5508-58-7 Usage
Description
Andrographolide is a bioactive diterpene lactone, the main constituent of Andrographis paniculata, a plant used in traditional medicines. It is known to have various biological activities such as anti-inflammatory, anti-malarial, anti-cancer, and hepatoprotective properties. Andrographolide also exhibits potent anti-viral effects against the dengue virus and has been used for liver complaints, fever, as an anti-inflammatory, and immunostimulant.
Uses
Used in Pharmaceutical Industry:
Andrographolide is used as an anti-inflammatory agent for its anti-inflammatory and anti-platelet aggregation activities. It is also used as an antineoplastic agent due to its potential cancer-fighting properties.
Used in Cardiovascular Protection:
Andrographolide is used as a cardiovascular-protective agent, as it inhibits tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule-1 (ICAM-1) expression and adhesion of HL-60 cells onto human umbilical vein endothelial cells (HUVEC), which are associated with inflammatory diseases.
Used in Antiviral Applications:
Andrographolide is used as an antiviral agent, particularly against the dengue virus, due to its potent anti-viral effects.
Used in Hepatoprotective Applications:
Andrographolide is used as a hepatoprotective agent, showing significant antihepatotoxic action in P. berghei K173induced hepatic damage in M. natalensis.
Used in Rheumatoid Arthritis and Autoimmune Diseases:
Andrographolide is used as an anti-growth and pro-apoptotic agent on human rheumatoid arthritis fibroblast-like synoviocytes, making it a potential treatment for rheumatoid arthritis and other autoimmune diseases.
Used in Analytical Chemistry:
Andrographolide may be used as a reference standard for the determination of andrographolide in various samples, such as leaves, roots, and stems of Andrographis paniculata, as well as rat plasma samples, through various analytical techniques like RP-HPLC, GC-MS, ESI-LC-MS/MS, and QqQLIT-ESI-MS/MS.
References
[1] Mari?a A. Hidalgo, Juan L. Hancke, Juan C. Bertoglio and Rafael A. Burgos (2013) Andrographolide a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis Disease in book “Innovative Rheumatology”
[2] https://www.drugs.com/npp/andrographis.html
[3] Mitchell Low, Cheang S Khoo, Gerald Münch, Suresh Govindaraghavan, Nikolaus J Sucher (2014) An in vitro study of anti-inflammatory activity of standardised Andrographis paniculata extracts and pure andrographolide, BMC Complementary and Alternative Medicine, 15:18
References
1) Xia et al. (2004), Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50; J. Immunol., 173 4207
2) Chen et al. (2004), Andrographolide suppresses endothelial cell apoptosis via activation of phosphatidyl inositol-3-kinase/Akt pathway; Biochem. Pharmacol., 67 1337
3) Yu et al. (2003), Antihyperglycemic effect of andrographolide is streptozotocin-induced diabetic rats; Planta Med., 69 1075
History
In 1911, Gorter firstly isolated a crystalline substance from Andrographis paniculata, identified it as a diterpene lactone compound, and named it andrographolide .Andrographolide structure is complex and difficult to artificially synthesize, so it
is often extracted from the plant.Andrographolide water solubility is poor and its bioavailability is low; its pharmacological effects are extensive but weak, so the preparation requirements are
strict. Therefore, from the 1970s, drugs and organic chemical researchers have done
a lot of work in the modification and transformation of andrographolide, mainly
concentrated in the α, β-unsaturated lactone double bond Michael addition, redox,
selective esterification of hydroxyl groups, oxidation and substitution reactions,
intramolecular cyclization, replacement of lactone rings, etc. They had obtained a
number of new derivatives. In the research of pharmacological effects, the main
study of the andrographolide derivatives focuses on antitumor, antivirus, and other
biological activities and has made some progress .
Biochem/physiol Actions
Diterpenoid lactone with anti-inflammatory properties. It blocks T-cell proliferation to allogenic stimuli and the chemotactic migration of macrophages induced by complement. Blocks the proliferation of several cancer cell lines in vitro.
Pharmacology
Modern pharmacological studies have shown that andrographolide has effects of
anti-inflammatory, antibacterial, antivirus, antitumor, and immune regulation and
can be used in treatment of cardiovascular-cerebrovascular diseases and protectionof the liver and gallbladder. Andrographolide can treat the fever caused by pneumococcus and hemolytic Streptococcus mutans, mainly by inhibiting the hypothalamus PGE2 and cAMP content to exert its antipyretic, nonetheless reducing the
chemotaxis (fMLP) CD11b + and CD18
+ may be the main mechanism of its antiinflammatory effect. Andrographolide has antagonistic effects on Hong Kong virus
(HKV), Ebola virus (EBOV), and respiratory syncytial virus (RSV) and has been
shown to inhibit HIV, SARS, and viral myocarditis ST2 in?vitroAndrographolide can also ameliorate myocardial ischemia and serve as protection from ischemia-reperfusion injury. It also has protection effect of vascular endothelial cells as well as can regulate lipid disorder, lower blood pressure, and exert
effect of anti-atherosclerosis. It can also prevent angiogenesis after restenosis and
improve blood rheology. Its mechanisms are mainly due to its free radical scavenging and antiplatelet aggregation properties. Andrographolide can increase the bile
flow, bile salt, bile acid, and deoxycholic acid in experimental rats and guinea pigs
and can reverse the reduction of bile and cholic acid and other secretions caused by
paracetamol and improve liver function .
