From ancient remedies to skincare innovation

Historically, traditional Chinese medicine practitioners have catalogued herbs, drawing on wisdom from centuries-old texts to concoct remedies aimed at a range of ailments. Now, scientists are sometimes validating and optimizing these treatments for safety and efficacy, while also working to identify potential active ingredients to extract and apply more efficiently.

Guyu, a skincare company based in Guangzhou, China, has embraced this practice and is using synthetic biology and bioengineering to reframe the relationship between cosmetics and natural ingredients.

“Guyu stands out as a skincare enterprise in China with in-house production capabilities for both raw materials and finished products. This ensures that our extensive R&D effort is reflected in our offerings,” says Anzhang Li, chief scientist at Guyu’s Qingnang R&D Centre.

Li leads a team of more than 100 scientists spanning disciplines including chemistry, molecular biology, bioengineering, and synthetic biology, as well as traditional Chinese medicine. The team applies diverse expertise to ingredient innovation, studies on molecular and cellular mechanisms, formula development, manufacturing process optimization, and rigorous safety and efficacy assessments. Their aim is to uncover useful components from plant extracts for use in skincare products.

Towards purification

One challenge the team faces is determining potential active ingredients from within vast array of herbs. They decided to focus on compounds with well-defined chemical structures and also work to rule out unsuitable compounds that are unstable at high temperatures or have unpleasant odours.

In recent years one compound they have focused on is glabridin, found in the root of the liquorice plant. Glabridin is known for its anti-inflammatory and anti-oxidative properties, and can inhibit tyrosinase — an important enzyme which stimulates melanin production¹. Because of these properties, the compound could have benefits in the skin — but making full use of it has proved challenging, due to the complexity of its extraction process.

Glabridin is one of nearly 200 flavonoids — a group of natural substances which give plants their vibrant colours — contained in the liquorice root. “Because they all have similar structural properties, it is hard to extract and purify, a reason skincare products have commonly used glabridin at only 40% purity,” says Li.

To ensure supply, Guyu built a liquorice cultivation facility in Xinjiang Province, China, and have since focused on addressing the issue of low yield during extraction.

To extract glabridin from liquorice roots, Li and his team applied melt-crystallization by heating the mixture until it melts, and then cooling it. This technique exploits the varying temperatures at which substances crystallize, allowing glabridin to be separated from impurities as it solidifies at its unique crystallization point.

The team is also working on another technique to extract pure glabridin: ‘CO₂ supercritical extraction’, which applies high pressure and temperatures to carbon dioxide to create a supercritical state of the gas, combining the properties of both gas and liquid.

In this state, CO₂ can deeply penetrate freeze-dried liquorice root, dissolving flavonoids for easy separation and purification. “Ultimately we have refined these techniques so it is possible to achieve glabridin purity of up to 99%,” says Li.

But extraction is not the end of the story. Glabridin dissolves poorly in water and barely in oil, which makes it difficult to incorporate it into skincare products.

Experiments have shown that cyclodextrin, a ring-shaped molecule designed to encapsulate substances and form complexes for skin delivery, cannot ensure the long-term stability of glabridin. The other contender, DMSO, a powerful solvent known for its ability to dissolve a wide range of materials, introduces risks of cellular toxicity when used for glabridin encapsulation.

Instead, the team developed a ‘nanoscale phospholipid bilayer encapsulation technology’ that researchers hope significantly enhances the bioavailability of glabridin in the skin.

The technology creates 28-nanometre-sized vesicles, with layers similar to cell membranes that swaddle the glabridin for delivery. Using these techniques, Guyu has developed a proprietary compound called NovaAuroGlab.

“We have also applied the encapsulation technique across a range of Guyu’s other skincare ingredients,” says Li.

Synthetic biology

Extracting active components from plants is not always feasible due to low concentrations, scarcity of source plants, and environmental concerns about overexploitation. Guyu is using synthetic biology to overcome some of these challenges and create targeted solutions.

“Bioengineering advancements have revolutionized our approach to natural ingredients like ginseng,” says Li.

Ginsenosides, active compounds within ginseng, come in a variety of forms, and the researchers believe some of these could have potential benefits ranging from reducing inflammation to reducing the visible effects of ageing.

Within ginseng plants the team turned to enzymatic engineering — this allowed them to use enzymes to chemically modify ginsenosides, making them more potent. “Our technique taps into the natural potency of ginsenosides, significantly boosting their effectiveness and advantages in a way that mimics ageing in mature ginseng plants, but is much faster and more controlled,” Li adds.

Synthetic biology enables the production of compounds not naturally synthesized by organisms through bioengineering tools, and has emerged as an increasingly popular alternative to direct extraction due to its superior yield.

Using this method, Guyu’s researchers have also biosynthesized lycopene, a bright red compound in tomatoes, recognized for anti-oxidant, anti-cancer and anti-inflammatory properties². This groundwork has paved the way for the biosynthesis of other active compounds, including ectoine, a natural compound with potential uses in the skin, that is found in salt-tolerant bacteria. Using a unique strain of bacteria isolated from a lake in Qinghai province, the team has been able to boost yields of ectoine significantly.

Uniting traditions

Li’s team is also researching the efficacy of plant extracts in skincare through strategic collaborations. The Guyu team has collaborated with various institutions, including the Shanghai Institute of Organic Chemistry, the Changchun Institute of Applied Chemistry — both of which are part of the Chinese Academy of Sciences — and the China Pharmaceutical University.

These collaborations are aimed at understanding the molecular mechanisms by which herbal skincare products work. Collaborations with the South China University of Technology and Beijing Technology and Business University, on the other hand, cover a broader range of research topics. The researchers are looking into skin pigmentation disorders, plant extract development, formulation technology, peptide synthetic biotechnology, traditional Chinese medicine theory, and skin-type studies in various populations.

At the same time, Guyu is developing a comprehensive database of Chinese herbal extracts that could have potential applications in cosmetics. “Our goal is to make this old treasure easily accessible for modern, scientific skincare applications,” Li says.