Andrographolide

Andrographolide is a labdane diterpenoid that has been isolated from the stem and leaves of Andrographis paniculata.^[1] Andrographolide is an extremely bitter substance.

Andrographolide

Andrographolide
Names
IUPAC name 3-[2-[Decahydro-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylene-1-napthalenyl]ethylidene]dihydro-4-hydroxy-2(3H)-furanone
Identifiers
CAS Number	5508-58-7 Y
3D model (JSmol)	Interactive image Interactive image
ChEBI	CHEBI:65408 N
ChEMBL	ChEMBL186141 N
ChemSpider	16735664 Y
ECHA InfoCard	100.024.411
PubChem CID	5318517
UNII	410105JHGR Y
CompTox Dashboard (EPA)	DTXSID3045980
InChI InChI=1S/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 Y Key: BOJKULTULYSRAS-FNTFRYDESA-N Y 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 Key: BOJKULTULYSRAS-UHFFFAOYAB 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 Key: BOJKULTULYSRAS-FNTFRYDEBY
SMILES O=C3OCC(O)C3=CCC1\C(=C)CCC2C(C)(CO)C(O)CCC12C OC3COC(=O)\C3=C\C[C@@H]1C(=C)CC[C@@H]2C(C)(CO)[C@H](O)CC[C@@]12C
Properties
Chemical formula	C20H30O5
Molar mass	350.455 g·mol−1
Appearance	Rhombic prisms or plates from ethanol or methanol
Density	1.2317 g/cm3
Melting point	230 to 231 °C (446 to 448 °F; 503 to 504 K)
Solubility in water	Sparingly soluble
Related compounds
Related labdanes	14-deoxyandrographolide
Related compounds	Xiyanping
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Andrographolide has been studied for its effects on cell signaling, immunomodulation, and stroke.^[2] Study has shown that andrographolide may bind to a spectrum of protein targets including NF-κB and actin by covalent modification.^[3][4]

Andrographolide is a non-ATP-competitive, substrate-competitive GSK-3β inhibitor.^[5][6][7] When the substrate concentration is 25µM, the IC₅₀ of andrographolide for GSK-3β is 5.58±0.40µM. When the substrate concentration is increased to 90µM, the IC₅₀ increases to 37.7µM.^[5]

Biosynthesis

While andrographolide is a relatively simple diterpene lactone, the biosynthesis by Andrographis paniculata was determined in the 2010s.^[8][9] Andrographolide is a member of the isoprenoid family of natural products. The precursors to isoprenoid biosynthesis, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), can be synthesized through either the mevalonic acid pathway (MVA) or deoxyxylulose pathway (DXP).^[10] Through selective C13 labeling of the precursors to both the MVA and DXP pathways, it was determined that the majority of the andrographolide precursors are synthesized through the DXP pathway.^[10] There are a small portion of andrographolide precursors synthesized through the MVA pathway. The biosynthesis of andrographolide begins with the addition of IPP to DMAPP, which forms geranyl pyrophosphate. Another molecule of IPP is then added, yielding farnesyl pyrophosphate (FPP). The final IPP molecule is added to the FPP to complete the backbone of the diterpene. The double bond originating from DMAPP is oxidized to an epoxide prior to the ring closing cascade that forms two six-membered rings. A series of oxidations form a five-membered lactone in addition to adding on the alcohol groups. The order of these post-synthetic modifications is not entirely known.^[10]

Biosynthesis of andrographolide

Research

In 2022, a research found that the combinatorial drug of guaifenesin and andrographolide has potential anticonvulsant activity using network virtual screening. The possible mechanism of action is the two drugs synergistically affect NMDA receptors.^[11]

See also

• Xiyanping WINDOSE-Tablet