Crocetin Protected Human Hepatocyte LO2 Cell From TGF-β-Induced Oxygen Stress and Apoptosis but Promoted Proliferation and Autophagy via AMPK/m-TOR Pathway

Guo, Hongxing; Ruan, Chenyu; Zhan, Xiuhong; Pan, Hao; Luo, Yuan; Gao, Ke

doi:10.3389/fpubh.2022.909125

Cited by 6 publications

(6 citation statements)

References 33 publications

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“…Crocin, by modulating the MAPK signaling pathway and reducing TNF-α levels, exhibits anti-inflammatory and anti-apoptotic activity [35]. Furthermore, Crocetin, through promoting cell proliferation and autophagy and regulating the AMPK signaling pathway, inhibits cell apoptosis and inflammation, thereby protecting cells from damage [36]. These research results are consistent with our experimental results, further illustrating that WG may achieve efficacy in treating jaundice and hepatitis through its anti-inflammatory effects.…”

Section: In Vitro Validationsupporting

confidence: 87%

Comparative Analysis of Gardenia. jasminoides Ellis and G. jasminoides var. Radicans Makino Based on Network Pharmacology

Hou,

Zeng,

Huang

et al. 2024

Preprint

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Gardenia fruits, commonly used in traditional Chinese medicine, historically treated jaundice and hepatitis. Despite the pharmacopeial identification of the source plant as Gardenia jasminoides Ellis (MG), market occurrences of adulteration with G. jasminoides var. Radicans Makino (WG) have been noted. This study aims to compare and analyze the therapeutic potential of the main components of MG and WG on jaundice and hepatitis using network pharmacology methods, exploring WG as an alternative or supplementary resource to MG. Network pharmacology and molecular docking methods compared the main components of WG and MG, as well as their mechanisms of action in treating jaundice, hepatitis, and related disorders. Additionally, cell experiments using RAW 264.7 cells assessed the effects of Geniposide, Genipin, Crocin, Crocin II, and Crocetin on Cell Counting Kit-8 (CCK-8), nitric oxide (NO) production, and the secretion levels of TNF-α, IL-6, and IL-1β, measured through enzyme-linked immunosorbent assay (ELISA). WG and MG exhibited common targets in treating jaundice, hepatitis, and related disorders, with GO and KEGG analysis showing high similarity, all pointing to inflammation-related pathways. Toxicity prediction and molecular docking identified five shared compounds (Crocin, Crocin II, Geniposide, Genipin, and Crocetin) among WG and MG, demonstrating significant pro-proliferative effects on LPS-induced RAW 264.7 cells and inhibitory effects on inflammatory factors NO, TNF-α, IL-6, and IL-1β. Through network pharmacology comparative analysis, we found that WG and MG have a similar chemical basis for treating jaundice and hepatitis, with the analysis of their mechanisms of action pointing to inflammation-related pathways. Shared components such as Geniposide, Genipin, Crocin, Crocin II, and Crocetin exhibited significant anti-inflammatory activity, effectively countering the inflammatory effects induced in LPS-treated RAW 264.7 cells. Despite the limited acceptance of WG in medical practice, this study provides new perspectives and clues for its development.

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Section: In Vitro Validationsupporting

confidence: 87%

Comparative Analysis of Gardenia. jasminoides Ellis and G. jasminoides var. Radicans Makino Based on Network Pharmacology

Hou,

Zeng,

Huang

et al. 2024

Preprint

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“…NR0B1 has been reported to transcriptionally repress the expression of GSK3β in cervical cancer, 28 and inhibition of GSK3β activity activates the adenosine monophosphate‐activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway, 29 resulting in the activation of autophagic molecules. 30 , 31 In this case, we speculated that NR0B1 may regulate autophagy through controlling the GSK3β‐targeted molecules in HCC cells. Then, we confirmed that NR0B1 OE clearly decreased GSK3β expression in the levels of mRNA and protein (Figure 6A,B ), whereas NR0B1 KD increased its expression (Figure 6C ).…”

