Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

中文翻译：

---

一种源自环鼻梢端的新型天然产物通过抑制线粒体功能障碍和细胞凋亡，为大鼠提供心脏代谢保护，防止肥胖诱导的心脏功能障碍


背景长期以来，人们一直认为开发一种新的肥胖药理学靶点在减轻全球心血管并发症和死亡率方面具有挑战性。鉴于与各种抗肥胖药物相关的细胞毒性作用，人们对探索新的天然产物作为生物活性剂的潜在来源越来越感兴趣，以最小的副作用治疗肥胖相关疾病。虽然 Cyclosorus terminans 提取物已在脂肪来源的干细胞中证明具有抗糖尿病和抗肥胖的功效，但其在高脂饮食 （HFD） 诱导的肥胖胰岛素抵抗大鼠模型中的心脏保护作用从未阐明。目的 检查 HFD 诱导的肥胖胰岛素抵抗大鼠模型中长期 Cyclosorus 末端活性处理对代谢、心脏和线粒体功能以及细胞凋亡的影响方法 雄性 Wistar 大鼠 （n=10） 持续喂食 HFD 并用载体（HFV，初榨油 2 ml/kg/天，p.o.，n=5）或环虫末端（HFC，100 mg/kg/天、 PO，n=5）持续 12 周。以正常饮食 （NDV， n=5） 喂养的大鼠作为对照，确认 HFD 诱导的肥胖的发展。使用超声心动图测量左心室射血分数 （LVEF） 和早期 （E） 和晚期 （A） 心室充盈速度之间的比率，并使用血清确定胰岛素抵抗的稳态模型评估 （HOMA-IR）。对心脏组织进行处理，通过红/绿荧光强度比值评估线粒体活性氧 （ROS） 水平、膜电位 （MMP） 变化和凋亡蛋白。结果 HFV 大鼠肥胖，心脏代谢功能受损，分别表现为降低 LVEF、E/A 比值和增加 HOMA-IR [图 1A-C]。 这些肥胖大鼠还存在线粒体 ROS 过量、MMP 去极化（红/绿比降低）和细胞凋亡（Bax 蛋白表达增加）（图 1D-F）。用环索斯末端聚糖 （HFC） 治疗显着减轻了线粒体功能障碍和细胞凋亡，从而在 HFD 喂养的大鼠中产生心脏代谢保护（图 1A-F）。结论 源自 Cyclosorus 末端的一种新的天然产物通过减少线粒体功能障碍和细胞凋亡，有效地保护心脏免受长期 HFD 诱导的心脏代谢损害。这些发现表明 Cyclosorus 末端是针对肥胖相关心脏并发症的新型心脏代谢保护措施。