<i>Lactobacillus reuteri</i> attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow

Koppinger, Matthew P.; Lopez-Pier, Marissa A.; Skaria, Rinku; Harris, Preston R.; Konhilas, John P.

doi:10.1152/ajpheart.00569.2019

Cited by 15 publications

(8 citation statements)

References 54 publications

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“…Previous studies have reported the anti‐inflammatory effects of L. reuteri [ 18 ] and found the gavage of this bacteria reduced cardiac injury in low‐density lipoprotein receptor (LDLR)‐deficient mice [ 19 ] we set out to explore the cardioprotective potential of L. reuteri in the context of I/R ( Figure 1 A ). Male C57BL/6J were given oral antibiotics for seven days to deplete the original gut microbiota to facilitate the colonization of L. reuteri (copies of bacterial 16S, p < 0.001, Figure 1B ) and daily gavage of L. reuteri as a prophylactic (2 × 10 8 CFU per mouse) or PBS (control) was carried out daily for 7 days.…”

Section: Resultsmentioning

confidence: 99%

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury

Wang,

Zhang,

Yuan

et al. 2024

Advanced Science

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The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. Ischemia/reperfusion (I/R) after myocardial infarction is a serious complication and whether certain gut bacteria can serve as a treatment option remains unclear. Lactobacillus reuteri (L. reuteri) is a well‐studied probiotic that can colonize mammals including humans with known cholesterol‐lowering properties and anti‐inflammatory effects. Here, the prophylactic cardioprotective effects of L. reuteri or its metabolite γ‐aminobutyric acid (GABA) against acute ischemic cardiac injury caused by I/R surgery are demonstrated. The prophylactic gavage of L. reuteri or GABA confers cardioprotection mainly by suppressing cardiac inflammation upon I/R. Mechanistically, GABA gavage results in a decreased number of proinflammatory macrophages in I/R hearts and GABA gavage no longer confers any cardioprotection in I/R hearts upon the clearance of macrophages. In vitro studies with LPS‐stimulated bone marrow‐derived macrophages (BMDM) further reveal that GABA inhibits the polarization of macrophages toward the proinflammatory M1 phenotype by inhibiting lysosomal leakage and NLRP3 inflammasome activation. Together, this study demonstrates that the prophylactic oral administration of L. reuteri or its metabolite GABA attenuates macrophage‐mediated cardiac inflammation and therefore alleviates cardiac dysfunction after I/R, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.

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Section: Resultsmentioning

confidence: 99%

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury

Wang,

Zhang,

Yuan

et al. 2024

Advanced Science

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“…IL-1β is regulated by the NF-κB, c-Jun N-terminal kinase (JNK), and p38 MAPK pathways [ 29 ]. IL-6 can be released by myocardial and immune cells [ 30 ], and is primarily triggered and regulated by signaling pathways such as NF-κB and MAPK [ 31 ]. It is reported that total glucosides of V. officinalis attenuate chronic nonbacterial prostatitis in rat models by reducing the release of IL-2, IL-1β, and TNF-α in the prostate [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Bioactive Constituents of Verbena officinalis Alleviate Inflammation and Enhance Killing Efficiency of Natural Killer Cells

Dai

Zhou

Shao

et al. 2023

IJMS

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Natural killer (NK) cells play key roles in eliminating pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine for its anti-tumor and anti-inflammatory activities, but its effects on immune responses remain largely elusive. This study aimed to investigate the potential of V. officinalis extract (VO extract) to regulate inflammation and NK cell functions. We examined the effects of VO extract on lung injury in a mouse model of influenza virus infection. We also investigated the impact of five bioactive components of VO extract on NK killing functions using primary human NK cells. Our results showed that oral administration of VO extract reduced lung injury, promoted the maturation and activation of NK cells in the lung, and decreased the levels of inflammatory cytokines (IL-6, TNF-α and IL-1β) in the serum. Among five bioactive components of VO extract, Verbenalin significantly enhanced NK killing efficiency in vitro, as determined by real-time killing assays based on plate-reader or high-content live-cell imaging in 3D using primary human NK cells. Further investigation showed that treatment of Verbenalin accelerated the killing process by reducing the contact time of NK cells with their target cells without affecting NK cell proliferation, expression of cytotoxic proteins, or lytic granule degranulation. Together, our findings suggest that VO extract has a satisfactory anti-inflammatory effect against viral infection in vivo, and regulates the activation, maturation, and killing functions of NK cells. Verbenalin from V. officinalis enhances NK killing efficiency, suggesting its potential as a promising therapeutic to fight viral infection.

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“…. IL-6 can be released by myocardial and immune cell [39] , mainly triggered and regulated by signalling pathways like NF-κB and MAPK [40] . It is reported that total glucosides of V. officinalis attenuate chronic nonbacterial prostatitis in rat model by reducing the release of IL-2, IL-1β and TNF-α in prostate [41] .…”

Section: Discussionmentioning

confidence: 99%

Bioactive constituents ofVerbena officinalisalleviate inflammation and enhance killing efficiency of natural killer cells

Shao

Zhou

Zhao

et al. 2021

Preprint

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Verbena officinalis L. (V. officinalis) has been used as a medical plant in traditional and modern medicine, exhibiting anti-tumor and anti-inflammation activity. In this work, we investigated the impact of bioactive constituents of V. officinalis on immune regulation. Using network pharmacology approaches, we analyzed potential regulatory roles of five compounds (Acteoside, Apigenin, Kaempferol, Verbenalin and Hastatoside) from V. officinalis on immune cell functions and revealed NK cells as a major target. The effect of these compounds on NK killing efficiency was examined with real-time killing assay, and Verbenalin enhanced NK killing efficiency significantly. Further investigation showed that Verbenalin did not affect proliferation, expression of cytotoxic proteins, or lytic granule degranulation, but rather reduced contact time required for killing therefore enhancing total killing events per NK cell, suggestively via inhibition of inhibitory receptors as determined by docking assay. Our findings reveal the underlying mechanisms how V. officinalis regulates functions of immune cells, especially NK cells, suggesting Verbenalin from V. officinalis as a promising therapeutic reagent to fight cancer and infection.

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Lactobacillus reuteri attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow

Cited by 15 publications

References 54 publications

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury

Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury

Bioactive Constituents of Verbena officinalis Alleviate Inflammation and Enhance Killing Efficiency of Natural Killer Cells

Bioactive constituents ofVerbena officinalisalleviate inflammation and enhance killing efficiency of natural killer cells

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