Chinese Medical Journal article reviews classification, synthesis, and applications of ‘herbzymes’

Ever since Youyou Tu won the 2015 Nobel Prize in Physiology or Medicine for her discovery of anti-malarial compounds from an herbaceous plant Artemisia annua, there has been a remarkable increase in research efforts on traditional Chinese medicine (TCM). The integration of modern nanotechnology into TCM practices has contributed to deepening our practical understanding of Chinese medicines and the development of nanomedicines.

Nanomedicines developed from Chinese herbs retain the characteristic pharmacological properties of the herb while also exhibiting enzymatic activities typical of nanozymes. These have found applications across diverse fields like medical therapy, bio-imaging, food science, and environmental monitoring. Although the various applications and functionalities of nanozymes derived from Chinese herbs have been reported previously, their synthesis, classification, catalytic properties, potential applications, mechanisms of action, and pharmacological properties have not been carefully reviewed yet. With this in mind, Professor Mingzhen Zhang and Associate Professor Mingxin Zhang from Xi’an Jiaotong University and Xi’an Medical University led a team of researchers from China to review ‘herbzymes’, its synthesis methods, biomedical applications, and challenges. This review was published on May 05, 2025 in Volume 138 Issue 9 of the Chinese Medical Journal and was made available online on April 01, 2025.

The authors first describe the basic concepts and functionalities of nanozymes. “Nanozymes are a group of enzyme mimics that exhibit the distinctive characteristics and catalytic functions of nanomaterials. Nanozymes possess catalytic activities similar to various natural enzymes, such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), Glutathione peroxidase (GPx), oxidases (OXD), glucose OXD, proteases, esterases, and nucleases”, explains Prof. Zhang about the main catalytic functions of nanozymes. One of the first POD-like nanozymes to be discovered—Fe₃O₄ nanozymes—have been extensively used in tumor diagnosis and therapy. SOD-like nanozymes catalyze the conversion of superoxide anion into molecular O₂ and H₂O and with their better stability and cost-effectiveness are used to treat oxidative stress-related diseases like strokes or inflammatory bowel diseases. Similarly, CAT-like nanozymes are anti-oxidants that can treat hypoxia in tumors or inflammation, and can be used for sonodynamic therapy and radiotherapy. GPx—a protein enzyme involved in reducing H₂O₂ to H₂O—also protect cells from oxidative damage. Although research on GPx-like nanozymes are still growing, these also have potential applications in biomedical therapy. OXD-like nanozymes activity is exhibited by many inorganic materials and are widely applied in several industries.  Research on nanozymes have rapidly advanced in the past years, but they are primarily made of inorganic material, limiting their applicability and sustainability.

A new class of nanozymes made of organic materials have been introduced in past years. “Among them, a subset of nano-TCM synthesized from herbs has been found to exhibit enzyme-like catalytic activities. We therefore introduce the concept of ‘herbzymes’, which refers to nanozymes derived from TCM”, Dr. Zhang introduces ‘herbzymes’. These are three main types: herb carbon dot (CD) enzymes, polyphenol-metal nanozymes, and herb extract nanozymes. CDs are advanced zero-dimensional carbonaceous nanomaterials in a size range of 2–10 nm, and are derived from various sources like vegetables, fruits, food, and beverages. CDs extracted from TCMs have multiple biological activities like maintaining redox balance, bio-imaging, and disease treatments. CDs are typically synthesized using ‘bottom-up’ approaches which include hydrothermal processes, pyrolysis, microwave-assisted methods, etc., and exhibit multiple redox enzymatic activities like SOD, CAT, GPx, and OXD and are extracted from several herbs including garlic, ginger, and safflower. They are used in treating inflammatory diseases, food preservation, bacterial diseases, and tumors. Polyphenol-metal nanozymes are typically synthesized using a one-pot method where metal ions and polyphenolic compounds can spontaneously react in a solution. Extracted from polyphenol-rich TCMs like turmeric and rosemary plant, these help in treating acute kidney and lung injuries, ulcerative colitis and rheumatoid arthritis. Herb extract nanozymes are synthesized directly from TCMs by methods like boiling, steaming, baking etc., to reduce toxicity, side effects while improving their therapeutic abilities. Derived from several TCMs like Rhizoma polygonati and Goji, these exhibit proteolytic, phosphatase-like enzymatic activities.

There are several challenges to be addressed in the development of herbzymes for practical biomedical applications. These include optimization of their processing techniques that maximize pharmacological activities, identification of herbzymes’ catalytic sites and their exact mechanism of action, exploration of their catalytic functionalities beyond redox reactions, and focused research on their metabolism and distribution in the body to reduce toxicity. To this, Prof. Zhang adds, “The current literature and data on the classification and catalytic types of herbzymes is still limited. As the number of published studies increases, it will be necessary to establish a database for herbzymes based on existing TCM databases.”

Herbzymes present a unique therapeutic avenue for exploring TCMs and their clinical applications. As research continues to uncover their catalytic mechanisms and optimize synthesis strategies, herbzymes have the potential to significantly advance the modernization and global application of traditional Chinese medicine.

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Reference

DOI:  10.1097/CM9.0000000000003584