Inhibition ofS-Adenosyl-l-homocysteine Hydrolase Induces Immunosuppression

Wu, Qingli; Fu, Yunfeng; Zhou, Wen‐Liang; Wang, Junxia; Feng, Yonghong; Liu, Jing; Xu, Jiasheng; He, Pei‐Lan; Zhou, Ru; Tang, Wei; Wang, Guifeng; Zhou, Yu; Yang, Ye; Ding, Jian; Li, Xiaoyü; Chen, Xiaoru; Yuan, Chong; Lawson, Brian R.; Zuo, Jian‐Ping

doi:10.1124/jpet.104.080416

Cited by 58 publications

(80 citation statements)

References 29 publications

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“…However, in addition to the antiproliferative effect of c3Ado on VSMCs, the previously described inhibitory effects of c3Ado on ROS production, 5 adhesion molecule expression, 3,7 leukocyte recruitment, and monocyte and T-cell activation 26 may further contribute to the effective reduction of vascular lesion formation.…”

Section: Sedding Et Al C3ado Prevents Neointima Formationmentioning

confidence: 99%

3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling

Sedding

Tröbs

Reich

et al. 2009

Circulation Research

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Abstract-3-Deazaadenosine (c3Ado) is a potent inhibitor of S-adenosylhomocysteine hydrolase, which regulates cellular methyltransferase activity. In the present study, we sought to determine the effect of c3Ado on vascular smooth muscle cell (VSMC) function and neointima formation in vivo. c3Ado dose-dependently prevented the proliferation and migration of human coronary VSMCs in vitro. This was accompanied by an increased expression of the cyclindependent kinase inhibitors p21 WAF1/Cip1 , p27 Kip1 , a decreased expression of G 1 /S phase cyclins, and a lack of retinoblastoma protein hyperphosphorylation. In accordance with these findings, fluorescence-activated cell-sorting analysis of propidium iodide-stained cells indicated a cell cycle arrest in the G 0 /G 1 phase. Importantly, c3Ado did not affect the number of viable (trypan blue exclusion) or apoptotic cells (TUNEL). Mechanistically, c3Ado prevented FCS-induced Ras carboxyl methylation and membrane translocation and activity by inhibiting isoprenylcysteine carboxyl methyltransferase and reduced FCS-induced extracellular signal-regulated kinase (ERK)1/2 and Akt phosphorylation in a dose-dependent manner. Conversely, rescuing signal transduction by overexpression of a constitutive active Ras mutant abrogated c3Ado's effect on proliferation. For in vivo studies, the femoral artery of C57BL/6 mice was dilated and mice were fed a diet containing 150 g of c3Ado per day. c3Ado prevented dilation-induced Ras activation, as well as ERK1/2 and Akt phosphorylation in vivo. At day 21, VSMC proliferation (proliferating-cell nuclear antigen [PCNA]-positive cells), as well as the neointima/media ratio (0.7Ϯ0.2 versus 1.6Ϯ0.4; PϽ0.05) were significantly reduced, without any changes in the number of apoptotic cells. Our data indicate that c3Ado interferes with Ras methylation and function and thereby with mitogenic activation of ERK1/2 and Akt, preventing VSMC cell cycle entry and proliferation and neointima formation in vivo. Thus, therapeutic inhibition of S-adenosylhomocysteine hydrolase by c3Ado may represent a save and effective novel approach to prevent vascular proliferative disease. (Circ Res. 2009;104:1192-1200.) Key Words: neointima formation Ⅲ restenosis Ⅲ signal transduction Ⅲ smooth muscle cells Ⅲ vascular smooth muscle cell proliferation V ascular smooth muscle cell (VSMC) migration, proliferation, and hypertrophy triggered by inflammatory responses of the vessel wall are considered to be key events in the development of atherosclerosis, postangioplasty restenosis, and venous bypass graft failure. 1,2 Consequently, antiinflammatory and antiproliferative 2 strategies have been demonstrated to successfully prevent the development of vascular proliferative disease. Therefore, the identification of novel compounds with combined antiinflammatory/antiproliferative properties holds promise to improve existing therapeutic strategies by limiting late cardiovascular complications like in-stent restenosis or bypass graft failure.3-Deazaadenosine (c3Ado), a structural ...

