Andrographolide is a labdane diterpenoid that has been isolated from the stem and leaves of ''

Andrographis paniculata ''Andrographis paniculata'', commonly known as creat or green chiretta, is an annual herbaceous plant in the family Acanthaceae, native to India and Sri Lanka. It is widely cultivated in Southern and Southeastern Asia, where it has been believ ...

''. Andrographolide is an extremely bitter substance. Andrographolide has been studied for its effects on

cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

immunomodulation Immunomodulation is modulation (regulatory adjustment) of the immune system. It has natural and human-induced forms, and thus the word can refer to the following: * Homeostasis in the immune system, whereby the system self-regulates to adjust immun ...

, and

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

. Study has shown that andrographolide may bind to a spectrum of protein targets including NF-κB and

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

covalent modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosomes ...

Biosynthesis

While andrographolide is a relatively simple diterpene lactone, the biosynthesis by Andrographis paniculata was determined in the 2010s. Andrographolide is a member of the

isoprenoid The terpenoids, also known as isoprenoids, are a class of naturally occurring organic chemicals derived from the 5-carbon compound isoprene and its derivatives called terpenes, diterpenes, etc. While sometimes used interchangeably with "terpenes", ...

family of natural products. The precursors to isoprenoid biosynthesis, isopentenyl pyrophosphate (IPP) and

dimethylallyl pyrophosphate Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynt ...

(DMAPP), can be synthesized through either the mevalonic acid pathway (MVA) or deoxyxylulose pathway (DXP). 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. 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 Geranyl pyrophosphate (GPP), also known as geranyl diphosphate (GDP), is the pyrophosphate ester of the terpenoid geraniol. Its salts are colorless. It is a precursor to many natural products. Occurrence GPP is an intermediate in the isoprenoid ...

. Another molecule of IPP is then added, yielding

farnesyl pyrophosphate Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport cha ...

(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. Biosynthesis Figure

References

{{reflist Bitter compounds Diterpenes Lactones Primary alcohols Secondary alcohols Decalins

Biosynthesis

See also

References