Echinacoside attenuates inflammatory response in a rat model of cervical spondylotic myelopathy via inhibition of excessive mitochondrial fission

Zhou, Long‐yun; Yao, Min; Tian, Z. Ryan; Song, Yong-Jia; Sun, Yue‐Li; Ye, Jie; Gan, Li; Sng, Kim Sia; Xu, Leqin; Cui, Xue‐jun; Wang, Yongjun

doi:10.1016/j.freeradbiomed.2020.01.014

Cited by 27 publications

(16 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Echinacoside (ECH), the major active constituent of Chinese herb Cistanches Herba (Cistanche deserticola Y. C. Ma), reportedly exerts neuroprotective properties in PD models (Chen et al, 2007;Geng et al, 2007;Zhang et al, 2017). There is evidence that ECH also decreases IL-6 expression in the MPTP-induced PD mice (Zhang et al, 2021), ischemia/reperfusion injured rat (Li et al, 2018b), and cervical spondylotic myelopathy rat model (Zhou et al, 2020) and significantly diminishes IL-6 level in 6-OHDA-treated PC12 cells (Wang YH et al, 2015) and lipopolysaccharides-(LPS-) induced BV2 cells (Zhou et al, 2020). Additionally, ECH inhibits the phosphorylation of STAT3 on tyrosine 705 (tyr705) in the LPStreated rat intestinal epithelial cells (Li et al, 2018a).…”

Section: Introductionmentioning

confidence: 99%

Echinacoside Protects Dopaminergic Neurons Through Regulating IL-6/JAK2/STAT3 Pathway in Parkinson’s Disease Model

Yang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Echinacoside (ECH), the major active constituent of Cistanche deserticola, was found to exert neuroprotection through neurotrophic and anti-inflammatory functions in Parkinson’s disease (PD) models. However, a clear intermediate molecule or pathway that unifies these two effects has to be found. In this study, our results demonstrate that ECH can protect DA neurons in PD mice with Western blot and immunohistochemistry staining. The quantitative real-time polymerase chain reaction was adapted to confirm its anti-inflammatory function with decreased cytokines (interleukin- (IL-) 6, IL-1β, and TNF-α) in PD mice and LPS-induced BV2 cells. Further studies found that ECH inhibited the IL-6/JAK2/STAT3 pathway and decreased phosphorylation of STAT3 on tyr705 by Western blot. It can also increase p-STAT3 (ser727) and brain-derived neurotrophic factor (BDNF) expression in PD mice and LPS-induced BV2 cells. This study revealed that ECH exerts neurotrophic and anti-inflammatory effects by regulating the IL-6/JAK2/STAT3 pathway and the phosphorylation of STAT3, promoting the mutually beneficial influence of the two effects to maximize its neuroprotective function.

show abstract

Section: Introductionmentioning

confidence: 99%

Echinacoside Protects Dopaminergic Neurons Through Regulating IL-6/JAK2/STAT3 Pathway in Parkinson’s Disease Model

Yang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…It had been proposed that mitochondrial dysfunction led to the activation of the nod-like receptor family pyrin domain-containing 3 (NLRP3) through mitochondrial ROS (mt ROS). Zhou reported that Mdivi-1 treatment decreased the expression of pro-inflammatory cytokines and activated (NLRP3) inflammasome and NF-κB ( Zhou et al, 2020 ). Previous studies showed that dysfunctional mitochondria induced and enhanced inflammatory responses by producing mitochondrial ROS and releasing mitochondrial damage-associated molecular patterns (DAMPs) ( van Horssen et al, 2019 ), whether Mdivi-1 is related to DAMPs in alleviating inflammation are needed to further investigation.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Inhibition of Mitochondrial Fission on Organ Function After Sepsis

Zhu

Kuang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo. Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases.

show abstract

“…Two novel ECH derivatives entered clinical trials in China [ 44 ], and the European Commission regards ECH as a novel food and attaches great importance to the formulation of relevant rules [ 47 ], guaranteeing the safety of it used in the human body. ECH has been identified to possess the properties of natural anti-inflammatory [ 38 ], antiaging [ 40 ], and anti-OS [ 41 ] properties. According to the experimental results, we speculate that ECH can perform multiple functions as anti-inflammatory and antioxidants in the clinical treatment of OA.…”

Section: Discussionmentioning

confidence: 99%

“…Cistanche is an endangered species but a precious, tonic Chinese medicine, honored as “Ginseng of the Deserts” [ 37 ]. Echinacoside (ECH) is a natural phenethyl alcohol commonly found in Cistanche [ 38 , 39 ], and with potent anti-inflammatory [ 38 ], antiaging [ 40 ], and anti-OS [ 41 ] properties. Moreover, as the main ingredient that functions in Cistanche , a number of recent studies confirmed numerous ECH benefits, such as in repairing radiation damage [ 41 ], nerve damage [ 42 ], resisting Alzheimer's disease [ 43 ], and regulating the gut microbiota diversity, increasing beneficial bacteria [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo

Lin

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. Purpose. We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. Methods. After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. Results. We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. Conclusion. In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.

show abstract

Echinacoside attenuates inflammatory response in a rat model of cervical spondylotic myelopathy via inhibition of excessive mitochondrial fission

Cited by 27 publications

References 58 publications

Echinacoside Protects Dopaminergic Neurons Through Regulating IL-6/JAK2/STAT3 Pathway in Parkinson’s Disease Model

Echinacoside Protects Dopaminergic Neurons Through Regulating IL-6/JAK2/STAT3 Pathway in Parkinson’s Disease Model

Protective Effects of Inhibition of Mitochondrial Fission on Organ Function After Sepsis

Echinacoside Upregulates Sirt1 to Suppress Endoplasmic Reticulum Stress and Inhibit Extracellular Matrix Degradation In Vitro and Ameliorates Osteoarthritis In Vivo

Contact Info

Product

Resources

About