1: Phytother Res. 2007 Jul 18; [Epub ahead of print] Related Articles, Links
Screening of Indian medicinal plants for acetylcholinesterase inhibitory activity.
Mukherjee PK, Kumar V, Houghton PJ.
Department of Pharmacy, Pharmacognosy Research Laboratories, Franklin‐Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
The cholinergic hypothesis of Alzheimer's disease (AD) has provided the rationale for the current pharmaco-therapy of this disease, in an attempt to reduce the cognitive decline caused by cholinergic deficits. Nevertheless, the search for potent and long-acting acetylcholinesterase (AChE) inhibitors that exert minimal side effects in AD patients is still ongoing. AChE inhibitors are currently the only approved therapy for the treatment of Alzheimer's disease; only a limited number of drugs are commercially available. Hydroalcohol extracts of six herbs, Andrographis paniculata, Centella asiatica, Evalvulus alsinoides, Nardostachys jatamansi, Nelumbo nucifera, Myristica fragrans used in Indian systems of medicine, were tested for in vitro acetylcholinesterase inhibitory activity based on Ellman's method in 96-well microplates using AChE obtained from bovine erythrocytes. The results showed that the hydroalcohol extract from Centella asiatica, Nardostachys jatamansi, Myristica fragrans, Evalvulus alsinoides inhibited 50% of AChE activity at concentrations of 100-150 microg/mL. Andrographis paniculata and Nelumbo nucifera extracts showed a weak inhibition of acetylcholinesterase with IC(50) values of 222.41 +/- 19.87 microg/mL and 185.55 +/- 21.24 microg/mL, respectively. Physostigmine was used as a standard and showed inhibition of acetylcholinesterase with an IC(50) value of 0.076 +/- 0.0042 microg/mL. Copyright (c) 2007 John Wiley & Sons, Ltd.
PMID: 17639556 [PubMed - as supplied by publisher]
2: Bioorg Med Chem. 2007 Jun 15;15(12):4247-55. Epub 2007 Mar 24. Related Articles, Links
Synthesis of andrographolide derivatives: a new family of alpha-glucosidase inhibitors.
Xu HW, Dai GF, Liu GZ, Wang JF, Liu HM.
New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450052, PR China.
Andrographolide (1), the cytotoxic agent of the plant Andrographis paniculata, was subjected to semi-synthetic studies leading to a series of new derivatives, a novel family of glucosidase inhibitors. Nicotination of 3,19-hydroxyls in 15-alkylidene andrographolide derivatives (9) was favorable to alpha-glucosidase inhibition activity. Among them, 15-p-chlorobenzylidene-14-deoxy-11,12-didehydro-3,19-dinicotinateandrographolide (11c) was a very potent inhibitor against alpha-glucosidase with an IC50 value of 6 microM. However, all compounds concerned for beta-glucosidase showed no inhibition. All compounds synthesized were characterized by the analysis of NMR, IR, HRMS spectra and the stereochemistry of 2 was confirmed by X-ray analysis.
Publication Types:
PMID: 17428667 [PubMed - indexed for MEDLINE]
3: Planta Med. 2007 Jun;73(6):503-11. Related Articles, Links
Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts.
Yoopan N, Thisoda P, Rangkadilok N, Sahasitiwat S, Pholphana N, Ruchirawat S, Satayavivad J.
Toxicology Graduate Programme, Faculty of Science, Mahidol University, Bangkok, Thailand.
Andrographis paniculata has been widely used as a traditional medicine for the treatment of common cold, diarrhea and hypertension. The three major active diterpenoids are andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3) and neoandrographolide (AP4). It has been reported that AP3 has hypotensive and vasorelaxation effects. However, there is only limited information on the cardiovascular effects of the other diterpenoids and crude extracts containing different levels of AP3. Therefore, the present study investigated the effects of these diterpenoids, AP1, AP3, and AP4, isolated from A. paniculata, and different aqueous plant extracts on blood pressure, vascular and chronotropic responses by using conscious rats and their isolated aortas and right atria as the test models. Among the three major diterpenoids, AP3 was the most potent compound for inducing vasorelaxation and decreasing heart rate. In addition, Extract B (high level of AP3) had greater hypotensive effect in conscious rats than Extract A (low level of AP3). Verapamil, a Ca2+ channel blocker, also had a hypotensive effect less than that of Extract C containing a high level of AP3. At the doses and durations of Extract A and B which produced hypotension, the responses of the Extract A-treated aorta to norepinephrine, and the vascular muscarinic responses to acetylcholine of both extracts were decreased. However, repeated doses of both extracts did not alter cardiac beta-adrenoceptor and muscarinic responses of extract-treated rats to NE and ACh, respectively. The results of this study suggest that vascular smooth muscle is the major site of these hypotensive effects of both AP3 and A. paniculata extracts. Furthermore, the consumption of A. paniculata products containing high levels of AP3 may be responsible for causing hypotension in some patients taking this herbal drug.