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Section: Sedding Et Al C3ado Prevents Neointima Formationmentioning

confidence: 99%

3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling

Sedding

Tröbs

Reich

et al. 2009

Circulation Research

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“…Cells were cultured in 96-well tissue culture plates with 0.2 x 10 6 cells per well. They were incubated at 37°C for 24 hours in a humidified atmosphere of 5% CO 2 for the indicated period [21]. The respective vehicle controls (DMSO) were kept in the assay for comparison.…”

Section: Mouse Splenocyte Culturesmentioning

confidence: 99%

Impact of Biofield Energy Treated Herbomineral Formulation (The Trivedi Effect®) on Mouse Dendritic and Splenocyte Cells for Modulation of Pro-inflammatory Cytokines

Trivedi¹

2016

IJI

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Abstract:The use of herbomineral formulation in the healthcare sector for different chronic diseases is gaining popularity due to its fewer side effects, high safety profile, and cost effectiveness. A new proprietary herbomineral formulation was formulated, consisting of four essential ingredients viz. herbal root extract (ashwagandha), and minerals (zinc, magnesium, and selenium). The study aims to evaluate the in vitro effect of Biofield Energy Healing (The Trivedi Effect ® ) on the test formulation using murine dendritic (DCs) and splenocyte cells. The herbomineral formulation was divided into two parts; one was represented as control, while the other part was treated with the Biofield Energy Healing Treatment remotely by eighteen renowned Biofield Energy Healers (The Trivedi Effect ® ) and defined as the Biofield Treated formulation. The effect of the test formulation on these cells were monitored by an estimation of pro-inflammatory cytokines level such as tumor necrosis factor (TNF-α), macrophage inflammatory protein (MIP-1α), and interleukin (IL-1β) in cell culture supernatants at the non-cytotoxic concentrations of the test formulation using MTT assay. The DCs were treated with the Biofield Energy Treated test formulation at different concentrations (i.e. 1.05 to 1052.5 µg/mL) for 24 hours, and the results showed significant (p≤0.001) suppression of TNF-α levels at all the tested concentrations with a maximum percentage decrease by 43.64% at 5.2 µg/mL concentration in the Biofield Treated formulation as compared with the untreated test formulation. Further, the Biofield Treated formulation also demonstrated inhibition of MIP-1α and IL-1β at a concentration range of 0.0000105 to 10.5 µg/mL in LPS stimulated splenocyte cells. There was a significant (p≤0.001) inhibition of MIP-1α (26.52%) and IL-1β (35.28%) in the Biofield Treated test formulation at concentration 0.000105 µg/mL and 0.0000105 µg/mL, respectively in comparison to the untreated test formulation. Overall, these results suggest that the Biofield Energy Healing based herbomineral formulation (The Trivedi Effect ® ) significantly down-regulated the tested cytokines expression in DCs and splenocyte cells as compared to the untreated formulation. Therefore, the Biofield Healing based formulation might be useful as a better anti-inflammatory product for many chronic and acute inflammatory disease conditions and autoimmune disorders. The Biofield Energy Treatment based 36 Mahendra Kumar Trivedi et al.: Impact of Biofield Energy Treated Herbomineral Formulation (The Trivedi Effect ® ) on Mouse Dendritic and Splenocyte Cells for Modulation of Pro-Inflammatory Cytokines formulation can also be effectively applied in cases of organ transplants, stress management and anti-aging by improving overall health.

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“…The cells were cultured in 96-well tissue culture plates with 0.2 x 10 6 cells per well. They were incubated at 37°C in a humidified atmosphere of 5% CO 2 for the indicated period [36].…”

Section: Isolation Of Murine Splenocytesmentioning

confidence: 99%

Evaluation of Pro-Inflammatory Cytokines Expression in Mouse Splenocytes After Incubation with Biofield Treated Herbomineral Formulation: Effect of Biofield Energy Healing Treatment - The Trivedi Effect®

