Painful diabetic neuropathy (PDN) is a highly prevalent complication in patients suffering from diabetes mellitus. Given the inadequate pain-relieving effect of current therapies for PDN, there is a high unmet medical need for specialized therapeutic options. In traditional Chinese medicine (TCM), various herbal formulations have been implemented for centuries to relieve pain, and one commonly used plant in this context is Paeonia lactiflora (P. lactiflora). Here, we summarize the chemical constituents of P. lactiflora including their pharmacological mechanisms-of-action and discuss potential benefits for the treatment of PDN. For this, in silico data, as well as preclinical and clinical studies, were critically reviewed and comprehensively compiled. Our findings reveal that P. lactiflora and its individual constituents exhibit a variety of pharmacological properties relevant for PDN, including antinociceptive, anti-inflammatory, antioxidant, and antiapoptotic activities. Through this multifaceted and complex combination of various pharmacological effects, relevant hallmarks of PDN are specifically addressed, suggesting that P. lactiflora may represent a promising source for novel therapeutic approaches for PDN.
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