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Andrographis is a bush which grows in India , China , the South East of Asia, and in the West Indies . It reaches a height of 30 to 100 cmts. With square stems and lanceolate leaves. In India it is also called Kalmegh or Kiryat.
Andrographis has historically been used en the case of epidemics and during the last decade it has become the most popular natural product against flue, particularly in the Scandinavian countries. It is the most sold natural product in Sweden where it has been distinguished over 12 consecutive years as the adaptogene of the year.
Traditional Use
The geographic distribution of this plant has led to its traditional use in Ayurvedic ( India ), Thailandese, and Chinese medicine. In accordance with this, andrographis is anti-fever and antitoxic. It has been uses in cases of bacillary dysentery, unspecified diarrheas, superior respiratory infections, tonsillitis, pharyngitis, laryngitis, pneumonia, tuberculosis, and nephritis. Also for dermatological diseases like crusty tetter and herpes, and helminthic intestinal infestation.
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Active Compounds:
Its principle active compounds are: Flavonoids, glycosides, and ditherpenic lactones (called andrographolids, bitter compounds in the stems and leaves).
Fig. 1: Structure of the andrographolid:
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Medicine Kinetics:
After the oral administration of a dose of 20 mg of andrographolid, absorption was fast and reached the highest plasmatic level within 1,5 - 2 hours with an average plasmatic lifetime of 10 hours (Panossian et al 2000).
The andrographolid is distributed in the whole body, including brain and spinal marrow. After 72 hours, approximately 90% of the andrographolids are excreted, mainly by the urinal way.
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| Indications:
Scientific studies during the last 15 years in various countries, published in Western magazines, have confirmed many of the traditional uses of andrographis.
1) Andrographis offers immunmodulatory, anti-inflammatory, and antineoplasic effects. Although its mechanism of action is not exactly known, the studies realized suggest that it stimulates the immunological systems and that it activates the macrophages. Furthermore, andrographis has direct antiviral and antiparasitory effects, but has no direct antibacterial effect.
2) Andrographis has anti-thrombosic, hypotensory, and anti-arteriosclosic effects. This plant is useful for the prevention of coronary ischemic cardiopathy, particularly under difficult conditions associated with the treatment of this disease: re-stenosis after angioplasty. Its action is explained by its anti-thrombotic effects, a result of the reduction of thromboxanes and the inhibition of the added platelet factor.
3) Hepatic-protective and hepatic-antioxidant effects.
4) Choleretic effect.
5) Treatment of urinary infections post extracorporeal lithotripsy.
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Safety:
Possibly the best indicator for the safety of andrographis paniculata is its extensive use as a herbalist remedy in South East Asia, Chine, and Europe to prevent and treat the common flue, without any warning or secondary effects caused by this plant having been reported.
High dosages for animals or humans have not produced any toxicity (Sandberg 1994). In animals, no acute toxicity has been observed, even at very high dosages (1 - 10 g/kg weight), in three species and no secondary effect on important organs.
Patient who received andrographis in recommended therapeutic dosages did not show any change in their hepatic, renal, hematological functions or in their blood chemistry (Hancke et al 1995). Humans treated with high dosages, up to 50 - 80 mg/kg, administered during 2 months by intravenous means, did not show any toxicity (Sandberg 1994).
In experimental animals, andrographis showed anti-fertility effects, in males as well as in females. Male rats became infertile at dosages of 20 mg/day (Akbarsha et al 1990) and female rats at high dosages (Zoha et al 1989). There were also abortions with rats (Sandberg 1994).
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Recommended Dosage:
Two capsules of 500 mg three times per day.
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Contraindications:
Its safety during pregnancy, lactancy, and infancy has not been established.
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Precautions:
Because of the stimulation of the contraction of the gall bladder, its use in patients with gall calculus should be overseen by a physician.
Conclusions
Andrographis paniculata, a plant of Indian origin, is a traditional remedy used in cases of fever and various infections. Controlled studies indicate that it is effective in the reduction of prevalence and intensity of the common flue and sinusitis, and shortens the duration of the symptoms. Some studies indicate that it may be useful in the treatment of cardiovascular diseases and the prevention of hepatic toxicity. Although it has not been reported any toxicity in organs caused by andrographis paniculata, its use in animals has shown a decrease of fertility, and therefore should not be used by women who wish to conceive and neither by their males. It should not been used during pregnancy either. |
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References
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1: Vestn Otorinolaringol. 2003;(3):48-50.
Effectiveness of using the drug Kan-Yang in children with acute respiratory viral infection (clinico-functional data).
Shakhova EG, Spasov AA, Ostrovskii OV, Konovalova IV.
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A randomized trial of the effectiveness of the preparation Kan-Yang ( Sweden ) consisting of andrographis and eleutherococcus extracts was performed in 53 children with acute respiratory viral infection (ARVI). 40 ARVI children given conventional treatment served control. It is shown that in early acute noncomplicated respiratory disease Kan-Yang tablets relieves considerably the treatment course and promoted cure in good tolerance.
Publication Types: Clinical Trial , Randomized Controlled Trial |
2: Zhongguo Zhong Yao Za Zhi. 2002 Feb;27(2):147-50.
Modulation of lianbizi injection (andrographolide) on some immune functions
Peng GY, Zhou F, Ding RL. Department of Microbiology and Immunology, Nanjing Medical University , Nanjing China .
OBJECTIVE: To study the effects of andrographolide on immune functions and the immune mechanism of its clinical application. METHOD: The amounts of IFN-alpha, IFN-gamma, TNF-alpha, IL-8 in the peripheral blood mononuclear cells(PBMCs) culture supernatants deal with by different concentrations of LianBiZhi (LBZ) injection made of andrographolide were detected by biological activity test or ELISA in vitro. The effects of LBZ injection on macrophage phagocytotic function and natural killer cells cytotoxicity were examined by means of macrophage to phagocytize cock erythrocyte and measurement of lactate dehydrogenase(LDH) activity released from the damaged cells, respectively. RESULT: The LBZ injection could promote IFN-alpha, IFN-gamma, TNF-alpha inductions of PBMCs, but had no effect on IL-8. At the same time, the LBZ injection could not only enhance the phagocytosis activity of peritoneal macrophage from guinea pig to phagocytosis cock erythrocyte, but also augment the cytotoxicity mediated by natural killer cells from PBMCs to damage the K562 cell lines. CONCLUSION: Andrographolide is an immunostimulant agent which can modulate both antigen specific and nonspecific immune function by means of its natural killer cells and macrophage and cytokines induction.
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3: Phytomedicine. 2002 Oct;9(7):598-605.
Effect of andrographolide and Kan Jang--fixed combination of extract SHA-10 and extract SHE-3--on proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture.
Panossian A, Davtyan T, Gukassyan N. ExLab Laboratories of Armenian Drug Agency, Yerevan , Armenia .
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The immunomodulatory properties of a diterpene lactone andrographolide and Kan Jang--a standardized fixed combination of Andrographis paniculata extract SHA-10 and Eleutherococcus senticosus extract SHE-3 were investigated. Their role on spontaneous and phytohemagglutinin (PHA)-induced proliferation of human peripheral blood lymphocytes (PBL) and on production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) were determined in vitro. Proliferation of PBL induced by PHA was enhanced by co stimulation with andrographolide and Kan Jang. At the same time andrographolide and Kan Jang inhibit spontaneous proliferation of PBL in vitro. These preparations also have effect on the formation of INF-gamma, TNF-alpha and some immune activation markers such as neopterin (Neo), beta-2-microglobulin (beta2MG), and soluble receptor for interleukin-2 (sIL-2R or sCD25) in blood cells culture. Andrographolide and Kan Jang stimulate the INF-gamma, Neopterin and beta2MG formation, but do not have any significant effect on the production of INF-gamma and Neopterin in PHA stimulated blood cells. An opposite effect on these immune makers was observed in the PHA-stimulated blood cells: both andrographolide and Kan Jang increase the formation of TNF-alpha and beta2MG in cultivated whole blood cells. Thus, andrographolide and Kan Jang can have an in vitro effect on the activation and proliferation of immunocompetent cells as well on the production of key cytokines and immune activation markers. The results show an overall higher effect of the fixed combination as compared with the equivalent amount of the pure substance andrographolide. The data are consistent with results from clinical studies of Kan Jang and contributed to a better understanding of these results. |
4: Biol Pharm Bull. 2002 Sep;25(9):1169-74.
Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata.
Batkhuu J, Hattori K, Takano F. Experimental Station for Medicinal Plant Studies, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
In this study, we investigated the in vitro and ex vivo suppressive effects of Andrographis paniculata on nitric oxide (NO) production in mouse peritoneal macrophages elicited by bacillus Calmette-Guein (BCG) and stimulated by lipopolysaccharide (LPS). Incubation of BCG-induced macrophages with the methanol extract of A. paniculata reduced LPS stimulated NO production. The diterpene lactones andrographolide and neoandrographolide were isolated as active components from the extract. These compounds suppressed NO production in a concentration-dependent manner in the concentration range from 0.1 to 100 microM and their IC50 values were 7.9 and 35.5 microM. Neoandrographolide also suppressed NO production by 35 and 40% when the macrophages were collected after oral administration of neoandrographolide at doses of 5 and 25 mg/kg/d and LPS stimulated NO production was examined. However, andrographolide did not reduce NO production on oral administration at the same doses. These results indicate that neoandrographolide, which inhibited NO production both in vitro and ex vivo may play an important role in the use of A. paniculata as an anti-inflammatory crude drug.
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5: Immunol Invest. 2002 May;31(2):137-53.
Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers.
See D, Mason S, Roshan R. Center for Advanced Medicine, Encinitias , California , USA .
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Natural products may increase cytotoxic activity of Natural Killer Cells (NK) Tumor Necrosis Factor alpha (TNF-alpha) while decreasing DNA damage in patients with late-stage cancer. Pilot studies have suggested that a combination of Nutraceuticals can raise NK cell function and TNF-alpha alpha activity and result in improved clinical outcomes in patients with late stage cancer. The objective of the study is to determine if Nutraceuticals can significantly raise NK function and TNF levels in patients with late stage cancer. After informed consent was obtained, 20 patients with stage IV, end-stage cancer were evaluated (one bladder, five breast, two prostate, one neuroblastoma, two non-small cell lung, three colon, 1 mesothelioma, two lymphoma, one ovarian, one gastric, one osteosarcoma). Transfer Factor Plus (TFP+, 3 tablets 3 times per day), IMUPlus (non denatured milk whey protein, 40 gm/day); Intravenous (50 to 100 gm/day) and oral (1-2 gm/day) ascorbic acid; Agaricus Blazeii Murill teas (10 gm/day); Immune Modulator Mix (a combination of vitamin, minerals, antioxidants and immune-enhancing natural products); nitrogenated soy extract (high levels of genistein and dadzein) and Andrographis Paniculata (500 mg twice, daily) were used. Baseline NK function by standard 4 h 51Cr release assay and TNF alpha and receptor levels were measured by ELISA from resting and phytohemagglutinin (PHA) stimulated adherent and non-adherent Peripheral Blood Mononuclear Cell (PBMC). Total mercaptans and glutathione in plasma were taken and compared to levels measured 6 months later. Complete blood counts and chemistry panels were routinely monitored. As of a mean of 6 months, 16/20 patients were still alive. The 16 survivors had significantly higher NK function than baseline (p < .01 for each) and TNF-alpha levels in all four cell populations studied (p < .01 for each). Total mercaptans (p < .01) and TNF-alpha receptor levels were significantly reduced (p < .01). It was also observed that hemoglobin, hematocrit and glutathione levels were significantly elevated. The only toxicity noted was occasional diarrhea and nausea. The quality of life improved for all survivors by SF-36 form evaluation. An aggressive combination of immunoactive Nutraceuticals was effective in significantly increasing NK function, other immune parameters and hemoglobin from PBMC or plasma in patients with late stage cancers. Nutraceutical combinations may be effective in late stage cancers. Clinical outcomes evaluations are ongoing. |
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6: J Agric Food Chem. 2002 Jul 31;50(16):4662-5.
Mechanism of the superoxide scavenging activity of neoandrographolide - a natural product from Andrographis paniculata Nees.
Kamdem RE, Sang S, Ho CT. Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey, USA. |
It was hypothesized that neoandrographolide might scavenge free radicals by donating the allylic hydrogen of the unsaturated lactone ring. It was found that the stoichiometry of the reaction between neoandrographolide and superoxide radical generated from KO(2) in DMSO was 2 to 1. One major reaction product was isolated and determined to be a diacid formed by the opening of the lactone ring. It was concluded that the antiradical activity of neoandrographolide proceeded by hydrogen abstraction from carbon C-15. A reaction mechanism was proposed. |
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7: Br J Pharmacol. 2002 Jan;135(2):399-406.
Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect.
Shen YC, Chen CF, Chiou WF. National Research Institute of Chinese Medicine, 155-1, Li-Nung Street Section 2, Shih-Pai, Taipei , Taiwan . |
We have reported that andrographolide (ANDRO), an active component of Andrographis paniculata, inhibits inflammatory responses by rat neutrophils. To further elucidate the possible mechanism(s) underlying the ANDRO's effect, N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion and transmigration of isolated peripheral human neutrophils were studied. Pretreatment with ANDRO (0.1 - 10 microM) concentration-dependently prevented fMLP-induced neutrophil adhesion and transmigration. We further examined the up-expression of surface Mac-1 (CD11b/CD18), an essential integrin mediated in neutrophil adhesion and transmigration. ANDRO pretreatment significantly decreased fMLP-induced up-expression of both CD11b and CD18. Accumulation of reactive oxygen species (ROS) as well as quick intracellular calcium ([Ca(++)](i)) mobilization induced by fMLP displays two important signalling pathways in regulating the up-expression of Mac-1 by neutrophils. That ANDRO pretreatment diminished fMLP-induced production of H(2)O(2) and O(2)*(-), but failed to block that of [Ca(++)](i) mobilization suggested that the ROS but not [Ca(++)](i) signalling could be modulated by ANDRO. To clarify whether ROS production impeded by ANDRO could be an antagonism of fMLP binding, phorbol-12-myristate-13-acetate (PMA), a direct protein kinase C (PKC) activator, was introduced to activate ROS production. PMA triggered remarkable ROS production and adhesion, and were partially reversed by ANDRO. This indicated that a PKC-dependent mechanism might be interfered by ANDRO. We conclude that the prevention of ROS production through, at least in part, modulation of PKC-dependent pathway could confer ANDRO the ability to down-regulate Mac-1 up-expression that is essential for neutrophil adhesion and transmigration. |
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8: Phytother Res. 2001 Aug;15(5):382-90.
Modulatory influence of Andrographis paniculata on mouse hepatic and extrahepatic carcinogen metabolizing enzymes and antioxidant status.
