Ali Dalia E, Sweilam Sherouk Hussein, Atwa Ahmed M, Elgindy Ali M, Mustafa Aya M, Esmail Manar M, Alkabbani Mahmoud Abdelrahman, Senna Mohamed Magdy, El-Shiekh Riham A
Pharmacognosy and Natural Products Department, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia.
Inflammopharmacology. 2025 Mar 31. doi: 10.1007/s10787-025-01660-x.
The oleoresins of the Araucaria bidwillii Hook. (A.B.) are commonly used for the treatment of several conditions. However, the full phytochemical profile of its active compounds and its mechanism of action to protect the liver from toxicity remain unclear. The purpose of this research was to investigate the complete set of data relating to the A.B. active metabolites and explore the hepatoprotective properties of AB ethanolic extract on MTX-induced liver injury mainly due to its anti-inflammatory role. Hepatic markers, oxidative stress, inflammatory mediators, the NOTCH/NICD signaling cascade, HES1 expression, HMGB1/TLR4, and the PI3K/mTOR axis were assessed. HPLC-HRMS/MS analysis of A.B. led to the annotation of fifteen compounds from different classes, where diterpenes are the dominant class. Additionally, A.B. (100 and 200 mg/kg) significantly decreased hepatic markers, oxidative stress, and inflammatory mediators. Moreover, the extract significantly increased NOTCH pathway stimulation and HES1 expression, accompanied by a significant decline in the NUMB and HMGB1/TLR4 axes. In addition, it significantly inhibited the PI3K/mTOR pathway, with a prominent effect at the higher dose. This study presents A.B. as a promising hepatoprotective agent through stimulation of the NOTCH pathway and inhibition of the HMGB1/TLR4 pathway, as well as the PI3K/mTOR/NF-κB axis, besides its antioxidant and anti-inflammatory effects.
南洋杉（Araucaria bidwillii Hook.，简称A.B.）的含油树脂常用于治疗多种病症。然而，其活性化合物的完整植物化学特征及其保护肝脏免受毒性作用的机制仍不清楚。本研究的目的是调查与A.B.活性代谢物相关的全套数据，并探索A.B.乙醇提取物对甲氨蝶呤（MTX）诱导的肝损伤的保肝特性，主要是因其抗炎作用。评估了肝脏标志物、氧化应激、炎症介质、NOTCH/NICD信号级联、HES1表达、HMGB1/TLR4以及PI3K/mTOR轴。对A.B.进行的HPLC-HRMS/MS分析鉴定出了15种不同类别的化合物，其中二萜类是主要类别。此外，A.B.（100和200 mg/kg）显著降低了肝脏标志物、氧化应激和炎症介质。此外，该提取物显著增加了NOTCH途径的激活和HES1表达，同时NUMB和HMGB1/TLR4轴显著下降。此外，它显著抑制了PI3K/mTOR途径，在较高剂量时效果显著。本研究表明，A.B.除了具有抗氧化和抗炎作用外，还通过刺激NOTCH途径、抑制HMGB1/TLR4途径以及PI3K/mTOR/NF-κB轴，是一种有前景的保肝剂。
