Puerarin Ameliorates 5-Fluorouracil–Induced Intestinal Mucositis in Mice by Inhibiting JAKs

Wang, Liang; Song, Baohui; Hu, Yan; Zhang, Shuaishuai; Chen, Dapeng; Wang, Jingyu

doi:10.1124/jpet.121.000677

Cited by 12 publications

(5 citation statements)

References 36 publications

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“…Recently, it has been documented that the JAK/STAT3 pathway is implicated in the pathogenesis of intestinal mucosal inflammation involving 5-FU-induced IM [28]. In our study, intestinal p-STAT3 expression was markedly activated following a 5-FU injection.…”

Section: Discussionsupporting

confidence: 60%

“…In our study, intestinal p-STAT3 expression was markedly activated following a 5-FU injection. Similarly, mice injected with 5-FU exhibited a marked upregulation in p-STAT3 protein expression in colon tissue [28]. Moreover, in 2015, Yuan and his colleagues reported that IL-17 stimulates STAT3 activation, in which Tyr 705 phosphorylation is important for IL-17's mediation of the activation of STAT3 [15].…”

Section: Discussionmentioning

confidence: 98%

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IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment

et al. 2022

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5-Fluorouracil (5-FU) is an anticancer drug with intestinal mucositis (IM) as a deleterious side effect. Thymol is a monoterpene phenol which has been reported to possess an antioxidant and anti-inflammatory activity versus 5-FU-induced IM. The Notch pathway affects multiple cellular activities, such as cellular proliferation, in addition to inflammatory responses modulation. Accordingly, this work was carried out in order to elucidate the role of the Notch pathway in 5-FU-induced IM and to further elucidate the immunomodulatory protective mechanisms of thymol. Experimental rats were divided randomly into four groups: Control, 5-FU, 5-FU+thymol (60 mg/kg/day), and 5-FU+thymol (120 mg/kg/day). 5-FU was injected intraperitoneally at a dose of 150 mg/kg on days 6 and 7, while thymol was orally administered daily for 11 days. By the end of the study, intestinal tissues were collected for the determination of IL-17, CD4, CD8, Notch1, Hes-1, pSTAT3, and STAT-3 protein expressions. The effect of thymol on 5-FU cytotoxicity was also examined using WST1 assay. 5-FU induced a marked increase in IL-17 levels, along with a marked downregulation of CD4 and the upregulation of CD8, Notch1, Hes-1 protein expressions, and activation of STAT3 in the intestinal tissue when compared with the control group. Thymol ameliorated the changes that occurred in these parameters. Additionally, cytotoxicity testing revealed that thymol augmented the antiproliferative action of 5-FU against breast and colorectal human cancer cell lines. This study was the first to show that the IL-17/Notch1/STAT3 pathway is involved in the molecular mechanism of 5-FU-induced IM, as well as the immunomodulatory activity of thymol.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 98%

IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment

et al. 2022

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“…Puerarin also modulates other chemotherapeutic side effects through non-ion channel mechanisms [118]. For example, 5-fluorauracil (5-FU) associated intestinal mucositis has been shown to be improved through JAK inhibition after puerarin administration [119].…”

Section: Phytochemicals Modulating Cancer Symptomatologymentioning

confidence: 99%

Phytochemical Modulation of Ion Channels in Oncologic Symptomatology and Treatment

Rao,

Mohammed,

Alschuler

et al. 2024

Cancers

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Modern chemotherapies offer a broad approach to cancer treatment but eliminate both cancer and non-cancer cells indiscriminately and, thus, are associated with a host of side effects. Advances in precision oncology have brought about new targeted therapeutics, albeit mostly limited to a subset of patients with an actionable mutation. They too come with side effects and, ultimately, ‘self-resistance’ to the treatment. There is recent interest in the modulation of ion channels, transmembrane proteins that regulate the flow of electrically charged molecules in and out of cells, as an approach to aid treatment of cancer. Phytochemicals have been shown to act on ion channels with high specificity regardless of the tumor’s genetic profile. This paper explores the use of phytochemicals in cancer symptom management and treatment.

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“…Wang et al established a mouse model of intestinal mucositis by intraperitoneal injection of 5-fluorouracil (5-Fu), and then injected puerarin. They found that puerarin could block the production of Janus kinase (JAK), which was originally significantly activated, and thus attenuated the oxidative response in 5-Fu-induced mucositis [ 12 ]. Wu et al used a piglet model infected with porcine epidemic diarrhea virus (PEDV) to give puerarin orally, and found that the activities of total superoxide dismutase, glutathione peroxidase, and catalase in the intestine and plasma of infected piglets increased while the behavior of myeloperoxidase and the concentration of hydrogen peroxide decreased, which alleviated oxidative stress [ 13 ] ( Figure 1 ).…”

Section: Antioxidantmentioning

confidence: 99%

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

Wang

et al. 2022

Antioxidants

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As a kind of medicine and food homologous plant, kudzu root (Pueraria lobata (Willd.) Ohwi) is called an “official medicine” in Chinese folk medicine. Puerarin is the main active component extracted from kudzu root, and its structural formula is 8-β-D-grapes pyranose-4, 7-dihydroxy isoflavone, with a white needle crystal; it is slightly soluble in water, and its aqueous solution is colorless or light yellow. Puerarin is a natural antioxidant with high health value and has a series of biological activities such as antioxidation, anti-inflammation, anti-tumor effects, immunity improvement, and cardio-cerebrovascular and nerve cell protection. In particular, for the past few years, it has also been extensively used in clinical study. This review focuses on the antioxidant activity of puerarin, the therapy of diverse types of inflammatory diseases, various new drug delivery systems of puerarin, the “structure-activity relationship” of puerarin and its derivatives, and pharmacokinetic and clinical studies, which can provide a new perspective for the puerarin-related drug research and development, clinical application, and further development and utilization.

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Puerarin Ameliorates 5-Fluorouracil–Induced Intestinal Mucositis in Mice by Inhibiting JAKs

Cited by 12 publications

References 36 publications

IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment

IL-17/Notch1/STAT3 Pathway Contributes to 5-Fluorouracil-Induced Intestinal Mucositis in Rats: Amelioration by Thymol Treatment

Phytochemical Modulation of Ion Channels in Oncologic Symptomatology and Treatment

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

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