Singh RP, Banerjee S, Rao AR. Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India. |
The effects of two doses (50 and 100 mg/kg body wt/day for 14 days) of an 80% hydroalcohol extract of Andrographis paniculata and butylated hydroxyanisole (BHA) were examined on drug metabolizing enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the liver of Swiss albino mice (6-8 weeks old). The effect of the extract and BHA were also examined on lung, kidney and forestomach for the activities of glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD) and catalase. A significant increase in the levels of acid soluble sulphydryl (-SH) content, cytochrome P450, cytochrome P450 reductase, cytochrome b5 reductase, GST, DTD and SOD were observed at both dose levels of extract treatment while catalase, glutathione peroxidase and glutathione reductase (GR) showed significant increases only at the higher dose in the liver. Both Andrographis treated groups showed a significant decrease in activity of LDH and malondialdehyde (MDA) formation. BHA treated mice showed a significant increase in the levels of cytochrome b(5), GST, DTD, -SH content, GR and catalase in liver; while LDH and MDA levels were reduced significantly compared with their control values. In the lung, SOD, catalase and DTD, in the kidney catalase, DTD and GST, and in the forestomach SOD and DTD showed a significant increase at both dose levels of treatment. In BHA treated mice GST, DTD and catalase were significantly induced in the lung and along with these enzymes SOD was also induced in the kidney. In the case of the forestomach of BHA treated mice GST, DTD and SOD were enhanced significantly. These findings indicate the chemopreventive potential of Andrographis paniculata against chemotoxicity including carcinogenicity. |
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9: Phytomedicine. 2000 Oct;7(5):341-50.
Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection.
Melchior J, Spasov AA, Ostrovskij OV. Hallehalsan, Clinic, Ulricehamn , Sweden .
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Two randomized double-blind, placebo-controlled parallel group clinical trials were performed to investigate the effect of a standardized extract (SHA-10) of Andrographis paniculata fixed combination ( Kan jang) in the treatment of uncomplicated upper-respiratory tract infections. 46 patients in the pilot study and 179 patients in the phase III study completed the study according to the protocol. Medication was taken three times daily for a minimum of 3 days and a maximum of 8 days for the pilot study, and for exactly three days in the phase III study. The primary outcome measures in the patients self-evaluation were: related to pain in the muscle, cough, throat symptoms, headache, nasal symptoms and eye symptoms and temperature. The physician's fixed score diagnosis was based mainly on sign/symptoms: ears, nose, oral cavity, lymph glands-tonsils and eyes. The total symptom score showed a tendency toward improvement in the pilot study (p = 0,08), while both the total symptom score and total diagnosis score showed highly significant improvement (p < or = 0.0006 resp. 0.003) in the verum group as compared with the placebo. In both studies throat symptoms/signs, were found to show the most significant improvement.
Publication Types: Clinical Trial, Clinical Trial, Phase III, Randomized Controlled Trial
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10: Phytother Res. 2000 Aug;14(5):333-8.
A phase I trial of andrographolide in HIV positive patients and normal volunteers.
Calabrese C, Berman SH, Babish JG. Bastyr University Research Institute, Bastyr University , Washington , USA
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A phase I dose-escalating clinical trial of andrographolide from Andrographis paniculata was conducted in 13 HIV positive patients and five HIV uninfected, healthy volunteers. The objectives were primarily to assess safety and tolerability and secondarily to assess effects on plasma virion HIV-1 RNA levels and CD4(+) lymphocyte levels. No subjects used antiretroviral medications during the trial. Those with liver or renal abnormalities were excluded. The planned regimen was 5 mg/kg bodyweight for 3 weeks, escalating to 10 mg/kg bodyweight for 3 weeks, and to 20 mg/kg bodyweight for a final 3 weeks. The trial was interrupted at 6 weeks due to adverse events including an anaphylactic reaction in one patient. All adverse events had resolved by the end of observation. A significant rise in the mean CD4(+) lymphocyte level of HIV subjects occurred after administration of 10 mg/kg andrographolide (from a baseline of 405 cells/mm(3) to 501 cells/mm(3); p = 0.002). There were no statistically significant changes in mean plasma HIV-1 RNA levels throughout the trial. Andrographolide may inhibit HIV-induced cell cycle dysregulation, leading to a rise in CD4(+) lymphocyte levels in HIV-1 infected individuals.
Publication Types: Clinical Trial, Clinical Trial, Phase I |
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11: Planta Med. 2000 May;66(4):314-7.
Suppression of rat neutrophil reactive oxygen species production and adhesion by the diterpenoid lactone andrographolide.
Shen YC, Chen CF, Chiou WF. National Research Institute of Chinese Medicine, Taipei , Taiwan . |
The present study was to examine whether andrographolide, a diterpenoid lactone isolated from the anti-inflammatory herbal medicine Andrographis paniculata (Burm. f.) Nees. (Acanthaceae), has the ability to prevent phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion by rat neutrophils. Results demonstrated that PMA (100 ng/ml) induced rapid accumulation of H2O2 and O2. in neutrophils within 30 minutes. Andrographolide (0.1 to 10 microM) pretreatment (10 min, 37 degrees C) significantly attenuated the accumulation of these two oxygen radical metabolites. Administration of andrographolide also significantly prevented fMLP-induced neutrophil adhesion. These data suggest that preventing ROS production and neutrophils adhesion may confer andrographolide the ability to be an anti-inflammatory drug. |
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12: Br J Pharmacol. 2000 Apr;129(8):1553-60.
Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide.
Chiou WF, Chen CF, Lin JJ. National Research Institute of Chinese Medicine, Taipei , Taiwan .
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Andrographolide, an active component found in leaves of Andrographis paniculata, has been reported to exhibit nitric oxide (NO) inhibitory property in endotoxin-stimulated macrophages, however, the detailed mechanisms remain unclear. In the present study we investigated the effect of andrographolide on the expression of inducible NO synthase (iNOS) mRNA, protein, and enzyme activity in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). RAW 264.7 cells stimulated with LPS/IFN-gamma activated NO production; in this condition andrographolide (1-100 microM) inhibited NO production in a dose-dependent manner with an IC(50) value of 17.4+/-1.1 microM. Andrographolide also reduces the expression of iNOS protein level but without a significant effect on iNOS mRNA. The reduction of iNOS activity is thought to be caused by decreased expression of iNOS protein. In a protein stability assay, andrographolide moderately but significantly reduced the amount of iNOS protein as suggested by accelerating degradation. Furthermore, andrographolide also inhibited total protein de novo synthesis as demonstrated by [(35)S]-methionine incorporation. As a whole, these data suggest that andrographolide inhibits NO synthesis in RAW 264.7 cells by reducing the expression of iNOS protein and the reduction could occur through two additional mechanisms: prevention of the de novo protein synthesis and decreasing the protein stability via a post-transcriptional mechanism. It is also possible that inhibition of iNOS protein expression and NO production under immune stimulation and/or bacteria infection may explain, in part, the beneficial effects of andrographolide as an anti-inflammatory agent. |
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13: Phytomedicine. 1999 Oct;6(4):217-23.
Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study.
Caceres DD, Hancke JL, Burgos RA. Facultad de Medicina, Universidad de Chile, Santiago, Chile. |
The objective of our study was to measure the effectiveness of Andrographis paniculata SHA-10 extract in reducing the prevalence and intensity of symptoms and signs of common cold as compared with a placebo. A group of 158 adult patients of both sexes completed the randomized double blind study in Valdivia , Chile . The patients were divided in two equal size groups, one of which received Andrographis paniculata dried extract (1200 mg/day) and the other a placebo during a period of 5 days. Evaluations for efficacy were performed by the patient at day 0, 2, and 4 of the treatment; each completed a self-evaluation (VAS) sheet with the following parameters: headache, tiredness, earache, sleeplessness, sore throat, nasal secretion, phlegm, frequency and intensity of cough. In order to quantify the magnitude of the reduction in the prevalence and intensity of the signs and symptoms of common cold, the risk (Odds Ratio = OR) was calculated using a logistic regression model. At day 2 of treatment a significant decrease in the intensity of the symptoms of tiredness (OR = 1.28; 95% CI 1.07-1.53), sleeplessness (OR = 1.71; 95% CI 1.38-2.11), sore throat (OR = 2.3; 95% CI 1.69-3.14) and nasal secretion (OR = 2.51; 95% CI 1.82-3.46) was observed in the Andrographis SHA-10 group as compared with the placebo group. At day 4, a significant decrease in the intensity of all symptoms was observed for the Andrographis paniculata group. The higher OR values were for the following parameters: sore throat (OR = 3.59; 95% CI 2.04-5.35), nasal secretion (OR = 3.27; 95% CI 2.31-4.62) and earache (OR = 3.11; 95% CI 2.01-4.80) for Andrographis paniculata treatment over placebo, respectively. It is concluded that Andrographis paniculata had a high degree of effectiveness in reducing the prevalence and intensity of the symptoms in uncomplicated common cold beginning at day two of treatment. No adverse effects were observed or reported.
