Cucurbitacin

Cucurbitacin is a class of biochemical compounds that some plants – notably members of the pumpkin and gourd family, Cucurbitaceae – produce and which function as a defence against herbivores. Cucurbitacins are chemically classified as triterpenes, formally derived from cucurbitane, a triterpene hydrocarbon – specifically, from the unsaturated variant cucurbit-5-ene, or 19(10→9β)-abeo-10α-lanost-5-ene. They often occur as glycosides. They and their derivatives have been found in many plant families (including Brassicaceae, Cucurbitaceae, Scrophulariaceae, Begoniaceae, Elaeocarpaceae, Datiscaceae, Desfontainiaceae, Polemoniaceae, Primulaceae, Rubiaceae, Sterculiaceae, Rosaceae, and Thymelaeaceae), in some mushrooms (including Russula and Hebeloma) and even in some marine mollusks.

Cucurbitacins may be a taste deterrent in plants foraged by some animals and in some edible plants preferred by humans, like cucumbers and zucchinis. In laboratory research, cucurbitacins have cytotoxic properties and are under study for their potential biological activity.

Biosynthesis

The biosynthesis of cucurbitacin C has been described. Zhang et al. (2014) identified nine cucumber genes in the pathway for biosynthesis of cucurbitacin C and elucidated four catalytic steps. These authors also discovered the transcription factors ''Bl'' (Bitter leaf) and ''Bt'' (Bitter fruit) that regulate this pathway in leaves and fruits, respectively. The Bi gene confers bitterness to the entire plant and is genetically associated with an operon-like gene cluster, similar to the gene cluster involved in thalianol biosynthesis in ''Arabidopsis''. Fruit bitterness requires both Bi and the dominant Bt (Bitter fruit) gene. Nonbitterness of cultivated cucumber fruit is conferred by bt, an allele selected during domestication. Bi is a member of the oxidosqualene cyclase (OSC) gene family. Phylogenetic analysis showed that Bi is the ortholog of cucurbitadienol synthase gene CPQ in squash (''Cucurbita pepo'') 

Variants

The cucurbitacins include:

Cucurbitacin A

* Cucurbitacin A found in some species of ''Cucumis''
** Pentanorcucurbitacin A, or 22-hydroxy-23,24,25,26,27-pentanorcucurbit-5-en-3-one , white powder

Cucurbitacin B

* Cucurbitacin B from ''Hemsleya endecaphylla'' (62 mg/72 g) and other plants (e.g. ''Cucurbita andreana''); anti-inflammatory, any-hepatotoxic
** Cucurbitacin B 2-O-glucoside, from ''Begonia heracleifolia''
** 23,24-Dihydrocucurbitacin B from ''Hemsleya endecaphylla'', 49 mg/72 g
** 23,24-Dihydrocucurbitacin B 2-O-glucoside from roots of '' Picrorhiza kurrooa''
** Deacetoxycucurbitacin B 2-O-glucoside from roots of '' Picrorhiza kurrooa''
** Isocucurbitacin B, from '' Echinocystis fabacea''
** 23,24-Dihydroisocucurbitacin B 3-glucoside from ''Wilbrandia ebracteata''
** 23,24-Dihydro-3-epi-isocucurbitacin B, from ''Bryonia verrucosa''
** Pentanorcucurbitacin B or 3,7-dioxo-23,24,25,26,27-pentanorcucurbit-5-en-22-oic acid, , white powder

Cucurbitacin C

* Cucurbitacin C, from ''Cucumis sativus'' (cucumber)

Cucurbitacin D

* Cucurbitacin D, from ''Trichosanthes kirilowii'' and many other plants (e.g. ''Cucurbita andreana'')
** 3-Epi-isocucurbitacin D, from species of '' Physocarpus'' and ''Phormium tenax''
** 22-Deoxocucurbitacin D from ''Hemsleya endecaphylla'', 14 mg/72 g
** 23,24-Dihydrocucurbitacin D from ''Trichosanthes kirilowii'' also from ''H. endecaphylla'', 80 mg/72 g
** 23,24-Dihydro-epi-isocucurbitacin D, from ''Acanthosicyos horridus''
** 22-Deoxocucurbitacin D from ''Wilbrandia ebracteata''
** Anhydro-22-deoxo-3-epi-isocucurbitacin D from ''Ecballium elaterium''
** 25-O-Acetyl-2-deoxycucurbitacin D (amarinin) from '' Luffa amara''
** 2-Deoxycucurbitacin D, from '' Sloanea zuliaensis''