PMID: 17650544 [PubMed - indexed for MEDLINE]
4: Glycoconj J. 2007 May 25; [Epub ahead of print] Related Articles, Links
Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources.
Sathisha UV, Jayaram S, Harish Nayaka MA, Dharmesh SM.
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, 570 020, India, shylaakshu@yahoo.com.
Pectic polysaccharides from dietary sources such as Decalepis hamiltonii-swallow root (SRPP), Hemidesmus indicus (HPP), Nigella sativa-black cumin (BCPP), Andrographis serpyllifolia-(APP), Zingiber officinale-ginger (GRPP) and, citrus pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a) galectin-3 of MDA-MB-231 cells induced hemagglutination of red blood cells; (b) galectin-3 mediated interaction between normal/metastatic human buccal cells (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was assessed. Results indicated that SRPP inhibited hemagglutination at Minimum Inhibitory Concentration (MIC) of 1.86 mug ml(-1) equivalent of carbohydrate as apposed to those of BCPP (130 mug ml(-1)), APP (40 mug ml(-1)), HPP (40 mug ml(-1)) and CPP (25 mug ml(-1)). GRPP even at concentration >1-6 mg ml(-1) did not inhibit agglutination. Also SRPP showed approximately 15 and 2 fold potent anti hemagglutination activity relative to that of galectin-3 specific sugars-galactose (MIC-27.1 mug ml(-1)) and lactose (MIC-4.16 mug ml(-1)) respectively. Further, SRPP at 10 mug ml(-1) inhibited agglutination of NBC by galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide (MSRPP) of 50 kDa retained anti hemagglutination activity (MIC of 1.03 mug ml(-1)) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC(50) of 136 and 200 mug ml(-1) respectively. Both SRPP and MSRPP induced apoptosis up to 80% at 100 mug ml(-1) concentration by activating approximately 2 and 8 folds of Caspase-3 activity. Sugar composition analysis and its correlation with the galectin inhibitory property indicated that pectic polysaccharides with higher arabinose and galactose content-arabinogalactan inhibited hemagglutination significantly.
PMID: 17525829 [PubMed - as supplied by publisher]
5: Phytomedicine. 2007 May 3; [Epub ahead of print] Related Articles, Links
In vitro cytogenetic effects of Andrographis paniculata (kalmegh) on arsenic.
Avani G, Rao MV.
Department of Zoology, University School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380 009, Gujarat, India.
In vitro effects of arsenic in human peripheral lymphocytes (HPL) at three different doses - 3.6x10(-4), 1.4x10(-3) and 0.72x10(-3)muM for 24h before harvesting on sister chromatid exchanges (SCE), Cell cycle proliferative index/replicative index (CCPI/RI), %M(1), %M(2) and %M(3), population doubling time (PDT) and average generation time (AGT) were examined. Andrographis paniculata (commonly referred to as 'kalmegh') has been used for centuries in traditional Indian and Chinese herbal medicine as a safe, natural folk remedy for assorted health concerns. In the present study, kalmegh (0.01mug/7ml culture media) was used along with the highest dose of arsenic; the results showed that arsenic induced increase in these genotoxic endpoints were fairly diminished by kalmegh. In addition, mutagenic in vitro effect of ethyl methanesulphonate (EMS) was used as a positive control in this study. It is thus concluded from this study that Andrographis has a protective role in arsenic toxicity.
PMID: 17482447 [PubMed - as supplied by publisher]
6: J Ethnopharmacol. 2007 Apr 20;111(1):13-21. Epub 2006 Oct 28. Related Articles, Links
Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice.
Singha PK, Roy S, Dey S.
Microbiology and Immunology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal, India.
