Baicalin Inhibits the Lethality of Ricin in Mice by Inducing Protein Oligomerization

Dong, Jing; Zhang, Yong; Niu, Xiaodi; Li, Rui; Yang, Cheng; Wang, Quan; Li, Xuemei; Deng, Xuming

doi:10.1074/jbc.m114.632828

Cited by 14 publications

(10 citation statements)

References 33 publications

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“…Taking into account information about flavonoids, the focus of our paper is to discuss Baicalin, which is also the flavonoid derivatives, the principal component in the roots of Scutellaria radix, known as Huang Qin in Chinese traditional medicine [21,24]. In recent years, several studies have shown that Baicalin displays a potent neuroprotective effect in various in vitro and in vivo models of neuronal injuries [25]. In particular, Baicalin effectively prevents neurodegenerative diseases through various pharmacological mechanisms, including antiexcitotoxicity, antiapoptosis, and anti-inflammation, promoting the expression of neuronal protective factors [26].…”

Section: Introductionmentioning

confidence: 99%

Baicalin Represses C/EBPβ via Its Antioxidative Effect in Parkinson’s Disease

Lei

Shen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Parkinson’s disease (PD) is a neurodegenerative disease characterized by the gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the formation of intracellular Lewy bodies (LB) in the brain, which aggregates α-synuclein (α-Syn) as the main component. The interest of flavonoids as potential neuroprotective agents is increasing due to its high efficiency and low side effects. Baicalin is one of the flavonoid compounds, which is a predominant flavonoid isolated from Scutellaria baicalensis Georgi. However, the key molecular mechanism by which Baicalin can prevent the PD pathogenesis remains unclear. In this study, we used bioinformatic assessment including Gene Ontology (GO) to elucidate the correlation between oxidative stress and PD pathogenesis. RNA-Seq methods were used to examine the global expression profiles of noncoding RNAs and found that C/EBPβ expression was upregulated in PD patients compared with healthy controls. Interestingly, Baicalin could protect DA neurons against reactive oxygen species (ROS) and decreased C/EBPβ and α-synuclein expression in pLVX-Tet3G-α-synuclein SH-SY5Y cells. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model, the results revealed that treatment with Baicalin improved the PD model’s behavioral performance and reduced dopaminergic neuron loss in the substantia nigra, associated with the inactivation of proinflammatory cytokines and oxidative stress. Hence, our study supported that Baicalin repressed C/EBPβ via redox homeostasis, which may be an effective potential treatment for PD.

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Section: Introductionmentioning

confidence: 99%

Baicalin Represses C/EBPβ via Its Antioxidative Effect in Parkinson’s Disease

Lei

Shen

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…The successful use of the structure information of the ricin-BAI complex to identify the key residues on Stx2 important for its interactions with BAI suggests that BAI targets Stx2 with a similar mechanism, namely, induction of protein oligomerization to occlude its active site (20). These results also suggest that chemical modification of BAI to obtain molecules with higher affinity for the toxins is feasible and clearly is a direction worth pursuing in future research.…”

Section: Discussionmentioning

confidence: 71%

“…Our results from both in vitro and in vivo experiments suggest that BAI exerts its protective activity by targeting rStx2 directly. Our previous study revealed that BAI inhibits the activity of ricin, another RIP, by inducing the A subunit of ricin (RTA) to form enzymatically less active oligomers (20). Given the fact that the activities of RTA and Stx2a are highly similar and that these two toxins share high-level resemblance in their structures (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Baicalin Inhibits the Lethality of Shiga-Like Toxin 2 in Mice

Dong

Zhang

Niu

et al. 2015

Antimicrob Agents Chemother

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e Shiga-like toxins (Stxs), produced by pathogenic Escherichia coli, are a major virulence factor involved in severe diseases in human and animals. These toxins are ribosome-inactivating proteins, and treatment for diseases caused by them is not available. Therefore, there is an urgent need for agents capable of effectively targeting this lethal toxin. In this study, we identified baicalin, a flavonoid compound used in Chinese traditional medicine, as a compound against Shiga-like toxin 2 (Stx2). We found that baicalin significantly improves renal function and reduces Stx2-induced lethality in mice. Further experiments revealed that baicalin induces the formation of oligomers by the toxin by direct binding. We also identified the residues important for such interactions and analyzed their roles in binding baicalin by biophysical and biochemical analyses. Our results establish baicalin as a candidate compound for the development of therapeutics against diseases caused by Stxs.

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“…Two compounds (out of 50,000) showed modest to strong ricin inhibition in a cell-based assay, which was, however, accompanied by some cytotoxicity [ 189 ]. In a recent study [ 190 ], baicalin, extracted from the plant Scutellaria baicalensis and used as a Chinese medical herb, reduced ricin-mediated cytotoxicity in vitro and conferred significant post-exposure protection in mice intraperitoneally exposed to ricin. Baicalin is an RTA inhibitor with a novel mechanism of action.…”

Section: Countermeasures For Ricin Intoxicationmentioning

confidence: 99%

Treatments for Pulmonary Ricin Intoxication: Current Aspects and Future Prospects

Gal

Mazor

Falach

et al. 2017

Toxins

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Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor beans), is one of the most lethal toxins known, particularly if inhaled. Ricin is considered a potential biological threat agent due to its high availability and ease of production. The clinical manifestation of pulmonary ricin intoxication in animal models is closely related to acute respiratory distress syndrome (ARDS), which involves pulmonary proinflammatory cytokine upregulation, massive neutrophil infiltration and severe edema. Currently, the only post-exposure measure that is effective against pulmonary ricinosis at clinically relevant time-points following intoxication in pre-clinical studies is passive immunization with anti-ricin neutralizing antibodies. The efficacy of this antitoxin treatment depends on antibody affinity and the time of treatment initiation within a limited therapeutic time window. Small-molecule compounds that interfere directly with the toxin or inhibit its intracellular trafficking may also be beneficial against ricinosis. Another approach relies on the co-administration of antitoxin antibodies with immunomodulatory drugs, thereby neutralizing the toxin while attenuating lung injury. Immunomodulators and other pharmacological-based treatment options should be tailored according to the particular pathogenesis pathways of pulmonary ricinosis. This review focuses on the current treatment options for pulmonary ricin intoxication using anti-ricin antibodies, disease-modifying countermeasures, anti-ricin small molecules and their various combinations.

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Baicalin Inhibits the Lethality of Ricin in Mice by Inducing Protein Oligomerization

Cited by 14 publications

References 33 publications

Baicalin Represses C/EBPβ via Its Antioxidative Effect in Parkinson’s Disease

Baicalin Represses C/EBPβ via Its Antioxidative Effect in Parkinson’s Disease

Baicalin Inhibits the Lethality of Shiga-Like Toxin 2 in Mice

Treatments for Pulmonary Ricin Intoxication: Current Aspects and Future Prospects

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