Dihydrokaempferol attenuates CCl4-induced hepatic fibrosis by inhibiting PARP-1 to affect multiple downstream pathways and cytokines

Huang, Hancheng; Wei, Shuchun; Wu, Xiaohan; Zhang, Mengke; Zhou, Benhong; Huang, De-Bin; Dong, Weiguo

doi:10.1016/j.taap.2023.116438

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…[19][20][21] Currently, it is important to find more reliable biomarkers linked to infantile pneumonia. DHK was identified as having an important function in severe acute pancreatitis, 11 hepatic fibrosis, 12 and liver injury, 13…”

Section: Discussionmentioning

confidence: 99%

“…11 CCl4induced hepatic fibrosis is weakened by DHK by suppressing poly(ADP-ribose) polymerase 1 (PARP-1) and its downstream cytokines and pathways. 12 DHK exerts a protective function on liver injury induced by acetaminophen-via modulating sirtuin-1 (SIRT1). 13 Nevertheless, whether DHK has a role in the progression of infantile pneumonia remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cells

Wang,

Zhang,

Pang

2023

Allergol Immunopathol

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Background: Globally, pneumonia has been associated as a primary cause of mortality in children aged less than 5 years. Dihydrokaempferol (DHK) has been proposed for being correlated with the process of various diseases. Nevertheless, whether DHK has a role in the progression of infantile pneumonia remains unclear. This study aimed at exploring whether DHK was involved in the progression of infantile pneumonia. Methods: Human fibroblast cells WI-38 were treated with lipopolysaccharide (LPS). The viability of WI-38 cells was measured via Cell counting kit-8. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed the protein levels of IL-1β, IL-6, TNF-α, Bax, and cleaved-caspase 3. Flow cytometry was applied for exploring the apoptosis of WI-38 cells. The concentrations of IL-1β, IL-6, and TNF-α were assessed via enzyme-linked-immunosorbent serologic assay. Results: DHK modulated the viability of WI-38 cells in infantile pneumonia. Furthermore, we identified that DHK treatment inversely changed LPS induction-mediated elevation on the levels of inflammation biomarkers. Besides, DHK counteracted LPS-induced production of reactive oxygen species (ROS) in WI-38 cells. DHK also decreased LPS-induced elevation of WI-38 cells apoptosis and mediated the levels of apoptosis-associated indexes. Moreover, modulating sirtuin-1 (SIRT1) protein level was lowered by the induction of LPS, and was reversed by DHK treatment. In addition, DHK counteracted LPS induction-mediated elevation of p-p65 and phosphorylated inhibitor of nuclear factor kappa-B kinase subunit alpha (p-IκBα) protein levels. Conclusion: DHK alleviated LPS-induced WI-38 cells inflammation injury in infantile pneumonia through SIRT1/NF-κB pathway. The results shed light on the implications of DHK on the prevention and treatment of infantile pneumonia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cells

Wang,

Zhang,

Pang

2023

Allergol Immunopathol

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“…This pathological condition is characterized by the excessive accumulation of extracellular matrix (ECM) proteins, such as collagen, in organs and tissues, leading to organ dysfunction and failure (Henderson et al, 2020 ). Recent studies show that many NAD metabolism enzymes, including NAMPT, sirtuins, PARPs, and CD38, play a key role in ECM remodeling and fibrosis (Huang et al, 2023 ; Shi et al, 2021 ; Wu et al, 2023 ; Xu et al, 2021 ; Zhen et al, 2021 ). CD38, for example, has been linked with the development of pulmonary, renal, and systemic sclerosis through its role in regulating the expression of proinflammatory cytokines, chemokines, and senescence (Cui et al, 2022 ; Shi et al, 2021 ; Tao et al, 2023 ).…”

Section: Nad Metabolism In Age‐related Diseasesmentioning

confidence: 99%

NAD metabolism: Role in senescence regulation and aging

Chini,

Cordeiro,

Tran

et al. 2023

Aging Cell

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The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field.

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“…Aromadendrin ( Figure 1 ), or dihydrokaempferol, is a flavanonol that exerts anti-inflammatory, antioxidant, and anti-diabetic properties ( Lee et al, 2013 ). It has been reported to attenuate, in vivo , induced hepatic injury and hepatic fibrosis ( Huang et al, 2023 ), and it shows a protective effect against experimental cardiac hypertrophy ( Cui et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Optimization of flavanonols heterologous biosynthesis in Streptomyces albidoflavus, and generation of auronols

Magadán-Corpas,

Ye,

Braune

et al. 2024

Front. Microbiol.

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Aromadendrin and taxifolin are two flavanonols (derived from the precursor naringenin) displaying diverse beneficial properties for humans. The carbon skeleton of these flavonoids may be transformed by the human gastrointestinal microbiota into other compounds, like auronols, which exert different and interesting biological activities. While research in flavonoids has become a certainly extensive field, studies about auronols are still scarce. In this work, different versions of the key plant enzyme for flavanonols biosynthesis, The flavanone 3-hydroxylase (F3H), has been screened for selecting the best one for the de novo production of these compounds in the bacterial factory Streptomyces albidoflavus UO-FLAV-004-NAR, a naringenin overproducer strain. This screening has rendered 2.6 μg/L of aromadendrin and 2.1 mg/L of taxifolin final production titers. Finally, the expression of the chalcone isomerase (CHI) from the gut bacterium Eubacterium ramulus has rendered a direct conversion (after feeding experiments) of 38.1% of (+)-aromadendrin into maesopsin and 74.6% of (+)-taxifolin into alphitonin. Moreover, de novo heterologous biosynthesis of 1.9 mg/L of alphitonin was accomplished by means of a co-culture strategy of a taxifolin producer S. albidoflavus and a CHI-expressing Escherichia coli, after the observation of the high instability of alphitonin in the culture medium. This study addresses the significance of culture time optimization and selection of appropriate enzymes depending on the desired final product. To our knowledge, this is the first time that alphitonin de novo production has been accomplished.

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Dihydrokaempferol attenuates CCl4-induced hepatic fibrosis by inhibiting PARP-1 to affect multiple downstream pathways and cytokines

Cited by 10 publications

References 33 publications

Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cells

Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cells

NAD metabolism: Role in senescence regulation and aging

Optimization of flavanonols heterologous biosynthesis in Streptomyces albidoflavus, and generation of auronols

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