Zyflamend

• How It Works

  Zyflamend has not been shown to treat cancer. Studies in humans are very limited.

  Zyflamend is an herbal supplement consisting of Holy basil, turmeric, ginger, green tea, rosemary, hu zhang, Chinese goldthread, barberry, oregano, and skullcap. Promoters of Zyflamend claim that it has anti-inflammatory and antiaging effects. In a few in lab studies, it has been shown to reduce inflammation and levels of certain enzymes that produce estrogen. It can also cause cell death. Results from a small study indicate it may help lower prostate-specific antigen (PSA), a marker of prostate cancer. More research is needed.

• Purported Uses
  • Cancer treatment
    A few lab studies show that Zyflamend can reduce the number of prostate cancer cells and also decrease some markers related to some types of breast cancer. Zyflamend did not cause serious adverse events in men with prostatic intraepithelial neoplasia and also decreased certain prostate disease-related markers. More research is needed.
  • Inflammation
    A few lab studies show that Zyflamend reduces inflammation but there are no data from clinical trials.
• Do Not Take If
  • You have hypersensitivity to any of the constituents.
  • You are taking chemotherapy drugs: Zyflamend may increase their effects.
  • You are taking prescription medications: There are many botanicals in Zyflamend, and therefore a greater chance for herb-drug interactions.
• Side Effects

  Bad taste in the mouth, heartburn, and diarrhea.

• Clinical Summary

  Zyflamend is a formulation containing 10 different herbs. It is marketed as a dietary supplement for healthy inflammation response and normal cardiovascular and joint function ⁽¹⁾.

  Preliminary studies suggest that the ingredients in Zyflamend have anti-inflammatory, antiangiogenic, and antiproliferative properties ^{(2) (12) (13) (14)}. Zyflamend inhibits the proliferation of oral squamous carcinoma ⁽³⁾, pancreatic cancer ⁽⁴⁾, and melanoma ⁽⁵⁾, and cisplatin-resistant bladder cancer cells ⁽¹⁵⁾.

  In an animal model, it inhibited the growth of both hormone-sensitive and hormone-insensitive prostate cancer, and reduced the expression of prostate specific antigen (PSA) ⁽⁶⁾. It can also suppress elevated levels of proinflammatory mediators and aromatase in obese models ⁽⁷⁾and significantly reduced adipose tissue in mice ⁽¹⁶⁾.

  In a phase I trial in men with prostatic intraepithelial neoplasia, Zyflamend did not cause any serious adverse events, and significant reductions in serum levels of C-reactive protein and nuclear factor-kappa B levels were observed ⁽⁸⁾. There have also been a few cases of clinical response to combination therapy that included a Zyflamend regimen in patients with castration-resistant prostate cancer ⁽¹⁷⁾. More studies are warranted to evaluate safety and effectiveness.

  Zyflamend may potentiate the cytotoxic effects of certain chemotherapeutic agents, including gemcitabine ⁽⁴⁾, taxol ⁽²⁾, doxorubicin ⁽²⁾, and bicalutamide ⁽⁹⁾.

• Purported Uses
  • Antiaging
  • Cancer treatment
  • Inflammation
• Mechanism of Action

  Ingredients in Zyflamend, including holy basil, turmeric, ginger, green tea, rosemary, hu zhang, Chinese gold thread, and Scutellaria, inhibit cyclooxygenase-2 (COX-2) activity and thereby reduce inflammation.

  In vitro studies show that Zyflamend inhibits inflammatory enzymes, decreases retinoblastoma (Rb) protein phosphorylation ⁽¹⁰⁾, and induces apoptosis in human prostate cancer cells ^{(2) (3) (4) (11)}. It also reduced androgen receptor signaling and enhanced bicalutamide-induced apoptosis ⁽⁹⁾. Other studies in prostate cancer cell lines suggest that Zyflamend inhibits class I and class II histone deacetylase expression, upregulates p21 expression ⁽¹³⁾, and regulates upstream kinases LKB1 and CaMKK2 via AMPK activation ⁽¹⁴⁾.

  In melanoma cells, Zyflamend induces autophagy and apoptosis sequentially by activating the intrinsic caspase cascade. Cell migration and COX-2 expression were also suppressed ⁽⁵⁾. It was also shown to inhibit NF-kappa B activation in myeloid leukemia, lung adenocarcinoma ⁽²⁾, pancreatic ⁽⁴⁾, and cisplatin-resistant bladder cancer cells ⁽¹⁵⁾. In leukoplakia and skin cell lines, both Zyflamend and carnosol, an antioxidant phenolic constituent, inhibited mutagenesis via Hsp90 ATPase inhibition, which led to reduced aryl hydrocarbon receptor levels and CYP1A1 and CYP1B1 suppression ⁽¹²⁾.

