Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Wang, Han; Zhou, Xiaoming; Wu, Lingyun; Liu, Guangjie; Xu, Weidong; Zhang, Xiangsheng; Gao, Yongyue; Tao, Tao; Zhou, Yan; Lu, Yue; Wang, Juan; Deng, Cong; Zhuang, Zong; Hang, Chunhua; Li, Wei

doi:10.21203/rs.2.24391/v2

Cited by 14 publications

(17 citation statements)

References 31 publications

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“…has been widely used to treat many kinds of orthopaedic diseases in Asian countries for thousands of years. 23,24 The iridoid glycoside aucubin (C 15 H 22 O 9 ), the principle bioactive component of Eucommia ulmoides Oliv., has been reported to exert several pharmacological effects against inflammation, oxidation and bone loss. [23][24][25] In fact, aucubin has recently been shown to prevent apoptosis by regulating the level of autophagy in several disease models.…”

Section: Introductionmentioning

confidence: 99%

“…23,24 The iridoid glycoside aucubin (C 15 H 22 O 9 ), the principle bioactive component of Eucommia ulmoides Oliv., has been reported to exert several pharmacological effects against inflammation, oxidation and bone loss. [23][24][25] In fact, aucubin has recently been shown to prevent apoptosis by regulating the level of autophagy in several disease models. 26,27 However, little is known about whether and how aucubin might influence steroid-induced autophagy and apoptosis in osteoblast.…”

Section: Introductionmentioning

confidence: 99%

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Aucubin prevents steroid‐induced osteoblast apoptosis by enhancing autophagy via AMPK activation

Chen

Jin

Zhang

et al. 2021

J Cellular Molecular Medi

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Steroid-induced osteoblast apoptosis is a crucial pathological process in steroidinduced osteonecrosis of the femoral head (SONFH). Autophagy can resist apoptosis and AMPK plays an important role in autophagy regulation. Aucubin from the small tree Eucommia ulmoides Oliv., which has a long history of use in orthopaedics and traumatology in Asian medicine, can promote bone formation, but whether it can slow or prevent steroid-osteoblast apoptosis is unclear. Therefore, we investigated the pathogenesis of SONFH and how the osteoblast responds to aucubin under the dexamethasone stimulation. In human femoral head osteonecrosis specimens, we found that the autophage and apoptosis level were increased, and the AMPK signalling was crucial to autophagy. We observed that aucubin could prevent dexamethasone-induced apoptosis in osteoblasts by enhancing the level of autophagy. Further, we confirmed that the regulatory effect of aucubin on autophagy and apoptosis was achieved by activating AMPK signalling. We have demonstrated a mechanism of disease progression and shown that aucubin could enhance autophagy through AMPK signalling to prevent osteoblast apoptosis. These findings provide a basis for the further investigation of the potential therapeutic role of aucubin in the SONFH.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aucubin prevents steroid‐induced osteoblast apoptosis by enhancing autophagy via AMPK activation

Chen

Jin

Zhang

et al. 2021

J Cellular Molecular Medi

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“…The primary compounds present in O. vulgaris are phenylethanol glycosides, iridoids, and flavonoids. Some compounds have been shown to have certain anti-inflammatory effects (Gong et al, 2020;Nigro et al, 2020;Wang et al, 2020d;Cicek et al, 2021;Tian et al, 2021). Through interviews with the local populace and hospital personnel in Inner Mongolia, we found that O. vulgaris is often used to treat RA; therefore, we conducted an in-depth study on the effects of O. vulgaris on RA.…”

Section: Introductionmentioning

confidence: 99%

Integrated Phytochemical Analysis Based on UPLC–MS/MS and Network Pharmacology Approaches to Explore the Effect of Odontites vulgaris Moench on Rheumatoid Arthritis

Wang

Yang

et al. 2021

Front. Pharmacol.

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Odontites vulgaris Moench has the effect of clearing away heat, detoxification, dispelling wind, and clearing dampness. In this study, the potential anti-inflammatory compounds of O. vulgaris were investigated using ultra-high-performance liquid chromatography–mass spectrometry (UPLC–MS/MS) combined with the network pharmacology approach and further confirmed on an LPS-activated RAW 264.7 macrophage model. Monomer compounds were prepared from the active fraction using modern advanced separation and purification methods. UPLC–Q-Exactive HRMS was used to identify the chemical compounds in the active fractions of O. vulgaris. D-mannitol, geniposidic acid, salidroside, shanzhiside methyl ester, eleutheroside B, geniposide, 7,8-dihydroxycoumarin, gardoside methyl ester, arenarioside, vanillic acid, p-hydroxy-cinnamic acid, melampyroside, syringaresinol, tricin, and diosmetin were isolated from O. vulgaris for the first time. A compound database of O. vulgaris was established based on the existing literature to predict the mechanism of O. vulgaris in the treatment of rheumatoid arthritis. The results suggest that the PI3K-Akt pathway mediates O. vulgaris and deserves more attention in the treatment of RA. Finally, the anti-rheumatoid arthritis effects of the four target compounds were validated with the decreased levels of NO, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophage cells treated with LPS. The present study explored the potential targets and signaling pathways of O. vulgaris in the treatment of RA, which may help to illustrate the mechanisms involved in the action of O. vulgaris and may provide a better understanding of the relationship between O. vulgaris and RA. This study provides novel insights into the development of new drugs and utilization of Mongolian traditional Chinese medicine resources.

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“…18 Boosting Nrf2 antioxidant signaling provides remarkable neuroprotective effects against TBI-induced brain damage and neurological deficits. 19 –21 Therefore, Nrf2 is an interacting target for the treatment of TBI.…”

Section: Introductionmentioning

confidence: 99%

Sestrin2 protects against traumatic brain injury by reinforcing the activation of Nrf2 signaling

Liu

Zhu

et al. 2020

Hum Exp Toxicol

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Sestrin2 (SESN2) is stress-inducible protein that confers cytoprotective effects against various noxious stimuli. Accumulating evidence has documented that SESN2 has potent anti-apoptosis and anti-oxidative stress functions. However, whether it provides neuroprotection in traumatic brain injury (TBI) models remains unexplored. The purpose of this study was to explore the regulatory effect of SESN2 on TBI using in vivo and in vitro models. We found that TBI resulted in a marked induction of SESN2 in the cerebral cortex tissues of mice. SESN2 overexpression in the brain by in vivo gene transfer significantly decreased neurological deficit, brain edema, and neuronal apoptosis of mice with TBI. Moreover, the overexpression of SESN2 significantly decreased the oxidative stress induced by TBI in mice. In vitro studies of TBI demonstrated that SESN2 overexpression decreased apoptosis and oxidative stress in scratch-injured cortical neurons. Notably, SESN2 overexpression increased the nuclear levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 antioxidant signaling in in vivo and in vitro models of TBI. In addition, the inhibition of Nrf2 significantly abolished SESN2-mediated neuroprotective effects in vivo and in vitro. In conclusion, these results of our work demonstrate that SESN2 protects against TBI by enhancing the activation of Nrf2 antioxidant signaling.

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Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Cited by 14 publications

References 31 publications

Aucubin prevents steroid‐induced osteoblast apoptosis by enhancing autophagy via AMPK activation

Aucubin prevents steroid‐induced osteoblast apoptosis by enhancing autophagy via AMPK activation

Integrated Phytochemical Analysis Based on UPLC–MS/MS and Network Pharmacology Approaches to Explore the Effect of Odontites vulgaris Moench on Rheumatoid Arthritis

Sestrin2 protects against traumatic brain injury by reinforcing the activation of Nrf2 signaling

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