As I mentioned last month,Pueraria mirificais amazingly beneficial in so many ways. In October 2016, we discussed the clinical studies with Dr. Christian Northrup showing thatP. mirificais not only better than the leading pharmaceutical for treating menopausal symptoms, but it is also safer. In November 2016, we discussed with Dr. Margaret Ritchie how P. mirificareduces the risk of cancer and examined the epidemiological and mechanistic evidence. Last month, we discussed howP. mirificahelps build stronger, healthier bones with Professor Suchinda Malaivijitnond, Ph.D. More people could be helped by this herb if only they knew more about it. This is why I wrote “Pueraria mirifica: Chemistry and Biology” in 2017 (Nutritional Research Press ISBN: 978-0-692-11135-2).

Now, let’s continue our discussion with Professor Suchinda Malaivijitnond, Ph.D. and discuss even another important health benefit ofP. mirificafor menopausal women:P. mirificaimproves mental function, too.

Dr. Suchinda Malaivijitnond is a Professor at the Department of Biology, Faculty of Science at Chulalongkorn University in Bangkok, Thailand. Her research focus is about the effects of phytoestrogens from endemic Thai plantPueraria mirificaon reproductive organs, bone (osteoporosis) and brain (Alzheimer’s disease) tested in vitro and in laboratory animals (rodents and monkeys). Based on the vast knowledge on non-human primates gained both from the laboratory and field studies, she has established the National Primate Research Center of Thailand.

Passwater:Professor Suchinda, last month we discussed your research with P. mirificaand bone health in post-menopause. However, you also research the relationship between P. mirifica and brain health. You made the relationship to bone health clear to us, but just what could the relationship be between P. mirificaand brain health? Your 2016 publication showed that P. mirifica had "Neurotherapeutic Effects in Early- and Late-Stage Cognitive Impairment” (1). How can this be? What mechanism could be involved with neurons?

Suchinda:It may surprise some that both men and women have estrogen receptors in their brains. Reduced estrogen levels due to menopause in women and normal aging in men have been associated with memory decline. Estrogen receptors are found in the hippocampus, cortex, and striatum—regions of the brain that are important for mental processes related to perception, memory, judgment, and reasoning. It is no wonder then that estrogens have effects on brain structure and function. Estrogens are recognized as important regulators of neuronal function, including neuronal development, proliferation, and survival.

Estrogens exert a profound influence upon multiple brain circuits. These effects are mediated mostly by estrogen receptor alpha (ER-α), but estrogen receptor beta (ER-β) controls several important brain functions and helps modulate ER-α. ER-α and ER-β are usually tightly interrelated in the estrogen-dependent control of a particular brain function, and the roles of ER-α and ER-β within a particular neural network may be synergistic or antagonistic.

Postmenopausal women are in an estrogen-deprived state and are at risk of neurodegenerative disease with a decline in cognitive function. Menopause shifts the balance of the hypothalamic-pituitary-ovarian axis. This shift is due to the loss of feedback by estrogens resulting in a three- to fourfold increase in the concentration of blood levels of luteinizing hormone (LH). LH is produced in the pituitary of both men and women, and it has varying functions in each. The brain has LH receptors with the highest density being found within the hippocampus, the region connected specifically with learning and memory. There is a relationship between high plasma LH levels and impaired cognitive performance. Reports suggest that the LH peak following menopause might be a critical factor in brain dysfunction such as foggy thinking and memory decline.P. mirifica, with its SERM-estrogenic activity that has been shown to boost LH synthesis and secretion, would be expected to provide a safe and effective therapeutic alternative for neuronal dysfunction in postmenopausal women.

Passwater:When did you start studying brain health andP. mirifica?

