Lotfy Mohamed, Khalaf Abdallah, AlBarghouthy Faisal, Alhashmi Abdulla, Adam Hesham, Almesmari Abdulla, Kundu Biduth, Ksiksi Taoufik
Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
PLoS One. 2025 Jun 26;20(6):e0326676. doi: 10.1371/journal.pone.0326676. eCollection 2025.
Diabetes mellitus, characterized by chronic hyperglycemia, is a global health challenge. Effective management strategies often focus on improving insulin sensitivity and enhancing antioxidant defenses to mitigate diabetes-related complications. This study explored the therapeutic potential of Conocarpus lancifolius (Co) and crocin in modulating insulin signaling and antioxidant gene expression in diabetic rats.
Male Wistar rats were rendered diabetic via alloxan injection and treated orally with C. lancifolius and crocin. Control groups included normal healthy control and untreated diabetic rats. Insulin signaling pathways were assessed by measuring key markers such as protein kinase B (AKT) through western blot and RT-PCR analysis. Antioxidant gene expressions, including superoxide dismutase (SOD), were quantified to evaluate oxidative stress response.
C. lancifolius and crocin treatment significantly improved fasting blood-glucose levels and insulin sensitivity in diabetic rats. Notably, C. lancifolius and crocin administration resulted in the upregulation of AKT, promoting glucose uptake in peripheral tissues. Additionally, C. lancifolius and crocin increased the expression of the SOD gene, improving antioxidant defense in diabetic rats.
C. lancifolius and crocin had a dual beneficial effect on diabetic rats by modulating key components of the insulin signaling pathway and bolstering antioxidant defenses. The upregulation of AKT as a key gene in insulin signaling pathways suggests an improvement in insulin sensitivity, which is crucial for glycemic control. Concurrently, the elevated antioxidant SOD gene expression indicates reduced oxidative stress, which is vital for preventing diabetic complications.
Our findings demonstrate that C. lancifolius and crocin significantly improved glucose tolerance, reduced fasting blood glucose levels, and enhanced antioxidant defense in diabetic rats. Histopathological improvements in the pancreas, liver, kidney, and heart further highlight their protective effects against diabetes-induced tissue damage. Additionally, the upregulation of SOD and AKT at both gene and protein levels suggests a role in modulating oxidative stress and insulin signaling pathways. While promising, further studies are needed to clarify their molecular mechanisms, particularly regarding insulin receptor interaction. These findings support the use of C. lancifolius and crocin as natural adjunct therapies to enhance diabetes treatment outcomes.
糖尿病以慢性高血糖为特征，是一项全球性的健康挑战。有效的管理策略通常侧重于提高胰岛素敏感性和增强抗氧化防御能力，以减轻糖尿病相关并发症。本研究探讨了窄叶红树（Co）和藏红花素对糖尿病大鼠胰岛素信号传导和抗氧化基因表达的调节作用。
通过注射四氧嘧啶使雄性Wistar大鼠患糖尿病，并口服窄叶红树和藏红花素进行治疗。对照组包括正常健康对照和未治疗的糖尿病大鼠。通过蛋白质印迹法和逆转录-聚合酶链反应（RT-PCR）分析测量关键标志物，如蛋白激酶B（AKT），以评估胰岛素信号通路。对包括超氧化物歧化酶（SOD）在内的抗氧化基因表达进行定量，以评估氧化应激反应。
窄叶红树和藏红花素治疗显著改善了糖尿病大鼠的空腹血糖水平和胰岛素敏感性。值得注意的是，给予窄叶红树和藏红花素导致AKT上调，促进外周组织对葡萄糖的摄取。此外，窄叶红树和藏红花素增加了SOD基因的表达，改善了糖尿病大鼠的抗氧化防御能力。
窄叶红树和藏红花素通过调节胰岛素信号通路的关键成分和增强抗氧化防御能力，对糖尿病大鼠具有双重有益作用。作为胰岛素信号通路中的关键基因，AKT的上调表明胰岛素敏感性得到改善，这对血糖控制至关重要。同时，抗氧化SOD基因表达的升高表明氧化应激降低，这对于预防糖尿病并发症至关重要。
我们的研究结果表明，窄叶红树和藏红花素显著改善了糖尿病大鼠的葡萄糖耐量，降低了空腹血糖水平，并增强了抗氧化防御能力。胰腺、肝脏、肾脏和心脏的组织病理学改善进一步突出了它们对糖尿病诱导的组织损伤的保护作用。此外，SOD和AKT在基因和蛋白质水平上的上调表明它们在调节氧化应激和胰岛素信号通路中发挥作用。虽然前景广阔，但需要进一步研究来阐明其分子机制，特别是关于胰岛素受体相互作用的机制。这些发现支持使用窄叶红树和藏红花素作为天然辅助疗法来提高糖尿病治疗效果。