To find out the active principles against ethanol-induced toxicity in mice, Andrographis paniculata Nees. (Ap) was chosen and isolated andrographolide (ANDRO) and arabinogalactan proteins (AGPs). ANDRO was detected by HPTLC, FTIR and quantified by HPLC (10mg/g of Ap powder). AGPs was detected by beta-glucosyl Yariv staining of SDS-PAGE gel, FTIR and quantified by single radial gel diffusion assay with beta-glucosyl Yariv reagent (0.5mg/g Ap powder). The mice are pretreated intra-peritoneally (i.p.) with different doses (62.5, 125, 250, and 500mg/kg) of body weight of mice] of ANDRO and AGPs for 7 days and then ethanol (7.5g/kg of body weight) was injected, i.p. Besides, silymarin was used as standard hepatoprotective agent for comparative study with ANDRO and AGPs. The ameliorative activity of ANDRO and AGP against hepatic renal alcohol toxicity was measured by assessing GOT, GPT, ACP, ALP and LP levels in liver and kidney. It has been observed that pretreatment of mice with ANDRO and AGPs at 500mg/kg of body weight and 125mg/kg of body weight respectively could able to minimize the toxicity in compare to ethanol treated group as revealed by the different enzymatic assay in liver and kidney tissues and the results were comparable with silymarin. Hence, out of several ill-defined compounds present in Ap, ANDRO and AGPs are the potential bioactive compounds responsible for protection against ethanol-induced toxicity.
Publication Types:
PMID: 17127022 [PubMed - indexed for MEDLINE]
7: Int Immunopharmacol. 2007 Apr;7(4):515-23. Epub 2007 Jan 17. Related Articles, Links
Modulation of immune response in mice immunised with an inactivated Salmonella vaccine and gavaged with Andrographis paniculata extract or andrographolide.
Xu Y, Chen A, Fry S, Barrow RA, Marshall RL, Mukkur TK.
Department of Biological and Physical Sciences, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia.
Gavage of mice, immunised with an inactivated S. typhimurium vaccine, with Andrographis paniculata extract [APE] or andrographolide [AND] resulted in an enhancement of Salmonella-specific antibody response and induction of cell-mediated response against salmonellosis. Mice were vaccinated with either one or two doses of killed S. typhimurium vaccine and fed two different quantities of APE or AND, for 14 days in mice immunised with one dose of the vaccine, and for 28 days in mice immunised with two doses of vaccine, respectively. Both APE and AND were found to enhance IgG antibody levels against S. typhimurium, the enhancement being statistically significant in mice receiving two doses of the vaccine. Splenocyte cultures, prepared from mice immunised with the killed Salmonella vaccine and treated with APE or AND, showed a remarkable increase in the production IFN-gamma following stimulation with the bacterial lysate, indicating an induction of Salmonella-specific cell-mediated response/immune response.
Publication Types:
PMID: 17321475 [PubMed - indexed for MEDLINE]
8: Mol Cell Biochem. 2007 Apr;298(1-2):49-57. Epub 2006 Nov 16. Related Articles, Links
Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage.
Liu J, Wang ZT, Ji LL, Ge BX.
Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Hi-Tech Park, Shanghai, 201203, P. R. China.
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)>- Research Support, Non-U.S. Gov't
PMID: 17109078 [PubMed - indexed for MEDLINE]
9: Altern Med Rev. 2007 Mar;12(1):25-48. Related Articles, Links
Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations.
Roxas M, Jurenka J.
Thorne Research, PO Box 25, Dover, ID 83825, USA. m.roxas@comcast.net
The common cold is the leading cause of doctor visits in the United States and annually results in 189 million lost school days. In the course of one year the U.S. population contracts approximately 1 billion colds. Influenza infection is still a leading cause of morbidity and mortality, accounting for 20-25 million doctor visits and 36,000 deaths per year in the United States. Conventional therapies for colds and flu focus primarily on temporary symptom relief and include over-the-counter antipyretics, anti-inflammatories, and decongestants. Treatment for influenza also includes prescription antiviral agents and vaccines for prevention. This article reviews the common cold and influenza viruses, presents the conventional treatment options, and highlights select botanicals (Echinacea spp., Sambucus nigra, larch arabinogalactan, Astragalus membranaceous, Baptisia tinctoria, Allium sativa, Panax quinquefolium, Eleutherococcus senticosus, Andrographis paniculata, olive leaf extract, and Isatis tinctoria) and nutritional considerations (vitamins A and C, zinc, high lactoferrin whey protein, N-acetylcysteine, and DHEA) that may help in the prevention and treatment of these conditions.
