The Paeoniaceae family contains only the Paeonia genus and is considered the major group of flowering plants. Several traditional and pharmacological applications of Paeoniaceae herbs have been described. The current paper aimed to determine the pharmacological activities of the most prevalent herbs from the genus Paeonia by focusing on the underlying mechanism of action and signaling pathways to provide insight for further in-depth research on the medicinal resources of Paeonia. The "Paeoniaceae" keyword was searched from 1st January 1995 to 15th May 2024 through the PubMed and Scopus databases. Only papers related to pharmacology, pharmaceutics, and toxicology were extracted. The possible pharmacological activity of the Paeonia plants underlying their mechanism of action and signaling pathways was subsequently discussed. Following our venture, only 15 Paeonia herbs were adequately evaluated for their pharmacological applications. Paeonia lactiflora Pall., Paeonia suffruticosa Andrews, and Paeonia emodi Royle are among the most prevalent Paeonia plants that have attracted increased amounts of attention in modern pharmacological studies. Paeonia herbs possess various pharmacological applications, such as anti-inflammatory, anti-allergic, anticancer, antimicrobial, cardiovascular protective, cosmetic and skincare, radical scavenging, hepatoprotective and anti-ulcerative, anti-diabetic, musculoskeletal, and neuroprotective effects, and can be used as alternative therapies under critical medical conditions. Among the applications of Paeonia herbs, anti-inflammatory and antioxidant activities are critical, as most of the other pharmacological effects are attributed to them. In other words, nuclear factor (NF)-κB and nuclear factor erythroid 2-related factor 2 (Nrf2) can be considered the most important signaling pathways involved in the pharmacological activity of Paeonia herbs.
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