Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways

Yan, Fang; Chu, Lisheng; Li, Lin; Wang, Jun; Yang, Yan; Gu, Jingjing; Zhang, Jianping

doi:10.1248/bpb.b17-00524

Cited by 31 publications

(17 citation statements)

References 31 publications

(37 reference statements)

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“…Its promote neural progenitor/precursor cells migration (Kong et al 2016) and protects neurons from oxygen–glucose deprivation-induced death (Shao et al 2017). TMP also protects bone marrow-derived mesenchymal stem cells against H 2 O 2 -induced apoptosis by regulating the PI3K/Akt and ERK1/2 signalling pathways (Fang et al 2017; Li et al 2017).…”

Section: Introductionmentioning

confidence: 99%

High tetramethylpyrazine production by the endophytic bacterial Bacillus subtilis isolated from the traditional medicinal plant Ligusticum chuanxiong Hort.

et al. 2018

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Tetramethylpyrazine (TMP) with significant protective effects on cardiovascular is the active ingredient of traditional Chinese medicine Rhizoma Chuanxiong (RC). However, many studies have reported the low content of TMP in RC. The endophytes of medicinal plants have the biosynthetic potential to produce the same or similar active metabolites as the host, while few reports were conducted to explore the endophytic bacteria of Ligusticum chuanxiong Hort. and its productive capacity for the important ingredient TMP. The present paper focuses on the isolation and identification of TMP producing endophytic bacteria from RC. In this study, the endophytic bacteria were isolated from the rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). Yeast extract peptone glucose medium (YP) was used for fermentation medium (37 °C, 220 rpm agitation, 144 h). GC and GC/MS were performed to determine and verify the product, the fermentation characteristics were investigated. Morphological observation, physiological and biochemical indexes combining with 16S rRNA sequence analysis were carried out to identify the endophytic bacteria. As a result, five strains of endophytic Bacillus subtilis were firstly isolated and identified from RC, named as LB3, LB3-2-1, LB6-2, LB4, LB5 respectively. All five strains of endophytic B. subtilis produced TMP, while LB5 had the highest production of 10.69 g/L at the 144 h fermentation. This work demonstrates the fact that the endophytic B. subtilis of RC can produce a high level of TMP, indicating the endophytic B. subtilis might play a role in the accumulation of TMP during the growth period of RC.

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Section: Introductionmentioning

confidence: 99%

High tetramethylpyrazine production by the endophytic bacterial Bacillus subtilis isolated from the traditional medicinal plant Ligusticum chuanxiong Hort.

et al. 2018

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“…Additionally, an increasing amount of evidence indicates that TMP exerts anticerebral ischemia effects both in vivo and in vitro. Various mechanisms have been suggested to underlie the activities of TMP, including the activation of free radical scavenging [35,36], the inhibition of Ca 2+ overload [35], the maintenance of mitochondrial function [35], the suppression of apoptosis [37,38] and inflammation [23,39], and the stimulation of neuronal differentiation [40]. Current in vivo results have shown that treating with TMP can significantly reduce brain infarction, behavioral functional impairment, and cerebral water content [32,33,35,39,41] in rats with middle cerebral artery occlusion-(MCAO-) induced cerebral ischemia.…”

mentioning

confidence: 99%

“…Bone marrow-derived mesenchymal stem cells (BMSCs) pretreated with TMP (10, 25, 50, 100, and 200 μmol•L -1 ) for 24 h and then exposed to 500 μmol•L -1 H 2 O 2 for 24 h exhibited significantly increased viability and decreased apoptosis and ROS generation. Furthermore, the protective effects of TMP were related to increased Bcl-2 expression, attenuated Bax expression, and 3 Oxidative Medicine and Cellular Longevity 5 Oxidative Medicine and Cellular Longevity enhanced levels of phosphorylated AKT (p-AKT) and p-ERK1/2 [37].…”

mentioning

confidence: 99%

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

Zhu

Wang²,

Feng³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Stroke is a leading cause of death and disability worldwide, and approximately 87% of cases are attributed to ischemia. The main factors that cause ischemic stroke include excitotoxicity, energy metabolism disorder, Ca+ overload, oxidative damage, apoptosis, autophagy, and inflammation. However, no effective drug is currently available for the comprehensive treatment of ischemic stroke in clinical applications; thus, there is an urgent need to find and develop comprehensive and effective drugs to treat postischemic stroke. Traditional Chinese medicine (TCM) has unique advantages in treating ischemic stroke, with overall regulatory effects at multiple levels and on multiple targets. Many researchers have studied the effective components of TCMs and have achieved undeniable results. This paper reviews studies on the anticerebral ischemia effects of TCM monomers such as tetramethylpyrazine (TMP), dl-3-n-butylphthalide (NBP), ginsenoside Rg1 (Rg1), tanshinone IIA (TSA), gastrodin (Gas), and baicalin (BA) as well as effective extracts such as Ginkgo biloba extract (EGB). Research on the anticerebral ischemia effects of TCMs has focused mostly on their antioxidative stress, antiapoptotic, anti-inflammatory, proangiogenic, and proneurogenic effects. However, the research on the use of TCM to treat ischemic stroke remains incompletely characterized. Thus, we summarized and considered this topic from the perspective of pharmacokinetics, pharmacological effects, and mechanistic research, and we have provided a reference basis for future research and development on anticerebral ischemia TCM drugs.

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“…Other studies indicated that AKT signaling is involved in the regulation of MSC survival, proliferation, differentiation, apoptosis, and migration. [22][23][24]37,38 Wu T et al noted that activation of PTEN/AKT signaling further activates NF-κB to promote TGFβ1 expression, thereby enhancing the immunosuppressive capacity of MSCs. 39 We hypothesized that CMA also regulates the activity of the AKT signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory factor-stimulated AKT activation mediates CMA inhibition AKT signaling has been widely investigated in the proliferation, differentiation, and survival of MSCs, [22][23][24] but few reports have shown whether AKT signaling participates in the regulation of MSC immunosuppression. We found that the phosphorylation level of AKT at Ser473 and Thr308 increased following IFN-γ plus TNF-α stimulation with time ( Fig.…”

Section: Cma Negatively Regulates Inos Expression In Mscsmentioning

confidence: 99%

Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells

Zhang

Huang

et al. 2020

Cell Mol Immunol

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Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells (MSCs). However, the biological function of chaperone-mediated autophagy (CMA) in MSCs remains elusive. Here, we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2 (LAMP-2A) in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation, and as expected, LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation. This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10 (CXCL10), which recruits inflammatory cells, especially T cells, to MSCs, and inducible nitric oxide synthase (iNOS), which leads to the subsequent inhibition of T cell proliferation via nitric oxide (NO). Mechanistically, CMA inhibition dramatically promoted IFN-γ plus TNF-α-induced activation of NF-κB and STAT1, leading to the enhanced expression of CXCL10 and iNOS in MSCs. Furthermore, we found that IFN-γ plus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs. More interestingly, CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury. Taken together, our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines and highlighted a previously unknown function of CMA.

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Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways

Cited by 31 publications

References 31 publications

High tetramethylpyrazine production by the endophytic bacterial Bacillus subtilis isolated from the traditional medicinal plant Ligusticum chuanxiong Hort.

High tetramethylpyrazine production by the endophytic bacterial Bacillus subtilis isolated from the traditional medicinal plant Ligusticum chuanxiong Hort.

Classical Active Ingredients and Extracts of Chinese Herbal Medicines: Pharmacokinetics, Pharmacodynamics, and Molecular Mechanisms for Ischemic Stroke

Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells

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