Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy

Zhao, Jun; Zheng, Haoyi; Sui, Zhongguo; Jing, Fanbo; Quan, Xianghua; Zhao, Wenwen; Liu, Guangwei

doi:10.1016/j.cyto.2019.05.013

Cited by 54 publications

(35 citation statements)

References 31 publications

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“…Macrophages are one of the innate leukocytes that accumulate in the kidney and promote inflammation in the acute phase of AKI (Lech et al, 2014). Zhao et al, (2019) demonstrated that treatment with ursolic acid (UA, a natural pentacyclic triterpene carboxylic acid found in several plants such as apples, bilberries, and cranberries, among others, which promotes cancer cell autophagy) increases autophagy of macrophages and ameliorates LPS-induced AKI. More importantly, treatment with UA enhances macrophage autophagy by increasing the expression of both LC3B and Beclin-1, altering macrophage function, and inhibiting the secretion of inflammatory factors TNF-α, IL-6, and IL-1β in macrophages in response to LPS stimulation.…”

Section: Inflammation Regulation By Autophagy In Immune Cells In Akimentioning

confidence: 99%

Autophagy and Inflammation Regulation in Acute Kidney Injury

2020

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Autophagy at an appropriate juncture in the cell cycle exerts protective effects in acute kidney injury (AKI), whereas abnormal autophagy may lead to cell death. Inflammatory response plays a pivotal role in the pathophysiological process of kidney injury and repair during AKI. Several studies have reported an interaction between autophagy and inflammation in the pathogenesis of AKI. This review outlines recent advances in the investigation of the role of autophagy in inflammatory response regulation based on the following aspects. (1) Autophagy inhibits inflammatory responses induced in AKI through the regulation of mTOR and AMPK pathways and the inhibition of inflammasomes activation. (2) Autophagy can also help in the regulation of inflammatory responses through the nuclear factor kappa B pathway, which is beneficial to the recovery of kidney tissues. These studies reviewed here provide better insight into the mechanisms underlying the protective effects of the autophagy-inflammatory pathway. Through this review, we suggest that the autophagy-inflammatory pathway may serve as an alternative target for the treatment of AKI.

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Section: Inflammation Regulation By Autophagy In Immune Cells In Akimentioning

confidence: 99%

Autophagy and Inflammation Regulation in Acute Kidney Injury

2020

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“…Autophagy is a typical cell death pathway which has been related to many pathological conditions and can serve to resist stress and, consequently, promote cell survival [13]. In addition, autophagy can pass on metabolic substrates to enable cells to meet their energy requirements, thereby accelerating cell growth and survival [14]. Therefore, an autophagy activator may be an effective drug in preventing and treating cisplatin-induced inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

“…Nrf2 is correlated with the induction of HO-1, GPx, glutathione-S-transferase, and Trx-1, allowing for the scavenging of free radicals caused by oxidative damage in cells [42]. Nrf2 functions to maintain cellular homeostasis through its ability to 14 Oxidative Medicine and Cellular Longevity regulate antioxidant proteins, detoxification enzymes, and other stress response proteins [34]. Our results indicate that the protective effects of WCC regulated the Nrf2/HO-1 signaling pathway in cisplatin-challenged mice.…”

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confidence: 99%

“…It can protect the proximal tubules of the kidney from AKI by eliminating the mitochondria that produce ROS during CP treatment. Autophagy involves many important molecules, such as Beclin-1 (autophagosome nucleation) [13], LC3B (autophagosome membrane expansion and fusion), and p62 (cargo receptors involved in selective autophagy) [14]. The effects of WCC on macrophage autophagy were thus studied.…”

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confidence: 99%

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Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

Deng

Jiang

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

103

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Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1β, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds—adenosine and N6-(2-hydroxyethyl) adenosine (HEA)—inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

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“…48 It reduced inammatory factors TNFa, IL-6 and IL-1b secretion in macrophages in response to LPS stimulation. 49 b glycyrrhetinic acid, isoliquiritigenin, and ursolic acid inhibited the gene expressions of TNF-a, and iNOS, partly through inhibiting NF-kB expression and attenuating NF-kB nuclear translocation. 50 In addition, glycyrrhizin was revealed to have anti-inammatory and protective effects on LPS-induced ALI in mice through inhibition of pro-inammatory cytokines playing a key role in the initial phase of inammatory response of pulmonary inammation, which suggests that inhibition of the TLR-4/NF-kB signal pathway would be a possible mechanism underlying its action.…”

Section: Multi-target Constituents and Medicinal Plants Identicationmentioning

confidence: 94%

Potential role of medicinal plants and their constituents in the mitigation of SARS-CoV-2: identifying related therapeutic targets using network pharmacology and molecular docking analyses

2020

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Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy

Cited by 54 publications

References 31 publications

Autophagy and Inflammation Regulation in Acute Kidney Injury

Autophagy and Inflammation Regulation in Acute Kidney Injury

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

Potential role of medicinal plants and their constituents in the mitigation of SARS-CoV-2: identifying related therapeutic targets using network pharmacology and molecular docking analyses

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