Publication Types: Clinical Trial, Randomized Controlled Trial |
14: Chem Pharm Bull ( Tokyo ). 1994 Jun;42(6):1216-25.
Cell differentiation-inducing diterpenes from Andrographis paniculata Nees.
Matsuda T, Kuroyanagi M, Sugiyama S. School of Pharmaceutical Sciences, University of Shizuoka , Japan .
The methanol extract of the aerial part of Andrographis paniculata Nees showed potent cell differentiation-inducing activity on mouse myeloid leukemia (M1) cells. From the ethyl acetate-soluble fraction of the methanol extract, six new diterpenoids of ent-labdane type, 14-epi-andrographolide (3), isoandrographolide (4), 14-deoxy-12-methoxyandrographolide (7), 12-epi-14-deoxy-12-methoxyandrographolide (8), 14-deoxy-12-hydroxyandrographolide (9) and 14-deoxy-11-hydroxyandrographolide (10) as well as two new diterpene glucosides, 14-deoxy-11,12-didehydroandrographi-side (12) and 6'-acetylneoandrographolide (14), and four new diterpene dimers, bis-andrograpolides A (15), B (16), C (17) and D (18), were isolated along with six known compounds. The structures of the diterpenoids were determined by means of spectral methods. Some of these compounds showed potent cell differentiation-inducing activity towards M1 cells.
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15: J Nat Prod. 1993 Jul;56(7):995-9.
Immunostimulant agents from Andrographis paniculata.
Puri A, Saxena R, Saxena RP. Division of Biochemistry, Central Drug Research Institute, Lucknow , India . |
EtOH 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 nonspecific immune response of the animals measured in terms of macrophage migration index (MMI) phagocytosis of 14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and nonspecific immune response was, however, of lower order with andrographolide than with the EtOH extract, suggesting thereby that substance(s) other than andrographolide present in the extract may also be contributing towards immunostimulation. |
16: J Med Assoc Thai. 1991 Oct;74(10):437-42.
Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults.
Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W. Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok.
One hundred and fifty-two adult patients with pharyngotonsillitis were enrolled in the randomized double blind study to assess the efficacy of Andrographis paniculata. The patients were randomized to receive either paracetamol or 3 g/day of Andrographis paniculata or 6 g/day of Andrographis paniculata for 7 days. The baseline characteristics of the patients among the three groups were not different. The efficacy of paracetamol or high dose Andrographis paniculata was significantly more than that of low dose Andrographis paniculata at day 3 in terms of the relief of fever and sore throat. The clinical effects were not different at day 7. Minimal and self limiting side effects were found in about 20 per cent in each group.
Publication Types: Clinical Trial, Randomized Controlled Trial
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17: Proc Soc Exp Biol Med. 1991 May;197(1):59-66.
Dehydroandrographolide succinic acid monoester as an inhibitor against the human immunodeficiency virus.
Chang RS, Ding L, Chen GQ. Department of Medical Microbiology, University of California, Davis. USA. |
Dehydroandrographolide succinic acid monoester (DASM) is the dehydroandrographolyl ester of succinic acid; and andrographolide, from which DASM is made, is the major diterpenoid lactone found in the Chinese medicinal herb, Andrographis paniculata. DASM has been found to be an inhibitor against the human immunodeficiency virus (HIV) in vitro. It was nontoxic to the H9 cell at the concentrations of 50-200 (average, 108) micrograms/ml and was inhibitory to the HIV-1 (IIIB) at the minimal concentration of 1.6-3.1 (average 2.0) micrograms/ml. It was also inhibitory to two other strains of HIV-1 and a strain of HIV-2. This inhibitory effect could also be demonstrated in cultures of activated human blood mononuclear cells; the 50% toxic dose and the 50% HIV inhibitory dose were about 200-greater than or equal to 400 and 0.8-2 micrograms/ml, respectively. At the subtoxic concentration, DASM partially interfered with HIV-induced cell fusion and with the binding of HIV to the H9 cell. Presumably, it also interfered with HIV replication at another unidentified step(s). |
18: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997 Sep;17(9):547-9.
[Effects of Andrographis paniculata component on nitric oxide, endothelin and lipid peroxidation in experimental atherosclerotic rabbits]
Wang HW, Zhao HY, Xiang SQ.
Department of Cardiovascular Diseases, Tongji Hospital, Tongji Medical University, Wuhan.
OBJECTIVE: To observe the effects of Andrographis Paniculata component (API0134) on nitric oxide (NO), endothelin (ET), cyclic guanosine monophosphate (cGMP), lipid peroxide (LPO) and superoxide dismutase (SOD) in experimental atherosclerotic rabbit. METHODS: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and API0134 treated group. Blood samples were collected before 4 weeks and 8 weeks after relevent treatment. RESULTS: Before 4 and after 8 weeks API0134 administration, compared with model group, the NO, cGMP and activity of SOD increased (P < 0.01), while LPO and ET decreased (P < 0.01). CONCLUSIONS: API0134 possesses the effects of antioxidation, preserving endothelial function, and maintaining the balance of NO/ET. |
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19: Phytomedicine. 1999 Mar;6(1):27-31.
Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation.
Amroyan E, Gabrielian E, Panossian A. Yerevan State Medical University , Armenia . |
Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and antiatherosclerotic drug, was investigated for its suggested influence on the biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in isolated human polymorph-nuclear leukocytes (PMNL) no influence on the biosynthesis was found, it could be shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner (IC50-5 microM). These results indicate that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata. |
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20: Br J Pharmacol. 1998 Sep;125(2):327-34.
Andrographolide suppresses the expression of inducible nitric oxide synthase in macrophage and restores the vasoconstriction in rat aorta treated with lipopolysaccharide.
Chiou WF, Lin JJ, Chen CF. National Research Institute of Chinese Medicine, Taipei , Taiwan , ROC. |
1. We investigated whether andrographolide, a diterpenoid lactone found at Andrographis paniculata, influences the induction of the inducible nitric oxide synthase (iNOS) in RAW264.7 cells activated by bacterial endotoxin (LPS), as well as in the rats with endotoxic shock and in aortic rings treated with LPS. 2. Incubation of RAW264.7 cells with andrographolide (1 to 50 microM) inhibited the LPS (1 microg ml(-1))-induced nitrite accumulation in concentration- and time-dependent manners. Maximum inhibition was observed when andrographolide was added together with LPS and decreased progressively as the interval between andrographolide and LPS was increased to 20 h. 3. Western blot analysis demonstrated that iNOS expression was markedly attenuated in the presence of andrographolide for 6-24 h, suggesting that andrographolide inhibited iNOS protein induction. 4. Thoracic aorta incubation with LPS (300 ng ml(-1)) for 5 h in vitro exhibited a significant decrease in the maximal contractile response to phenylephrine (10(-9)-10(-5) M). Andrographolide (30 microM) restored the contractile response to control level. 5. In anaesthetized rats, LPS (10 mg kg(-1), i.v.) caused a fall in mean arterial blood pressure (MAP) from 116+/-4 to 77+/-5mmHg. The pressor effect of phenylephrine (10 microg ml(-1), i.v.) was also significantly reduced at 30, 60, 120 and 180 min after LPS injection. In contrast, animals pretreated with andrographolide (1 mg kg(-1), i.v., 20 min prior to LPS) maintained a significantly higher MAP when compared to LPS-rats given with vehicle. Administration of andrographolide 60 min after LPS caused a increase in MAP and significantly reversed the reduction of the pressor response to phenylephrine. 6. Our results indicated that andrographolide inhibits nitrite synthesis by suppressing expression of iNOS protein in vitro. And, this inhibition of iNOS synthesis may contribute to the beneficial haemodynamic effects of andrographolide in endotoxic shock. |
21: J Tongji Med Univ. 1996;16(4):193-7.
