Esculetin protects against early sepsis via attenuating inflammation by inhibiting NF-κB and STAT1/STAT3 signaling

Cheng, Yaojun; Tian, Xiaochen; Zeng, Ya-Zhi; Lan, Nan; Guo, Ling-Feng; Liu, Kefeng; Fang, Huilong; Fan, Hong; Peng, Zhonglu

doi:10.1016/s1875-5364(21)60042-0

Cited by 9 publications

(12 citation statements)

References 32 publications

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“…In response to LPS stimulation, esculetin downregulates the phosphorylation of IKKα and IκBα. It also inhibits the JMJD3 phosphorylation, thus exhibiting anti-inflammatory properties [44]. Previous findings revealed that esculetin inhibits the nuclear translocation of NFκB by downregulating the LPS-mediated IκBα degradation, thus inhibiting inflammation [45].…”

Section: Esculetin In Inflammationmentioning

confidence: 99%

Mechanistic insights into the biochemical and pharmacological profile of esculetin

Garg¹,

Gupta²,

Sahu³

et al. 2022

Preprint

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Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, and many others. Glycosides and caffeic acid conjugates are the common forms of esculetin present in medicinal plants. Esculetin acts as an antioxidant, anti-inflammatory, anti-diabetic, anti-hepatic, and anti-cancer agent by inhibiting the production of free radicals, inflammatory mediators, and genes that cause liver diseases and cancer. It also aids in the regulation of blood sugar. Scientists developing pharmaceutical formulations require some rationale and preliminary studies for drug design, but a small number of clinical studies on humans containing esculetin limit its potential for use as a safe alternative drug. Therefore, in this review article, the published studies have been reviewed to identify the pathogenesis of cancer, oxidative stress, inflammation, arthritis, diabetes and fatty liver along with the discussion on potential therapeutic strategies of esculetin. Advancements in our understanding of these diseases will aid in the development of new and innovative medications for treating many ailments. In conclusion, esculetin has immense potential to be used as a safe drug against many diseases but requires further testing and confirmation through clinical trials.

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Section: Esculetin In Inflammationmentioning

confidence: 99%

Mechanistic insights into the biochemical and pharmacological profile of esculetin

Garg¹,

Gupta²,

Sahu³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, the translocation of p65 from the cytoplasm to the nucleus was also inhibited upon esculetin treatment in macrophages. The phosphorylation of IKKα/β, IKBα, ERK1/2, JNK, and JMJD3 was also observed to downregulate in esculetin-treated LPS-induced macrophage cells [ 67 ]. Esculetin with a 12 µg/mL dose potentially inhibits the TNF-α, IL-1β, ROS, and LPS-mediated nuclear translocation of NF-κB p65 by suppressing the IKβ-degradation in RAW 264.7 cells [ 68 ].…”

Section: Therapeutic Applications Of Esculetinmentioning

confidence: 99%

Pharmacological and Therapeutic Applications of Esculetin

Garg

Gupta

Sahu

et al. 2022

IJMS

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Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, etc. Free radicals lead to the development of oxidative stress causing inflammation, arthritis, cancer, diabetes, fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver enzymes. For instance, the current treatment modalities used in arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives. Esculetin has an immense antioxidative potential thereby alleviating arthritis, diabetes, malignancies, and hepatic disorders. Structurally, esculetin contains two hydroxyl groups, which enhance its ability to function as an antioxidant by inhibiting oxidative stress in pathological conditions. Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory cytokine production are the main causes of bone and joint deterioration in arthritis, whereas esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-β-mediated expression and dysfunction of antioxidant enzymes is inhibited by esculetin therapy, thus reducing liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory cytokines, TGF-β and oxidative stress may be a therapeutic strategy to alleviate arthritis and liver fibrosis.

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“…A broad range of inflammatory or oxidative conditions have been shown to be impacted by esculetin. These include lung injury and fibrosis ( 356 , 357 , 520 ); fibromyalgia ( 521 ); neuronal oxidative stress ( 522 ); psoriasis ( 523 ); arthritis ( 358 ); nociception ( 359 ); colitis ( 360 ); allergy, immunity, and asthma ( 282 , 354 , 380 – 383 ); and sepsis ( 361 ). The effects of esculetin on numerous cancer cell types have been extensively studied ( 94 , 321 – 342 , 519 , 524 , 525 ) and are the basis for efforts to develop novel therapeutics ( 98 , 341 ).…”

Section: Effects Of Bioactive Compounds Found In a Scopariamentioning

confidence: 99%

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

et al. 2022

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Botanicals have a long history of medicinal use for a multitude of ailments, and many modern pharmaceuticals were originally isolated from plants or derived from phytochemicals. Among these, artemisinin, first isolated from Artemisia annua, is the foundation for standard anti-malarial therapies. Plants of the genus Artemisia are among the most common herbal remedies across Asia and Central Europe. The species Artemisia scoparia (SCOPA) is widely used in traditional folk medicine for various liver diseases and inflammatory conditions, as well as for infections, fever, pain, cancer, and diabetes. Modern in vivo and in vitro studies have now investigated SCOPA’s effects on these pathologies and its ability to mitigate hepatotoxicity, oxidative stress, obesity, diabetes, and other disease states. This review focuses on the effects of SCOPA that are particularly relevant to metabolic health. Indeed, in recent years, an ethanolic extract of SCOPA has been shown to enhance differentiation of cultured adipocytes and to share some properties of thiazolidinediones (TZDs), a class of insulin-sensitizing agonists of the adipogenic transcription factor PPARγ. In a mouse model of diet-induced obesity, SCOPA diet supplementation lowered fasting insulin and glucose levels, while inducing metabolically favorable changes in adipose tissue and liver. These observations are consistent with many lines of evidence from various tissues and cell types known to contribute to metabolic homeostasis, including immune cells, hepatocytes, and pancreatic beta-cells. Compounds belonging to several classes of phytochemicals have been implicated in these effects, and we provide an overview of these bioactives. The ongoing global epidemics of obesity and metabolic disease clearly require novel therapeutic approaches. While the mechanisms involved in SCOPA’s effects on metabolic, anti-inflammatory, and oxidative stress pathways are not fully characterized, current data support further investigation of this plant and its bioactives as potential therapeutic agents in obesity-related metabolic dysfunction and many other conditions.

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Esculetin protects against early sepsis via attenuating inflammation by inhibiting NF-κB and STAT1/STAT3 signaling

Cited by 9 publications

References 32 publications

Mechanistic insights into the biochemical and pharmacological profile of esculetin

Mechanistic insights into the biochemical and pharmacological profile of esculetin

Pharmacological and Therapeutic Applications of Esculetin

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

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