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

Abstract

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 γ-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.

Andrographolide inhibits the expression and metabolic activity of cytochrome P450 3A4 in the modified Caco-2 cells

“…It has been reported that andrographolide (Fig. 1) has many bioactivities, such as anti-inflammatory (Abu-Ghefreh et al, 2009;Bao et al, 2009), antiplatelet aggregation (Thisoda et al, 2006), antihyperglycemic (Yu et al, 2003), choleretic (Shukla et al, 1992), anti-tumor (Trivedi et al, 2009) and anti-human immunodeficiency virus (HIV) activities (Basak et al, 1999). This compound has been widely used in clinical situations in China for the treatment of fever, cold, inflammation, diarrhea and other infectious diseases.…”

Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P‐glycoprotein

“…Supporting Information Correspondence to: Zhongqiu Liu (Telephone: +86-20-6164-8596; Fax: +86-20-6164-8596; E-mail: liuzq@smu.edu.cn), Ming Hu (Telephone: +713-795-8320; Fax: +713-795-8305; E-mail: mhu@uh.edu) active oxygen species-dependent apoptosis in lymphoma lines, 1 reverse liver carcinogenesis induced by hexachlorocyclohexane, 2 and inhibit the migration and invasion of human colorectal carcinoma (LoVo) cells via downregulation of matrix metalloproteinase-7 expression. 3 In many cancer cell types, AP was also capable of inducing G 0 /G 1 cell-cycle arrest, 4,5 promoting tumor necrosis factor-related apoptosisinducing ligand (TRAIL; an important member of extrinsic apoptosis)-mediated apoptosis, 6 activating p53 via enhanced phosphorylation, and inhibiting nuclear factor-kappa B (NF-6B)-associated transcriptional and angiogenic factors.…”

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

“…This study indicated a reversal of the histomorphological and ultrastructural changes induced by BHC, along with improved glycogenesis in the liver due to increased activities of glucose-6-phosphate and phosphorylase. Regenerative effects elicited by andrographolide were the result of decreased activities of serum glutamate pyruvate transaminase, serum glutamate oxalate transaminase, alkaline phosphatase (AP), ornithine carbomoyl transferase and acid phosphatase, all of which are markers of liver damage [138] . A recent investigation by Dhanasekaran et al [139] on the epoxy clerodane diterpene extracted from Tinospora cordifolia proposed increases in the hepatic antioxidant status of Wistar rats administered with DENA to induce HCC.…”