A new two-phase study found that Mindrevive, a formulation of Japanese pagoda tree and sage extracts marketed by Monteloeder, exhibits protective effects on cognitive function. The study, published in Applied Sciences, spanned the process from laboratory analysis of various botanical compounds to assess their cognitive potential to the clinical study on a final selected composition.

A combination of sage (Salvia officinalis) and Japanese pagoda tree (Saphora japonica) emerged as the combination with the strongest potential, and was finally tested on a group of older adults to determine if supplementation could make a difference in measures of learning, memory, and execution.

Across a battery of in vitro, biomarker, and cognitive tests, the final formulation was associated with reduced oxidative stress, increased neuronal survival and regeneration, antioxidant activity, enhanced memory and learning measures, release of growth factors (NGF, BDNF, VEGF), and improved overall cognitive performance.

The study began with an in vitro analysis of water-ethanol extracts of bilberry, blueberry, bacopa, sage, saffron, rhodiola, ginkgo biloba, panax ginseng, gotu kola, and Japanese pagoda tree. Each extract was tested in human neural stem cell cultures exposed to oxidative stress, for potential to suppress reactive oxygen and reactive nitrogen species, to promote cell survival, and to stimulate neural cell growth factors.

The sage extract, standardized for rosmarinic acid, exhibited the most notable impact on oxidative stress and cell death. It also maintained brain-derived neurotrophic factor (BDNF), a protein involved in brain cell growth, memory, and cognitive function. Nerve growth factor (NGF) levels were also increased. Additionally, the production of vascular endothelial growth factor (VEGF) was significantly enhanced. VEGF plays a role in supporting healthy circulation, which contributes to oxygen and nutrient delivery to brain cells.

When the researchers added the Japanese pagoda extract, standardized to 95% rutin, the BDNF effect was significantly augmented. Rutin is an antioxidant which has previously been associated with reduced age-related neuronal degeneration. The rutin addition also reduced AChE (acetylcholinesterase) activity activity by more than 60%. High AChE activity impairs nerve signaling through the breakdown of acetylcholine, a neurotransmitter crucial for learning, memory, and muscle function.

“The nine botanicals selected for analysis are widely recognized for their antioxidant properties and role in supporting cognitive function, with extensive documentation in scientific research,” said Jonathan Jones, chief scientific officer at Monteloeder. “Some of these ingredients have been evaluated in clinical studies exploring cognitive health. Sage, in particular, has often been overlooked in discussions about cognitive support, yet it stood out in our screening trials. In fact, sage was the only extract to increase the expression of all analyzed factors associated with neuronal function and antioxidant defenses. When combined with rutin, we observed significant enhancements in the production of BDNF, a key molecule involved in brain signaling and cognitive processes. Specifically, it is the major growth factor implicated in memory processes and learning. Research suggests that maintaining optimal BDNF levels is important for overall brain health.”

Human Clinical Study

A subsequent randomized, double-blind, placebo-controlled clinical study tested the effects of the chosen composition on 121 healthy volunteers between the ages of 50 and 65 years old who reported suffering from mild cognitive impairment.

They were assigned to take either 250 mg of Mindrevive, 400 mg of Mindrevive, or a placebo every morning after breakfast over 3 months.

At six weeks, and again at 12 weeks, the participants were assessed through the MoCA (Montreal Cognitive Assessent) and ADAS-Cog (Alzheimer’s Disease Assessment Scale-Cognitive Subscale) questionnaires, which cover cognitive function, memory, language, attention, and problem-solving.

The group taking the low-dose supplement saw significant improvements in short-term memory recall by week 6, while the higher-dose group improved in both short-term memory recall and abstract reasoning, consistently outperforming the placebo group.

Both doses of the supplement were linked to significant cognitive improvements in the ADAS-Cog test compared to placebo after 12 weeks, with the rate and degree of improvement dose-dependent. Supplementation appeared to impact language skills at week 12 and motor skills by week 6 in the test battery. Within these two categories, there were significant improvements in measures of word recall, word recognition, and command performance across both doses compared to placebo.

“Cognitive function naturally changes with age,” said Mariana Ortega, science marketing manager of Suannutra, parent company of Monteloeder. “Mindrevive is formulated with clinically studied ingredients to help maintain cognitive performance and support brain health. This is especially relevant for older adults who are proactively looking for natural solutions to preserve mental sharpness and overall well-being.”