A phase I trial of andrographolide in HIV positive patients and normal volunteers

Calabrese, Carlo; Berman, Sheryl H.; Babish, John G.; Ma, Xiaohong; Shinto, Lynne; Dorr, Melissa; Wells, Kameron; Wenner, Cynthia A.; Standish, Leanna J.

doi:10.1002/1099-1573(200008)14:5<333::aid-ptr584>3.3.co;2-4

Cited by 86 publications

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“…Andrographolide is bitter crystalline compound, colorless having antithrombotic, hyphoglycemic and antipyretic properties. A recent study conducted by USA University that this plant is having anti HIV activity (Calabrese, 2000). This plant ranks seventeenth position among their thirty two prioritized medicinal plants and annual growth of this plant is 3.1 percent (Anonymous, 2007).…”

Section: Introductionsupporting

confidence: 89%

Variation of Andrographolide Content in Andrographis paniculata from Different Sites of Balaghat Region of Jabalpur (M.P.)

2017

IJCRR

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Aim:The main objective of this investigation was to show the variation of Andrographolide content in Andrographis paniculata from thirty seven different sites of Balaghat (Jabalpur MP) region. Methodology:In order to study the variation in andrographolide content, plant material was collected from different sites and were analyzed through quick and accurate HPLC chromatographic method using C-18 column (4.6 x 250 mm, 5µ particle size). Result and Discussion:The average andrographolide content varied from 0.01 to 1.2%. Highest percent of andrographolide in Andrographis paniculata were estimated from site Kera of south Balaghat 1.2%. Lowest content of andrographolide in Andrographis paniculata were estimated from the site of Salhen north Balaghat region that is 0.02%. Conclusion:The content of this active ingredient in this plant varies with in the plant parts and with the geographical distribution.

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Section: Introductionsupporting

confidence: 89%

Variation of Andrographolide Content in Andrographis paniculata from Different Sites of Balaghat Region of Jabalpur (M.P.)

2017

IJCRR

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“…1), is one of the main active constituents of Andrographis paniculate (BURM) NEES, a famous traditional Chinese medicine. Andrographolide has many bioactivities, such as antiinflammatory and antimicrobial, 1,2) antiplatelet aggregation, 3,4) hepatoprotective, 5,6) and anti-human immunodeficiency virus (HIV) activity. 7) Andrographolide is widely used clinically with good results, but it did not show efficacy in activity assays in vitro.…”

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confidence: 99%

Six New Andrographolide Metabolites in Rats

Gao

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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Andrographolide chemically designated as 2(3H)-furanone, 3-[2-[decahydro-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylene-1-napthalenyl] ethylidene] dihydro-4-hydroxy ( Fig. 1), is one of the main active constituents of Andrographis paniculate (BURM) NEES, a famous traditional Chinese medicine. Andrographolide has many bioactivities, such as antiinflammatory and antimicrobial, 1,2) antiplatelet aggregation, 3,4) hepatoprotective, 5,6) and anti-human immunodeficiency virus (HIV) activity. 7) Andrographolide is widely used clinically with good results, but it did not show efficacy in activity assays in vitro. Andrographolide has aroused the interest of many pharmacologists, and numerous experiments have been performed, although much remains to be clarified. A few investigations of the pharmacokinetics have been reported after oral administration of andrographolide. 8,9) However, to the best of our knowledge, there has been no report on its metabolites either in humans or animals. We isolated and analyzed the metabolites of andrographolide in blood, urine, bile, and the contents of the small intestine and stomach of rats. So far, we have identified 10 new metabolites. In this paper, six new metabolites are presented including their extraction, isolation, and identification.Metabolite 5 (M-5), colorless powder, melting point Ͼ300°C (decomposed), was positive for the Legal and Kedde reactions, suggesting the presence of an a,b-unsaturated lactone. The IR spectrum showed the presence of hydroxyl (3433 cm Ϫ1 ), ester carbonyl (1744 cm Ϫ1 ), carbon-carbon double bond (1643 cm Ϫ1 ), and sulfonate (1205 cm Ϫ1 ) groups in the molecule. In the high-resolution second ionization mass spectrum (HR-SI-MS), a quasimolecular peak [MϪH] Ϫ at m/z 493.1205 (Calcd 493.1207) was seen, and thus the molecular formula of C 20 H 30 O 10 S 2 was derived.Wide variation in the chemical shifts at C 2 , C 3 , C 9 , and C 11 -C 16 were observed, while the other carbons were almost the same when metabolite 5 was compared with the parent drug andrographolide, suggesting that the difference of metabolite 5 occurred at the side chain of lactone and ring A. The carbon signal of carbonyl shifted from 172.6 to 176.7 ppm, while the oxygen-linked carbon of C-15 shifted from 76.1 to 72.7 ppm. The changes in chemical shifts showed that the double bond at 12(13) of andrographolide changed to the 13(14) double bond, by which the double bond transferred from the outside to the inside of the lactone ring. In the heteronuclear multiple bond connectivity (HMBC) spectrum, the signal of H-15 (4.94, 2H) had peaks correlated with C-13 (131.3 ppm) and C-14 (151.7 ppm), indicating that a carboncarbon double bond is located at 13(14). The singlet of H-14 (7.73, H, br s) had a cross-peak with 55.8 (C-12), and H-12 (3.97, H, br d, Jϭ10.2 Hz) correlated with 131.3 (C-13), 151.7 (C-14), and 176.7 ppm (C-16). These correlated peaks showed that the sulfonate group is linked at C-12.The carbon signals of metabolite 5 at ring A differed from those of andrographolide. The...

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“…It was found that andrographolide had wide bioactivities, such as anti-inflammatory antibiotic (Sinha et al, 2000;Shen et al, 2002), anti-platelet aggregation (Zhang and Tan, 1997;Amroyan et al, 1999), and anti-human immunodeficiency virus activities (Calabrese et al, 2000). Andrographolide was widely used in the clinic, but it was not effective in vitro.…”

mentioning

confidence: 99%

Identification of a Rare Sulfonic Acid Metabolite of Andrographolide in Rats

Li²,

Gao³

et al. 2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Andrographolide is widely used in clinic as an anti-inflammatory and antibiotic drug. In this paper, the metabolites of andrographolide in rats after single oral doses of 120 mg/kg were investigated. The structures of the metabolites were elucidated by high-resolution mass spectra, NMR spectroscopy including 1 H NMR, 13 C NMR, and two-dimensional NMR, through comparison to a synthetic standard. The main metabolite of andrographolide in rats was 14-deoxy-12(R)-sulfo andrographolide. In the proposed mechanism, the ␤-carbon of ␣, ␤-unsaturated carbonyl was attacked by sulfonic acid, to form the sulfonate compound. This was a rare metabolic reaction. It may be the main metabolic pathway of andrographolide in rats. The polarity of the sulfonate metabolite increased greatly and could be easily eliminated from body.

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A phase I trial of andrographolide in HIV positive patients and normal volunteers

Cited by 86 publications

References 0 publications

Variation of Andrographolide Content in Andrographis paniculata from Different Sites of Balaghat Region of Jabalpur (M.P.)

Variation of Andrographolide Content in Andrographis paniculata from Different Sites of Balaghat Region of Jabalpur (M.P.)

Six New Andrographolide Metabolites in Rats

Identification of a Rare Sulfonic Acid Metabolite of Andrographolide in Rats

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