Ahmad Zaved, Ishfaq Pir Mohammad, Jain Subodh Kumar, Mishra Siddhartha Kumar
Cancer Biology Laboratory, Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Central University, Sagar, MP 470003, India.
Department of Biochemistry, University of Lucknow, Lucknow, UP 226007, India.
Environ Toxicol Pharmacol. 2025 Mar;114:104648. doi: 10.1016/j.etap.2025.104648. Epub 2025 Jan 30.
Chaga mushroom (Inonotus obliquus) has been a component of folk medicine treating several disorders mainly through its anti-inflammatory and antioxidant properties, yet its effects on liver carcinoma needed elucidation. This study investigated the effect of an aqueous extract of Inonotus obliquus (IOAE) against diethyl-nitrosamine/carbon tetrachloride (DEN/CCl) induced HCC in mice and addressed its molecular mechanism. HCC was induced by a single intraperitoneal injection (i.p.) of DEN (1 mg/kg b.w.) followed by CCl (0.2 ml/kg, i.p., twice a week) after six weeks. IOAE (200 mg/kg b.w.) was administered orally after the induction of HCC. Physiological and hematological parameters and biochemical assays for oxidative stress markers were performed. Histopathological and immunohistochemistry for inflammation and apoptosis were performed. DEN/CCl caused a reduction in mice body weight and an increase in the liver weight which was significantly restored by IOAE administration. The tumor incidence of DEN/CCl (100 %) was reduced to about 25 % by IOAE supplementation. DEN/CCl caused alterations in the hematological parameters, serum total protein albumin globulin, A/G ratio, liver function markers (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase gamma-glutamyl transferase, acid phosphatase and bilirubin) and lipid profile markers that were significantly restored by IOAE administration. Oxidative stress markers (malondialdehyde, superoxide dismutase, catalase, nitric oxide, lactate dehydrogenase, and glutathione-s-transferase) were reduced by DEN/CCl which were significantly restored by IOAE treatment. The liver histopathology alterations caused by DEN/CCl were significantly ameliorated by IOAE treatment. Immunohistochemical studies suggest that AFP, caspase-3, COX-2, and iNOS were chronically overexpressed in DEN/CCl-exposed mice which were notably attenuated by IOAE administration. Collectively IOAE was found to suppress tumor incidence by suppressing iNOS-COX-2-dependent inflammation and caspase-3 mediated apoptosis. Chaga mushroom showed remarkable anticancer effects against liver carcinoma through induction of apoptosis and suppression of inflammation.
桦褐孔菌（Inonotus obliquus）一直是民间医学的组成部分，主要通过其抗炎和抗氧化特性来治疗多种疾病，但其对肝癌的影响仍需阐明。本研究调查了桦褐孔菌水提取物（IOAE）对二乙基亚硝胺/四氯化碳（DEN/CCl）诱导的小鼠肝癌的影响，并探讨了其分子机制。通过腹腔注射（i.p.）单次给予DEN（1 mg/kg体重）诱导肝癌，六周后给予CCl（0.2 ml/kg，i.p.，每周两次）。肝癌诱导后口服IOAE（200 mg/kg体重）。进行了生理和血液学参数以及氧化应激标志物的生化检测。进行了炎症和凋亡的组织病理学和免疫组织化学检测。DEN/CCl导致小鼠体重减轻和肝脏重量增加，IOAE给药后显著恢复。补充IOAE可使DEN/CCl的肿瘤发生率（100 %）降至约25 %。DEN/CCl导致血液学参数、血清总蛋白、白蛋白、球蛋白、A/G比值、肝功能标志物（天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶、酸性磷酸酶和胆红素）以及脂质谱标志物发生改变，IOAE给药后显著恢复。DEN/CCl降低了氧化应激标志物（丙二醛、超氧化物歧化酶、过氧化氢酶、一氧化氮、乳酸脱氢酶和谷胱甘肽-S-转移酶），IOAE治疗后显著恢复。IOAE治疗显著改善了DEN/CCl引起的肝脏组织病理学改变。免疫组织化学研究表明，AFP、caspase-3、COX-2和iNOS在DEN/CCl暴露的小鼠中慢性过度表达，IOAE给药后明显减弱。总体而言，发现IOAE通过抑制iNOS-COX-2依赖性炎症和caspase-3介导的凋亡来抑制肿瘤发生率。桦褐孔菌通过诱导凋亡和抑制炎症对肝癌显示出显著的抗癌作用。