  Both a cellular model of obesity-related inflammation and an obese animal model indicate that Zyflamend blocks proinflammatory mediators and aromatase induction as well as Akt and NF-kB activation. Increased aromatase mRNA levels and mammary gland activity were also partially inhibited ⁽⁷⁾. Reduction of adiposity was attributed to AMPK activation ⁽¹⁶⁾.

  In a murine xenograft model of prostate cancer, Zyflamend inhibited androgen-dependent tumor growth and histone deacetylase-5, biomarkers linked to prostate cancer progression ⁽⁶⁾. It also reduced the number of inflammatory cells, hyperplasia and dysplasia, and tumor incidence and number, and inhibited cell proliferation in an animal model of oral squamous cell carcinoma ⁽³⁾.

• Contraindications

  Hypersensitivity to any of the constituents

• Adverse Reactions

  Bad taste in the mouth, heartburn, and diarrhea ⁽⁸⁾

• Herb-Drug Interactions

  • Chemotherapy drugs (gemcitabine, taxol, doxorubicin, bicalutamide): Zyflamend may have additive effects ^{(2) (4) (9)}.
  • Other prescriptions drugs: Because Zyflamend contains many herbal constituents, it can potentially interact with prescription drugs.

• References

  1. New Chapter Inc. Zyflamend – Herbals from New Chapter. Available at: http://www.newchapter.com/zyflamend. 2012. Accessed October 29, 2013.

  2. Sandur SK, Ahn KS, Ichikawa H, et al. 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. Nutr Cancer. 2007;57(1):78-87.

  3. Yang P, Sun Z, Chan D, et al. Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model. Carcinogenesis. Nov 2008;29(11):2182-2189.

  4. Kunnumakkara AB, Sung B, Ravindran J, et al. Zyflamend suppresses growth and sensitizes human pancreatic tumors to gemcitabine in an orthotopic mouse model through modulation of multiple targets. Int J Cancer. Aug 1 2012;131(3):E292-303.

  5. Ekmekcioglu S, Chattopadhyay C, Akar U, et al. Zyflamend mediates therapeutic induction of autophagy to apoptosis in melanoma cells. Nutr Cancer. 2011;63(6):940-949.

  6. Huang EC, McEntee MF, Whelan J. Zyflamend, a combination of herbal extracts, attenuates tumor growth in murine xenograft models of prostate cancer. Nutr Cancer. 2012;64(5):749-760.

  7. Subbaramaiah K, Sue E, Bhardwaj P, et al. Dietary polyphenols suppress elevated levels of proinflammatory mediators and aromatase in the mammary gland of obese mice. Cancer Prev Res (Phila). Sep 2013;6(9):886-897.

  8. Capodice JL, Gorroochurn P, Cammack AS, et al. Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial. J Soc Integr Oncol. Spring 2009;7(2):43-51.

  9. Yan J, Xie B, Capodice JL, et al. Zyflamend inhibits the expression and function of androgen receptor and acts synergistically with bicalutimide to inhibit prostate cancer cell growth. Prostate. Feb 2012;72(3):244-252.

  10. Yang P, Cartwright C, Chan D, et al. Zyflamend-mediated inhibition of human prostate cancer PC3 cell proliferation: effects on 12-LOX and Rb protein phosphorylation. Cancer Biol Ther. Feb 2007;6(2):228-236.

  11. Bemis DL, Capodice JL, Anastasiadis AG, et al. Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. Nutr Cancer. 2005;52(2):202-212.

  12. Mohebati A, Guttenplan JB, Kochhar A, et al. Carnosol, a constituent of Zyflamend, inhibits aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and mutagenesis. Cancer Prev Res (Phila). Apr 2012;5(4):593-602.

  13. Huang EC, Zhao Y, Chen G, et al. Zyflamend, a polyherbal mixture, down regulates class I and class II histone deacetylases and increases p21 levels in castrate-resistant prostate cancer cells. BMC Complement Altern Med. Feb 21 2014;14:68.

  14. MacDonald AF, Bettaieb A, Donohoe DR, et al. Concurrent regulation of LKB1 and CaMKK2 in the activation of AMPK in castrate-resistant prostate cancer by a well-defined polyherbal mixture with anticancer properties. BMC Complement Altern Med. Jun 18 2018;18(1):188.

  15. Xue Y, Yang L, Li J, et al. Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NFkappaB signaling pathway. Onco Targets Ther. 2018;11:4413-4429.

  16. Tague ED, Bourdon AK, MacDonald A, et al. Metabolomics Approach in the Study of the Well-Defined Polyherbal Preparation Zyflamend. J Med Food. Mar 2018;21(3):306-316.

  17. Bilen MA, Lin SH, Tang DG, et al. Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series. Case Rep Oncol Med. 2015;2015:471861.