Cancer: Leukemia, colorectal, lung
Action: Immunomodulatory,anti-inflammatory,anti-metastatic
Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata [(Burm. f.) Wall. Ex Nees], is known to possess multiple pharmacological activities. Andrographolide has been shown to exhibit antioxidative, anti-cancer, anti-inflammatory, anti-diabetes, and anti-aging properties (Trivedi et al., 2007; Chao et al., 2010).
Immunomodulatory Activity
The immunomodulatory activity of HN-02, an extract containing a mixture of andrographolides, was evaluated at 1.0, 1.5, and 2.5 mg/kg on different in vivo and in vitro experimental models. It was also found that HN-02 treatment stimulated phagocytosis in mice. A significant increase in total WBC count and relative weight of spleen and thymus was observed in mice during 30 days of treatment with HN-02.
The present experimental findings demonstrate that HN-02 has the ability to enhance immune function, possibly through modulation of immune responses altered during antigen interaction, and to reverse the immunosuppression induced by CYP (Naik, 2009).
The ethanol extract and purified diterpene andrographolides of Andrographis paniculata (Acanthaceae) induced significant stimulation of antibody and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) in mice. The plant preparations also stimulated non-specific immune response of the animals measured in terms of macrophage migration index (MMI) phagocytosis of Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and non-specific immune response was, however, of lower order with andrographolide than with the ethanol extract, suggesting that substance(s) other than andrographolide present in the extract may also be contributing towards immunostimulation (Puri, 1993)
Anti-inflammatory and Leukemic Therapies
Andrographolide has been shown to attenuate MMP-9 expression, with its main mechanism likely involving the NF-κB signal pathway. These results provide new opportunities for the development of new anti-inflammatory and leukemic therapies. This activity was shown in a study in which andrographolide (1–50µM) exhibited concentration-dependent inhibition of MMP-9 activation, induced by either tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS), in THP-1cells.
Anti-inflammatory
Lee et al (2012) found that andrographolide could significantly inhibit the degradation of inhibitor-κB-α (IκB-α) induced by TNF-α. They used electrophoretic mobility shift assay and reporter gene detection to show that andrographolide also markedly inhibited NF-signaling, anti-translocation and anti-activation. These results provide new opportunities for the development of new anti-inflammatory and leukemic therapies.
Lung Cancer Metastasis
Andrographolide is known to have the potential to be developed as a chemotherapeutic agent, in particular in the treatment of lung cancer. In order to understand the anti-cancer properties of andrographolide, its effect on migration and invasion in human lung cancer A549 cells was examined. The results of the wound-healing assay and the in vitro transwell assay revealed that andrographolide inhibited dose-dependently the migration and invasion of A549 cells under non-cytotoxic concentrations.
These results indicated that andrographolide exerted an inhibitory effect on the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The andrographolide-inhibited MMP-7 expression or activity appeared to occur via activator protein-1 (AP-1) because its DNA binding activity was suppressed by andrographolide. Additionally, the transfection of Akt over-expression vector (Akt1 cDNA) to A549 cells could result in an increase expression of MMP-7 concomitantly with a marked induction on cell invasion. These findings suggested that the inhibition on MMP-7 expression by andrographolide may be through suppression on PI3K/Akt/AP-1 signaling pathway, which in turn leads to the reduced invasiveness of the cancer cells (Lee, 2010).
Colorectal Cancer
Andrographolide has also been shown to have potent anti-cancer activity against human colorectal carcinoma Lovo cells by inhibiting cell-cycle progression. To further investigate the mechanism for the anti-cancer properties of andrographolide, it was used to examine the effect on migration and invasion of Lovo cells. The results of wound-healing assay and in vitro transwell assay revealed that andrographolide inhibited dose-dependently the migration and invasion of Lovo cells under non-cytotoxic concentrations.
The down-regulation of MMP-7 appeared to be via the inactivation of activator protein-1 (AP-1) since the treatment with andrographolide suppressed the nuclear protein level of AP-1, which was accompanied by a decrease in DNA-binding level of the factor. Taken together, these results indicate that andrographolide reduces the MMP-7-mediated cellular events in Lovo cells, and provide a new mechanism for its anti-cancer activity (Shi, 2009)
Anti-inflammatory, Induces Apoptosis
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important member of the tumor necrosis factor subfamily with great potential in cancer therapy; additionally andrographolide is known to possess potent anti-inflammatory and anti-cancer activities which may be attributed to its action on TRAIL. It has been shown that pre-treatment with andrographolide significantly enhances TRAIL-induced apoptosis in various human cancer cell lines, including those TRAIL-resistant cells.
Pre-treatment with an anti-oxidant (N-acetylcysteine) or a c-Jun NH(2)-terminal kinase inhibitor (SP600125) effectively prevented andrographolide-induced p53 activation and DR4 up-regulation and eventually blocked the andrographolide-induced sensitization on TRAIL-induced apoptosis. Taken together, these results present a novel anti-cancer effect of andrographolide and support its potential application in cancer therapy to overcome TRAIL resistance (Zhou, 2008).
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