Formulation Progress, Challenges, and Perspectives of Anti-Inflammatory Natural Products

Inflammation is a complex and highly regulated defensive response of the body to injury, infection, or abnormal stimuli (such as pathogens, toxins, and physical/chemical damage). Natural anti-inflammatory drugs hold significant potential in the pharmaceutical field due to their multi-target effects, high safety profiles, and low toxicity. For example, EGCG can inhibit the phosphorylation of p38 and JNK, thereby reducing the activation of the AP-1 transcription factor and subsequently downregulating the expression of inflammatory genes. Luteolin inhibits inflammasome assembly by blocking potassium ion efflux, suppressing mitochondrial reactive oxygen species generation, or directly binding to NLRP3. Over the past decade, extensive research has been conducted on their physicochemical properties and dosage forms, leading to the development of various natural anti-inflammatory drug formulations using both traditional and modern technologies. Furthermore, the combination of these natural anti-inflammatory agents with other drugs can further expand their therapeutic applications. Meanwhile, emerging technologies such as 3D printing and AI-assisted design have demonstrated significant potential for application in formulation development. Despite these advancements, the current research field still faces critical challenges: the use of toxic excipients in certain formulations poses biosafety risks (for example, glutaraldehyde offers advantages such as high cross-linking efficiency, strong cross-linking strength, and mature manufacturing processes, but it also exhibits high toxicity and biosafety deficiencies); and the translation of research findings on natural anti-inflammatory drugs into commercial products remains insufficient (due to challenges in large-scale production, storage difficulties, and regulatory standards). Through this review, we hope to draw more attention to the development potential of natural anti-inflammatory drugs and the aforementioned issues, as well as to offer some foresight for the exploration and development of other natural products.