Publication Types:
PMID: 17397266 [PubMed - indexed for MEDLINE]
10: Chem Pharm Bull (Tokyo). 2007 Mar;55(3):455-8. Related Articles, Links
Secondary metabolites from Andrographis paniculata.
Li W, Xu X, Zhang H, Ma C, Fong H, van Breemen R, Fitzloff J.
Department of Medicinal Chemistry and Pharmacognosy (m/c 781), University of Illinois at Chicago, IL 60612, USA.
Two new flavonoid glycosides, 5-hydroxy-7,8-dimethoxy (2R)-flavanone-5-O-beta-D-glucopyranoside (1) and 5-hydroxy-7,8,2',5'-tetramethoxy-flavone-5-O-beta-D-glucopyranoside (2), and a new diterpenoid, andrographic acid (3), along with andrographidine A (4) were isolated from Andrographis paniculata, and their structures were determined on the basis of physicochemical and spectroscopic analysis. Compound 3 was evaluated for cytotoxicity to KB cells along with andrographolide, isoandrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide obtained from A. paniculata in the present study. Cytotoxicity was observed for andrographolide and isoandrographolide with ED50 values of 6.5 and 5.1 microg/ml, respectively.
Publication Types:
PMID: 17329890 [PubMed - indexed for MEDLINE]
11: Integr Cancer Ther. 2007 Mar;6(1):66-73. Related Articles, Links
Modulation of natural killer cell activity, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by andrographolide in normal and Ehrlich ascites carcinoma-bearing mice.
Sheeja K, Kuttan G.
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
Modulation of immune responses is highly relevant in tumor cell destruction. The present study is focused on the effect of Andrographis paniculata extract (APE) and its isolated compound andrographolide (ANDLE) on cell-mediated immune responses in normal and tumor-bearing control animals. Treatment with APE and ANDLE significantly enhanced natural killer cell activity in normal (APE, 46.82% cell lysis; ANDLE, 40.79% cell lysis) and tumor-bearing animals (APE, 48.66% cell lysis; ANDLE, 42.19% cell lysis) on the fifth day, and it was observed earlier than in tumor-bearing control animals (12.89% cell lysis on day 9). Antibody-dependent cellular cytotoxicity was also increased in APE (45.17% cell lysis on day 11) as well as ANDLE (39.92% cell lysis on day 11)-treated normal and tumor-bearing animals (APE, 47.39% cell lysis; ANDLE, 41.48% cell lysis on day 11) compared to untreated tumor-bearing control animals (maximum of 11.76% cell lysis on day 17). An early enhancement of antibody-dependent complement-mediated cytotoxicity was also observed by the administration of APE and ANDLE in normal as well as tumor-bearing animals. APE and ANDLE administration could significantly enhance the mitogen-induced proliferation of splenocyte, thymocyte, and bone marrow cells. Moreover, treatment of APE and ANDLE significantly elevated the production of interleukin-2 and interferon-gamma in normal and Ehrlich ascites carcinoma-bearing animals.
PMID: 17351028 [PubMed - indexed for MEDLINE]
12: Phytochemistry. 2007 Mar;68(6):904-12. Epub 2007 Jan 17. Related Articles, Links
Semisynthesis and in vitro anticancer activities of andrographolide analogues.
Jada SR, Subur GS, Matthews C, Hamzah AS, Lajis NH, Saad MS, Stevens MF, Stanslas J.
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
The plant Andrographis paniculata found throughout Southeast Asia contains Andrographolide 1, a diterpenoid lactone, which has antitumour activities against in vitro and in vivo breast cancer models. In the present study, we report on the synthesis of andrographolide derivatives, 3,19-isopropylideneandrographolide (2), 14-acetyl-3,19-isopropylideneandrographolide (3) and 14-acetylandrographolide (4), and their in vitro antitumour activities against a 2-cell line panel consisting of MCF-7 (breast cancer cell line) and HCT-116 (colon cancer cell line). Compounds 2 and 4 were also screened at the US National Cancer Institute (NCI) for their activities against a panel of 60 human cancer cell lines derived from nine cancer types. Compound 2 was found to be selective towards leukaemia and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian and renal cancer cells at all the dose-response parameters. Compounds 2 and 4 showed non-specific phase of the cell cycle arrest in MCF-7 cells treated at different intervals with different concentrations. NCI's COMPARE and SOM mechanistic analyses indicated that the anticancer activities of these new class of compounds were not similar to that of standard anticancer agents, suggesting novel mechanism(s) of action.
