Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca2+Entry and Ca2+Release in Beating Rabbit Atria

Cui, Hao; Oh, Hyun Cheol; Li, Xiang; Lee, Yun Jung; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

doi:10.1089/jmf.2012.2487

Cited by 8 publications

(6 citation statements)

References 22 publications

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“…The combination of Ca 2+ influx and release increases the cytosolic concentration of Ca 2+ . In this study, LTCC blockade and RyR inhibition suppressed the BA-induced increase in intracellular levels of Ca 2+ and eNOS-Ser1177 phosphorylation, which is consistent with the effects of BA on Ca 2+ influx from the SR in beating rabbit atria and enhancement of arterial dynamics …”

Section: Discussionsupporting

confidence: 87%

“…29 In this study, LTCC blockade and RyR inhibition suppressed the BA-induced increase in intracellular levels of Ca 2+ and eNOS-Ser1177 phosphorylation, which is consistent with the effects of BA on Ca 2+ influx from the SR in beating rabbit atria and enhancement of arterial dynamics. 40 Schneider et al reported the involvement of CaMKII in endothelial NO production and endothelium-dependent relaxation and concluded that the agonist-induced increase in Ca 2+ levels leads to Ca 2+ /calmodulin-mediated eNOS activation and potentiates NO synthesis by CaMKII-dependent eNOS phosphorylation. 7 In our study, W7 (a CaM antagonist) and KN-93 (a CaMKII inhibitor) attenuated BA-induced eNOS-Ser1177 phosphorylation and NO production, which suggests that BA increases eNOS activity via the CaM/CaMKII pathway.…”

Section: ■ Discussionmentioning

confidence: 99%

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Betulinic Acid Increases eNOS Phosphorylation and NO Synthesis via the Calcium-Signaling Pathway

Jin

Choi²,

Hwang³

et al. 2016

J. Agric. Food Chem.

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Betulinic acid (BA) is a naturally occurring pentacyclic triterpene that attenuates vascular diseases and atherosclerosis, but the mechanism by which it stimulates endothelial nitric oxide synthase (eNOS) is unclear. eNOS is the key regulatory enzyme in the vascular endothelium. This study examined the intracellular pathways underlying the effects of BA on eNOS activity and endothelial nitric oxide (NO) production in endothelial cells. BA treatment induced both eNOS phosphorylation at Ser1177 and NO production. It also increased the level of intracellular Ca(2+) and phosphorylation of Ca(2+)/calmodulin-dependent kinase IIα (CaMKIIα) and Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ). Inhibition of the L-type Ca(2+) channel (LTCC) and the ryanodine receptor (RyR) abolished BA-induced intracellular levels of Ca(2+) and eNOS phosphorylation. Treatment with W7 (a CaM antagonist), KN-93 (a selective inhibitor of CaMKII), and STO 609 (a selective inhibitor of CaMKK) suppressed eNOS phosphorylation and NO production. Moreover, AMP-activated protein kinase (AMPK) was induced by BA, and BA-induced eNOS phosphorylation was inhibited by compound C, an AMPK inhibitor. Taken together, these results indicate that BA activates eNOS phosphorylation and NO synthesis via the Ca(2+)/CaMKII and Ca(2+)/CaMKK/AMPK pathways. These findings provide further insight into the eNOS signaling pathways involved in the antiatherosclerosis effects of BA.

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Section: Discussionsupporting

confidence: 87%

Section: ■ Discussionmentioning

confidence: 99%

Betulinic Acid Increases eNOS Phosphorylation and NO Synthesis via the Calcium-Signaling Pathway

Jin

Choi²,

Hwang³

et al. 2016

J. Agric. Food Chem.

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“…Lycopus lucidus Turcz (LLT) is a perennial herb known as ‘Taekran’ in Korea ( 25 ). Traditionally, LLT has been used to treat amenorrhea, dysmenorrhea, edema, carbuncles and sores ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

“…Traditionally, LLT has been used to treat amenorrhea, dysmenorrhea, edema, carbuncles and sores ( 26 ). Recently, LLT has been reported to have various biological properties, including effects on the blood circulation ( 25 ), anti-inflammatory ( 27 ), antioxidant ( 28 ), anti-vascular inflammation and wound-healing effects ( 27 , 29 ), suggesting that LLT may also affect the mechanism underlying AD.…”

