Carrier-Free Supramolecular Hydrogel Self-Assembled from Triterpenoid Saponins from Traditional Chinese Medicine: Preparation, Characterization, and Evaluation of Anti-Inflammatory Activity

Inflammation is the body's natural immune response to invasion by foreign pathogens and is closely linked to many diseases. Chronic inflammation, if not properly controlled, can pose serious health risks and even threaten life. Currently, the main anti-inflammatory drugs are classified into steroidal and non-steroidal anti-inflammatory drugs, but both have significant side effects that limit their clinical applications. α-Hederin, a pentacyclic triterpenoid saponin, is derived from various plants, including <i>Pulsatilla chinensis</i>, <i>Hedera helix</i>, and <i>Nigella sativa</i>. It has been reported that α-hederin can be used to treat both acute and chronic inflammatory diseases. However, it has poor water solubility and low bioavailability. This study shows that α-hederin can directly self-assemble into a hydrogel through hydrogen bonds and van der Waals forces, called He-Gel. The mechanical properties of He-Gel were further characterized using rheological and microrheological methods. Its self-assembly mechanism was comprehensively elucidated through a combination of spectroscopic analyses and computational chemistry. Furthermore, in vitro experiments showed that He-Gel exhibits lower cytotoxicity and more excellent anti-inflammatory activity compared to free α-hederin. In conclusion, this research provides a solution for the further development of α-hederin. Unlike conventional approaches that rely on polymers as drug carriers, this preparation method is both green and economical. More importantly, it highlights that direct self-assembly of natural small molecules represents a promising strategy for anti-inflammatory therapy.