Section: Resultsmentioning

confidence: 97%

NR0B1 augments sorafenib resistance in hepatocellular carcinoma through promoting autophagy and inhibiting apoptosis

Tan,

Wang,

Liao

et al. 2023

Cancer Science

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NR0B1 is frequently activated in hepatocellular carcinoma (HCC). However, the role of NR0B1 is controversial in HCC. In this study, we observed that NR0B1 was an independent poor prognostic factor, negatively correlated with the overall survival of HCC and the relapse‐free survival of patients treated with sorafenib. Meanwhile, NR0B1 promoted the proliferation, migration, and invasion of HCC cells, inhibited sorafenib‐induced apoptosis, and elevated the IC50 of sorafenib in HCC cells. NR0B1 was further displayed to increase sorafenib‐induced autophagic vesicles and activate Beclin1/LC3‐II‐dependent autophagy pathway. Finally, NR0B1 was revealed to transcriptionally suppress GSK3β that restrains AMPK/mTOR‐driven autophagy and increases BAX‐mediated apoptosis. Collectively, our study uncovered that the ectopic expression of NR0B1 augmented sorafenib‐resistance in HCC cells by activating autophagy and inhibiting apoptosis. Our findings supported that NR0B1 was a detrimental factor for HCC prognosis.

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“…CCT has been shown to have both antioxidant and anti-inflammatory properties [ 15 , 21 , 53 , 54 ]. It has been shown that CCT is capable of lowering the levels of oxidative stress biomarkers such as malondialdehyde (MDA) [ 55 , 56 ]. In fact, a recent publication has shown that CCT (from saffron) at the same concentration as the one we used (10 μM) is the most effective dose for reducing MDA levels [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Crocetin on Basal Lipolysis in 3T3-L1 Adipocytes

et al. 2023

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Crocetin (CCT) is a natural saffron-derived apocarotenoid that possesses healthy properties such as anti-adipogenic, anti-inflammatory, and antioxidant activities. Lipolysis is enhanced in obesity and correlates with a pro-inflammatory, pro-oxidant state. In this context, we aimed to investigate whether CCT affects lipolysis. To evaluate CCT’s possible lipolytic effect, 3T3-L1 adipocytes were treated with CCT10μM at day 5 post-differentiation. Glycerol content and antioxidant activity were assessed using colorimetric assays. Gene expression was measured using qRT-PCR to evaluate the effect of CCT on key lipolytic enzymes and on nitric oxide synthase (NOS) expression. Total lipid accumulation was assessed using Oil Red O staining. CCT10μM decreased glycerol release from 3T3-L1 adipocytes and downregulated adipose tissue triglyceride lipase (ATGL) and perilipin-1, but not hormone-sensitive lipase (HSL), suggesting an anti-lipolytic effect. CCT increased catalase (CAT) and superoxide dismutase (SOD) activity, thus showing an antioxidant effect. In addition, CCT exhibited an anti-inflammatory profile, i.e., diminished inducible NOS (NOS2) and resistin expression, while enhancing the expression of adiponectin. CCT10μM also decreased intracellular fat and C/EBPα expression (a transcription factor involved in adipogenesis), thus revealing an anti-adipogenic effect. These findings point to CCT as a promising biocompound for improving lipid mobilisation in obesity.

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Crocetin Protected Human Hepatocyte LO2 Cell From TGF-β-Induced Oxygen Stress and Apoptosis but Promoted Proliferation and Autophagy via AMPK/m-TOR Pathway

Cited by 6 publications

References 33 publications

Comparative Analysis of Gardenia. jasminoides Ellis and G. jasminoides var. Radicans Makino Based on Network Pharmacology

Comparative Analysis of Gardenia. jasminoides Ellis and G. jasminoides var. Radicans Makino Based on Network Pharmacology

NR0B1 augments sorafenib resistance in hepatocellular carcinoma through promoting autophagy and inhibiting apoptosis

Effect of Crocetin on Basal Lipolysis in 3T3-L1 Adipocytes

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