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ETHNOPHARMACOLOGICAL RELEVANCE Paeoniae Radix Alba (PRA, called baishao in China), the root of Paeonia lactiflora Pall., has shown a rich medicinal value for more than 2000 years. PRA is used in local medicine and traditional medicine for autoimmune diseases associated with inflammation. At present, total glucosides of paeony (TGP), the main active ingredient of PRA, has been developed into a preparation for the treatment of autoimmune diseases, as TGP exhibits the effect of regulating immunity, anti-inflammatory, and analgesic effects. AIM OF THE REVIEW TGP was developed and applied to inflammation-related autoimmune diseases in modern clinical practice. Based on its application in traditional prescriptions, this article reviews PRA's botany and phytochemistry (including its extraction process and quality control), and discusses the clinical application and pharmacological research of TGP as an anti-inflammatory drug from the perspective of ethnopharmacology. Additionally, we review modern pharmacological and molecular-target research on TGP and discuss the mechanisms of TGP in treating autoimmune diseases. Through a systematic literature review, we also highlight the clinical efficacy of TGP in the treatment of immune diseases, and provide a reference for the continued scientific development and quality control of TGP so that its wider application and clinical value can be fully realized. MATERIALS AND METHODS Literature search was conducted through the Web of Science, Baidu Scholar, ScienceDirect, PubMed, CNKI, and WanFang DATA using the keywords "Total glucosides of paeony", "Paeonia lactiflora Pall. ", "Paeonia veitchii Lynch", "Paeoniae Radix Alba or white peony", "Paeoniae Radix Rubra or red peony", "Paeoniflorin", "Albiflorin", "Autoimmune diseases", and their combinations. In addition, information was collected from relevant textbooks, reviews, and documents. RESULTS Approximately 15 compounds have been identified in TGP, of which paeoniflorin and albiflorin are the most common constituents. In recent years, studies have found that TGP and its main chemical components are effective in the treatment of autoimmune diseases, such as rheumatoid arthritis, psoriasis, oral lichen planus, and Sjogren's syndrome. TGP has a variety of pharmacological effects related to PRA traditional effects, including anti-organ-damage, anti-inflammatory, analgesic, antioxidant, cardiovascular, and nervous-system protection. Previously published reports on TGP treatment of autoimmune diseases have shown that TGP regulates intracellular pathways, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways. However, there is no standardized preparation method for TGP, and there is insufficient quality control of formulations. Many related pharmacological studies have not tested TGP components, and the validity of such pharmacological results requires further verification. CONCLUSIONS Modern pharmacological research on TGP is based on the traditional usage of PRA, and its folk medicinal value in the treatment of autoimmune diseases has now been verified. In particular, TGP has been developed into a formulation used clinically for the treatment of autoimmune diseases. The combination of TGP capsules and chemicals to treat autoimmune diseases has the effect of increasing efficacy and reducing toxicity. Based on further research on its preparation, quality control, and mechanisms of action, TGP is expected to eventually play a greater role in the treatment of autoimmune diseases.