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A new bis-andrographolide ether from Andrographis paniculata nees and evaluation of anti-HIV activity.

Novel bis-andrographolide ether (1) and six known compounds andrographolide, 14-deoxy-11,12-didehydroandrographolide, andrograpanin, 14-deoxyandrographolide, (+/-)-5-hydroxy-7,8-dimethoxyflavanone, and 5-hydroxy-7,8-dimethoxyflavone have been isolated from the aerial parts of Andrographis paniculata and their structures were established by spectral data. All the isolates were tested for the anti-HIV and cytotoxic activity.

Andrographis↗

Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata.

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-Guéin (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.

Andrographis↗

Two new flavonoids from Andrographis rothii.

Two new flavonoids, 5, 7, 2', 5'-tetramethoxyflavanone (1) and 5-hydroxy-7, 2'-dimethoxyflavone (2), together with two known flavones, skullcapflavone I (3) and echioidin (4) were isolated from the whole plant of Andrographis rothii. The structures of the new compounds were established by extensive one- and two-dimensional (1D- and 2D-) NMR spectral studies.

Andrographis↗

A new chalcone and a flavone from Andrographis neesiana.

Two new flavonoids, 2',4',6',2,3,4-hexamethoxychalcone (1) and 5-hydroxy-7,2',5'-trimethoxyflavone (2) together with a known flavone glycoside, echioidinin 5-O-beta-D-glucopyranoside (3) were isolated from the whole plant of Andrographis neesiana, and the structures were elucidated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and one- and two-dimensional (1D- and 2D)-NMR spectral studies including 1H-1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser enhancement spectroscopy (NOESY) experiments.

Andrographis↗

[Study on extraction of active ingredients from Andrographis paniculatal using the orthogonal experiment with supercritical carbon dioxide].

This paper studied the extraction technology of active ingredients from Andrographis paniculatal using the orthogonal experiment with supercritical CO2. The active ingredients of this extract had higher purity and more stable quality than those came from conventional extract technology. And the target ingredients, dehydrated andrographolidume and andrographolidume, had higher content. Furthermore this method had shorter technology process and saved a great deal of solvent than conventional ethanol extraction, which was exactly suitable for industrialization manufacture. The optimization condition was: extractor pressure 25 MPa, extractor temperature 46 degrees C, separator I pressure 6 MPa, separator I temperature 65 degrees C, separator II pressure 6 MPa, separator II temperature 45 degrees C, CO2 rate of flow 40 kg/h.

Andrographis↗

Studies on psychopharmacological activity of Andrographis paniculata extract.

Psychopharmacological studies were conducted on an extract of Andrographis paniculata herbs. The extract exhibited a significant alteration in behaviour pattern and a reduction in spontaneous motility. The extract also produced a prolongation of the pentobarbitone-induced sleeping time and lowered the body temperature in different experimental animal models.

Acetic Acid↗

Andrographis paniculata (Ness) induces relaxation of uterus by blocking voltage operated calcium channels and inhibits Ca(+2) influx.

The possible relaxation of uterine smooth muscle by Andrographis paniculata dried extract via a blockade of voltage operated calcium channels was investigated in rats. Uterine horns pretreated with oestradiol were incubated in Ca(+2) -free Jalon's solution and stimulated with KCl (20-60 mM) in order to produce depolarization of the membrane. The isometric contractile response to 1 mM or cumulative concentrations of CaCl2 were blockaded by 0.2, 0.4 and 0.8 mg/mL of A. paniculata. The maximum contractile response induced by acetylcholine was moderately antagonized by A. paniculata. The possible blockade of Ca(+2) entry by A. paniculata was evaluated with (45)Ca(+2) uptake in uterine rings incubated with free-Ca(+2)-Ringer's solution high in K+ (KCl 40 mM). The influx was completely blockaded with 0.4 mg/mL of A. paniculata. These results strongly suggest that A. paniculata blockades voltage operated calcium channels inhibiting the entry of Ca(+2) from the external medium.

Animals↗

Hepatoprotective effects of Andrographis paniculata against carbon tetrachloride-induced liver damage.

