Kumatakenin

Kumatakenin is a flavonoid natural product isolated from cloves or astragalus, with oral activity as an apoptosis inducer and autophagy inhibitor^[1-2]. Kumatakenin induces apoptosis in cancer cells by increasing the activity of caspase-3, caspase-8, and caspase-9. Kumatakenin can be used in research related to ovarian cancer, esophageal cancer, bladder cancer, depression, and colitis^[3-4].

In vitro, esophageal cancer cell lines (including KYSE410, TE-1, TE-10, and Case17 cells) were treated with Kumatakenin (0–40μM) for 12 hours. Kumatakenin inhibited the mRNA expression of TRIM65 and FASN, suppressed cell migration and invasion, and regulated the expression of epithelial-mesenchymal transition (EMT)-associated markers^[5]. Human ovarian cancer SKOV3 cells were treated with Kumatakenin (0–100μM) for 24 hours. Kumatakenin induced apoptosis, increased the proportion of sub-G1 phase cells, and enhanced the active forms of caspase-3, caspase-8, and caspase-9. THP-1-derived macrophages (stimulated with SKOV3 cell-conditioned medium to mimic tumor-associated macrophages) were treated with Kumatakenin (0–100μM) for 24 hours. Kumatakenin significantly inhibited the expression of M2 phenotype markers (CD206, Trem-2) and pro-tumor factors (IL-10, VEGF, MMP-2, MMP-9)^[6].

In vivo, Kumatakenin (0.56-2.25mg/kg) was intraperitoneally injected once daily into C57BL/6J mice with depression for 3 consecutive weeks. Kumatakenin significantly alleviated depressive-like behaviors in the mice, increased plasma levels of 5-hydroxytryptamine, dopamine, and brain-derived neurotrophic factor (BDNF), reduced corticosterone levels, and promoted neuronal repair in the hippocampus^[7]. Kumatakenin (25mg/kg and 100mg/kg) was orally administered once daily to C57BL/6 mice with colitis for 9 days. Kumatakenin significantly alleviated colitis symptoms, including the recovery of mucosal hemorrhage, vascular pattern, inflammatory cell infiltration, and intestinal villus atrophy. Kumatakenin increased colon length, reduced the disease activity index score, and relieved diarrhea and rectal bleeding^[8].

References:
[1] Qu T, Zhang N, Cai J, et al. Integrated bioinformatics and multi-omics reveal Astragalus extract's gut-kidney axis mechanism in hyperuricemic nephropathy via purine metabolism. Phytomedicine. 2025 Oct;146:157121.
[2] Leal CM, Leitão SG, Sausset R, et al. Flavonoids from Siparuna cristata as Potential Inhibitors of SARS-CoV-2 Replication. Rev Bras Farmacogn. 2021;31(5):658-666.
[3] Zhuang J, Mo J, Huang Z, et al. Mechanisms of Xiaozheng decoction for anti-bladder cancer effects via affecting the GSK3β/β-catenin signaling pathways: a network pharmacology-directed experimental investigation. Chin Med. 2023 Aug 22;18(1):104.
[4] Al-Aboudi A, Abu Zarga M, Hourani W, et al. Multi-target anti-inflammatory and cytotoxic activities of flavonoids from Varthemia iphionoides Boiss. & C. I. Blanche. Nat Prod Res. 2025 May 2:1-9.
[5] Tingting Zhang, Zhengqiang Yang, Xu Li, et al. Supplementary kumatakenin prevents esophagus cancer progression by blocking TRIM65-FASN axis-mediated metabolic reprogramming. Journal of Functional Foods. 2024;117:106223.
[6] Woo JH, Ahn JH, Jang DS, et al. Kumatakenin Isolated From Cloves on the Apoptosis of Cancer Cells and the Alternative Activation of Tumor-Associated Macrophages. J Agric Food Chem. 2017 Sep 13;65(36):7893-7899.
[7] Li L, Gu L, Hua Y, et al. Kumatakenin alleviates depressive-like behaviors by suppressing excessive autophagy in hippocampus via ATG5. Eur J Pharmacol. 2025 Jul 15;999:177688.
[8] Arenbaoligao, Guo X, Xiong J, et al. Kumatakenin inhibited iron-ferroptosis in epithelial cells from colitis mice by regulating the Eno3-IRP1-axis. Front Pharmacol. 2023 Mar 17;14:1127931.

Kumatakenin是一种从丁香或黄芪中分离得到的黄酮类天然产物，具有口服活性的凋亡诱导剂和自噬抑制剂^[1-2]。Kumatakenin可通过提高caspase-3、caspase-8和caspase-9的活性来诱导癌细胞凋亡。Kumatakenin可用于卵巢癌、食管癌、膀胱癌、抑郁症和结肠炎的相关研究^[3-4]。

在体外，Kumatakenin（0–40μM）处理食管癌细胞系（包括KYSE410、TE-1、TE-10及Case17细胞）12小时。Kumatakenin可抑制TRIM65与FASN的mRNA表达，同时抑制细胞的迁移与侵袭，并调节上皮-间质转化（EMT）相关标志物的表达^[5]。Kumatakenin（0–100μM）处理人卵巢癌细胞SKOV3 24小时。Kumatakenin诱导细胞凋亡并增加亚G1期细胞比例，同时增加caspase-3、caspase-8和caspase-9的活化形式。Kumatakenin（0–100μM）处理THP-1来源的巨噬细胞（用SKOV3细胞条件培养基刺激以模拟肿瘤相关巨噬细胞）24小时。Kumatakenin显著抑制M2表型标志物（CD206、Trem-2）及促癌因子（IL-10、VEGF、MMP-2、MMP-9）的表达^[6]。

在体内，Kumatakenin（0.56-2.25mg/kg）每天一次腹腔注射于抑郁症C57BL/6J小鼠，连续3周。Kumatakenin显著改善了小鼠的抑郁样行为，增加了血浆中5-羟色胺、多巴胺和脑源性神经营养因子的水平，降低了皮质酮水平，并促进了海马神经元的修复^[7]。Kumatakenin（25mg/kg和100mg/kg）每天一次灌胃给药于结肠炎C57BL/6小鼠，连续9天。Kumatakenin显著缓解了小鼠的结肠炎症状，包括恢复黏膜出血、血管模式、炎症细胞浸润和肠绒毛萎缩，增加结肠长度，降低疾病活动指数评分，并缓解腹泻和直肠出血^[8]。