Paeoniflorin modulates oxidative stress, inflammation and hepatic stellate cells activation to alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1 in mice

Wang, Ting; Xu, Zhou; Kuang, Ge; Jiang, Rong; Guo, Xinyi; Wu, Shengwang; Wan, Jingyuan; Liang, Yin

doi:10.1093/jpp/rgaa042

Cited by 20 publications

(8 citation statements)

References 44 publications

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“…This model exhibits a strong inflammatory response and high levels of apoptosis. [52][53][54][55] This is consistent with the results of the present study. It is important to emphasize that SS and ST at equimolar doses administered with silibinin more significantly reduced the expression of proinflammatory factors in the liver and also better regulated the expression of apoptosis-related proteins.…”

Section: Discussionsupporting

confidence: 93%

Silibinin Schiff Base Derivatives Counteract CCl4-Induced Acute Liver Injury by Enhancing Anti-Inflammatory and Antiapoptotic Bioactivities

Xu¹,

Qiu²,

Zhang³

et al. 2022

DDDT

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Background: Silibinin (Sil), a flavonoid lignan-like natural compound derived from milk thistle seeds, has been used to treat hepatic diseases, including early-phase hepatocirrhosis and fatty liver, for many years. However, its poor water solubility limits its gastrointestinal absorption and bioavailability. It clinical use has been limited due to its slow onset of action. Faced with this problem, research on the derivatives of silibinin has been receiving much attention. Purpose: A series of silibinin derivatives with good biosafety and higher hepatoprotective activity were obtained by a safe, efficient and green chemical synthesis method. Patients and Methods: First, the carbonyl group in the structure of silibinin was used to obtain silibinin Schiff base derivatives by dehydration condensation with the carboxyl group in the sulfur-containing amino acid. Next, relevant experiments were performed to characterize the structure, physical form and solubility of the derivatives. Then, toxicity tests of the derivatives were performed in LO-2 cells and SD rats to evaluate their biosafety. Finally, the anti-inflammatory and antiapoptotic activities were observed using a carbon tetrachloride (CCl 4 )-induced acute liver injury model in C57BL/6J mice using silibinin as a control. Results:The studies showed that SS and ST behaved as amorphous substances and showed a significant increase in solubility compared to silibinin. These two derivatives showed low toxicity in biosafety tests and higher bioactivity (anti-inflammatory and antiapoptotic) than silibinin against acute liver injury induced by CCl 4 . Conclusion: Two silibinin derivatives (SS and ST) obtained by the Schiff base reaction improved the solubility of the silibinin parent nucleus in biological media with the help of the hydrophilic and amorphous morphology of the ligand. The low toxicity in vivo and in vitro ensures the biosafety of the derivatives. The hepatoprotective activity (anti-inflammatory and anti-apoptotic) was significantly improved compared to silibinin.

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Section: Discussionsupporting

confidence: 93%

Silibinin Schiff Base Derivatives Counteract CCl4-Induced Acute Liver Injury by Enhancing Anti-Inflammatory and Antiapoptotic Bioactivities

Xu¹,

Qiu²,

Zhang³

et al. 2022

DDDT

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“…PF is a novel HSP-inducing compound that enhances the expression of Heat Shock Proteins (HSPs). In addition, it exhibits protective effects against various stressors [39]. Numerous studies have highlighted the potential bene ts of PF, including ROS generation reduction [29,40] and maintenance of a balanced Excessive ROS accumulation is a key contributor to apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin alleviates oxidative stress and apoptosis in heat stress-induced H9c2 cells