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.

Animals↗

Protective effects of andrographis paniculata nees on post-infarction myocardium in experimental dogs.

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.

Animals↗

Experimental studies on prevention of atherosclerotic arterial stenosis and restenosis after angioplasty with Andrographis Paniculata Nees and fish oil.

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.

Angioplasty, Balloon↗

Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata.

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.

Alanine Transaminase↗

A flavone glycoside from Andrographis alata.

A new flavone glycoside, echioidinin 5-glucoside along with its known aglycone, echioidinin have been isolated from the whole plant of Andrographis alata. The structure of the new compound was established as 5,2'-dihydroxy-7-methoxyflavone 5-O-beta-D-glucopyranoside on the basis of spectral and chemical studies.

Journal Article↗

Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat.

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.

1-Butanol↗

Andrographis paniculata (Nees) selectively blocks voltage-operated calcium channels in rat vas deferens.

The possible blockade of voltage-operated calcium channels (VOCs) by Andrographis paniculata dried extract in vas deferens smooth muscle was investigated in rats. The tissues were incubated in Ca(2+)-free Kreb's solution and stimulated with KCl (40 mM) to produce depolarisation of the membrane. The isometric contractile response to cumulative concentrations of CaCl(2) was effectively blockaded by 0.2 and 0.4 mg/ml A. paniculata. In other experiments, the maximum contractile response induced by norepinephrine was not antagonised by 0.2, 0.4 or 0.8 mg/ml A. paniculata. The possible blockade of Ca(2+) entry by A. paniculata was evaluated with 45Ca(2+) uptake in vas deferens treated with reserpine (5 and 2.5 mg/kg) 48 and 24 h before the experiments. Epididymal segments were incubated with Ca(2+)-free Kreb's solution with KCl, 25 and 50 mM. The influx was completely blockaded with 0.4 mg/ml A. paniculata. These results suggest that A. paniculata selectively blockades VOCs, hence inhibiting the 45Ca(2+) influx.

Animals↗

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.

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.

Adolescent↗

Filaricidal properties of a wild herb, Andrographis paniculata.

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.

Animals↗

Immunostimulant agents from Andrographis paniculata.

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.

Adjuvants, Immunologic↗

Biosynthesis of trans, trans- and cis, trans-farnesols by soluble enzymes from tissue cultures of Andrographis paniculata.

A cell-free system obtained from tissue cultures of Andrographis paniculata produces 2-trans,6-trans-farnesol (trans,trans-farnesol) and 2-cis,6-trans-farnesol (cis,trans-farnesol) (5:1), incorporating 10% of the radioactivity from 3R-[2-(14)C]mevalonate. There is total loss of (3)H from 3RS-[2-(14)C,(4S)-4-(3)H(1)]mevalonate and total retention from the (4R) isomer in both the trans,trans-farnesol and cis,trans-farnesol formed. When 3RS-[2-(14)C,5-(3)H(2)]mevalonate is used as substrate, there is total retention of (3)H in the trans,trans-farnesol, but loss of one-sixth of the (3)H in the cis,trans-farnesol. With (1R)- and (1S)-[4,8,12-(14)C(3),1-(3)H(1)]-trans,trans -farnesol and (1R)- and (1S)-[4,8,12-(14)C(3),1-(3)H(1)]-cis, trans-farnesol as substrates, the label is lost from the (1R)-cis,trans and (1S)-trans,trans isomers but retained in the (1R)-trans,trans and (1S)-cis,trans isomers; this shows that the pro-1S hydrogen is exchanged in the conversion of trans,trans-farnesol into cis,trans-farnesol and the pro-1R hydrogen in the conversion of cis,trans-farnesol into trans,trans-farnesol. (1R)-[1-(3)H(1)]-trans,trans-Farnesol and (1R)-[1-(3)H(1)]-cis,trans-farnesol have been synthesized by asymmetric chemical synthesis and exchanged with liver alcohol dehydrogenase. Both the trans- and the cis-alcohol exchange the pro-1R hydrogen atom.

Chemical Phenomena↗