Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Zyflamend, a polyherbal preparation, was designed based on constituents that exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and apoptotic activities through a mechanism that is not well defined. Because the nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion, and metastasis of tumor cells, we postulated that Zyflamend modulates the activity of NF-kappa B. To test this hypothesis, we examined the effect of this preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that Zyflamend inhibited receptor activator of NF-kappa B ligand-induced osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B activation induced by both TNF and cigarette smoke condensate. The expression of NF-kappa B-regulated gene products involved in antiapoptosis (inhibitor-of-apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like interleukin-1betaconverting enzyme/caspase-8 inhibitory protein, TNF receptor-associated factor-1, and survivin) and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2, intercellular adhesion molecule, and matrix metalloproteinase-9) was also down-regulated by Zyflamend. This correlated with potentiation of cell death induced by TNF and chemotherapeutic agents. Overall, our results indicate that Zyflamend suppresses osteoclastogenesis, inhibits invasion, and potentiates cytotoxicity through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
Rafailov S, Cammack S, Stone BA, Katz AE. The role of Zyflamend, an herbal anti-inflammatory, as a potential chemopreventive agent against prostate cancer: a case report. Integr Cancer Ther. 2007;6(1):74-76.
Chronic or recurrent inflammation is thought to be the major predisposing factor for prostate cancer. The authors discuss a case report involving Zyflamend(r) (New Chapter Inc., Brattleboro, Vermont; an herbal anti-inflammatory formulation composed of extracts of rosemary [Rosmainus officinalis], turmeric [Curcuma longa], ginger [Zingiber officinale], holy basil [Ocimum tenuiflorum], green tea [Camellia sinensis], Japanese knotwood [a.k.a. hu zhang; Polygonum cuspidatum], coptis [a.k.a. Chinese goldthread; Coptis teetoides], barberry [Berberis vulgaris], oregano [Origanum vulgare], and Chinese or Baikal skullcap [Scutellaria baicalensis]) and its ability to prevent prostate cancer by inhibiting cylcooxygenase (COX)-2 activity in a patient with high-grade prostate intraepithelial neoplasia (PIN). Increasing evidence suggests that COX-2 plays a role in human carcinogenesis and is overexpressed in prostate cancer tissue.
A 70-year old African American man with no significant past medical history presented with an elevated prostate-specific antigen (PSA) level of 9.7 ng/mL. A biopsy in May 2004 revealed high-grade PIN in 1 of 12 cores. The patient agreed to participate in a phase 1 clinical trial at Columbia University Medical Center using Zyflamend.
As a study participant, this patient took Zyflamend orally 3 times a day with each meal and returned to the clinic every 3 months for routine blood tests. At 6, 12, and 18 months, he underwent 12-core prostate biopsies. At baseline, and at 6, 12, and 18 months, the patient had an electrocardiogram.
Throughout the study, the patient's mean PSA level was 8.93 ng/mL (range, 8.0-10.2 ng/mL). Of the three biopsies, the one at 6 months revealed benign prostate hyperplasia (BPH) alone. The 12-month biopsy showed PIN in 1 of 12 cores, and the final 18-month biopsy was negative for cancer and PIN. At the end of the trial in March 2006, this patient was free of cancer and high-grade PIN. The authors observed decreased COX-2 levels in this patient.
The authors report that although Zyflamend did not appear to affect the measured PSA level, it possibly prevented an increase in the PSA level.
The authors caution that the absence of high-grade PIN on the biopsy may have been a result of a sample error. Because of a small amount of high-grade PIN discovered in one of the 12 cores on the initial biopsy, they say, it is possible that it was narrowly confined to a region that was missed in the biopsy. Results from the other study participants will help determine if Zyflamend warrants further assessment as a prostate cancer chemopreventive agent in a double-blind, randomized, placebo-controlled clinical trial.
Zyflamend=antiangiogenic, antiinflammatory, antioxidant.
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