Trivedi¹,

Branton²,

Trivedi³

et al. 2016

AJBLS

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Abstract:The use of herbomineral formulations in the healthcare sector has increased due to their high safety and better therapeutic action. A new proprietary herbomineral formulation was formulated with a mixture of the herbal root extract of ashwagandha and three minerals viz. zinc chloride, magnesium gluconate, and sodium selenate. The aim of the study was to evaluate the immunomodulatory potential of Biofield Energy Healing (The Trivedi Effect ® ) on the formulation when applied to splenocyte cells isolated from mice spleen. The formulation was divided into two parts; one was the control without any Biofield Energy Treatment, while the other part was defined as the Biofield Energy Treated sample, which received Biofield Energy Healing Treatment remotely by seven renowned Biofield Energy Healers. The test formulation was evaluated to find the expression of pro-inflammatory cytokines such as TNF-α, MIP-1α, and IL-1β along with non-cytotoxic concentrations by MTT assay. The splenocytes were given the Biofield Energy Treated and untreated sample at concentrations range (0.00001053 to 10.53 µg/mL) for 48 hours and was reported with safe concentration up to 1.053 µg/mL with percentage viability range from 76.7% to 109.2% in both samples. Biofield Energy Healing significantly enhanced the cell viability as compared with the untreated formulation. The expression of TNF-α was significantly inhibited in the Biofield Treated formulation at 0.01053, 0.1053, and 1.053 µg/mL by 1.77%, 1.93%, and 3.55%, respectively compared with the untreated formulation. The rest of the tested concentrations of the Biofield Treated formulation showed an increase in TNF-α expression at 0.00001053, 0.0001053, and 0.001053 µg/mL by 7.26%, 8.50%, and 8.50%, respectively compared to the vehicle control group. Similarly, the MIP-1α expression was inhibited by the Biofield Energy Treated formulation and showed immunosuppression activity at 0.01053 µg/mL by 18.47% (p≤0.001) compared to the untreated formulation. MIP-1α expression was reported as 628.94 ± 13.0 pg/mL in the untreated formulation, while it decreased to 512.74 ± 1.9 pg/mL in the Biofield Treated formulation at 0.01053 µg/mL. In addition, the IL-1β secretion was also significantly inhibited by the Biofield Treated formulation at concentrations 0.001053, 0.01053, 0.1053, and 1.053 µg/mL by 72.02%, 50.16%, 30.68%, and 22.11%, respectively as compared with the untreated formulation. Overall, The Trivedi Effect ® significantly down-regulated the proinflammatory cytokines and potentiated the immunosuppressive effect of the treated formulation, which can be better utilized in organ transplants, anti-aging, stress management, autoimmune disorders, and inflammatory disorders, etc. to modulate the immune system by improving overall health.

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Inhibition ofS-Adenosyl-l-homocysteine Hydrolase Induces Immunosuppression

Cited by 58 publications

References 29 publications

3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling

3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling

Impact of Biofield Energy Treated Herbomineral Formulation (The Trivedi Effect<sup>®</sup>) on Mouse Dendritic and Splenocyte Cells for Modulation of Pro-inflammatory Cytokines

Evaluation of Pro-Inflammatory Cytokines Expression in Mouse Splenocytes After Incubation with Biofield Treated Herbomineral Formulation: Effect of Biofield Energy Healing Treatment - The Trivedi Effect<sup>®</sup>

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Inhibition ofS-Adenosyl-l-homocysteine Hydrolase Induces Immunosuppression

Cited by 58 publications

References 29 publications

3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling

3-Deazaadenosine Prevents Smooth Muscle Cell Proliferation and Neointima Formation by Interfering With Ras Signaling

Impact of Biofield Energy Treated Herbomineral Formulation (The Trivedi Effect&lt;sup&gt;®&lt;/sup&gt;) on Mouse Dendritic and Splenocyte Cells for Modulation of Pro-inflammatory Cytokines

Evaluation of Pro-Inflammatory Cytokines Expression in Mouse Splenocytes After Incubation with Biofield Treated Herbomineral Formulation: Effect of Biofield Energy Healing Treatment - The Trivedi Effect&lt;sup&gt;®&lt;/sup&gt;

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Product

Resources

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Impact of Biofield Energy Treated Herbomineral Formulation (The Trivedi Effect<sup>®</sup>) on Mouse Dendritic and Splenocyte Cells for Modulation of Pro-inflammatory Cytokines

Evaluation of Pro-Inflammatory Cytokines Expression in Mouse Splenocytes After Incubation with Biofield Treated Herbomineral Formulation: Effect of Biofield Energy Healing Treatment - The Trivedi Effect<sup>®</sup>