Protective effects of API0134 on myocardial ischemia and reperfusion injury.
Guo Z, Zhao H, Fu L. Department of Internal Medicine, Tongji Hospital, Tongji Medical University, Wuhan.
Previous studies have demonstrated that a crude extract from Chinese medicinal herb Andrographis Paniculata Nees (APN) could prevent myocardial ischemia and reperfusion injury. A refined extract API0134 was studied further. LAD was ligated for 90 min in 20 dogs and then reperfused for 120 min. The animals were randomly divided into 2 groups, API0134 treated group (n = 10), 45 min after ischemia receiving a slow i.v. bolus of 1 mg/kg and then an infusion of 80 micrograms.kg-1/min for 60 min and control group (n = 10) which was given only 5% glucose in saline. Result showed that the hemodynamics in API0134 treated group showed better effects of preventing the increase of the LVEDP and maintaining relatively normal CO as compared with control group. Ischemic ECGs were significantly milder. Malignant arrhythmia did not appear in API0134 treated group. After reperfusion, the infarct size was smaller (5.06 +/- 2.67% vs 10.45 +/- 3.11%, P < 0.01), the damages found in myocardial ultrastructure were significantly milder. It is concluded that API0134 may protect the myocardium from ischemic reperfusion injury. |
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22: J Ethnopharmacol. 1997 Apr;56(2):97-101.
Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat.
Zhang CY, Tan BK. Department of Pharmacology, Faculty of Medicine, National University of Singapore , Singapore . |
The cardiovascular activities of crude water extract (WE) of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), its three semi-purified ethyl acetate (FA), n-butanol (FB) and aqueous (FC) fractions, as well as andrographolide, a major plant constituent, were elucidated in anaesthetized Sprague-Dawley (SD) rats for the very first time. FA and andrographolide, which possesses multiple pharmacological activities, elicited no drop in mean arterial blood pressure (MAP), while WE, FB and FC produced a significant fall in MAP in a dose-dependent manner without significant decrease in heart rate. The ED50 values for WE, FB and FC were 11.4, 5.0 and 8.6 mg/kg-respectively. These suggested that the hypotensive substance(s) of the crude water extract was concentrated in FB. Pharmacological antagonist studies were consequently only tested in FB (5 mg/kg). The hypotensive action of FB was not mediated through effects on the beta-adrenoceptor, muscarinic cholinergic receptor and angiotensin-converting enzyme, for it was not affected by propranolol, atropine and captapril, respectively. However, it seems to work via alpha-adrenoceptors, autonomic ganglion and histaminergic receptors, since the hypotensive effect of FB was negated or attenuated in the presence of phentolamine, hexamethonium as well as pyrilamine and cimetidine. |
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23 : Clin Exp Pharmacol Physiol. 1996 Aug;23(8):675-8.
Hypotensive activity of aqueous extract of Andrographis paniculata in rats.
Zhang CY, Tan BK. Department of Pharmacology, Faculty of Medicine, National University of Singapore , Singapore . |
1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p.) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar-Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by the thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract- and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats. |
24: J Tongji Med Univ. 1995;15(4):205-8.
An experimental study of the mechanism of andrographis paniculata nees (APN) in alleviating the Ca(2+)-overloading in the process of myocardial ischemic reperfusion.
Guo ZL, Zhao HY, Zheng XH. Department of Medicine, Tongji Hospital , Tongji Medical University , Wuhan .
The aim of this experiment is to study the mechanism of APN in alleviating the Ca(2+)-overloading in dog model during the process of ischemic reperfusion. In comparison with the sustained ischemic group, the parameters in the ischemic reperfusion group demonstrated: Ca(2+) of ischemic region of myocardial cell increased (P < 0.05), Na+ increased remarkably (P < 0.01), the activity of Ca(2+)-ATPase dropped remarkably (P < 0.01), and MDA increased significantly (P < 0.01). Whereas in the group pretreated with APN, the Ca(2+) in the relevant area reduced (P < 0.05), Na+ decreased significantly (P < 0.01), the activity of Ca(2+)-ATPase and Na+-K+ ATPase increased remarkably (P < 0.01), and MDA decreased significantly (P < 0.01). These findings indicate tha APN may improve the activity of sarcolemma ATPase in alleviating the Ca(2+) and Na+ -overloading by decreasing the harmful effect of oxygen free radicals.
25: Chin Med J (Engl). 1994 Jun;107(6):464-70.
Prevention of atherosclerotic arterial stenosis and restenosis after angioplasty with Andrographis paniculata nees and fish oil. Experimental studies of effects and mechanisms.
Wang DW. Cardiology Department, Tongji Hospital , Tongji Medical University , Wuhan .
Restenosis rate after coronary angioplasty has been up to 30%-40%. To solve this problem, we studied the effects of Andrographis Paniculata Nees (APN) and fish oil (FO, omega 3 polyunsaturated fatty acids over 70%) on atherosclerotic stenosis and restenosis after experimental angioplasty and the relevant mechanisms of APN and FO. Preliminary results showed that APN can significantly alleviate atherosclerotic iliac artery stenosis induced by both deendothelialization and high cholesterol diet (HCD) and restenosis following angioplasty in rabbits. FO showed the same but milder effects than APN did. Both APN and FO significantly inhibited blood monocytes to secrete growth factors in vivo. Ca(++)-ATPase activity of cell membrane of atherosclerotic rabbits was significantly decreased, while APN or FO, especially the former alleviated this reduction. Refined extract of APN significantly decreased in vitro resting platelet [Ca++]i and in vivo the resting and thrombin-stimulated platelet [Ca++]i after oral administration of APN for 2 weeks. APN significantly inhibited cell growth or DNA synthesis in dose-dependent manner. In conclusion because of the mechanisms described above, APN can alleviate atherosclerotic artery stenosis induced by both deendothelialization and HCD as well as lower restenosis rate after experimental angioplasty. The effects of APN are evidently superior to those of FO.
26: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994 Jan;14(1):28-30, 34, 5.
[Study of Andrographis paniculata extracts on antiplatelet aggregation and release reaction and its mechanism]
Zhang YZ, Tang JZ, Zhang YJ. Tongji Hospital , Tongji Medical University , Wuhan .
63 patients of cardiac and cerebral vascular diseases were observed at 3 hours and/or one week after taking Andrographis paniculata (AP) extracts. Results showed that both 1 min. and 5 min. platelet aggregation induced by ADP were significantly inhibited (P < 0.001), 33 cases of them were observed for one week. The aggregation rate was even significantly lower than that of 3 hours. Serotonin (5-HT) release reaction from platelet was observed in 20 volunteers taking AP. Result showed 5-HT released from platelet decreased (P < 0.01), but plasma 5-HT level remained unchanged. The ultrastructural observation showed that AP could inhibit the releasing of dense and alpha agranules from platelet and dilating of canalicular system. It suggested that a raise of platelet cAMP level might be the mechanism of antiplatelet effect of AP.
