Paeoniflorin is a pinane monoterpene glycoside extracted from the roots of Paeonia plants of the Ranunculaceae family, possessing multiple biological activities[1-2]. Through mechanisms such as activating adenosine A1 receptors, inhibiting COX-2 expression, and downregulating HIF-1α, Paeoniflorin exerts anti-inflammatory, immunomodulatory, analgesic, anti-tumor, antioxidant stress, and anti-platelet aggregation effects. Paeoniflorin can be used in research related to rheumatoid arthritis, cardiovascular diseases, neurological disorders, and tumors[3-4].
In vitro, Paeoniflorin (60μM) pretreatment of ER-positive breast cancer cell lines T47D and MCF-7 for 48 hours, followed by combination treatment with Tamoxifen (8μM for T47D, 16μM for MCF-7), Paeoniflorin significantly enhanced Tamoxifen-induced apoptosis, upregulated the Bax/Bcl-2 protein expression ratio and Caspase 3 activity, while inhibiting STAT3 phosphorylation and its downstream target gene c-Myc expression by promoting SIRT4 expression[5]. Paeoniflorin (1-30μM) co-treatment with TGF-β1 (2ng/mL) in human alveolar epithelial cells A549 for 48 hours, Paeoniflorin significantly inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT), reduced cell migration ability and Vimentin and α-SMA expression, while downregulating the transcription factor Snail expression through the Smad-dependent pathway and reducing type I and III collagen secretion[6].
In vivo, Paeoniflorin (50, 100, 200mg/kg/day) intraperitoneal injection in acetaminophen (APAP; 300mg/kg)-induced drug-induced liver injury C57BL/6J male mice (preventive administration starting 5 days before modeling, for 5 consecutive days), Paeoniflorin significantly reduced serum ALT, AST, ALP, γ-GT, and TBIL levels, alleviated liver tissue inflammation and edema, and protected hepatocytes from APAP damage by activating autophagy through inhibiting the MAPK/mTOR signaling pathway, reducing oxidative stress and apoptosis[7]. Paeoniflorin (5, 10mg/kg/day) intraperitoneal injection in LPS-induced cognitive dysfunction ICR male mice (starting after LPS injection, for 3 consecutive weeks), Paeoniflorin significantly improved spatial memory, recognition memory, and long-term learning ability in mice, and alleviated LPS-induced cognitive deficits by inhibiting the expression of APP, BACE, PS1, and PS2 proteins in the brain and reducing β-amyloid production[8].
References:
[1] Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther. 2020 Mar;207:107452.
[2] Zhang XX, Zuo JQ, Wang YT, et al. Paeoniflorin in Paeoniaceae: Distribution, influencing factors, and biosynthesis. Front Plant Sci. 2022 Sep 2;13:980854.
[3] Ma Y, Lang X, Yang Q, et al. Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis. Int Immunopharmacol. 2023 Jun;119:110247.
[4] Wang XL, Feng ST, Wang YT, et al. Paeoniflorin: A neuroprotective monoterpenoid glycoside with promising anti-depressive properties. Phytomedicine. 2021 Sep;90:153669.
[5] Zhang P, Wu N, Song ZJ, et al. Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4. Evid Based Complement Alternat Med. 2022 Jan 15;2022:6730559.
[6] Ji Y, Dou YN, Zhao QW, et al. Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway. Acta Pharmacol Sin. 2016 Jun;37(6):794-804.
[7] Deng X, Li Y, Chen Y, et al. Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway. Cell Mol Biol Lett. 2024 Sep 7;29(1):119.
[8] Meng HW, Kim JH, Kim HY, et al. Paeoniflorin Attenuates Lipopolysaccharide-Induced Cognitive Dysfunction by Inhibition of Amyloidogenesis in Mice. Int J Mol Sci. 2023 Mar 2;24(5):4838.
Paeoniflorin是一种从毛茛科植物芍药根中提取的蒎烷单萜糖苷，具有多种生物学活性[1-2]。Paeoniflorin通过激活腺苷A1受体、抑制COX-2表达和下调HIF-1α等机制，发挥抗炎、免疫调节、镇痛、抗肿瘤、抗氧化应激、抗血小板聚集等功能，Paeoniflorin可用于类风湿关节炎、心血管疾病、神经系统疾病和肿瘤等相关研究[3-4]。
在体外，Paeoniflorin（60μM）预处理ER阳性乳腺癌细胞系T47D和MCF-7 48小时，随后与Tamoxifen（8μM for T47D，16μM for MCF-7）联合处理，Paeoniflorin显著增强Tamoxifen诱导的细胞凋亡，并上调Bax/Bcl-2蛋白表达比例及Caspase 3活性，同时通过促进SIRT4表达抑制STAT3磷酸化及其下游靶基因c-Myc的表达[5]。Paeoniflorin（1-30μM）与TGF-β1（2ng/mL）处理人肺泡上皮细胞A549 48小时，Paeoniflorin显著抑制TGF-β1诱导的上皮-间质转化（EMT），降低细胞迁移能力及波形蛋白（Vimentin）和α-SMA表达，同时通过Smad依赖性途径下调转录因子Snail表达，减少I型和III型胶原分泌[6]。
在体内，Paeoniflorin（50，100，200mg/kg/day）腹腔注射处理Administered acetaminophen (APAP； 300mg/kg)诱导的药物性肝损伤C57BL/6J雄性小鼠（从造模前5天开始预防性给药，连续5天），Paeoniflorin显著降低血清ALT、AST、ALP、γ-GT和TBIL水平，减轻肝组织炎症和水肿，并通过抑制MAPK/mTOR信号通路激活自噬、减少氧化应激和细胞凋亡，从而保护肝细胞免受APAP损伤[7]。Paeoniflorin（5，10mg/kg/day）腹腔注射处理LPS诱导的认知功能障碍ICR雄性小鼠（从LPS注射后开始，连续3周），Paeoniflorin显著改善小鼠的空间记忆、识别记忆以及长期学习能力，并通过抑制脑内APP、BACE、PS1和PS2蛋白表达，减少β-淀粉样蛋白生成，从而缓解LPS诱导的认知缺陷[8]。