Bee Venom Phospholipase A2 Ameliorates Atherosclerosis by Modulating Regulatory T Cells

Kang, Geun‐Hyung; Choi, Da Bin; Shin, Dasom; Kim, Jahee; Yang, Hyejin; Bae, Hyunsu

doi:10.3390/toxins12100609

Cited by 9 publications

(16 citation statements)

References 34 publications

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“…NF-κB signaling cascade was also inhibited by bvPLA2. Consistent with our findings, recent studies have shown that bvPLA2 decreased cytokine production in several inflammatory diseases such as acute lung inflammation [9], atherosclerosis [10], and allergic asthma [12] in rodents.…”

Section: Discussionsupporting

confidence: 93%

“…Cholestatic liver diseases are associated with a significant morbidity and mortality in infants and children [1,2], but medical therapies are limited. Emerging evidence suggests that bvPLA2 has a therapeutic effect against various inflammatory diseases [8][9][10][11][12][13]. In this study, we aimed to investigate the potential effect of bvPLA2 against cholestatic liver disease.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that bvPLA2 increased the Treg population in DDC diet-fed mice. Previous studies have shown that bvPLA2 suppressed inflammation and tissue injury by increasing the Treg population [8][9][10]. Therefore, we next investigated whether bvPLA2 regulates the accumulation of Treg cells in livers of DDC diet-fed mice.…”

Section: Administration Of Bvpla2 Modulated Immune Cell Infiltration In Ddc Diet-fed Micementioning

confidence: 97%

“…Regulatory T (Treg) cells are a specialized subset of CD4 + T-cells that express the Treg-specific transcription factor Foxp3 and play major roles in suppressing excessive immune responses through secreting immunosuppressive cytokines such as IL-10 [22]. Previous studies have shown that bvPLA2 suppressed inflammation and tissue injury by increasing the Treg population [8][9][10]. Therefore, we next investigated whether bvPLA2 regulates the accumulation of Treg cells in livers of DDC diet-fed mice.…”

Section: Administration Of Bvpla2 Modulated Immune Cell Infiltration In Ddc Diet-fed Micementioning

confidence: 99%

“…Although many of the mechanisms of action still remain unclear, accumulating evidence suggests that bee venom-derived sPLA2 (bvPLA2) exerts several beneficial actions, including anti-bacterial, anti-tumor, anti-neuronal injury and anti-nociceptive effects [7]. Moreover, it has been shown that the administration of bvPLA2 ameliorated a variety of inflammatory diseases in rodents, such as acute kidney injury [8], acute lung inflammation [9], atherosclerosis [10], atopic dermatitis [11], and allergic asthma [12]. In addition, mice injected with bvPLA2 have been reported to exhibit less liver damage after the administration of high-dose acetaminophen compared to control mice [13].…”

Section: Introductionmentioning

confidence: 99%

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Protective Effects of Bee Venom-Derived Phospholipase A2 against Cholestatic Liver Disease in Mice

et al. 2021

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Hepatocyte apoptosis and inflammation play important roles in cholestatic liver diseases. Bee venom-derived secretory phospholipase A2 (bvPLA2) has been shown to ameliorate various inflammatory diseases. However, whether bvPLA2 has a therapeutic effect against cholestatic liver disease has not been evaluated. Therefore, we investigated the effects of bvPLA2 on cholestatic liver injury and fibrosis in a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding. The administration of bvPLA2 ameliorated liver damage, cholestasis, and fibrosis in DDC diet-fed mice, as assessed by serum biochemical tests and histological examinations. In addition, bvPLA2 reduced myofibroblast accumulation, concomitant with suppression of transforming growth factor-β signaling cascade. The administration of bvPLA2 inhibited hepatocyte apoptosis in DDC diet-fed mice as represented by a reduction in the number of cells stained with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and suppression of caspase-3 activation. Moreover, bvPLA2 reduced cytokine production along with the inhibition of the nuclear factor kappa-B pathway. The number of regulatory T-cells was increased by bvPLA2, while the number of other immune cells, including neutrophils, macrophages, and CD8+ T-cells, was decreased. Our data indicate that the administration of bvPLA2 ameliorates cholestatic liver injury and fibrosis by inhibiting hepatocyte apoptosis and inflammation.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Administration Of Bvpla2 Modulated Immune Cell Infiltration In Ddc Diet-fed Micementioning

confidence: 97%

Section: Administration Of Bvpla2 Modulated Immune Cell Infiltration In Ddc Diet-fed Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective Effects of Bee Venom-Derived Phospholipase A2 against Cholestatic Liver Disease in Mice

et al. 2021

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Medicinal Benefits of Bee Venom

Sekar¹,

Lum²,

Bonam³

et al. 2023

Honey

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Immunomodulatory activities and biomedical applications of melittin and its recent advances

Jafari,

Sadeghi,

Dehaghi

et al. 2024

Archiv der Pharmazie

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Melittin (MLT), a peptide containing 26 amino acids, is a key constituent of bee venom. It comprises ∼40%–60% of the venom's dry weight and is the main pricing index for bee venom, being the causative factor of pain. The unique properties of MLT extracted from bee venom have made it a very valuable active ingredient in the pharmaceutical industry as this cationic and amphipathic peptide has propitious effects on human health in diverse biological processes. It has the ability to strongly impact the membranes of cells and display hemolytic activity with anticancer characteristics. However, the clinical application of MLT has been limited by its severe hemolytic activity, which poses a challenge for therapeutic use. By employing more efficient mechanisms, such as modifying the MLT sequence, genetic engineering, and nano‐delivery systems, it is anticipated that the limitations posed by MLT can be overcome, thereby enabling its wider application in therapeutic contexts. This review has outlined recent advancements in MLT's nano‐delivery systems and genetically engineered cells expressing MLT and provided an overview of where the MLTMLT's platforms are and where they will go in the future with the challenges ahead. The focus is on exploring how these approaches can overcome the limitations associated with MLT's hemolytic activity and improve its selectivity and efficacy in targeting cancer cells. These advancements hold promise for the creation of innovative and enhanced therapeutic approaches based on MLT for the treatment of cancer.

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Bee Venom Phospholipase A2 Ameliorates Atherosclerosis by Modulating Regulatory T Cells

Cited by 9 publications

References 34 publications

Protective Effects of Bee Venom-Derived Phospholipase A2 against Cholestatic Liver Disease in Mice

Protective Effects of Bee Venom-Derived Phospholipase A2 against Cholestatic Liver Disease in Mice

Medicinal Benefits of Bee Venom

Immunomodulatory activities and biomedical applications of melittin and its recent advances

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