Xanthohumol

Xanthohumol is the main prenylflavonoid in hops that inhibits diacylglycerol acyltransferase (DGAT) with IC₅₀ value of 50.3μM^[1]. Xanthohumol has been associated with a wide range of health benefits, due to its anti-inflammatory, anti-oxidative, and cancer-preventive properties^[2].

In vitro, Xanthohumol (0, 5, 10 and 20µM) treated human colon carcinoma HT-29 cells for 24h caused a dramatic decrease in cells viability and arrest of the cancer cells at the G2/M phase of the cell cycle with IC₅₀ value of 10μM^[3]. Xanthohumol treatment (5 to 20μM) on human umbilical vein endothelial (HUVE) cells for 24 or 48 hours exerted anti-angiogenic effect, led to increased AMPK phosphorylation and activity and also reduced nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation^[4]. Xanthohumol (1.5, 3, and 6μg/mL) incubated human whole blood or platelet-rich plasma (PRP) for 15min at 37°C before treated with adenosine 5’-diphosphate (ADP) significantly attenuated ADP-induced blood platelet aggregation^[5].

In vivo, Xanthohumol (10, 25, 50mg/kg) intraperitoneally injected into ovariectomy mice every 2 days for 12 weeks relieved cognitive impairment of ovariectomy mice by suppressing miRNA-532-3p and increased the downstream gene of miRNA-532-3p, Mpped1, in hippocampus^[6]. Xanthohumol (10mg/kg) treated human non-small cell lung cancer (NSCLC) A549 or H358 cells engrafted athymic nude mice every two days via intraperitoneal injection suppressed NSCLC xenograft tumor growth, increased the expression of pro-apoptotic protein PUMA in tumor tissues and downregulated the expression level of Ki67, a proliferation marker of cancer cells^[7].

References:
[1] Tabata N, Ito M, Tomoda H, Omura S. Xanthohumols, diacylglycerol acyltransferase inhibitors, from Humulus lupulus. Phytochemistry. 1997 Oct;46(4):683-7. 
[2] Neumann H F, Frank J, Venturelli S, Egert S. Bioavailability and Cardiometabolic Effects of Xanthohumol: Evidence from Animal and Human Studies. Mol Nutr Food Res. 2022 Mar;66(6):e2100831. 
[3] Liu X K, An L J, Li Y, et al. Xanthohumol chalcone acts as a powerful inhibitor of carcinogenesis in drug-resistant human colon carcinoma and these effects are mediated via G2/M phase cell cycle arrest, activation of apoptotic pathways, caspase activation and targeting Ras /MEK/ERK pathway. J BUON. 2019 Nov-Dec;24(6):2442-2447.
[4] Gallo C, Dallaglio K, Bassani B, et al. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation. Oncotarget. 2016 Sep 13;7(37):59917-59931.
[5] Luzak B, Kassassir H, Rój E, et al. Xanthohumol from hop cones (Humulus lupulus L.) prevents ADP-induced platelet reactivity. Arch Physiol Biochem. 2017 Feb;123(1):54-60.
[6] Liu Y, Shao J X, Qiao R Z, et al. Xanthohumol improves cognitive impairment by regulating miRNA-532-3p/Mpped1 in ovariectomized mice. Psychopharmacology (Berl). 2023 May;240(5):1169-1178.
[7] Li X Z, Jin L Y, Ma Y C, et al. Xanthohumol inhibits non-small cell lung cancer by activating PUMA-mediated apoptosis. Toxicology. 2022 Mar 30:470:153141.

Xanthohumol是啤酒花中主要的异戊烯基黄酮类化合物，能够抑制二酰甘油酰基转移酶（DGAT），IC₅₀值为50.3μM^[1]。Xanthohumol具有抗炎、抗氧化和预防癌症等特性^[2]。

体外实验中，Xanthohumol（0、5、10和20μM）处理人结肠癌HT-29细胞24小时，导致细胞活力显著下降，癌细胞在细胞周期的G2/M期停滞，IC₅₀值为10μM^[3]。Xanthohumol（5-20µM）处理人脐静脉内皮细胞（HUVE）24或48h，具有抗血管生成作用，可通过增加AMPK磷酸化与活性，抑制eNOS磷酸化，从而降低内皮细胞NO水平^[4]。Xanthohumol（1.5、3 和 6μg/mL）在 37°C 下孵育人全血或富血小板血浆（PRP）15 分钟后，用腺苷 5'-二磷酸（ADP）处理，可显著减弱 ADP 诱导的血小板聚集^[5]。

体内实验中，Xanthohumol（10、25、50mg/kg）每2天通过腹腔注射卵巢切除后小鼠，持续12周，通过抑制小鼠海马体中miRNA-532-3p上调，并提高miRNA-532-3p下游靶基因Mpped1的表达缓解卵巢切除小鼠的认知障碍^[6]。 Xanthohumol（10mg/kg）每两天腹腔注射非小细胞肺癌（NSCLC）A549或H358细胞异种移植瘤裸鼠模型，抑制肿瘤的生长，提高肿瘤组织促凋亡蛋白PUMA表达，下调肿瘤细胞增殖标志物Ki67^[7]。