Publication Types:
PMID: 17234223 [PubMed - in process]
13: Int Immunopharmacol. 2007 Feb;7(2):211-21. Epub 2006 Nov 2. Related Articles, Links
Antiangiogenic activity of Andrographis paniculata extract and andrographolide.
Sheeja K, Guruvayoorappan C, Kuttan G.
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
Inhibition of angiogenesis is currently perceived as one of the promising strategies in the treatment of cancer. In this study we analyzed the antiangiogenic activity of Andrographis paniculata extract (APE) and its major component andrographolide (ANDLE) using both in vitro and in vivo models. Intraperitoneal administration of APE and ANDLE significantly inhibited the B16F-10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis of serum cytokine profile showed a drastic elevation in the proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF and the most potent angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in B16F-10 cell line showed a reduced level of expression in the presence of APE and ANDLE. Serum NO level which was increased in B16F-10 melanoma injected control animals was also found to be significantly lowered by the administration of APE and ANDLE. Antiangiogenic factors such as TIMP-1 and IL-2 level was elevated in APE and ANDLE treated angiogenesis induced animals. In the rat aortic ring assay APE and ANDLE inhibited the microvessel outgrowth at non toxic concentrations. Taken together our results demonstrate that APE and ANDLE inhibit the tumor specific angiogenesis by regulating the production of various pro and antiangiogenic factors such as proinflammatory cytokine, nitric oxide, VEGF, IL-2 and TIMP-1.
Publication Types:
PMID: 17178389 [PubMed - indexed for MEDLINE]
14: J Chromatogr A. 2007 Jan 26;1140(1-2):71-7. Epub 2006 Dec 6. Related Articles, Links
On-line coupling of dynamic microwave-assisted extraction with high-performance liquid chromatography for determination of andrographolide and dehydroandrographolide in Andrographis paniculata Nees.
Chen L, Jin H, Ding L, Zhang H, Wang X, Wang Z, Li J, Qu C, Wang Y, Zhang H.
College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
A novel technique based on dynamic microwave-assisted extraction (DMAE) coupled on-line with high-performance liquid chromatography (HPLC) through a flow injection interface has been developed for determination of andrographolide and dehydroandrographolide in Andrographis paniculata Nees. A TM(010) microwave resonance cavity built in the laboratory was applied to concentrating the microwave energy. An extraction vessel was placed in microwave irradiation zone. The extraction was performed in a recirculating system. When a number of extraction cycles were completed, the fractional extract (20muL) was driven to the analytical column by 65% aqueous methanol and was measured by diode array detector (DAD) at 225nm. The optimized extraction conditions are follows: extraction solvent 60% aqueous methanol; microwave forward power 80W; extraction time 6min; extraction solvent flow-rate 1.0mLmin(-1). The detection and quantification limits obtained are 0.5 and 1.7microgmL(-1) for andrographolide and 0.6 and 1.9microgmL(-1) for dehydroandrographolide, respectively. The within-day and between-day precision (RSD) are 2.1% and 3.7% for andrographolide and 1.7% and 4.1% for dehydroandrographolide, respectively. Mean recoveries for andrographolide and dehydroandrographolide are 97.7% and 98.7%, respectively. Compared with ultrasonic extraction used in the Chinese pharmacopoeia, the proposed method was demonstrated to obtain higher extraction yield in a shorter time. In addition, only small quantities of solvent (5mL) and sample (10mg) were required.
Publication Types:
PMID: 17156791 [PubMed - indexed for MEDLINE]
15: Acta Pol Pharm. 2007 Jan-Feb;64(1):53-61. Related Articles, Links
Antihyperglycaemic effect of 'Ilogen-Excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus.
Umamaheswari S, Prince PS.
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India-608 002.
