Rifaximin (Xifaxan)

Rifaximin (Xifaxan) is an inhibitor of proviral integration of Moloney murine (PIM) kinase, with an IC₅₀ value of 26μM ^[1]. Rifaximin is an antiparasitic agent that inhibits CpACBP1 binding to NBD-palmitoyl-CoA, with an IC₅₀ value of 0.269μM ^[2]. Rifaximin acts as a non-systemic oral antibiotic that is widely used to inhibit Gram-positive and -negative, aerobic and anaerobic bacteria by blocking bacterial RNA polymerase^[3].

In vitro, Rifaximin treatment for 48 hours significantly inhibited the viability of MCF-7 cells and HEK293 cells with IC₅₀ values of 8.15±0.2μM and 87.13±9.6μM, respectively^[4].Pretreatment of HEp-2 cells with Rifaximin (32μg/ml) for 24h reduced enteroaggregative Escherichia coli (EAEC) attachment and internalization, and decreased the expression of multiple proinflammatory cytokines within cells^[5]. Treatment of SH-SY5Y cells with 64μg/ml Rifaximin for 24 hours inhibited iron overload induced by ferric ammonium citrate (FAC), restored cell viability, and reduced intracellular reactive oxygen species (ROS) levels^[6].

In vivo, Rifaximin treatment via oral administration (100mg/kg/day) for 4 weeks significantly reduced the severity of ankylosing spondylitis (AS) in a mouse model of AS, suppressed ileal histological changes, restored intestinal barrier function, and inhibited TLR-4/NF-κB signaling pathway activation^[7]. Rifaximin (100mg/kg/day; p.o.) treatment for 4 weeks significantly ameliorated hepatic steatosis, lobular inflammation, and fibrosis in C57BL/6 mice fed a choline deficient (MCD) diet^[8].

References:
[1] Rathi A, Noor S, Sulaimani M N, et al. FDA-approved drugs as PIM-1 kinase inhibitors: A drug repurposed approach for cancer therapy[J]. International Journal of Biological Macromolecules, 2025, 292: 139107.
[2] Fritzler J M, Zhu G. Novel anti-Cryptosporidium activity of known drugs identified by high-throughput screening against parasite fatty acyl-CoA binding protein (ACBP)[J]. Journal of antimicrobial chemotherapy, 2012, 67(3): 609-617.
[3] Calanni F, Renzulli C, Barbanti M, et al. Rifaximin: beyond the traditional antibiotic activity[J]. The Journal of antibiotics, 2014, 67(9): 667-670.
[4] Elloumi-Mseddi J, Msalbi D, Fakhfakh R, et al. Anti-diarrheal drug repositioning in tumour cell cytotoxicity[J]. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 2019, 19(8): 1037-1047.
[5] Brown E L, Xue Q, Jiang Z D, et al. Pretreatment of epithelial cells with rifaximin alters bacterial attachment and internalization profiles[J]. Antimicrobial agents and chemotherapy, 2010, 54(1): 388-396.
[6] Zhang Z, Yuan Q, Hu X, et al. Rifaximin protects SH‐SY5Y neuronal cells from iron overload‐induced cytotoxicity via inhibiting STAT3/NF‐κB signaling[J]. Cell Biology International, 2022, 46(7): 1062-1073.
[7] Yang L, Liu B, Zheng J, et al. Rifaximin alters intestinal microbiota and prevents progression of ankylosing spondylitis in mice[J]. Frontiers in cellular and infection microbiology, 2019, 9: 44.
[8] Jian J, Nie M T, Xiang B, et al. Rifaximin ameliorates non-alcoholic steatohepatitis in mice through regulating gut microbiome-related bile acids[J]. Frontiers in pharmacology, 2022, 13: 841132.

Rifaximin (Xifaxan)是一种proviral integration of Moloney murine (PIM)激酶抑制剂，IC₅₀值为26μM^[1]。作为抗寄生虫剂，Rifaximin可抑制CpACBP1与NBD-棕榈酰辅酶A的结合（IC₅₀=0.269μM）^[2]。Rifaximin 是一种非全身性口服抗生素，通过阻断细菌RNA聚合酶广泛抑制革兰氏阳性/阴性菌及需氧/厌氧菌^[3]。

在体外，Rifaximin处理48小时可显著抑制MCF-7和HEK293细胞活力，IC₅₀值分别为8.15±0.2μM和87.13±9.6μM^[4]。32μg/ml的Rifaximin预处理HEp-2细胞24小时能减少肠集聚性大肠杆菌（EAEC）的黏附与内化，并降低细胞内多种促炎细胞因子表达^[5]。64μg/ml的Rifaximin处理SH-SY5Y细胞24小时可抑制柠檬酸铁铵（FAC）诱导的铁超载，恢复细胞活力并降低细胞内活性氧（ROS）水平^[6]。

在体内，强直性脊柱炎（AS）小鼠模型每日口服Rifaximin（100mg/kg/day；持续4周）可显著减轻疾病严重程度，抑制回肠组织学改变，恢复肠道屏障功能并阻断TLR-4/NF-κB信号通路激活^[7]。胆碱缺乏（MCD）饮食喂养的C57BL/6小鼠每日口服100mg/kg剂量的Rifaximin（持续4周）能显著改善肝脏脂肪变性、小叶炎症和纤维化^[8]。