<i>Cynanchum wilfordii</i>ameliorates hypertension and endothelial dysfunction in rats fed with high fat/cholesterol diets

Choi, Deok Ho; Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

doi:10.3109/08923973.2011.569889

Cited by 33 publications

(21 citation statements)

References 32 publications

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“…In addition, 4-HAP has been isolated from Cynanchum paniculatum and Cynanchum wilfordii extracts, and is commonly used for its antiinflammatory and vascular-protective effects (43)(44)(45). It will be of interest to explore the possibility that 4-HAP may have an impact on the mechanics of vascular tissue, as well as to expand upon its ability to alter myosin II dynamics in other mammalian cell types, particularly cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological activation of myosin II paralogs to correct cell mechanics defects

Surcel¹,

Ng²,

West‐Foyle³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Current approaches to cancer treatment focus on targeting signal transduction pathways. Here, we develop an alternative system for targeting cell mechanics for the discovery of novel therapeutics. We designed a live-cell, high-throughput chemical screen to identify mechanical modulators. We characterized 4-hydroxyacetophenone (4-HAP), which enhances the cortical localization of the mechanoenzyme myosin II, independent of myosin heavy-chain phosphorylation, thus increasing cellular cortical tension. To shift cell mechanics, 4-HAP requires myosin II, including its full power stroke, specifically activating human myosin IIB (MYH10) and human myosin IIC (MYH14), but not human myosin IIA (MYH9). We further demonstrated that invasive pancreatic cancer cells are more deformable than normal pancreatic ductal epithelial cells, a mechanical profile that was partially corrected with 4-HAP, which also decreased the invasion and migration of these cancer cells. Overall, 4-HAP modifies nonmuscle myosin II-based cell mechanics across phylogeny and disease states and provides proof of concept that cell mechanics offer a rich drug target space, allowing for possible corrective modulation of tumor cell behavior. mechanical modulator | 3,4-dichloroaniline | 4-hydroxyacetophenone | myosin II | pancreatic cancer C ell shape change processes include cell growth, division, motility, and the formation of complex structures like tissues and organs, all of which are governed by the intersection of biochemistry, genetics, and mechanics. These three modules are integral not just for normal function in healthy cells but also in disease states. Pharmacological manipulation of some of these modules has already led to treatment strategies for inflammation and cancer (e.g., paclitaxel) (1, 2). However, many presently available therapies, which address only one aspect of cell shape change, typically either fail to abolish the disease completely or lead to compensatory regulatory changes, and therefore to drug resistance. Targeting cell mechanics remains an underused approach for drug development. In cancer, altered cell mechanics are a hallmark of metastatic efficiency: cell stiffness decreases up to 70% in many metastatic cancer cells (3-5). It is rational then that one therapeutic approach is to increase cellular elasticity, which would, in turn, reduce metastatic potential and act downstream of cancer-inducing genetic alterations.Known mechanical modulators (e.g., latrunculin, blebbistatin) are often lethal, have numerous off-site targets, and act to generate a softer and metastatic-like mechanical phenotype (6, 7). However, the field's ability to increase cellular elasticity on acute time scales is highly restricted. In an effort to close this gap and find modulators that stiffen cells, we leveraged our molecular and analytical understanding of cytokinesis, an evolutionarily conserved and highly mechanical cell shape change event, to establish an in vivo, large-scale, high-throughput chemical screen for small-molecule modulators of cell shap...

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Section: Discussionmentioning

confidence: 99%

Pharmacological activation of myosin II paralogs to correct cell mechanics defects

Surcel¹,

Ng²,

West‐Foyle³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…No mortality was observed and EAL was found to be safe at the given doses. The HFCD-fed SD rats developed a severe metabolic syndrome consistent with hypertension and hypercholesterolemia [18,19]. The potential toxicity of EAL was determined based on BUN, creatinine, albumin, GOT, and GPT levels in the plasma.…”

Section: Resultsmentioning

confidence: 99%

Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets

Lee

Choi

Cho

et al. 2012

BMC Complement Altern Med

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BackgroundArctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD).MethodEAL-I (100 mg·kg−1/day), EAL-II (200 mg·kg−1/day), and fluvastatin (3 mg·kg−1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks.ResultsTreatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model.ConclusionThe present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation.

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“…C. wilfordii is an ingredient for tonic herbal drugs, and it shows pharmaceutical benefits against tumors, antioxidants, vascular diseases, and diabetes mellitus [1][2][3][4]. In China, C. auriculatum has been used as a tonic agent having the activities of anti-tumor, gastroprotective, antidepressant, and anti-aging [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Metabolomics Based on UPLC-QTOF/MS Applied for the Discrimination of Cynanchum wilfordii and Cynanchum auriculatum

Lee¹,

Ji²,

Mi-Kyoung³

et al. 2015

Metabolomics

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Cynanchum wilfordiiameliorates hypertension and endothelial dysfunction in rats fed with high fat/cholesterol diets

Cited by 33 publications

References 32 publications

Pharmacological activation of myosin II paralogs to correct cell mechanics defects

Pharmacological activation of myosin II paralogs to correct cell mechanics defects

Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets

Metabolomics Based on UPLC-QTOF/MS Applied for the Discrimination of Cynanchum wilfordii and Cynanchum auriculatum

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