1: Planta Med. 2007 Oct 4; [Epub ahead of print]
Andrographolide Inhibits Human Hepatoma-Derived Hep3B Cell Growth through the Activation of c-Jun N-Terminal Kinase.
Ji L, Liu T, Liu J, Chen Y, Wang Z.
Key Laboratory of Standardization of Chinese Medicines of Education, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Andrographolide (Andro) is a potentially anti-inflammatory diterpenoid lactone isolated from the traditional herbal medicine ANDROGRAPHIS PANICULATA, which has been effectively used for the treatment of infection, inflammation, cold, fever and diarrhea in China for centuries. In the current study, we found that Andro significantly decreased the number of surviving hepatoma-derived Hep3B cells in the MTT assay and induced cell apoptosis. Further study showed that Andro induced activation of mitogen-activated protein kinases (MAPKs) including p38 kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-related kinases (ERK1/2), but had no significant effect on caspase-3, Bcl-xL and Bcl-2, which are apoptosis-related proteins. Moreover, inhibition of JNK activation partially rescued the toxic effect of Andro on Hep3B cells. Therefore, our results indicate that the JNK signaling pathway plays an important role in the toxic effect of Andro on Hep3B cells. Andro:andrographolide CDK:cyclin-dependent kinase ELISA:enzyme-linked immunosorbent assay ERK1/2:extracellular signal-related kinases FBS:fetal bovine serum HCC:hepatocellular carcinoma HPLC:high pressure liquid chromatography JNK:c-Jun N-terminal kinase MAPK:mitogen-activated protein kinase MEM:modified Eagle's medium RTKs:receptor tyrosine kinases.
PMID: 17918040 [PubMed - as supplied by publisher]
2: Toxicol Appl Pharmacol. 2007 Jul 28; [Epub ahead of print] Related Articles, LinkOut
Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes.
Jaruchotikamol A, Jarukamjorn K, Sirisangtrakul W, Sakuma T, Kawasaki Y, Nemoto N.
Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, beta-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 or AhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A. paniculata, according to its ability to induce CYP1A1 expression.
PMID: 17825862 [PubMed - as supplied by publisher]
3: Mol Biol Rep. 2007 Sep 5; [Epub ahead of print] Related Articles, LinkOut
Antioxidant action of Andrographis paniculata on lymphoma.
Verma N, Vinayak M.
Biochemistry & Molecular Biology Lab, Department of Zoology, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India, manjulavinayak@rediffmail.com.
Regulation of the balance between production of reactive oxygen species (ROS) by cellular processes and its removal by antioxidant defense system maintains normal physiological processes. Any condition leading to increased ROS results in oxidative stress which has been related with a number of diseases including cancer. Improvement in antioxidant defense system is required to overcome the damaging effects of oxidative stress. Therefore in the present study, effect of the aqueous extract of a medicinal plant Andrographis paniculata (AP) on antioxidant defense system in liver is investigated in lymphoma bearing AKR mice. Estimating catalase, superoxide dismutase and glutathione S transferase monitored the antioxidant action. Oral administration of the aqueous extract of A. paniculata in different doses causes a significant elevation of catalase, superoxide dismutase and glutathione S transferase activities. It reveals the antioxidant action of the aqueous extract of AP, which may play a role in the anticarcinogenic activity by reducing the oxidative stress. LDH activity is known to increase in various cancers due to hypoxic condition. Lactate dehydrogenase is used as tumor marker. We find a significant decrease in LDH activity on treatment with AP, which indicates a decrease in carcinogenic activity. A comparison with Doxorubicin (DOX), an anticancerous drug, indicates that the aqueous extract of AP is more effective than DOX with respect to its effect on catalase, superoxide dismutase, glutathione S transferase as well as on lactate dehydrogenase activities in liver of lymphoma bearing mice.
PMID: 17805989 [PubMed - as supplied by publisher]
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