Intracellular glutathione regulates Andrographolide-induced cytotoxicity on hepatoma Hep3B cells

Redox Rep. 2009;14(4):176-84.

Ji L, Shen K, Liu J, Chen Y, Liu T, Wang Z.

Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic China. jll_syc@yahoo.com.cn

Andrographolide (ANDRO), a diterpenoid lactone isolated from the traditional herbal plant Andrographis paniculata, was reported to induce apoptosis in hepatoma Hep3B cells in our previous study (Ji LL, Liu TY, Liu J, Chen Y, Wang ZT. Andrographolide inhibits human hepatoma-derived Hep3B cells growth through the activation of c-Jun N-terminal kinase. Planta Med 2007; 73: 1397-1401). The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in ANDRO-induced apoptosis. ANDRO initially increased intracellular GSH levels which then decreased later, while inhibition of cellular GSH synthesis by L-Buthionine-(S,R)-sulfoximine (BSO) augmented ANDRO-induced cytotoxicity and apoptosis in Hep3B cells. On the other hand, the thiol antioxidant dithiothreitol (DTT) rescued ANDRO-depleted cellular GSH, and abrogated ANDRO-induced cytotoxicity and apoptosis. Furthermore, BSO pretreatment augmented ANDRO-decreased expression of antioxidant protein thioredoxin 1 (Trx1), while DTT reversed this decrease. Further results showed that ANDRO increased the activity of the GSH-related antioxidant enzyme glutathione peroxidase (GPx) and the production of intracellular reactive oxygen species (ROS). Taken together, this study demonstrates that the intracellular redox system plays important roles in regulating the cytotoxicity of ANDRO on hepatoma Hep3B cells.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 19695125 [PubMed - in process]

Antinociceptive and Antiedematogenic Activities of Andrographolide Isolated From Andrographis paniculata in Animal Models

Biol Res Nurs. 2009 Aug 18. [Epub ahead of print]

Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas
J, Moin S, Israf DA.

The current study was performed to evaluate the antinociceptive and
antiedematogenic properties of andrographolide isolated from the
leaves of Andrographis paniculata using two animal models.
Antinociceptive activity was evaluated using the acetic acid-induced
writhing and the hot-plate tests, while antiedematogenic activity was
measured using the carrageenan-induced paw edema test. Subcutaneous
(s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did
not affect the motor coordination of the experimental animals but
produced significant (p < .05) antinociceptive activity when assessed
using both tests. However, 2 mg/kg naloxone failed to affect the 25
mg/kg andrographolide activity in both tests, indicating that the
activity was modulated via nonopioid mechanisms. Furthermore,
andrographolide showed significant (p < .05) antiedematogenic
activity. In conclusion, the results obtained suggest that
andrographolide has antinociceptive and antiedematogenic activities;
it may be useful for treating pain and inflammation once human studies
are conducted.

PMID: 19689990 [PubMed - as supplied by publisher]

Potency of Andrographolide as an Antitumor Compound in BHC-Induced Liver Damage

Integr Cancer Ther. 2009 Jun;8(2):177-89.

 
Trivedi NP, Rawal UM, Patel BP.

Department of Zoology, School of Sciences, Gujarat University.

Relevance. The present investigation relates to the influence of andrographolide, an active compound of Andrographis paniculata Nees. It reverses an experimental liver carcinogenic condition of mice to normal and might be a potential therapeutic/preventive agent for human liver cancer. Objective. A. paniculata (Kalmegh) is extensively used in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have protective effect against different hepatotoxins. Materials and methods. Histomorphological, ultrastructural, and biochemical studies were performed for the effect of the andrographolide on control mice, mice treated with hexachlorocyclohexane (BHC) only and BHC + andrographolide. Enzymes for liver function tests were analyzed by spectrophotometric method. RESULTS: The BHC experimental model forms an irreversible liver tumor in male mice. The histological and ultrastructural changes observed in andrographolide supplementation emphasize the recovery of the damaged liver. This recovery was also reflected in the neoplastic nodule formation. The activity of phosphorylase and glucose-6-phosphatase in the liver of the andrographolide-supplemented group suggests improved glycogenolysis in liver. Serum glutamate pyruvate transaminase, serum glutamate oxalate transaminase, alkaline phosphatase, acid phosphatase, and gamma-glutamyl transpeptidase showed a significant decrease in andrographolide-supplemented animals as compared with BHC-treated animals, suggesting regenerative effects elicited by andrographolide. CONCLUSION: The study indicates that the regenerative capability elicited by andrographolide is possibly due to its ability to reactivate liver function enzymes that catalyze the reaction of several biochemical and synthetic processes and that it may be useful for severe liver damage conditions.

PMID: 19679627 [PubMed - in process]