Tilianin mediates neuroprotection against ischemic injury by attenuating CaMKII-dependent mitochondrion-mediated apoptosis and MAPK/NF-κB signaling

Jiang, Hailun; Fang, Jiansong; Xing, Jianguo; Wang, Linlin; Wang, Qian; Wang, Yu; Li, Zhuorong; Liu, Rui

doi:10.1016/j.lfs.2018.11.035

Cited by 35 publications

(44 citation statements)

References 24 publications

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“…Tilianin is the major effective component of the total flavonoid extract from D. moldavica (Zeng et al, 2016). Tilianin has been reported to have neuroprotective and cardioprotective effects in the treatment of cardiovascular and cerebrovascular diseases (Zeng et al, 2018;Jiang et al, 2019). Moreover, in previous studies, it was reported that tilianin displayed anti-tumor effects in human lung adenocarcinoma and anti-angiogenesis effects based on VEGF-A (Meng, 2018;Meng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Tilianin Extracted From Dracocephalum moldavica L. Induces Intrinsic Apoptosis and Drives Inflammatory Microenvironment Response on Pharyngeal Squamous Carcinoma Cells via Regulating TLR4 Signaling Pathways

et al. 2020

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Tilianin Regulates Tumor Immunosuppressive Microenvironment these results showed that tilianin treatment increased cytotoxicity as well as the apoptotic population of FaDu cells in a dose-dependent manner. Furthermore, tilianin treatment decreased the level of anti-apoptotic markers Bcl-2 and Bcl-xL, increased the level of apoptotic factors Bad and Bax, and stimulated cytochrome c release, caspase-3 and poly ADP ribose polymerase (PARP) activation in FaDu cells. Furthermore, our findings indicated that tilianin treatment activated TLR4/p38/JNK/NF-κB signaling pathways and increased the release of inflammatory cytokines. This promoted the maturation of DCs to enhance immune system function in the tumor microenvironment. Moreover, the effects of tilianin on immune system function were abolished by TLR4 siRNA and p65 siRNA. In conclusion, these findings suggested that tilianin may be of immunotherapeutic value for inhibiting human pharyngeal squamous cell carcinoma.

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Section: Introductionmentioning

confidence: 99%

Tilianin Extracted From Dracocephalum moldavica L. Induces Intrinsic Apoptosis and Drives Inflammatory Microenvironment Response on Pharyngeal Squamous Carcinoma Cells via Regulating TLR4 Signaling Pathways

et al. 2020

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“…Thus, 0.63 mM H 2 O 2 was chosen as the dose of H 2 O 2 for U87 cells. TFDM (5,25,50, and 100 μg/ml) dose-dependently restored cell viability (Fig. 1c).…”

Section: Tfdm Protected U87 Cells Against H 2 O 2 Injurymentioning

confidence: 80%

“…Dracocephalum moldavica L., the dry aerial parts of which are widely used as a traditional Chinese medicine in Xinjiang, is a member of the family Lamiaceae [2]. The active components of D. moldavica L. (TFDM) have heart-and brain-tonifying functions, activate blood circulation and improve blood stasis [3][4][5][6]; therefore, it is mainly used for the treatment of cerebrovascular diseases. TFDM contains the main active components of D. moldavica L., accounting for 53.06% of the total activity.…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that these flavonoids have antiinflammatory and antioxidant stress effects [7][8][9][10][11][12]. In general, flavonoids are the most powerful and widely used bioactive compounds in plants and have cardioprotective and neuroprotective effects and have cardioprotective and neuroprotective effects [13][14][15][16]. Single-drug preparations of D. moldavica L., called Yixin Badiran Jibuya granules, have been used in the treatment of angina pectoris.…”

Section: Introductionmentioning

confidence: 99%

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Total flavones of Dracocephalum moldavica L. protect astrocytes against H2O2-induced apoptosis through a mitochondria-dependent pathway

