Park Yea-Jin, Kim Hyo-Jung, Koh Duck-Jae, Kim Eunjoo, Lim Young-Woo, An Hyo-Jin
Department of Rehabilitative Medicine of Korean Medicine and Neuropsychiatry, College of Korean Medicine, Sangji University, Wonju, Gangwon-do, 26339, Republic of Korea.
Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
Heliyon. 2024 Apr 3;10(8):e29161. doi: 10.1016/j.heliyon.2024.e29161. eCollection 2024 Apr 30.
Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of , , , and . Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration.
肥胖与心血管疾病风险增加相关。甘比琼（GBJ）是太阴调胃汤的改良草药配方，可使高脂饮食（HFD）喂养的肥胖小鼠体重减轻。与此同时，人们对GBJ的主要草药麻黄（ES）可能产生的不良心血管影响表示担忧。然而，尚无关于ES及含麻黄碱产品对肥胖诱导的心脏细胞凋亡影响的报道。因此，为研究GBJ和ES对HFD诱导的心脏细胞凋亡的影响，我们对HFD喂养的肥胖小鼠心脏组织进行了蛋白质印迹分析、TUNEL染色和组织学染色。蛋白质印迹分析表明，HFD喂养小鼠心脏中抗凋亡标志物（B细胞淋巴瘤（BCL）蛋白2（BCL-2）、BCL-XL和X连锁凋亡抑制蛋白）和促凋亡标志物（Fas、Fas相关死亡结构域蛋白、细胞死亡的BCL-2激动剂、BCL-2相关X蛋白、细胞色素C和裂解的半胱天冬酶-9）的蛋白质水平有显著变化。相比之下，给予250mg/kg GBJ 12周可显著逆转与凋亡信号通路相关的蛋白质水平，且效果优于给予ES。此外，与HFD组相比，GBJ处理的小鼠TUNEL染色的凋亡细胞数量明显减少。此外，GBJ通过调节、、和的基因表达改善了线粒体功能。值得注意的是，苏木精和伊红组织学染色显示，GBJ和ES处理的小鼠心脏组织无变化，表明长期给予GBJ和ES对心脏组织无任何不良影响。本研究为支持GBJ保护HFD喂养诱导的心脏细胞凋亡的疗效以及验证GBJ给药的心脏安全性奠定了基础。