Section: Introductionmentioning

confidence: 99%

Lycopus lucidusTurcz ameliorates DNCB‑induced atopic dermatitis in BALB/c mice

et al. 2021

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Atopic dermatitis (AD) is a chronic inflammatory allergic skin disease, characterized by pruritic and eczematous skin lesions. Lycopus lucidus Turcz (LLT) is a perennial herb that has been reported to have various biological properties, including effects on blood circulation, as well as anti-inflammatory, antioxidant, anti-vascular inflammation and wound-healing effects. However, whether LLT improves dermatitis and the underlying mechanisms has yet to be determined. The aim of the present study was to determine whether LLT can improve 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis and to verify the inhibitory effect of LLT on the expression of chemokines and pro-inflammatory cytokines in the HaCaT immortalized keratinocyte cell line. In addition, the anti-inflammatory function of LLT in RAW264.7 mouse macrophages was investigated. In the DNCB-induced AD mouse model, LLT inhibited infiltration by mast cells, eosinophils and CD8 + cells in the dorsal skin tissue of AD mice, and suppressed the expression of IgE and IL-6 in serum. In addition, LLT inhibited the phosphorylation of ERK and JNK, as well as NF-κB in skin tissue. In the HaCaT cell model induced by TNF-α/IFN-γ, LLT inhibited the expression of thymus and activation-regulated chemokine, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, TNF-α and IL-1β, whilst inhibiting the phosphorylation of NF-κB. In addition, in the lipopolysaccharide-induced RAW 264.7 cell inflammation model, LLT inhibited the expression of TNF-α and IFN-γ, the nuclear translocation of NF-κB and the phosphorylation of ERK and JNK. These results suggested that LLT may be a promising candidate for the treatment of inflammatory dermatitis.

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“…Lycopus lucidus Turcz. ex Benth (LT) is a perennial herb widely used as a traditional medicine in Korea and China to promote blood circulation and remove blood stasis [ 12 – 14 ]. Recently, it has been reported that LT both inhibits vascular inflammation in human umbilical vein endothelial cells and reduces mast cell-mediated allergies [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ethanol Extract ofLycopus lucidusTurcz. ex Benth Inhibits Metastasis by Downregulation of Runx-2 in Mouse Colon Cancer Cells

Kim

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Lycopus lucidus Turcz. ex Benth (LT) has been broadly used as a traditional medicinal herb in Asia including Korea, China, and Japan due to its noted ability to promote blood circulation and remove blood stasis. However, its anticancer mechanism is not understood. This study aims to elucidate the effects of ethanol extracts of LT (ELT) relative to the role of Runt-related transcription factor- (Runx-) 2 in the invasive and metastatic potentials of mouse colon cancer to determine the underlying mechanisms involved. ELT was evaluated for the antimetastasis activity using CT-26 colon cancer using wound healing, transwell matrigel, and western blot analysis. We used Runx-2-specific siRNA to further determine the relationship between Runx-2 and matrix metalloprotease- (MMP-) 9 in the migration and invasion of CT-26 cells. Runx-2 was first demonstrated to be a transcription factor that plays a remarkable role in diverse biological processes of chondrocytes and osteoblasts, but recently, Runx-2 has been reported to be associated with the progression of certain human cancers. ELT was not altered in its effects on growth inhibition. However, ELT significantly inhibited wound closure and cell invasion in a dose-dependent manner. ELT decreased the metastasis by regulating the activity of MMP-9 and Runx-2 at the translational levels. Our results demonstrate that ELT decreases metastasis by inhibiting the Runx-2–MMP-9 axis. We suggest that it can be used as a novel agent in therapeutic strategies for combating colon cancer.

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Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca²⁺Entry and Ca²⁺Release in Beating Rabbit Atria

Cited by 8 publications

References 22 publications

Betulinic Acid Increases eNOS Phosphorylation and NO Synthesis via the Calcium-Signaling Pathway

Betulinic Acid Increases eNOS Phosphorylation and NO Synthesis via the Calcium-Signaling Pathway

Lycopus lucidusTurcz ameliorates DNCB‑induced atopic dermatitis in BALB/c mice

Ethanol Extract ofLycopus lucidusTurcz. ex Benth Inhibits Metastasis by Downregulation of Runx-2 in Mouse Colon Cancer Cells

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