'Ilogen-Excel', an Ayurvedic herbal formulation is composed of eight medicinal plants (Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata and Mimosa pudica). The present study evaluates the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg/kg body weight). Oral administration of 'Ilogen-Excel' (50 mg/kg and 100 mg/kg) for 60 days resulted in significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 'Ilogen-Excel' administration also decreased the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of 'Ilogen-Excel'. Administration of insulin normalized all the biochemical parameters studied in diabetic rats. The effect at a dose of 100 mg/kg was more pronounced than 50 mg/kg and brought back all the parameters to near normal levels. Thus, our study shows the antihyperglycemic effects of 'Ilogen-Excel' in STZ-induced diabetic rats. Our study also shows that combined therapy is better than individual therapy.
PMID: 17665851 [PubMed - in process]
16: Am J Chin Med. 2007;35(2):317-28. Related Articles, Links
In vivo and in vitro anti-inflammatory activities of neoandrographolide.
Liu J, Wang ZT, Ji LL.
Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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. 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. 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.
Publication Types:
PMID: 17436371 [PubMed - in process]
17: Immunopharmacol Immunotoxicol. 2007;29(1):81-93. Related Articles, Links
Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide.
Sheeja K, Kuttan G.
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, India.
The stimulatory effect of Andrographis paniculata extract and andrographolide on cytotoxic T lymphocyte (CTL) production was determined in BALB/c mice by Winn's neutralization assay using CTL sensitive EL4 thymoma cells as target cell. Extract and andrographolide showed a significant increase in CTL production in both the in vivo and in vitro models. The survival time of EL4 cells alone in animals was only 27.1 days and it was increased to 51.1 and 44.5 days in extract- and andrographolide treated animals with percentage increase in life span (%ILS) of 88.5 and 64.2, respectively. The survival rate of animals administered EL4 cells incubated with alloimmunized spleen cells (effector cells) from normal BALB/c mice was 35.8 (%ILS 32.1). When this group was treated with 10 doses of extract and andrographolide the life span was further increased to 52.1 days (%ILS 92.2 ) and 48.1 days (%ILS 77.4). Survival days of animal carrying EL4 cells incubated with alloimmunized spleen cells (effector cells) from extract and andrographolide treated animals were 55.5 and 50.3 days respectively. When these animals continued with extract and andrographolide treatment for 10 days their life spans were significantly increased to 62 and 53.8 days, respectively. The level of cytokines such as Interlevkin (IL)-2 and Interferon (IFN)-gamma also was enhanced in these animals when they were treated with extract and andrographolide. This study demonstrated that A. paniculata extract and andrographolide stimulate the CTL production through enhanced secretion of IL-2 and IFN-gamma by T cells and thereby inhibit the tumor growth.
PMID: 17464769 [PubMed - indexed for MEDLINE]
18: Pak J Pharm Sci. 2007 Jan;20(1):9-15. Related Articles, Links
Entrapment of andrographolide in cross-linked alginate pellets: II. Physicochemical characterization to study the pelletization of andrographolide.
Shariff A, PK M, KLK P, M M.
Department of Pharmaceutics, Krupanidhi College of Pharmacy, Koramangala, Bangalore. arshitan@yahoo.com
This paper deals with the characterization of pellets containing andrographolide in two parts. The first part deals with characterization of the pellets to ascertain the identity and integrity of andrographolide. Part two involves characterization of the pellets containing Andrographis paniculata extract (33.3%) prepared in the paper I for their micromeritic properties like Particle size, Particle size distribution, Sphericity measurements like Shape ratio and Aspect ratio, Tapped density, Compressibility index, Hausner's ratio and Angle of repose. In addition, our aim was also to derive information about the mechanism of gelation with entrapment of andrographolide to supplement results obtained about the release mechanisms deduced in paper I. Since this work requires use of techniques like FTIR, FTRaman, MTDSC and XRPD, it was necessary to prepare alginate micropellets using pure andrographolide (99.89%) rather than the multicomponent extract using the same procedure discussed in paper I. The integrity of the drug was maintained in the cross-linked micropellets as was seen in the MTDSC and FTIR spectra supported by the FTRaman spectra. The depolymerisation transitions, the reversing and non-reversing heat flow signals were determined using the MTDSC and interpreted to study the mechanism of pelletization. The MTDSC profiles also confirmed the integrity of the drug by exhibiting a sharp endotherm at 232(o)c that is the melting point of andrographolide. The XRPD spectrum of the micropellets ascertained that the crystallinity of andrographolide was maintained. The relationship of the nature of the drug present in the micropellets related to release mechanisms is discussed. In conclusion, it can be said that andrographolide can be successfully incorporated into cross-linked micropellets of alginate without affecting its integrity or nature to deliver it as a bitterless monoherbal preparation.
