• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.18-24
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• 2019

Andrographolide, the main compound of Andrographis paniculata (A. paniculata), shows various biological properties including anti-viral, anti-inflammatory, anti-diabetic, and hepatoprotective effects. Our previous study has shown that A. paniculata extract exerts antiaging effects by activation of stemness in epidermal stem cells (EpSCs). In this study, we investigated the effect of andrographolide as a main compound of A. paniculata on EpSCs and its mechnism of action using several in vitro assays. Andrographolide increased the proliferation of EpSCs and induced cell cycle progression. Additionally, andrographolide increased VEGF production and the expression of stem cell markers integrin ${\beta}1$ and p63. Furthermore, phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), S6 ribosomal protein (S6RP) and Akt were increased by andrographolide. Taken together, these results indicate that andrographolide-induced proliferation of EpSCs is mediated by the ERK1/2, Akt-dependent pathway with increased production of VEGF and upregulated stemness through integrin ${\beta}1$ and p63.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.103-111
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• 2019

The study is to investigate effects of andrographolide on experimental autoimmune myocarditis (EAM). Lewis rats were immunized on day 0 with porcine cardiac myosin to establish EAM. The EAM rats were treated with either andrographolide (25, 50, 100 mg/kg/day) or vehicle for 21 days. An antigen-specific splenocytes proliferation assay was performed by using the cells from control rats immunized with cardiac myosin. Survival rates, myocardial pathology and myocardial functional parameters (left ventricle end-diastolic pressure, ${\pm}dP/dt$ and left ventricular internal dimension) of EAM rats received andrographolide were significantly improved. Andrographolide treatment caused an decrease in the infiltration of $CD3^+$ and $CD14^+$ positive cells in myocardial tissue. Moreover, andrographolide treatment caused a reduction in the plasma levels of tumor necrosis factor-alpha, interleukin-17 (IL-17) and myosin-antibody, and an increase in the level of IL-10 in EAM rats. Oral administration of andrographolide resulted in the decreased expression of p-PI3K, p-Akt without any change of PI3K and Akt. Further results indicate andrographolide significantly inhibited myosin-induced proliferation in splenocytes, and this effect was inhibited by co-treatment of SC79 (Akt activator). Our data indicate andrographolide inhibits development of EAM, and this beneficial effect may be due to powerful anti-inflammatory activity and inhibitory effect on PI3K/Akt pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5701-5708
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• 2012

The aim of the study was to investigate the chemopreventive potential of andrographolide in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors developed in the buccal pouch of golden Syrian hamsters at a 100% incidence on painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Marked abnormalities in the status of detoxification enzymes, lipid perxodiation and antioxidants were noticed in hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also restored the status of the above mentioned biomarkers. The present study thus demonstrates the chemopreventive potential of andrographolide in DMBA-induced hamster buccal pouch carcinogenesis, which is probably due to its antioxidant potential as well as modulating effect on xenobiotic metabolising enzymes during DMBA-induced oral carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6001-6005
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• 2013

Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.

• CELLMED
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• v.4 no.3
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• pp.15.1-15.14
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• 2014

Andrographis paniculata (Burm. F.) Wall. Ex Nees (Family: Anthaceae) is a traditionally known Ayurvedic medicinal plant. Several well-controlled clinical trials conducted during recent years have consistently reconfirmed that Andrographis paniculata extracts are effective in suppressing cardinal symptoms of diverse inflammatory and infectious diseases. Despite extensive efforts though, many questions concerning bioactive constituents of such extracts and their modes of actions still remain unanswered. Amongst diverse diterpene lactones isolated to date from such extracts, andrographolide is often considered to be the major, representative, or bioactive secondary metabolite of the plant. Therefore, it has attracted considerable attention of several drug discovery laboratories as a lead molecule potentially useful for identifying structurally and functionally novel drug. Critical analysis of available preclinical and clinical information on Andrographis paniculata extracts and pure andrographolide strongly suggest that they are pharmacologically polyvalent and that they possess adaptogenic properties. Aim of this communication is to summarize and critically analyze such data, and to point out some possibilities for more rationally exploiting their adaptogenic properties for discovering novel therapeutic leads, or for obtaining pharmacologically better standardized phyto-pharmaceuticals.

• CELLMED
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• v.4 no.1
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• pp.7.1-7.8
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• 2014

Metabolic effects of ten daily doses of standardized extract of Andrographis paniculata leaves (AP) rich in andrographolide were evaluated in a rat model of type-2 diabetes and in diet induced obese rats. AP was administered per-orally as suspension in 0.3% carboxymethylcellulose at doses of 50, 100 and 200 mg/kg/day for 10 consecutive days. Blood glucose, insulin and lipid profile of rats were measured by using enzyme kits. In addition, effects of such treatments on anti-oxidant enzymes activity and histopathological changes in various organs of diabetic rats were assessed. AP treatments reversed body weight losses and increased plasma insulin level in diabetic rats. The anti-oxidant enzymes activity became normal and histopathological changes observed in pancreas, liver, kidney and spleen of diabetic animals were less severe in extract treated groups. On the other hand, hyperinsulinemia and increased body weight gains observed in high fat or fructose fed rats were less severe in the extract treated groups. These observations revealed therapeutic potentials of the extract for treatments of diabesity associated metabolic disorders, and suggest that the effects of the extract on insulin homeostasis depend on the metabolic status of animals. Activation of cytoprotective mechanisms could be involved in its mode of action.