Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage.

Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, P. R. China.
Molecular and Cellular Biochemistry (Impact Factor: 2.39). 04/2007; 298(1-2):49-57. DOI: 10.1007/s11010-006-9349-6
Source: PubMed

ABSTRACT 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. 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. 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.

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    ABSTRACT: During malaria infection in erythrocytes, critical markers including total cholesterol and triglyceride are markedly increased. Hence, finding new medicinal plants to have homeostatic effect on these markers during malaria infection are urgently needed. Andrographis paniculata is a medicinal plant and widely cultivated in Southeast Asia. This plant exhibits antioxidant property and used to treat liver disorder and control lipid profile. In this study, attempt is made to establish changes in plasma total cholesterol and triglyceride levels accompanying Plasmodium berghei ANKA infection in mice treated orally with aqueous crude extract of A. paniculata at 100, 300, and 600 mg/kg. Significant increases of total cholesterol and triglyceride levels in plasma were observed in infected untreated mice compared to normal control. However, treatment with 300 and 600 mg/kg of the extract produced significant reduction in plasma total cholesterol and triglyceride compared to untreated mice. Moreover, prolong survival time was found in infected mice treated with this extract. It can be concluded that the extract has anti-hyperlipemic property during malaria infection that can be explored for the management of malaria.
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    ABSTRACT: Objective: Aqueous extract of Andrographis paniculata leaves was subjected to analgesic activity in animal models. Materials and Methods: The study was carried out in male swiss albino mice weighing 25-30 gm.Analgesic activity of the aqueous extract of Andrographis paniculata leaves at doses 50,100,500mg/ kg p.o was evaluated using two animal models viz.acetic acid induced writhing and Eddy’s hot plate model. Results: Aqueous extract of Andrographis paniculata (AP) at doses 100mg and 500mg/Kg p.o. significantly reduced (P<0.01) acetic acid induced writhing in both acute and chronic study. The test drug at doses 100, 500mg/kg was better than the standard drug aspirin 150mg/kg in acute study.The percent reduction of abdominal constrictions was 20%, 56% and 57% at doses 50, 100 and 500mg/kg p.o. respectively compared to control in acute study. In chronic study the percent reduction of abdominal constriction was 15%, 69.4% and 70.4% at doses 50, 100 and 500mg/kg respectively. The extract increased the reaction time significantly at doses 50, 100 and 500mg/kg p.o in acute study at 15min, 30min and 60 min by Eddy’s hot plate model and maximum increase (P<0.01) was observed at dose 500mg/kg. In chronic study the analgesic activity of the extract was observed at all doses at 15 min and the mean reaction time increased significantly (P<0.001) at dose 500mg/kg at 30 min and diminished later. Conclusion: The results confirm the analgesic activity of Andrographis paniculata by both peripheral and central actions which were comparable to standard drug. The maximum effect was observed at dose 500mg/kg in both the models.
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    ABSTRACT: Since the emergence of drug resistant strains of malaria parasites, the rate of resistance has been increasing and limiting adequate treatment of malaria. Consequently, there is an urgent global need to isolate new classes of antimalarial compounds from natural sources. The aim of this study was to test Andrographis paniculata leaf extract for the ability to treat malaria. Methanolic leaf extract of A. paniculata was freshly dissolved in DMSO and diluted with 0.9% NaCl to obtain the doses of 2, 20, and 100 mg/kg. The four-day suppressive, curative effects against established infection and prophylactic models of the extract were carried out by intraperitoneal treatment the extracts in P. berghei ANKA infected ICR mice once a day, using chloroquine as a positive control. Parasitemia was then monitored, and percent inhibition was subsequently calculated. It was found that the extracts exerted dose dependent suppressive, prophylactic and curative effects. Interestingly, the extract at a dose of 100 mg/kg showed significantly (P<0.05) the highest activity for inhibition of malaria. Moreover, combination of chloroquine and the extract showed substantial enhancement in their antimalarial activity significantly (P<0.05) when compared to chloroquine treatment alone. It can be concluded that A. paniculata leaf extract has potential antimalarial property and in combination with chloroquine could be an effective, alternative source of herbal antimalarial drugs.
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