Neoandrographolide

Planta Med. 2010 Oct;76(15):1698-700.

Neoandrographolide from Andrographis paniculata as a potential natural chemosensitizer.[Pubmed: 20446243]

Extracts of the traditional medicinal herb Andrographis paniculata and its main constituents are described in the literature as showing anticancer activity. The aim of this study was to isolate the main constituents of a commercially available phytotherapeutic preparation of A. paniculata and to determine their chemosensitizing potential in a leukemia cell line.
METHODS AND RESULTS:
Chromatographic separation steps resulted in the isolation of the diterpenes andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (3) and the diterpene glucoside Neoandrographolide (2). The combination of these constituents with suboptimal concentrations of etoposide revealed compound 2 as chemosensitizer in S-Jurkat and X chromosome-linked inhibitor of apoptosis protein (XIAP)-overexpressing Jurkat cells, a model for chemoresistance.

Phytother Res. 2013 Apr;27(4):618-23.

Hypolipidemic effects of andrographolide and neoandrographolide in mice and rats.[Pubmed: 22744979]

Andrographolide (AND) and Neoandrographolide (NEO) are the diterpenoids from the Andrographis paniculata (Acanthaceae). It is reported the diterpenoids exhibit a wide spectrum of biological activities.
METHODS AND RESULTS:
The aim of this study was to investigate the hypolipidemic effect of AND and NEO in hyperlipidemic mice induced by 75% yolk emulsion and in hyperlipidemic rats induced by high fat emulsion, respectively. The results showed that the levels of triglyceride, total cholesterol (TC) and low-density lipoprotein cholesterol were reduced by AND and NEO in a dose-dependent tendency in mice. Compared with the model group, the plasma TC levels of experimental groups with AND and NEO at 100 mg/kg dosage decreased by 23.9 and 20.2% in rats, respectively (P < 0.05). It was also found that the plasma aspartate transaminase and alanine transaminase levels were significantly decreased by feeding with AND and NEO in rats, compared with positive group (simvastatin) (P < 0.01). Otherwise, AND and NEO could protect the cardiovascular due to down-regulation of iNOS expression and up-regulation of eNOS expression.
CONCLUSIONS:
In conclusion, AND and NEO have potent hypolipidemic effects and protect the cardiovascular without significant liver damage.

Am J Chin Med. 2007;35(2):317-28.

In vivo and in vitro anti-inflammatory activities of neoandrographolide.[Pubmed: 17436371]

Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for its anti-inflammatory activities and mechanism.
METHODS AND RESULTS:
Oral administration of Neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by dimethyl benzene in mice. Oral administration of Neoandrographolide (100-150 mg/kg) also reduced the increase in vascular permeability induced by acetic acid in mice. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of Neoandrographolide on suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Respiratory bursts were quantified by chemiluminescence (CL) measurements. Results showed that Neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 muM to 150 muM. Neoandrographolide also inhibited NO and TNF-alpha production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata.
CONCLUSIONS:
These results indicate that Neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.

Mol Cell Biochem. 2007 Apr;298(1-2):49-57.

Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage.[Pubmed: 17109078]

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), produce excessive amounts of nitric oxide (NO) and prostaglandin E(2) (PGE(2)), which play key roles in the processes of inflammation. Andrographis paniculata Nees is a traditional Chinese herb commonly used for treatment of infection, inflammation, and diarrhea. However, the mechanism of its therapeutic function is not well known.
METHODS AND RESULTS:
In the present study, the effect of Neoandrographolide, one of bioactive components in A. paniculata, on iNOS-mediated NO production and COX-2-mediated PGE(2) in bacterial lipopolysaccharide (LPS) stimulated-murine macrophages was investigated. Neoandrographolide at concentrations (30-90 microM) significantly (p<0.05) inhibited the productions of NO and PGE(2) in LPS stimulated macrophages without inducing cytotoxicity. The effect of Neoandrographolide also has been investigated on iNOS and COX-2 expression in activated macrophage by using RT-PCR and immunoblotting. The inhibition of NO release by Neoandrographolide can be attributed to the block of iNOS mRNA transcription followed by inhibiting protein expression. However, Neoandrographolide inhibited COX-2 protein expression only but without inhibiting COX-2 mRNA expression, which was involved in the inhibitory activity against the PGE(2 )overproduction. This suggests that the effect of Neoandrographolide on iNOS expression may occur at the transcriptional level and the inhibition of COX-2 expression occurs at the translational level. Furthermore, we have found that the addition of Neoandrographolide inhibited the activation of p38 mitogen-activated protein kinase (MAPKs) instead of JNK, ERK1/2, or NF-kappaB.
CONCLUSIONS:
These results indicated that the anti-inflammatory properties of Neoandrographolide might result from the inhibition of iNOS and COX-2 expression through inhibiting p38 MAPKs activation. Therefore, Neoandrographolide isolated from A. paniculata could be offered as a leading compound for anti-inflammation.