PHYSALIEN is a lipophilic carotenoid compound[1-2]. PHYSALIEN exhibits antioxidant and anti-inflammatory properties, which contribute to its hepatoprotective effects by mitigating oxidative stress and alleviating hepatic fibrosis. PHYSALIEN is utilized in research related to liver diseases and ocular disorders[3-4].
In vitro, BRL-3A rat normal hepatocytes were pretreated with PHYSALIEN (1µM) for 2 hours before co-incubation with ethanol for 24 hours. The treatment restored the ethanol-suppressed expression of key autophagy-related proteins (Atg5, Beclin-1, and LC3A/B) and reduced the accumulation of the autophagy substrate p62. The pretreatment with PHYSALIEN targeted the cell membrane receptors P2X7 and AdipoR1, thereby modulating the AMPK/FoxO3a and PI3K/Akt signaling pathways, which restored ethanol-inhibited mitophagy and attenuated the activation of the NLRP3 inflammasome[5].
In vivo, in a murine model of alcoholic fatty liver disease (AFLD) using male C57BL/6 mice, oral administration of PHYSALIEN (25mg/kg/day) from weeks 5 to 10 of the experiment. PHYSALIEN significantly alleviated typical AFLD symptoms induced by ethanol consumption. This included amelioration of liver histopathology (reduced lipid droplet deposition and inflammatory foci), lowered serum alanine aminotransferase (ALT) levels, and mitigation of hepatic oxidative stress and inflammation. The hepatoprotective effect was mediated through the regulation of the CYP2E1, NF-κB, and MAPK (p38 and ERK) signaling pathways[6]. In N-methyl-N-nitrosourea (MNU)-induced photoreceptor degeneration in adult male C57BL/6J mice, daily oral administration of PHYSALIEN (approximately 0.27mg/kg), starting one week before injury and continuing for a total of two weeks. PHYSALIEN significantly improved photoreceptor survival, enhanced retinal electrophysiological responses to light, and increased visual acuity in the injured mice[7].
References:
[1] Long JT, Fan HX, Zhou ZQ, et al. The major zeaxanthin dipalmitate derivatives from wolfberry. J Asian Nat Prod Res. 2020 Aug;22(8):746-753.
[2] Liu F, Liu X, Zhou Y, et al. Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways. J Neurochem. 2021 Sep;158(5):1131-1150.
[3] Kan X, Zhou W, Xu W, et al. Zeaxanthin Dipalmitate-Enriched Emulsion Stabilized with Whey Protein Isolate-Gum Arabic Maillard Conjugate Improves Gut Microbiota and Inflammation of Colitis Mice. Foods. 2022 Nov 16;11(22):3670.
[4] Bahaji Azami NL, Sun M. Zeaxanthin Dipalmitate in the Treatment of Liver Disease. Evid Based Complement Alternat Med. 2019 Aug 21;2019:1475163.
[5] Gao H, Lv Y, Liu Y, et al. Wolfberry-Derived Zeaxanthin Dipalmitate Attenuates Ethanol-Induced Hepatic Damage. Mol Nutr Food Res. 2019 Jun;63(11):e1801339.
[6] Xiao J, Wang J, Xing F, et al. Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic fatty liver disease model through modulating MAPK pathway. PLoS One. 2014 Apr 16;9(4):e95214.
[7] Chen X, Zhang S, Yang L, et al. Zeaxanthin dipalmitate-enriched wolfberry extract improves vision in a mouse model of photoreceptor degeneration. PLoS One. 2024 May 20;19(5):e0302742.
PHYSALIEN是一种脂溶性的类胡萝卜素类化合物[1-2]。PHYSALIEN可通过抗氧化和抗炎作用来保护肝脏细胞，同时通过减少氧化应激损伤以缓解肝纤维化。PHYSALIEN可用于肝脏疾病和眼部疾病的相关研究[3-4]。
在体外，PHYSALIEN（1μM）预处理大鼠正常肝细胞（BRL-3A）2小时后，再与乙醇共孵育24小鼠，PHYSALIEN能够恢复乙醇抑制的自噬蛋白（Atg5、Beclin-1、LC3A/B）的表达，并下调自噬底物p62的积累。PHYSALIEN预处理还通过靶向细胞膜受体P2X7和AdipoR1，进而调控AMPK/FoxO3a和PI3K/Akt信号通路，恢复被乙醇抑制的线粒体自噬功能，并减轻NLRP3炎性小体的激活[5]。
在体内，在雄性C57BL/6小鼠的酒精性脂肪肝病（AFLD）模型中，从实验第5周至第10周口服给予PHYSALIEN（25mg/kg/day），PHYSALIEN显著缓解了由乙醇摄入引起的典型AFLD症状，包括改善肝脏组织病理学（减少脂肪滴沉积和炎症灶），降低血清谷丙转氨酶（ALT）水平，减轻肝脏氧化应激和炎症反应，并通过调节CYP2E1、NF-κB和MAPK（p38和ERK）信号通路发挥肝保护作用[6]。在成年雄性C57BL/6J小鼠的N-甲基-N-亚硝基脲（MNU）诱导的光感受器变性模型中，从损伤前一周开始直至实验结束（共两周）每日灌胃给予PHYSALIEN（约0.27mg/kg），PHYSALIEN显著改善了光感受器的存活率，增强了视网膜对光的电生理反应，并提高了受损小鼠的视觉敏锐度[7]。