He Liangqian, Yang Guangmei, Li Tongyun, Li Wu, Yang Ruili
Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China.
School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
Eur J Nutr. 2025 Mar 8;64(3):113. doi: 10.1007/s00394-025-03638-5.
Procyanidins have strong potential for antioxidation and decreasing hepatic fat accumulation thus preventing non-alcoholic fatty liver disease (NAFLD). Procyanidin A2 (PCA2), predominately found in cranberries, avocado, peanut red skins and litchi fruit pericarp, is poorly absorbed in the gastrointestinal tract. However, literatures about its metabolic profile by gut microbiota and effects on lipid metabolism are limited. Therefore, the metabolites of PCA2 by human intestinal microbiota as well as their antioxidant and hypolipidemic potential were investigated.
PCA2 was incubated with human intestinal microbiota and the metabolites produced were characterized by UPLC-Q-TOF-MS. The antioxidant and hypolipidemic potential of PCA2 and its microbial metabolites (MPCA2) were evaluated and compared.
The metabolism of PCA2 resulted in the formation of 14 metabolites, and the highest antioxidant capacity values were reached after 6 h incubation. In addition, PCA2 and MPCA2 were effective in reducing oxidative stress and lipid accumulation induced by oleic acid (OA) in HepG2 cells. They significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK) and thus stimulated hepatic lipolysis by up-regulating of the expression of carnitine palmitoyl transferase I (CPT-I) and suppressed hepatic lipogenesis by down-regulation of the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA) reductase, fatty acid synthase (FAS) and sterol regulatory element binding proteins 1c (SREBP-1c).
Our results indicated that PCA2 and MPCA2 were effective to prevent OA-induced lipid accumulation and oxidative stress in HepG2 cells, implying that microbial metabolites may play a crucial role in the realization of human health effects of PCA2.
原花青素具有强大的抗氧化潜力，可减少肝脏脂肪堆积，从而预防非酒精性脂肪性肝病（NAFLD）。原花青素A2（PCA2）主要存在于蔓越莓、鳄梨、花生红皮和荔枝果皮中，在胃肠道中的吸收率较低。然而，关于其经肠道微生物群的代谢谱及其对脂质代谢影响的文献有限。因此，研究了PCA2在人肠道微生物群作用下的代谢产物及其抗氧化和降血脂潜力。
将PCA2与人肠道微生物群一起孵育，通过超高效液相色谱-四极杆飞行时间质谱联用仪（UPLC-Q-TOF-MS）对产生的代谢产物进行表征。对PCA2及其微生物代谢产物（MPCA2）的抗氧化和降血脂潜力进行评估和比较。
PCA2的代谢产生了14种代谢产物，孵育6小时后抗氧化能力值达到最高。此外，PCA2和MPCA2可有效减轻油酸（OA）诱导的HepG2细胞氧化应激和脂质积累。它们显著促进了腺苷酸活化蛋白激酶（AMPK）的磷酸化，从而通过上调肉碱棕榈酰转移酶I（CPT-I）的表达刺激肝脏脂肪分解，并通过下调3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA）、脂肪酸合酶（FAS）和固醇调节元件结合蛋白1c（SREBP-1c）的表达抑制肝脏脂肪生成。
我们的结果表明，PCA2和MPCA2可有效预防OA诱导的HepG2细胞脂质积累和氧化应激，这意味着微生物代谢产物可能在PCA2对人类健康影响的实现中发挥关键作用。