PMID: 17337421 [PubMed - indexed for MEDLINE]
19: Pak J Pharm Sci. 2007 Jan;20(1):1-9. Related Articles, Links
Entrapment of andrographolide in cross-linked alginate pellets: I. Formulation and evaluation of associated release kinetics.
Shariff A, PK M, KLK P, M M.
Department of Pharmaceutics, Krupanidhi College of Pharmacy, Koramangala, Bangalore. arshitan@yahoo.com
Andrographolide, the 'King of bitters' requires high doses in the form of an extract (33.3%w/w) to be used as a hepatoprotectant. Since a large dose of this herb is known to cause gastric distress, vomiting, loss of appetite and nausea on regurgitation, it was thought of to convert the drug itself into a bitterless micropellet. The technique of ionotropic gelation of sodium alginate with calcium ions with subsequent drug entrapment was employed. The optimization of process parameters like the bore diameter of the needle, % concentration of sodium alginate, method of drying, drying time and temperature, time of contact of the micropellets in calcium chloride solution and concentration of calcium chloride to be used for the gelation were undertaken. The micropellets were finally prepared by adding 2.5%w/v of sodium alginate into a 2%w/v solution of calcium chloride solution using 20-guage flat tip needle and dried using a hot air oven at 60(o)C for 6 hrs. The so formed pellets were completely bitterless and released the andrographolide preferably away from the stomach. Pellets with varied drug: polymer ratio (1:2, 1:1 and 2:1) were prepared accordingly and analyzed for release kinetics. Release studies showed only about 15% release upto 4 hrs in pH 1.2 and pH 4.0 respectively and released the remaining in pH 7.4.The data obtained in the dissolution studies was fitted into various mathematic models defining kinetics of drug release like the zero-order rate equation, first-order rate equation, Hixson-crowell, 2/3rd rule, Korsemeyer-Peppas, Baker-lonsdale, Higuchi, Weibull, Ford and Hopfenberg Equation. The release kinetics of andrographolide from the alginate pellets was found to be best described by the korsemeyer-peppas equation which provided n values ranging from 1.0-1.47 with good linearity of the best-fit line (R(2)=0.9973). In conclusion, andrographolide can be easily converted to bitterless multiple unit dose oral delivery systems with good entrapment efficiency and a maximum release of 86% by utilizing the technique of ionotropic gelation.
PMID: 17337420 [PubMed - indexed for MEDLINE]
20: Eur J Pharmacol. 2006 Dec 28;553(1-3):39-45. Epub 2006 Sep 30. Related Articles, Links
Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation.
Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J.
Toxicology Graduate Programme, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand; Laboratory of Pharmacology, Chulabhorn Research Institute, Vipavadee-Rangsit Highway, Laksi, Bangkok 10210, Thailand.
Andrographis paniculata has been widely used for the prevention and treatment of common cold especially in Asia and Scandinavia. The three active diterpenoids from this plant, including aqueous plant extracts, were investigated for the inhibitory effect on platelet aggregation in vitro. The results indicated that andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3)) significantly inhibited thrombin-induced platelet aggregation in a concentration-(1-100 microM) and time-dependent manner while neoandrographolide (AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the results indicated that the inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two compounds. In addition, standardized aqueous extracts of A. paniculata containing different amounts of AP(3) inhibited thrombin-induced aggregation to different degrees. The extracts significantly decreased platelet aggregation in a concentration-(10-100 microg/ml) and time-dependent manner. However, the extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml) showed less inhibitory activity against thrombin than the extract with lower level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results indicate that the standardized A. paniculata extract may contain other antiplatelet compounds rather than AP(1) and AP(3), which contribute to high antiplatelet activity. Therefore, the consumption of A. paniculata products may help to prevent or treat some cardiovascular disorders i.e. thrombosis; however, it should be used with caution by patients with bleeding disorders.
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PMID: 17081514 [PubMed - indexed for MEDLINE]
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