Anticancer Research
It is a labdane diterpenoid, which shows cytotoxic effect against different cancercell lines like human epidermoid cancer cells (KB), lymphocytic leukemia cells(P388), breast cancer cells (MCF-7), and colon cancer cells (HCT-116). It inhibitsthe proliferation of colon cancer cells (HT-29) and exerts pro-differentiative effecton mouse myeloid leukemia M1 cell line (Desai et al. 2008).
Clinical Use
This product is commonly used clinically for dysentery, leptospirosis, meningitis,
pneumonia, upper respiratory tract infection, and enhancing adrenal cortical function. In view of the requirement for clinical viral infection emergency, it is important to introduce the hydrophilic group in different lactone structure, enhance its
water solubility, and improve efficacy. There are a variety kinds of andrographolide
injection, including potassium dehydroandrograpolide succinate needle, potassium
sodium dehydroandrographolide succinate needle. Lianbizhi is the representative of
this class of drugs in current clinical application. Oral administration of andrographolide may induce bitter vomiting. Oral administration of this product and other
preparations in large doses can cause epigastric discomfort and loss of appetite. It
had been reported of drug eruption, upper abdominal pain, and anaphylactic shock
caused by intramuscular injection. Severe symptom response emerged such as chest
tightness, shortness of breath, pallor, lip bruising, cold sweats, weak pulse, decreased
blood pressure, etc. Light reactions include abdominal pain, vomiting, asthma, urticaria, pimples, dizziness, head swelling, sneezing, chest pain, etc. The reaction is
real time and also 5–20?min after injection and gradually improves 5–45?min after
rescue and individual recovered by 24?h. There are also reports of acute amniotic
fluid blockage caused by weaning lotion exchange. In addition, taking into account
the adverse effects of andrographolide on reproduction, it is recommended to be
used cautiously by fertility couples and pregnant women.
in vitro
andrographolide was found to suppress the expression of inducible nitric oxide synthase in a concentration-dependent manner. in the andrographolide-treated group, a reduction of akt, c-jun n-terminal kinase and p65 phosphorylation was observed. andrographolide also caused a decrease in bcl-2/nf-κb expression and a dose-dependent increase in the expression of cleaved-caspase3/bax protein [1].
in vivo
rats were dosed with andrographolide intragastrically for 5 consecutive days in a hepatoprotection study. results indicated that andrographolide could up-regulate glutamate cysteine ligase catalytic and modifier subunits, heme oxygenase-1, superoxide dismutase-1, glutathione s-transferase protein and mrna expression in the heart, liver, and kidney [2].
IC 50
11.0 ± 0.28 μg/ml for α-glucosidase; 11.3 ± 0.29 μg/ml for α-amylase
Check Digit Verification of cas no
The CAS Registry Mumber 5508-58-7 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 5,5,0 and 8 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 5508-58:
(6*5)+(5*5)+(4*0)+(3*8)+(2*5)+(1*8)=97
97 % 10 = 7
So 5508-58-7 is a valid CAS Registry Number.
InChI:InChI=1/C20H30O5/c1-12-4-7-16-19(2,9-8-17(23)20(16,3)11-21)14(12)6-5-13-15(22)10-25-18(13)24/h5,14-17,21-23H,1,4,6-11H2,2-3H3/b13-5+/t14-,15-,16?,17-,19+,20+/m1/s1
5508-58-7Relevant articles and documents
Enantioselective Total Synthesis of Andrographolide and 14-Hydroxy-Colladonin: Carbonyl Reductive Coupling and trans-Decalin Formation by Hydrogen Transfer
Krische, Michael J.,Sharma Poudel, Binit,Wurm, Thomas,Yang, Lin
, p. 23169 - 23173 (2020/10/19)
An enantioselective total synthesis of the labdane diterpene andrographolide, the bitter principle of the herb Andrographis paniculata (known as “King of Bitters”), was accomplished in 14 steps (LLS). Key transformations include iridium-catalyzed carbonyl reductive coupling to form the quaternary C4 stereocenter, diastereoselective alkene reduction to establish the trans-decalin ring, and carbonylative lactonization to install the α-alkylidene-β-hydroxy-γ-butyrolactone.