Suchinda:Our study aboutP. mirificaand brain just began a few years ago, but based on our preliminary results, we found thatP. mirificahelps to battle with neurodegeneration, either the prevention or therapeutic approaches, but the prevention gives better results. Because the hallmark of neurodegenerative disease is the deposition of amyloid beta between the neurons and hyperphosphorylated Tau protein inside the cells, these disrupt the communication between neurons and leads to neuronal cell death. We found that P. mirificaextract can reduce the expression of genes associated with amyloid beta production and Tau hyperphosphorylation; we then assume thatP. mirificacan be used for neurodegenerative disease. Although at this step we determined only at the mRNA levels, we could see the improvement of cognition in rats fed withP. mirificaextract. Thus, our next goal is the use ofP. mirificafor neurodegeneration for humans.

We determined the neurotherapeutic effects ofP. mirificacompared to the estrogen estradiol in early- and late-stage cognitive impaired rats. A spatial memory test utilizing the Morris water maze test was used to measure cognition. As expected, the early and late stages of cognitive impairment showed different degrees of memory loss, with decline being greater in the later stages. Treatment withP. mirificawas effective at restoring memory in both stages, but it was more effective in the early stage.

Passwater:Very interesting. It is the results that count, but did you have any biological confirmation?

Suchinda:Follow-up with measurement of mRNA (a messenger molecule involved in the transmission of genetic information) also confirmed that the improvements in memory were accompanied by a reduction in LH and expression of the LH genes, as expected. The improvement in the impaired cognition is likely to occur via other pathways, such as antioxidants as well.

There are at least 17 phytoestrogens inP. mirifica.Puerarin is an isoflavone found inP. mirificaand several other plants of the Pueraria species. It is an antioxidant and has been studied in China in terms of protecting brain cells and preventing cognitive impairment. Puerarin works via a different biochemical pathway than miroestrol and deoxymiroestrol, but it does have a protective effect.P. mirifica,the only plant to contain miroestrol and deoxymiroestrol, is much more effective because it has a unique synergistic combination of phytoestrogens.

Passwater: Did you have any additional findings pertaining to Alzheimer’s disease?

Suchinda:Yes. We found thatP. mirificadecreased ER-α mRNA levels. Since studies have indicated that the ER-α mediates the effects of estrogenic chemicals on neuroprotection during the process of Alzheimer’s disease, we wanted to examine this further. The cause of Alzheimer’s disease is not proven, but leading theories center on extracellular deposits of beta amyloid (which consists of 36 to 43 amino acids), defects in the tau proteins, or both. The beta-amyloid peptides result from the amyloid precursor protein, also known as APP. Tau proteins are proteins that stabilize microtubules in the nerve cells.

We found thatP. mirificaexerts positive anti-Alzheimer’s disease effects on hippocampal H19-7 neuronal cell lines and in laboratory rats whose ovaries have been removed. In laboratory rats,P. mirificashowed either neuroprotective or neurotherapeutic action by decreasing expression of genes associated with amyloid plaques (APP, Adam10, and Bace1) and neurofibrillary tangles (tau-3 and tau-4) at mRNA and protein levels, and cognitive impairment. It significantly decreased the levels of APP and Adam10 mRNA. The reduction in APP means that less amyloid precursor protein is produced, and the reduction in Adam10 means that less beta amyloid is produced. Our results also indicate thatP. mirificacould be a better neurotherapeutic agent for recovering from late-stage cognitive impairment via the amyloid beta pathway than using synthetic estrogens.

As pointed out before, hyperphosphorylation causes tau tangles. Eventually, these proteins begin to stick together in such a way as to impair brain cell function. In our study, theP. mirificaphytoestrogen puerarin decreased the tau-4 mRNA level, implying that fewer neurofibrillary tangles will be produced. This is because tau-4 protein has a higher possibility to be phosphorylated.

As mentioned earlier, both men and women have estrogen receptors in their hippocampus, cortex, and striatum. Having seen the promising effect ofP. mirificaon the brains of female rats, we are now testing the effect ofP. mirificain male rats.

Passwater:Thank you Professor Suchinda for discussing your research with us. It will help many of our readers.

Reference: 1. Malaivijitnond, S., et al. Neurotherapeutic Effects in Early- and Late-Stage Cognitive Impairment. Phytother Res. 2016 Feb 25. doi: 10.1002/ptr.5595