Honokiol: Phytoestrogen Concerns

Where are you seeing it is considered a phytoestrogen? Many people completely mischaracterize what that actually means. Also, many people completely misunderstand the role both testosterone and estrogen play in BOTH men and women. I have had women tell me that they think things that increase testosterone are bad for women, just because they associate testosterone with men. The same goes for men and estrogen. To start, honokiol does NOT raise estrogen levels. It also does not result in effects similar to elevated estrogen. In fact, higher estrogen activity is associated with breast cancer, but honokiol actually fights breast cancer. So if it did have any affinities for the estrogen receptor, which is not conclusive yet, then it would be an antagonist or allosteric modulator.

Honokiol: An anticancer lignan

Honokiol scavenges superoxide as well as peroxyl radicals. This antioxidative property is responsible for antitumor response, as NF-κβ(nuclear factor kappaB) is stimulated by reactive oxygen species (ROS)[26]. NF-κβactivation creates a gamut of inflammatory components such as MMP-9, TNF-α, IL-8, ICAM-1 and MCP-1, among others[27, 28]. Metastatic role of the proteolytic enzymes MMP-9 and the proangiogenic factors IL-8 is well-validated [29]. So, carcinogenesis can be prevented in its absence. Honokiol suppressed NF-kB activation, by inhibiting the nuclear translocation and phosphorylation of p65 sub-unit. Also, it enhanced TNF-α-induced apoptotic cell death [27].Honokiol can reduce hypoxia-inducible factor-1α(HIF-1α) protein level and suppressing the hypoxia-related signaling pathway. HIF-1αis a key mediator of for the adaptation of cancer cells to low oxygen levels [30].As hypoxia promotes tumor, anticancer role of honokiol is understandable [31].

Honokiol significantly inhibited the calcineurin inhibitor cyclos-porine A-induced survival of renal cancer cells, by downregulating VEGF (vascular endothelial growth facto) and HO-1 (heme oxygenase-1) [ 32]. VEGF is an angiogenic factor and is up-regulated in tumors for mediating autocrine signaling pathways [33]. Receptor tyrosine kinasec-Met can promote cancer growth by inducing differentiation, proliferation, cell cycle, motility, and apoptosis, through the regulation ofHO-1 [34]. HGF (hepatocyte growth factor) is a ligand for c-Met, and excess c-Met expression in gastric cancer and lung cancer has been observed [35, 36]. So, honokiol is likely to be interfering with the kinase function. Honokiol’s role in inhibition of STAT3 (signal transducers and activators of transcription 3) activation in hepatocellular carcinoma(HCC) cells by the interference of upstream kinases such as c-Src, Janus-activated kinase 1 (JAK 1), and Janus-activated kinase 2 (JAK 2) is well-known [37]. Constitutively activated STAT3 levels are correlated with cellular transformation and aggressive cancer forms [38]. c-Srckinase over-expression transforms cell phenotypes imparting ancho-rage-independent growth and tumorigenicity [39]. The interaction of honokiol with another oncogenic transcription factor FOXM1 and subsequent inhibition has been explained to result in anticancer effect[40]. The induction and over expression of FoxM1 by Ras, results in malignancies [41].

Honokiol is capable of suppressing high-glucose-induced inflammatory responses of human renal mesangial cells [42]. The ab-normal glucose metabolism, hyperglycemia, and cancer link has been proven [43]. Persistent hyperglycemic condition fuels NF-κβactivation which leads to the expression of a number of cytokines, chemokines and cell adhesion molecules [44]

So you can see its effects are very complex. It is not mimicking estrogen. If anything, it is blocking it somewhat.