Wang,

Liu,

et al. 2023

Preprint

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Purpose: The increasing annual mean temperature has exacerbated the severity of heat stress (HS) which could increase cardiac burden. Paeoniflorin (PF), the primary bioactive constituent extracted from the Paeonifloraceae, exhibits robust antioxidant properties. However, its protective potential against HS-induced cardiomyocyte injury remains unclear. This study aimed to investigate the protective effects of PF on H9c2 cells subjected to HS-induced injury and elucidate the underlying mechanisms. Methods: To establish the heat stress model, H9c2 cells were exposed to HS for 2 h at 45 °C in a 5% CO2 incubator. Before HS exposure, H9c2 cells were pretreated with PF (5 µM) for 24 h. Subsequently, we assessed cell viability, oxidative stress, cardiomyocyte apoptosis, and mitochondrial function. Results: HS treatment significantly increased oxidative stress and apoptosis in H9c2 cells. However, pretreatment with PF for 24 h attenuated the HS-induced damage in H9c2 cells, protecting against thermal injury. Conclusion: Current studies have not investigated the role of PF on oxidative damage and apoptosis in vitro after HS. Our experiment demonstrated that PF ameliorates HS-induced oxidative stress and apoptosis in H9c2 cells which suggest that PF can potentially be an effective preventive medicine against heat injury to cardiomyocyte.

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“…Stress in Hepatocytes. Previous studies have reported that CCL4 induces the accumulation of free radicals in hepatocytes, leading to oxidative stress injury [18]. Thus, to further study the biological basis of the protective effect of HBO1 on hepatocytes, we analyzed the effect of HBO1 on CCL4induced hepatic oxidative damage.…”

Section: Hbo1 Knockdown Alleviated Ccl4-induced Oxidativementioning

confidence: 99%

HBO1 as an Important Target for the Treatment of CCL4-Induced Liver Fibrosis and Aged-Related Liver Aging and Fibrosis

Xing

Lan

2022

Oxidative Medicine and Cellular Longevity

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The liver is the largest digestive organ in the human body. The increasing incidence of chronic liver fibrosis is one of the major health challenges in the world. Liver fibrosis is a wound-healing response to acute or chronic cellular damage of liver tissue. At present, despite a series of research progress on the pathophysiological mechanism of fibrosis that has been made, there is still a gap in identifying antifibrotic targets and converting them into effective treatments. Therefore, it is extremely important to seek a molecular target that can alleviate or reverse liver fibrosis, which has important scientific and clinical significance. In the current study, to evaluate the therapeutic effect of HBO1 as a molecular target on liver aging and fibrosis, naturally-aged mice and CCL4-induced liver fibrosis mice were used as animal models, and multiple experiments were performed. Experimental results showed that HBO1 knockdown could strongly mitigate the accumulation of hepatic collagen by Masson and Sirius Red staining. Further study showed that HBO1 knockdown reduced the expression of fibrosis-related marker molecules (α-SMA, collagen type I (ColI), and fibronectin). Further work showed that HBO1 knockdown could significantly alleviate HSC activation. On this basis, we analyzed the underlying mechanism by which HBO1 alleviates liver fibrosis. It was found that HBO1 knockdown may modulate liver fibrosis by regulating the processes of EMT, inflammation, and oxidative stress. We further studied the effect of HBO1 knockdown on liver aging and aging-related liver fibrosis, and the results showed that HBO1 knockdown could significantly reduce the level of aging-related liver fibrosis and relieve liver aging. In conclusion, we systematically investigated the potential of HBO1 as a therapeutic target to attenuate liver fibrosis and liver aging. The current study found a crucial target for liver fibrosis and liver-aging therapy, which has laid a solid foundation for the liver fibrosis-related research.

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Paeoniflorin modulates oxidative stress, inflammation and hepatic stellate cells activation to alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1 in mice

Cited by 20 publications

References 44 publications

Silibinin Schiff Base Derivatives Counteract CCl4-Induced Acute Liver Injury by Enhancing Anti-Inflammatory and Antiapoptotic Bioactivities

Silibinin Schiff Base Derivatives Counteract CCl4-Induced Acute Liver Injury by Enhancing Anti-Inflammatory and Antiapoptotic Bioactivities

Paeoniflorin alleviates oxidative stress and apoptosis in heat stress-induced H9c2 cells

HBO1 as an Important Target for the Treatment of CCL4-Induced Liver Fibrosis and Aged-Related Liver Aging and Fibrosis

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