“Hidden world” of phytonutrients: Brightseed unlocks plant molecules targeting liver and metabolic health

06 Jan 2021 --- Brightseed has identified plant molecules for clearing liver fat and promoting metabolic health. This research is conducted through Forager, the company’s artificial intelligence (AI) platform that maps phytonutrients and their impact on human health.

The company spotlights the potential of its technology to uncover a myriad of health-activating properties in plant compounds for future F&B and nutraceutical product development.

Forager is designed to help F&B manufacturers create “meaningfully differentiated” products produced from the “hero sources,” of specific plants.

To date, Forager has pinpointed approximately 700,000 compounds in the edible and medicinal plant kingdom for their health properties, and is on track to surpass 10 million by 2025.

“These preclinical findings are a key milestone that further validates the thesis behind Brightseed: nature is inherently powerful,” Dr. Jim Flatt, CEO of Brightseed, tells NutritionInsight.

“Two-thirds of small-molecule medicines were originally derived from natural compounds found in plants, bacteria and fungi, but 99 percent of these compounds remain undiscovered,” he continues.

“Our Forager AI is solving this ‘dark matter’ problem, illuminating the full spectrum of health benefits of phytonutrients, naturally-derived compounds hidden in the edible and medicinal plant kingdom.”

Clearing liver fat with powerful small molecules
Phytonutrients are plant compounds that can provide significant health benefits for humans, yet currently, less than 1 percent of these compounds are known to science.

Using a computational approach with data from Brightseed’s plant compound library, Forager identified two natural compounds with promising bioactive function, N-trans caffeoyltyramine (NTC) and N-trans-feruloyltyramine (NTF).

Forager is designed to help F&B manufacturers create “meaningfully differentiated” products produced from the health-activating properties, called “hero sources,” of specific plants.Researchers determined that these compounds acted through a novel biological mechanism governing the accumulation and clearance of liver fat. 

The activities of these small molecules were confirmed using a cell-based human insulin promoter activation assay. Notably, Forager found NTC and NTF in over 80 common edible plant sources.

In preclinical studies, NTC and NTF acted as potent HNF4a activators, promoting fat clearance from the steatotic livers of mice fed a high fat diet by inducing lipophagy. HNF4a is a central metabolic regulator that is impaired by elevated levels of fat in the bloodstream resulting from chronic overeating.

Administered in proper doses, NTC and NTF restored proper function of this central metabolic regulator, including maintaining healthy lipid and sugar levels in the bloodstream to normalize organ function. 

On the basis of their potent in vivo effects and excellent safety profile, these new agonists identified by Forager appear to be strong candidates for nutraceuticals and a starting point for therapeutics that can help maintain liver health and a healthy metabolism.

“The potent activity of these natural compounds on the central metabolic regulator has never been observed in scientific literature,” says Dr. Carol Lynn Berseth, senior vice president of Medical and Scientific Affairs at Brightseed.

“In addition, the clearance of fat cells from the liver is a hugely promising action, even in preclinical stages. Brightseed enables health and wellness brands to identify new natural solutions much more efficiently.

Food is medicine
Forager is designed to help F&B manufacturers create “meaningfully-differentiated” products produced from the health-activating properties, called “hero sources,” of specific plants.

“While many brands are more focused on ‘taking bad out’ (sugar, fat, salt and synthetics) versus ‘keeping good in’ and not optimizing for the active compounds that really support health, an increasing number of consumers are seeking functional foods and beverages that promote good health,” highlights Dr. Flatt.

“Phytonutrients are hidden in plain sight across agricultural supply chains, in pantries and medicine cabinets, and in the parts of plants that are wasted or go unused, providing ample opportunity for new product concepts.”

 Brightseed previously analyzed Danone’s raw soy to pinpoint newfound health benefits previously unlinked to the crop.Last June, Brightseed partnered with Danone to identify potential molecular connections between certain compounds present in Danone’s raw soy and newfound health benefits previously unlinked to the crop.

Meanwhile, Forager will be used by Pharmavite to similarly identify undiscovered plant phytonutrients to be integrated into Pharmavite’s portfolio of brands and supplements, including Nature Made.

“Similar to what we’re doing with Pharmavite, Forager can start with a specific health target and biological pathway we are seeking to impact, like sleep, and identify what phytonutrients exist across the plant supply chain that could have a measurable health benefit for that target,” Dr. Flatt explains. 

Nutraceuticals development for a healthy liver
The liver is the body’s primary metabolic organ and a healthy liver helps avoid metabolic conditions such as type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD).

NAFLD is a complex metabolic disorder that causes fat buildup in the liver, which impacts approximately one quarter of adults in the US. 

According to Brightseed, “phytonutrients are hidden in plain” sight across agricultural supply chains.Although there are many risk factors for developing NAFLD, the disease is closely linked to obesity, which afflicts more than 40 percent of the US adult population. There are no approved therapeutics to treat this major health condition. 

“We founded Brightseed with the thesis that the natural plant world is an incredibly rich and uncharted source of powerful small molecules for health,” says Dr. Lee Chae, Brightseed’s co-founder and CTO. 

“With AI and machine learning, we can now navigate this underexplored world at a pace, scale and level of accuracy that were previously unattainable. These preclinical findings provide compelling data for a natural solution that activates a specific human biological target to address an emerging global health crisis.”  

These findings could have profound implications for more than two billion people worldwide who are at elevated risk of chronic metabolic diseases. Brightseed will identify the lead compound candidate to move forward to clinical trials in 2021.

By Benjamin Ferrer