Periplogenin

Periplogenin is a natural cardiotonic steroid compound ^[1]. Periplogenin inhibits Na⁺/K⁺-ATPase activity, indirectly increases intracellular calcium concentration in cardiomyocytes, and thus enhances myocardial contractility ^[2-3]. Periplogenin is commonly used to treat psoriasis and cancer ^[4].

In SHEE cells, Periplogenin (1μM, 2μM, 4μM; 48h) inhibits the ESCC cell growth ^[5]. In rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), after administration of Periplogenin (0.1μg/mL, 0.25μg/mL, 0.5μg/mL, 1μg/mL, 2.5μg/mL, 5μg/mL, 7.5μg/mL, 10μg/mL, 12.5μg/mL, 15μg/mL, 20μg/mL; 24h), the proliferation rate of RA-FLS decreased with the increase of Periplogenin dose ^[6]. In bone marrow macrophages, Periplogenin (20μM, 40μM, 60μM, 80μM, 100μM; 96h) suppressed osteoclast differentiation in a dose-dependent manner ^[7].

In DU145 xenograft tumor model, Periplogenin (10mg/kg, 20mg/kg; ig; 30d) suppresses tumor growth ^[8]. In collagen induction-induced mouse model, Periplogenin (1mg/kg, 2mg/kg, 4mg/kg; sc; 33d) inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway ^[9]. In gastric cancer xenograft mice model, Periplogenin (6mg/kg; ip; 21d) inhibit the growth of tumor in vivo in nude mice ^[10].

References:
[1]. Han HS, Jeon H, Kang SC. Phellopterin isolated from Angelica dahurica reduces blood glucose level in diabetic mice. Heliyon. 2018 Mar 1; 4(3).
[2]. Ponce A, Flores-Maldonado C, Contreras RG. Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents. Biomolecules. 2025 Jun 17;15(6):885.
[3]. Panda S, Kar A. Periplogenin, isolated from Lagenaria siceraria, ameliorates L-T4-induced hyperthyroidism and associated cardiovascular problems. Hormone and Metabolic Research. 2011 Mar; 43(03): 188-193.
[4]. Zhang WJ, Song ZB, Bao YL, et al. Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA-and IMQ-induced psoriasis-like mouse models. Biochemical Pharmacology. 2016 Apr 1; 105: 66-79.
[5]. Hu Y, Liu F, Jia X, et al. Periplogenin suppresses the growth of esophageal squamous cell carcinoma in vitro and in vivo by targeting STAT3. Oncogene. 2021 Jun 10; 40(23): 3942-3958.
[6]. Ma X, Yang Y, Li H, et al. Periplogenin inhibits pyroptosis of fibroblastic synoviocytes in rheumatoid arthritis through the NLRP3/Caspase-1/GSDMD signaling pathway. International Immunopharmacology. 2024 May 30; 133: 112041.
[7]. Gan K, Lian H, Yang T, et al. Periplogenin attenuates LPS-mediated inflammatory osteolysis through the suppression of osteoclastogenesis via reducing the NF-κB and MAPK signaling pathways. Cell Death Discovery. 2024 Feb 17; 10(1): 86.
[8]. Zhang X, Pang T, Zhang H, et al. The natural compound periplogenin suppresses the growth of prostate carcinoma cells by directly targeting ATP1A1. Scientific Reports. 2024 Sep 3; 14(1): 20509.
[9]. Zhong X, Feng W, Liu L, et al. Periplogenin inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway. International Immunopharmacology. 2024 Feb 15; 128: 111487.
[10]. Guo JL, Hu HM, Lee SC, et al. Levistolide A and periplogenin inhibit the growth of gastric cancer cells in vitro and in vivo. Exploration of Drug Science. 2023 Mar 30; 1(2): 64-76.

Periplogenin是一种天然的强心类固醇化合物 ^[1]。Periplogenin通过抑制Na⁺/K⁺-ATPase活性，间接增加心肌细胞内钙浓度，从而增强心肌收缩力 ^[2-3]。Periplogenin常用于治疗银屑病和癌症 ^[4]。

在SHEE细胞中，Periplogenin（1μM、2μM、4μM；48h）可抑制ESCC细胞生长 ^[5]。在类风湿关节炎成纤维样滑膜细胞（RA-FLS）中，给予Periplogenin（0.1μg/mL、0.25μg/mL、0.5μg/mL、1μg/mL、2.5μg/mL、5μg/mL、7.5μg/mL、10μg/mL、12.5μg/mL、15μg/mL、20μg/mL；24h）后，RA-FLS的增殖率随Periplogenin剂量的增加而降低 ^[6]。在骨髓巨噬细胞中，Periplogenin（20μM、40μM、60μM、80μM、100μM；96h）以剂量依赖性方式抑制破骨细胞分化 ^[7]。

在DU145异种移植肿瘤模型中，Periplogenin（10mg/kg、20mg/kg；ig；30d）可抑制肿瘤生长 ^[8]。在胶原诱导的小鼠模型中，Periplogenin（1mg/kg、2mg/kg、4mg/kg；sc；33d）通过调节JAK2/3-STAT3通路抑制类风湿关节炎中的病理性滑膜增生和浸润 ^[9]。在胃癌异种移植小鼠模型中，Periplogenin（6mg/kg；ip；21d）可抑制裸鼠体内肿瘤的生长 ^[10]。