27: J Tongji Med Univ. 1994;14(1):49-51.
The effect of andrographis paniculata nees (APN) in alleviating the myocardial ischemic reperfusion injury.
Guo ZL. Department of Cardiology, Tongji Hospital , Tongji Medical University , Wuhan .
In experimental dogs, the effect of APN in alleviating the ischemia-reperfusion injury was prominent. Compared with the sustained ischemia group, superoxide dismutase (SOD) in the ischemic region of myocardial tissue in the ischemia-reperfusion group was significantly decreased and malondialdehyde (MDA) markedly increased: Ca2+ in myocardial cells was increased; and ultrastructural changes of myocardial tissues were severe. In the APN-pretreated ischemia-reperfusion group, on the contrary, all the above parameters showed reversely, i.e., SOD increased, MDA and intracellular Ca2+ decreased, the ultrastructure changes were less distorted.
28: J Tongji Med Univ. 1993;13(4):193-8.
Experimental studies on prevention of atherosclerotic arterial stenosis and restenosis after angioplasty with Andrographis Paniculata Nees and fish oil.
Wang DW. Cardiology Department, Tongji Hospital , Tongji Medical University , Wuhan .
In order to search for effective drugs to reduce restenosis incidence after coronary angioplasty, we studied the effects of a Chinese herb, extract of Andrographis Paniculata Nees (APN), and Fish Oil (FO) on atherosclerotic stenosis and restenosis after experimental angioplasty. Preliminary results showed that APN can significantly alleviate atherosclerotic iliac artery stenosis induced by both deendothelialization and high cholesterol diet (control group, stenosis incidence 100%, stenotic severe degree 60.53 +/- 31.03%, of which 30% arteries (6) are total occlusion; FO group: stenotic incidence and severe degree are 77% and 53.00 +/- 21.17%, respectively, and in APN group they are 70% and 25.39 +/- 10.52%, respectively, P < 0.01), and follow-up angiography 4 weeks after angioplasty showed that dilated iliac arteries in control group all had severe restenosis, but in APN group no or only mild restenosis occurs, and in FO group restenosis is as severe as stenotic degree prior to angioplasty. These preliminary results suggest that APN and FO can significantly alleviate stenosis induced by deendothelialization and high cholesterol diet and restenosis after angioplasty, while the former has a more marked effect. The above findings lead the authors to conclude that APN may play an important role in preventing restenosis after coronary angioplasty, but FO may be useful in reducing the extent of of restenosis after coronary angioplasty.
29: Chin Med J (Engl). 1991 Sep;104(9):770-5.
Antithrombotic effects of Andrographis paniculata nees in preventing myocardial infarction.
Zhao HY. Department of Internal Medicine, Tongji Hospital , Tongji Medical University , Wuhan .
In 16 dogs the endothelium of the left anterior descending coronary artery was injured mechanically. Then a copper wire was inserted into the lumen as a choke of flow and the vessel was slightly compressed from outside by a constrictor. Eight dogs had been treated beforehand with a preparation of flavone extracted from the root of the Chinese medicinal herb Andrographis paniculata (TFAP). In the control group, saline solution was given, the epicardially recorded ST segment started to elevate within 15 minutes, the platelet aggregation rate and the plasma levels of TXB2 increased rapidly, whereas the level of 6-k-PGF1 alpha remained stable. Platelet cGMP rose continuously; however, platelet cAMP rose only at 60 minutes. Histological findings confirmed the occurrence of arterial thrombus and myocardial necrosis. Contrariwise, in the pretreated group there was no elevation of the ST segment, plasma 6-k-PGF1 alpha and platelet cAMP were increased, the production of TXB2 and aggregation of platelets were inhibited, and no thrombus or myocardial infarction was induced. All data suggest that TFAP might promote the synthesis of PGI2, inhibit the production of TXA2, stimulate the synthesis of cAMP in platelets, impede aggregation of platelets, and thereby prevent the formation of thrombi as well as the development of myocardial infarction.
30: J Tongji Med Univ. 1990;10(4):212-7.
Protective effects of andrographis paniculata nees on post-infarction myocardium in experimental dogs.
Zhao HY. Department of Internal Medicine, Tongji Hospital , Tongji Medical University , Wuhan .
One hour after the development of myocardial infarction by formation of thrombus, watery extract of Andrographis paniculata Nees (APN) was injected intravenously to 7 dogs for observing the protective effect of this drug on ischemic myocardium, 6 dogs served as control group. In the treated group PGI2 increased remarkably, synthesis of TXA2 was inhibited, cAMP in platelets was elevated, CK-MB peak was lowered and appeared earlier, ELT was shortened, release of platelet beta-GT was decreased, platelet maximum aggregation rate was inhibited, the size of ischemic area recorded by epicardial ECG was reduced, the amplitude of ST segment elevation was lower than that in the control group, Q wave appeared in only one dog. Pathologically, the myocardial structure surrounding the initially appearing ischemic area, i.e, the reversibly damaged area, became relatively normal, while the degree of myocardial degeneration and necrosis in the central part of the ischemic area was mild. These data suggest that APN may limit the expansion of ischemic focus, exert marked protective effect on reversibly ischemic myocardium and demonstrate a weak fibrinolytic action.
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31: Indian J Exp Biol. 2001 Jan;39(1):41-6.
Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice.
Trivedi NP, Rawal UM. Zoology Department, Gujarat University , Ahmedabad , India . |
Andrographis paniculata (AP) treatment prevents BHC induced increase in the activities of enzymes y-Glutamyl transpeptidase, glutathione-S-transferase and lipid peroxidation. The activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and the levels of glutathione were decreased following BHC effect. Administration of AP showed protective effects in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase as well the level of glutathione. The activity of lipid peroxidase was also decreased. The result indicate antioxidant and hepatoprotective action of A. paniculata. |
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32: Arch Pharm Res. 1991 Mar;14(1):93-5.
Hepatoprotective effects of Andrographis paniculata against carbon tetrachloride-induced liver damage.
Rana AC, Avadhoot Y. College of Pharmacy, Shri Govindram Seksaria Institute of Technology and Science, Indore , India . |
Alcoholic extract of the leaves of Andrographis paniculata Ness (= AAP) was obtained by cold maceration. A dose of 300 mg/kg (1/6 of LD50) of the extract was selected to study hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters. |
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33: J Ethnopharmacol. 1993 Oct;40(2):131-6.
Andrographolide protects rat hepatocytes against paracetamol-induced damage.
Visen PK , Shukla B, Patnaik GK. ICMR Centre for Advanced Pharmacological Research on Traditional Remedies, Central Drug Research Institute, Lucknow , India . |
Andrographolide, the active constituent isolated from the plant Andrographis paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o. x 7) protective activity against paracetamol-induced toxicity on ex vivo preparation of isolated rat hepatocytes. It significantly increased the percent viability of the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It completely antagonized the toxic effects of paracetamol on certain enzymes (GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. Andrographolide was found to be more potent than silymarin, a standard hepatoprotective agent. |
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34: Biochem Pharmacol. 1993 Jul 6;46(1):182-5.
Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata.
