐α), and PI3K/AKT signaling‐related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real‐time polymerase chain reaction (qRT‐PCR) experiments, respectively.ResultsCrocin attenuated Aβ25‐35‐induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT‐PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aβ25‐35‐induced mice.ConclusionCrocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.

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Section: Discussionmentioning

confidence: 99%

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway

Su,

Wang,

Shao

et al. 2024

Brain and Behavior

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“…All pharmaceutical companies in China need to comply with this regulation. Modern pharmacological research has further shown that crocin I and II have memory-improving [ 8 ], radiation-protection [ 9 ], antidepressant [ 10 ], anticancer [ 11 ], and antioxidant effects [ 12 ], thereby demonstrating great potential for clinical application and advantages in new drug development, food, and cosmetics industries. However, saffron is commonly referred to as “red gold”, due to its lower yield and higher price [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Crocin I and Crocin II by Multigene Stacking in Nicotiana benthamiana

Xie,

Luo,

Jia

et al. 2023

IJMS

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Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer’s disease. Crocins are mainly biosynthesized in the stigmas of food–medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco.

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Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats

Zhang,

Mu,

Zhong

et al. 2024

CDM

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Background: High altitude environment affects the pharmacokinetic (PK) parameters of drugs and the PK parameters are an important theoretical basis for guiding the rational clinical use of drugs. Warfarin is an oral anticoagulant of the coumarin class commonly used in clinical practice, but it has a narrow therapeutic window and wide individual variation. However, the effect of high altitude environment on PK and pharmacodynamic (PD) of warfarin is unclear. Objective: The objective of this study is to investigate the effect of a high altitude environment on PK and PD of warfarin in rats. Method: Rats were randomly divided into plain group and high altitude group and blood samples were collected through the orbital venous plexus after administration of 2 mg/kg warfarin. Warfarin concentrations in plasma samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and PK parameters were calculated by the non-compartment model using WinNonlin 8.1 software. Meanwhile, the expression of PXR, P-gp and CYP2C9 in liver tissues was also determined by western blotting. The effect of high altitude environment on PD of warfarin was explored by measuring activated partial thromboplastin time (APTT) and prothrombin time (PT) values and then calculated international normalized ratio (INR) values based on PT. Results: Significant changes in PK behaviors and PD of warfarin in high altitude-rats were observed. Compared with the plain-rats, the peak concentration (Cmax) and the area under the plasma concentration-time curve (AUC) increased significantly by 50.9% and 107.46%, respectively. At the same time, high altitude environment significantly inhibited the expression of PXR, P-gp and CYP2C9 in liver tissues. The results of the PD study showed that high altitude environments significantly prolonged PT, APTT and INR values. Conclusion: High altitude environment inhibited the metabolism and increased the absorption of warfarin in rats and increased the effect of anticoagulant effect, suggesting that the optimal dose of warfarin for patients at high altitude should be reassessed.

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Comparison of the pharmacokinetics of Crocin-I in normoxic and hypoxic rats

Cited by 4 publications

References 11 publications

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway

Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway

Synthesis of Crocin I and Crocin II by Multigene Stacking in Nicotiana benthamiana

Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats

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