3,3′-Diindolylmethane attenuates inflammation and fibrosis in radiation-induced lung injury by regulating NF-κB/TGF-β/Smad signaling pathways

Xia, Zhou; Bao, Wu'an; Zhu, Xiang; Lin, Juan; Fan, Ju-Fen; Yang, Yang; Du, Xianghui; Wang, Yuezhen

doi:10.1080/01902148.2022.2052208

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the The drugs used to treat inflammation fall into two broad categories: Steroidal anti-inflammatory drugs and non-steroidal anti-inflammatory drugs. Steroidal anti-inflammatory drugs are mainly steroid hormones and adrenocortical hormones, such as dexamethasone which can be used to treat pleuritis (Miyasaka and Mikami, 1982), cerebral edema (Rosa et al, 2016), otitis media (Dohar et al, 2006), and inhibit the levels of TNF-α, IL-1β and IL-6 (Zhou et al, 2022). However, These drugs can induce serious adverse reactions such as osteoporosis (Wu et al, 2022), immune deficiency (Dehghani et al, 2021) and infection (Kooistra et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo

Cui

Peng²,

Li³

et al. 2023

Front. Pharmacol.

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Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy.Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved.Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels.Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1β and TNF-α) by LPS-induced RAW264.7 macrophages (p < .01).Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

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Section: Methodsmentioning

confidence: 99%

The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo

Cui

Peng²,

Li³

et al. 2023

Front. Pharmacol.

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“…Radiotherapy has gained broad public consensus as an adjuvant to activate immune responses. Jason R. Baird et al demonstrated synergistic local and distant tumor control when radiation therapy was combined with a novel STING ligand in a mouse model of pancreatic cancer [ 51 ]. Radiation therapy can act synergistically with PD-1 inhibitors to enhance their respective antitumor activity, particularly in patients with advanced tumors [ 52 ].…”

Section: Cgas/sting Pathway Combined With Radiotherapy Immunotherapymentioning

confidence: 99%

Role of the cGAS-STING pathway in radiotherapy for non-small cell lung cancer

Yang,

Liang,

Liu

et al. 2023

Radiat Oncol

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One of the most important therapeutic interventions for non-small cell lung cancer is radiotherapy. Ionizing radiation (IR) is classified by traditional radiobiology principles as a direct cytocidal therapeutic agent against cancer, although there is growing recognition of other antitumor immunological responses induced by this modality. The most effective therapeutic combinations to harness radiation-generated antitumor immunity and enhance treatment results for malignancies resistant to existing radiotherapy regimens could be determined by a more sophisticated understanding of the immunological pathways created by radiation. Innate immune signaling is triggered by the activation of cGAS-STING, and this promotes adaptive immune responses to help fight cancer. This identifies a molecular mechanism radiation can use to trigger antitumor immune responses by bridging the DNA-damaging ability of IR with the activation of CD8 + cytotoxic T cell-mediated killing of tumors. We also discuss radiotherapy-related parameters that affect cGAS-STING signaling, negative consequences of cGAS-STING activation, and intriguing treatment options being tested in conjunction with IR to support immune activation by activating STING-signaling. Improved therapeutic outcomes will result from a better understanding of how IR promotes cGAS-STING signaling in immune-based treatment regimens that maximize radiotherapy’s anticancer effectiveness.

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L-carnitine protects the lung from radiation-induced damage in rats via the AMPK/SIRT1/TGF-1ß pathway

Karakuyu,

Özseven,

Akın

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Radiotherapy (RAD) is a common cancer treatment method, but it can have unintended lung side effects. L-carnitine (LCAR) is an amino acid with antioxidant and anti-inflammatory properties. This study aims to demonstrate the effects of LCAR against radiation-induced acute lung injury and to elucidate its possible protective molecular mechanisms. A total of 32 Wistar albino rats were separated into four groups: control, RAD (10 Gy once on 1st day), RAD + LCAR (intraperitoneally, 200 mg/kg/d, for 10 days), and LCAR. At the end of the experiment, the rats were euthanized, and the lung tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analysis. Emphysema, pronounced hyperemia, increased total oxidant status, and increased caspase-3 and TNF-α immunostainings were all seen in the lung tissues of the RAD group. LCAR treatment reduced these negative effects. In addition, AMPK and SIRT1 gene expressions increased in the RAD + LCAR group compared to the RAD group, while TGF-1ß gene expression decreased. While RAD caused major damage to the lungs of rats, LCAR application reduced this damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Specifically, LCAR reduced fibrosis while attenuating RAD-induced inflammation and oxidative stress via the AMPK/SIRT1/TGF-1ß pathway. Therefore, LCAR can be considered a supplement to reduce complications associated with RAD. Graphical abstract

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3,3′-Diindolylmethane attenuates inflammation and fibrosis in radiation-induced lung injury by regulating NF-κB/TGF-β/Smad signaling pathways

Cited by 4 publications

References 35 publications

The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo

The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo

Role of the cGAS-STING pathway in radiotherapy for non-small cell lung cancer

L-carnitine protects the lung from radiation-induced damage in rats via the AMPK/SIRT1/TGF-1ß pathway

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