Kapil A, Koul IB, Banerjee SK. Department of Pharmacology, Regional Research Laboratory, Jammu , India . |
The diterpenes andrographolide (I), andrographiside (II) and neoandrographolide (III) isolated from Andrographis paniculata were investigated for their protective effects on hepatotoxicity induced in mice by carbon tetrachloride or tert-butylhydroperoxide (tBHP) intoxication. Pretreatment of mice with the diterpenes (I, II & III; 100 mg/kg, i.p.) for 3 consecutive days produced significant reduction in malondialdehyde formation, reduced glutathione (GSH) depletion and enzymatic leakage of glutamic-pyruvate transaminase (GPT) and alkaline phosphatase (AP) in either group of the toxin-treated animals. A comparison with the known hepatoprotective agent silymarin revealed that I exhibited a lower protective potential than II and III, which were as effective as silymarin with respect to their effects on the formation of the degradation products of lipid peroxidation and release of GPT and AP in the serum. GSH status was returned to normal only by III. The greater protective activity of II and III could be due to their glucoside groups which may act as strong antioxidants. |
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35: Indian J Med Res. 1990 Aug;92:284-92.
Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats.
Handa SS, Sharma A. Department of Pharmaceutical Sciences, Panjab University , Chandigarh |
Hepatoprotective effect of andrographolide (the major active diterpenoid lactone of the plant Andrographis paniculata) was studied on acute hepatitis induced in rats by single dose of galactosamine (800 mg/kg, ip)/paracetamol (3g/kg, po). Hepatoprotective activity was monitored by estimating the serum transaminases (GOT and GPT), alkaline phosphatase and bilirubin in serum, hepatic triglycerides, and by histopathological changes in the livers of experimental rats. Pre-treatment and/or post-treatment of rats at different time intervals with different doses of andrographolide in the two experimental models of hepatotoxicity showed that treatment of rats with 400 mg/kg, ip or 800 mg/kg, po, 48, 24 and 2 h before galactosamine administration or with 200 mg/kg, ip, 1, 4 and 7 h after paracetamol challenge leads to complete normalisation of toxin-induced increase in the levels of all the five biochemical parameters, and significantly ameliorates toxin-induced histopathological changes in the livers of experimental rats. The results confirmed the in vivo hepatoprotective effect of andrographolide against galactosamine or paracetamol-induced hepatotoxicity in rats. Since the protective effect of andrographolide was observed in two types of intoxication, which are very different in their primary mechanism of inducing hepatotoxicity, it is suggested that protective mechanisms of andrographolide which are not specific to galactosamine or paracetamol toxicity may be responsible for the hepatoprotective activity of the compound. |
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36: Indian J Med Res. 1990 Aug;92:276-83.
Hepatoprotective activity of andrographolide from Andrographis paniculata against carbontetrachloride.
Handa SS, Sharma A. Department of Pharmaceutical Sciences, Panjab University , Chandigarh . |
Andrographolide, a diterpenoid lactone, was isolated (yield 0.78% w/w) from A. paniculata (whole plant). Its LD50 in male mice was 11.46 g/kg, ip. Antihepatotoxic activity of andrographolide (100 mg/kg, ip) was compared with 861.33 mg/kg, ip, of the methanolic extract (equivalent to 100 mg/kg of andrographolide) and 761.33 mg/kg ip, of the andrographolide-free methanolic extract (equivalent to 861.33 mg/kg of the methanolic extract) of the plant, using CCl4-intoxicated rats. Biochemical parameters like serum transaminases--GOT and GPT, serum alkaline phosphatase, serum bilirubin and hepatic triglycerides were estimated to assess the liver function. Overall inhibition of CCl4-induced increase in the five biochemical parameters was found to be 48.6 per cent (andrographolide), 32.0 per cent (methanolic extract) and 15.0 per cent (andrographolide-free methanolic extract). These biochemical observations were supplemented by histopathological examination of the liver slices. Further, andrographolide (100 mg/kg, ip) was found to normalize completely the CCl4-induced increase in the pentobarbitone induced sleep time of mice. The results suggest that andrographolide is the major active antihepatotoxic principle present in A. paniculata. |
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37 : Methods Find Exp Clin Pharmacol. 1984 Sep;6(9):481-5.
Andrographolide and kalmegh (Andrographis paniculata) extract: in vivo and in vitro effect on hepatic lipid peroxidation.
Choudhury BR, Poddar MK.
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Single or repeated (for 15 consecutive days) oral administration of kalmegh leaf extract (500 mg/kg) or its bitter principle, andrographolide (5 mg/kg), to adult male albino rats (b.wt. 125-150 g) produced no significant change in NADPH induced hepatic microsomal lipid peroxidation. Carbontetrachloride (5 ml/kg) induced hepatic microsomal lipid peroxidation was decreased when the rats were pretreated (for 4 hr), but only with a single dose and not with long term administration of kalmegh or andrographolide. In vitro carbontetrachloride (1 microliter) induced hepatic microsomal lipid peroxidation was completely normalized by kalmegh leaf extract (0.5 and 5.0 micrograms/mg protein) or andrographolide (0.5 and 5.0 micrograms/mg protein). At the higher concentration of carbontetrachloride (2 microliter), hepatic microsomal lipid peroxidation remained significantly increased (25 %) in the presence of andrographolide (0.5 microgram/mg protein), but not in the presence of kalmegh extract (0.5 microgram/protein). These results suggest that kalmegh leaf extract has more protective action on carbontetrachloride-induced hepatic toxicity than its bitter principle, andrographolide. |
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38: Planta Med. 1992 Apr;58(2):146-9.
Choleretic effect of andrographolide in rats and guinea pigs.
Shukla B, Visen PK , Patnaik GK. ICMR Centre for Advanced Pharmacological Research on Traditional Remedies, Central Drug Research Institute, Lucknow , India . |
Andrographolide from the herb Andrographis paniculata (whole plant) per se produces a significant dose (1.5-12 mg/kg) dependent choleretic effect (4.8-73%) as evidenced by increase in bile flow, bile salt, and bile acids in conscious rats and anaesthetized guinea pigs. The paracetamol induced decrease in volume and contents of bile was prevented significantly by andrographolide pretreatment. It was found to be more potent than silymarin, a clinically used hepatoprotective agent. |
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39: J Ethnopharmacol. 1999 Mar;64(3):249-54.
Antimalarial activity of extracts of Malaysian medicinal plants.
Najib Nik A Rahman N, Furuta T. Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. |
In vitro and in vivo studies revealed that Malaysian medicinal plants, Piper sarmentosum, Andrographis paniculata and Tinospora crispa produced considerable antimalarial effects. Chloroform extract in vitro did show better effect than the methanol extract. The chloroform extract showed complete parasite growth inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period (Andrographis paniculata) as compared to methanol extract of drug dose of 2.5 mg/ml but under incubation time of 48 h of the same plant spesies. In vivo activity of Andrographis paniculata also demonstrated higher antimalarial effect than other two plant species. |
40: J Helminthol. 1982 Jun;56(2):81-4.
Filaricidal properties of a wild herb, Andrographis paniculata.
Dutta A, Sukul NC .
Water decoction of the leaves of Andrographis paniculata killed in vitro the microfilaria of Dipetalonema reconditum in 40 min. Three subcutaneous injections of the extract into infected dogs at 0.06 ml per kg body-weight reduced the number of microfilariae in blood by more than 85%. The larvae were not totally eliminated with more infections but the reduced microfilarial level persisted. No toxic effect of the extract was observed in rabbits. The treated dogs became lethargic initially for a week, probably due to the mass killing of microfilariae.
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41: Drug Deliv. 2000 Oct-Dec;7(4):209-13.
Targeting of liposomal andrographolide to L. donovani-infected macrophages in vivo.
Sinha J, Mukhopadhyay S, Das N. Biomembrane and Medicinal Chemistry Division, Indian Institute of Chemical Biology, Calcutta.
