Hussein Rehab A, AbouZeid Enaam M, Saleh Dalia O, Jaleel Gehad A Abdel, El Aty Abeer A Abd, Morita Hiroyuki, El-Beih Ahmed A
Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, 12622, Giza, Egypt.
Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, 12622, Giza, Egypt.
Sci Rep. 2025 Jul 2;15(1):23554. doi: 10.1038/s41598-025-05875-4.
The genus Chaetomium, Chaetomiaceae, is a promising source of secondary metabolites with proven pharmacological activities. In the present study, a new strain of Chaetomium globosum (KM651986) was investigated resulting in the isolation of two unreported lecanoric acid derivatives 1 and 2, for the first time, which were analyzed using spectroscopic methods, SwissSimilarity, and SwissTargetPrediction. Thus, predicting the possible biological targets for 1 and 2. Consequently, the crude methanol extract of C. globosum, compounds 1 and 2 were investigated for their anti-diabetic activity using streptozocin (STZ) - induced diabetic rat model. Results indicated that the crude extract C. globosum and compounds 1 and 2 significantly impacted serum glucose, insulin, HbA1c levels, hepatic glucose-6-phosphate dehydrogenase (G6PD) content, cAMP levels, and hepatic α-amylase content. Compound 2 showed a significant decrease in serum glucose by 40% and an increase in insulin level by 65% compared to STZ-diabetic rats, indicating its potent anti-hyperglycemic effect and potential in improving insulin secretion and cell regeneration. Compound 2 also elevated hepatic G6PD, normalized cAMP levels, and decreased hepatic α-amylase, indicating its potential in improving glucose metabolism at the hepatic level. Therefore, compound 2 emerges as particularly promising anti-diabetic candidate meriting further investigation into its potential therapeutic mechanisms of action.
毛壳菌属（Chaetomium）隶属毛壳菌科（Chaetomiaceae），是次生代谢产物的一个有前景的来源，其药理活性已得到证实。在本研究中，对一株新的球毛壳菌（Chaetomium globosum，KM651986）进行了研究，首次分离出两种未报道的地衣酸衍生物1和2，并使用光谱方法、SwissSimilarity和SwissTargetPrediction对其进行了分析。从而预测了化合物1和2可能的生物学靶点。因此，利用链脲佐菌素（STZ）诱导的糖尿病大鼠模型，对球毛壳菌的粗甲醇提取物、化合物1和2的抗糖尿病活性进行了研究。结果表明，球毛壳菌粗提取物、化合物1和2对血清葡萄糖、胰岛素、糖化血红蛋白（HbA1c）水平、肝葡萄糖-6-磷酸脱氢酶（G6PD）含量、环磷酸腺苷（cAMP）水平和肝α-淀粉酶含量有显著影响。与STZ诱导的糖尿病大鼠相比，化合物2使血清葡萄糖显著降低了40%，胰岛素水平升高了65%，表明其具有强大的降血糖作用以及改善胰岛素分泌和细胞再生的潜力。化合物2还提高了肝G6PD水平，使cAMP水平恢复正常，并降低了肝α-淀粉酶水平，表明其在肝脏水平改善葡萄糖代谢的潜力。因此，化合物2成为特别有前景的抗糖尿病候选物，值得进一步研究其潜在的治疗作用机制。
