Ajith Thekkuttuparambil Ananthanarayanan, Janardhanan Kainoor Krishnankutty
Department of Biochemistry, Amala Institute of Medical Sciences, Thrissur, Kerala, India.
J Exp Ther Oncol. 2006;5(4):309-21.
Chemoprevention is an important alternative approach to control cancer. Chemical substances with multiple inhibitory properties would be a welcome addition to the class of chemopreventive drugs. In this study, we investigated the antioxidant, anti-inflammatory, antimutagenic and cancer preventive activities of aqueous extract of a macrofungus Phellinus rimosus (Berk) Pilat. The extract exhibited superoxide anion (O2-), hydroxyl radical (OH), nitric oxide (NO) scavenging and lipid peroxidation inhibiting activities. The inhibitory concentrations required by the extract to scavenge 50% (IC50) of the superoxide anion, hydroxyl radical and nitric oxide generated were 126 +/- 5.1, 71 +/- 4.7 and 31 +/- 4.5 microg/ml respectively. The concentration required to inhibit 50% of Fe2+ induced lipid peroxidation in rat liver homogenate was 318 +/- 2.4 microg/ml. The extract showed significant (P<0.05) anti-inflammatory activity in a dose dependent manner. Extract (100 mg/kg body wt, p.o) inhibited 44.5, 45.4 and 47% carrageenen, dextran and formalin induced inflammations respectively. The antimutagenic activity was determined by the Ames' Salmonella mutagenecity assay using histidine mutant Salmonella typhimurium strains. The extract at concentration of 5 mg/plate showed antimutagenecity against benzo[a]pyrene (B[a]P) and 4-nitro-o-pheneylenediamine (NPDA) induced mutations of TA98 and TA100 respectively. Anticarcinogenic activity was evaluated using N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma (HCC) in rats. Serum gamma glutamyl transpeptidase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) activities and lipid peroxidation level (MDA) were elevated significantly (P<0.05) in the NDEA alone treated group of animals. Treatment of the extract (25 and 50 mg/kg body wt, p.o.) prior to the NDEA administration decreased the serum GGT, GOT, GPT and ALP activities and MDA level in a dose dependent manner. The NDEA alone treated animals showed altered serum albumin/globulin ratio (A:G ratio), hyperfibrinogenaemia, increased hepatic glutathione S-transferase (GST) activity, glutathione-peroxidsae (GPx) activity and reduced glutathione (GSH) level compared to the extract plus NDEA treated group. The extract also inhibited in vitro aniline hydroxylase (AH) activity of rat liver induced by phenobarbitone in a dose dependent manner. The results, thus suggest the significant chemopreventive properties of the aqueous extract of the Phellinus rimosus against NDEA induced hepatocellular carcinoma by its antioxidant, anti-inflammatory and antimutagenic activities.
化学预防是控制癌症的一种重要替代方法。具有多种抑制特性的化学物质将是化学预防药物类别的一个受欢迎的补充。在本研究中，我们研究了大型真菌皱盖乌芝（Phellinus rimosus (Berk) Pilat）水提取物的抗氧化、抗炎、抗诱变和癌症预防活性。该提取物表现出超氧阴离子（O2-）、羟基自由基（OH）、一氧化氮（NO）清除以及脂质过氧化抑制活性。提取物清除50%（IC50）超氧阴离子、羟基自由基和一氧化氮所需的抑制浓度分别为126±5.1、71±4.7和31±4.5微克/毫升。抑制大鼠肝匀浆中50% Fe2+诱导的脂质过氧化所需的浓度为318±2.4微克/毫升。提取物以剂量依赖性方式显示出显著（P<0.05）的抗炎活性。提取物（100毫克/千克体重，口服）分别抑制角叉菜胶、右旋糖酐和福尔马林诱导的炎症44.5%、45.4%和47%。抗诱变活性通过使用组氨酸突变鼠伤寒沙门氏菌菌株的Ames沙门氏菌诱变性试验来测定。浓度为5毫克/平板的提取物分别对苯并[a]芘（B[a]P）和4-硝基邻苯二胺（NPDA）诱导的TA98和TA100突变表现出抗诱变活性。使用N-亚硝基二乙胺（NDEA）诱导大鼠肝细胞癌（HCC）来评估抗癌活性。单独用NDEA处理的动物组中，血清γ-谷氨酰转肽酶（GGT）、谷氨酸草酰乙酸转氨酶（GOT）、谷氨酸丙酮酸转氨酶（GPT）和碱性磷酸酶（ALP）活性以及脂质过氧化水平（MDA）显著升高（P<0.05）。在给予NDEA之前用提取物（25和50毫克/千克体重，口服）处理以剂量依赖性方式降低了血清GGT、GOT、GPT和ALP活性以及MDA水平。与提取物加NDEA处理组相比，单独用NDEA处理的动物表现出血清白蛋白/球蛋白比值（A:G比值）改变、高纤维蛋白原血症、肝谷胱甘肽S-转移酶（GST）活性增加、谷胱甘肽过氧化物酶（GPx）活性增加以及还原型谷胱甘肽（GSH）水平降低。提取物还以剂量依赖性方式抑制苯巴比妥诱导的大鼠肝体外苯胺羟化酶（AH）活性。因此，结果表明皱盖乌芝水提取物通过其抗氧化、抗炎和抗诱变活性对NDEA诱导的肝细胞癌具有显著的化学预防特性。