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Despite the rapid development in medicinal and pharmaceutical technology, the targeting of drugs to phagocytic cells in macrophage-related diseases still remains a major unsolved problem. By using the mannosyl-fucosyl receptors on macrophages, attempts were made to target antileishmanial drugs encapsulated in mannosylated or fucosylated liposomes to treat experimental leishmaniasis in the hamster model. Mannosylated liposomes were found to be more potent in delivering antileishmanial drugs to phagocytic cells. Liposomes loaded with an indigenous drug, andrographolide, a labdane diterpenoid isolated from Indian medicinal plant Andrographis paniculata, were prepared and tested against experimental leishmaniasis in a hamster model. Mannosylated liposomes loaded with the drug were found to be most potent in reducing the parasitic burden in the spleen as well as in reducing the hepatic and renal toxicity. In addition, mannosylated drug-loaded liposome-treated animals showed a normal blood picture and splenic tissue histoarchitecture when compared with those treated with free drug or regular liposomal drug. Such a drug-vehicle formulation may be considered for clinical trials. |
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42: Acta Pharmacol Sin. 2000 Dec;21(12):1157-64.
Anti-diabetic property of ethanolic extract of Andrographis paniculata in streptozotocin-diabetic rats.
Zhang XF, Tan BK. Department of Pharmacology, Faculty of Medicine, National University of Singapore , Singapore . |
AIM: To investigate the anti-diabetic effect of a crude ethanolic extract of Andrographis paniculata in normal and streptozotocin (STZ)-induced diabetic rats. METHODS & RESULTS: Oral administration of the extract at different doses (0.1, 0.2, and 0.4 g/body weight) significantly reduced the fasting serum glucose level in STZ-diabetic rats compared to the vehicle (distilled water), but not in normal rats. This effect was dose-dependent. A similar result was seen with metformin (0.5 g/body weight). In the glucose tolerance test, an oral administration of the extract at the same doses suppressed the elevated glucose level in normal and diabetic rats, as did metformin. The effects were also dose-respondent. In the long-term experiment, the extract (0.4 g/body weight), metformin (0.5 g/body weight), and vehicle were given twice daily to diabetic rats for 14 d. On d 15, fasting serum glucose levels were found to be significantly lower in the extract- and metformin-treated groups (P < 0.001) than in the vehicle-treated group. The mean food and water intakes over 14 days were significantly lower in the extract-treated group (P < 0.05, P < 0.01, respectively) and also in the metformin-treated group (both P < 0.001) when compared to the vehicle-treated group. No significant change in insulin level was observed among the 3 groups of diabetic rats. The extract, like metformin, maintained the leptin levels after 14-d treatment, whereas this level was significantly decreased (P < 0.05) in the vehicle-treated group. The activity of hepatic glucose-6-phosphatase (G-6-Pase) was significantly reduced by the extract as well as by metformin (both P < 0.05). No significant difference in hepatic glycogen stores was noted among the 3 groups. The extract caused 49.8% reduction of fasting serum triglyceride levels, compared to 27.7% with metformin. However, neither the extract nor metformin significantly affected serum cholesterol level. CONCLUSION: The ethanolic extract of A paniculata possesses antidiabetic property. Its antidiabetic effect may be attributed at least in part to increased glucose metabolism. Its hypotriglyceridemic effect is also beneficial in the diabetic state. |
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43: Clin Exp Pharmacol Physiol. 2000 May-Jun;27(5-6):358-63.
Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats.
Zhang XF, Tan BK. Department of Pharmacology, Faculty of Medicine, National University of Singapore , Singapore .
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1. Oxidative stress is believed to be a pathogenetic factor in the development of diabetic complications. In the present study, we investigated the ethanolic extract of the aerial parts of Andrographis paniculata for antihyperglycaemic and anti-oxidant effects in normal and streptozotocin-induced type I diabetic rats. 2. Normal and diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water), metformin (500 mg/kg bodyweight) or the extract (400 mg/kg bodyweight), twice a day for 14 days. 3. At the end of the 14 day period, the extract, like metformin, significantly increased bodyweight (P < 0.01) and reduced fasting serum glucose in diabetic rats (P < 0.001) when compared with vehicle, but had no effect on bodyweight and serum glucose in normal rats. Levels of liver and kidney thiobarbituric acid-reactive substances (TBARS) were significantly increased (P < 0.0001, P < 0.01, respectively), while liver glutathione (GSH) concentrations were significantly decreased (P < 0.005) in vehicle-treated diabetic rats. Liver and kidney TBARS levels were significantly lower (P < 0.0001, P < 0.005, respectively), whereas liver GSH concentrations were significantly higher (P < 0.05) in extract- and metformin-treated diabetic rats compared with vehicle-treated diabetic rats. Andrographis paniculata significantly decreased kidney TBARS level (P < 0.005) in normal rats. Hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly lower in vehicle-treated diabetic rats compared with vehicle-treated normal rats. The extract, as well as metformin, significantly increased the activity of SOD and CAT, but had no significant effect on GSH-Px activity in diabetic rats. The extract and metformin did not produce significant changes in the activity of these anti-oxidant enzymes in normal rats. 4. Our results show that oxidative stress is evident in streptozotocin-diabetic rats and indicate that the ethanolic extract of A. paniculata not only possesses an antihyperglycaemic property, but may also reduce oxidative stress in diabetic rats. |
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44: Phytomedicine. 2000 Oct;7(5):351-64.
Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human.
Panossian A, Hovhannisyan A, Mamikonyan G. Guelbenkian Research & Drug Quality Control Laboratory of ADMTA, Yerevan, Armenia.
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Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of andrographolide (AND) in the blood plasma of rats and human volunteers following the oral administration of Andrographis paniculata extract (APE) and Andrographis paniculata fixed combination Kan Jang tablets were developed and used for the pharmacokinetic study. Andrographolide was quickly and almost completely absorbed into the blood following the oral administration of APE at a dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND is bound to plasma proteins and only a limited amount can enter the cells, the pharmacokinetics of AND are described well by a one-compartment model. Renal excretion is not the main route for eliminating AND. It is most likely intensely and dose dependently metabolized. Following the oral administration of four Kan Jang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans, maximum plasma levels of approximately 393 ng/ml (approx. 1.12 microM) were reached after 1.5-2 hours, as quantified using a UV diode-array detection method. Half-life and mean residence times were 6.6 and 10.0 hours, respectively. AND pharmacokinetics in humans are explained well by an open two-compartment model. The calculated steady state plasma concentration of AND for multiple doses of Kan Jang (after the normal therapeutic dose regimen, 3 x 4 tablets/day, about 1 mg AND/kg body wt./day) was approximately 660 ng/ml (approx. 1.9 microM), enough to reveal any anti-PAF effect, particularly after drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx. 3.8 microM, while for anti-PAF effect EC50 - 5 microM). |
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45: Phytomedicine. 1999 Jul;6(3):157-61.
Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats.
Panossian A, Kochikian A, Gabrielian E. Guelbenkian Research and DQCL of Armenian Drug Agensy, Yerevan , Armenia .
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The effect of the powdered extract of Andrographis paniculata leaves (APE), an active principle of Kan Jang tablets [standardized for content of andrographolide (4.6%) and 14-deoxo-andrographolide (2.3%) content (total andrographolids--6.9%)] on blood progesterone content in rats was studied. Peroral administration of APE during the first 19 days of pregnancy in doses of 200, 600, and 2000 mg/kg (i.e. doses 30, 90, and 300 fold higher than its daily therapeutic dose in humans) does not exhibit any effect on the elevated level of progesterone in the blood plasma of rats. Let us assume then that in therapeutic dose, Andrographis paniculata extract cannot induce progesterone-mediated termination of pregnancy. |
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46: J Ethnopharmacol. 1997 Nov;58(3):219-24.
Testicular toxicity assessment of Andrographis paniculata dried extract in rats.
Burgos RA, Caballero EE, Sanchez NS. Instituto de Farmacologia, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia. |
The possible testicular toxicity of Andrographis paniculata, Nees (Acanthaceae) standardized dried extract was evaluated in male Sprague Daw | | | |