Zheng

Zeng

et al. 2020

BMC Complement Med Ther

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Background: The active components of Dracocephalum moldavica L. (TFDM) can inhibit myocardial ischemia by inhibiting oxidative stress. However, the effects of TFDM on astrocytes have not been investigated in vitro. The current study aimed to explore whether TFDM protects astrocytes against H 2 O 2-induced apoptosis through a mitochondria-dependent pathway. Methods: The human glioma cell line U87 was used to investigate the ability of TFDM to protect astrocytes against H 2 O 2-induced apoptosis. The cell counting kit-8 assay and flow cytometry were used to detect cell viability, apoptosis, MMP, Ca 2+ influx and reactive oxygen species (ROS). Lactate dehydrogenase (LDH) and malonic dialdehyde (MDA) levels were measured by ELISA. In addition, protein and mRNA expression changes were detected by Western blotting and qRT-PCR. Results: TFDM (0.78~200 μg/ml) had limited cytotoxic effects on the viability of U87 cells. Compared with the model group (treated with H2O2 only), cells treated with medium-and high-dose TFDM exhibited reduced MDA concentrations (P < 0.05) and ROS production (P < 0.05) and decreased MMP (P < 0.05) and reduced apoptosis (P < 0.05). The percentage of annexin V-FITC-stained cells was markedly suppressed by TFDM, confirming its antiapoptotic properties. WB results showed that protein expression of Bcl-2-associated X protein (BAX), Caspase-3, Caspase-9, Caspase-12, and B-cell leukemia/lymphoma 2 (Bcl2) was reduced in the TFDM group compared with that in the model group (P < 0.05) and that expression of these proteins was normalized by TFDM treatment in a dosedependent manner. According to RT-qPCR results, TFDM pretreatment resulted in reduced mRNA expression of BAX, Caspase-9, Caspase-12, p38MAPK, and CaMKII and increased mRNA expression of mTOR compared with the model group. Conclusions: The current study revealed the protective effects of TFDM on U87 cells under oxidative stress conditions through the inhibition of a mitochondria-dependent pathway that is associated with the CaMKII/ P38MAPK/ERK1/2 and PI3K/AKT/mTOR pathways.

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“…The pathogenesis of HI is complex and several mechanisms and pathways contribute for both early and delayed brain damage. The HI insult causes mitochondrial dysfunction characterized by mitochondrial swelling and exposure of permeability transition pores, associated with high production of reactive oxygen species (ROS), which leads to oxidative stress and consequent cell death (Jiang et al, 2019; Skulachev et al, 2018). Interestingly, the male neonate's brain is more susceptible to these effects, as compared to females, as well as to greater long‐term cognitive impairments (Hill and Fitch, 2012; Netto et al, 2017; Weis et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Phytoestrogen coumestrol attenuates brain mitochondrial dysfunction and long‐term cognitive deficits following neonatal hypoxia–ischemia

Anastácio

Sanches

Nicola

et al. 2019

Intl J of Devlp Neuroscience

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Introduction: Neonatal Hypoxia-Ischemia (HI) is a major cause of morbidity and mortality, and is frequently associated with short and long-term neurologic and cognitive impairments. The HI injury causes mitochondrial damage leading to increased production of reactive oxygen species (ROS). Phytoestrogens are non-steroidal plant substances structurally and functionally similar to estrogen. Coumestrol is a potent isolavonoid with a protective efect against ischemic brain damage in adult rats. Our aim was to determine if coumestrol treatment following neonatal HI attenuates the long-term cognitive deicits induced by neonatal HI, as well as to investigate one possible mechanism underlying its potential efect. Methods: On the 7th postnatal day, male Wistar rats were submitted to the Levine-Rice HI model. Intraperitoneal injections of 20 mg/kg of coumestrol, or vehicle, were administered immediately pre-hypoxia or 3 h post-hypoxia. At 12 h after HI the mitochondrial status and ROS levels were determined. At 60th postnatal day the cognitive deicits were revealed in the Morris water maze reference and working spatial memories. Following behavioral analysis, histological assessment was performed and reactive astrogliosis was measured by GFAP expression. Results: Results demonstrate that both pre-and post-HI administration of coumestrol were able to counteract the long-term cognitive and morphological impairments caused by HI, as well as to block the late reactive astrogliosis. The pre-HI administration of coumestrol was able to prevent the early mitochondrial dysfunction in the hippocampus of injured rat pups. Conclusion: Present data suggest that coumestrol exerts protection against experimental neonatal brain hypoxiaischemia through, at least in part, early modulation of mitochondrial function.

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Tilianin mediates neuroprotection against ischemic injury by attenuating CaMKII-dependent mitochondrion-mediated apoptosis and MAPK/NF-κB signaling

Cited by 35 publications

References 24 publications

Tilianin Extracted From Dracocephalum moldavica L. Induces Intrinsic Apoptosis and Drives Inflammatory Microenvironment Response on Pharyngeal Squamous Carcinoma Cells via Regulating TLR4 Signaling Pathways

Tilianin Extracted From Dracocephalum moldavica L. Induces Intrinsic Apoptosis and Drives Inflammatory Microenvironment Response on Pharyngeal Squamous Carcinoma Cells via Regulating TLR4 Signaling Pathways

Total flavones of Dracocephalum moldavica L. protect astrocytes against H2O2-induced apoptosis through a mitochondria-dependent pathway

Phytoestrogen coumestrol attenuates brain mitochondrial dysfunction and long‐term cognitive deficits following neonatal hypoxia–ischemia

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