Cucurbitacin E

* Cucurbitacin E (α-Elaterin), from roots of ''Wilbrandia ebracteata''. Strong antifeedant for the flea beetle, inhibits cell adhesion (also in e.g. ''Cucurbita andreana'')
** 22,23-Dihydrocucurbitacin E from ''Hemsleya endecaphylla'', 9 mg/72 g, and from roots of ''Wilbrandia ebracteata''
** 22,23-Dihydrocucurbitacin E 2-glucoside from roots of ''Wilbrandia ebracteata''
** Isocucurbitacin E, from '' Cucumis prophetarum''
** 23,24-Dihydroisocucurbitacin E, from ''Cucumis prophetarum''

Cucurbitacin F

* Cucurbitacin F from '' Elaeocarpus dolichostylus''
** Cucurbitacin F 25-acetate from '' Helmseya graciliflora''
** 23,24-Dihydrocucurbitacin F from '' Helmseya amabilis''
** 25-Acetoxy-23,24-dihydrocucurbitacin F from '' Helmseya amabilis'' ( hemslecin A)
** 23,24-Dihydrocucurbitacin F glucoside from ''Helmseya amabilis''
** Cucurbitacin II glucoside from ''Helmseya amabilis''
** Hexanorcucurbitacin F from '' Elaeocarpus dolichostylus''
** Perseapicroside A from ''Persea mexicana''
** Scandenoside R9 from ''Hemsleya panacis-scandens''
** 15-Oxo-cucurbitacin F from ''Cowania mexicana''
** 15-oxo-23,24-dihydrocucurbitacin F from ''Cowania mexicana''
** Datiscosides B, D, and H, from ''Datisca glomerata''

Cucurbitacin G

* Cucurbitacin G from roots of ''Wilbrandia ebracteata''
* 3-Epi-isocucurbitacin G, from roots of ''Wilbrandia ebracteata''

Cucurbitacin H

* Cucurbitacin H, stereoisomer of cucurbitacin G, from roots of ''Wilbrandia ebracteata''

Cucurbitacin I

* Cucurbitacin I ( elatericin B) from ''Hemsleya endecaphylla'', 10 mg/72 g, also from ''Ecballium elaterium'' ''Citrullus colocynthis'', ''Cucurbita andreana'', deters feeding by flea beetle
** Hexanorcucurbitacin I from ''Ecballium elaterium''
** 23,24-Dihydrocucurbitacin I see Cucurbitacin L
** Khekadaengosides D and K from the fruits of ''Trichosanthes tricuspidata''
** 11-Deoxocucurbitacin I, from ''Desfontainia spinosa''
** Spinosides A and B, from ''Desfontainia spinosa''
** 23,24-dihydro-11-Deoxocucurbitacin I from ''Desfontainia spinosa''

Cucurbitacin J

* Cucurbitacin J from ''Iberis amara''
** Cucurbitacin J 2-O-β-glucopyranoside from ''Trichosanthes tricuspidata''

Cucurbitacin K

* Cucurbitacin K, stereoisomer of cucurbitacin J, from ''Iberis amara''
** Cucurbitacin K 2-O-β-glucopyranoside from ''Trichosanthes tricuspidata''

Cucurbitacin L

* Cucurbitacin L, or 23,24-dihydrocucurbitacin I,
** Brydioside A from ''Bryonia dioica''
** Bryoamaride from ''Bryonia dioica''
** 25-O-Acetylbryoamaride from ''Trichosanthes tricuspidata''
** Khekadaengosides A and B from ''Trichosanthes tricuspidata''

Cucurbitacin O

* Cucurbitacin O from '' Brandegea bigelovii''
** Cucurbitacin Q 2-O-glucoside, from '' Picrorhiza kurrooa''
** 16-Deoxy-D-16-hexanorcucurbitacin O from ''Ecballium elaterium''
** Deacetylpicracin from ''Picrorhiza scrophulariaeflora''
** Deacetylpicracin 2-O-glucoside from ''Picrorhiza scrophulariaeflora''
** 22-Deoxocucurbitacin O from ''Wilbrandia ebracteata''

Cucurbitacin P

* Cucurbitacin P from '' Brandegea bigelovii''
** Picracin from ''Picrorhiza scrophulariaeflora''
** Picracin 2-O-glucoside from ''Picrorhiza scrophulariaeflora''

Cucurbitacin Q

* Cucurbitacin Q from ''Brandegea bigelovii''
** 23,24-Dihydrodeacetylpicracin 2-O-glucoside from ''Picrorhiza kurrooa''
** Cucurbitacin Q1 from ''Cucumis'' species, actually Cucurbitacin F 25-acetate

Cucurbitacin R

* Cucurbitacin R is actually 23,24-dihydrocucurbitacin D.

Cucurbitacin S

* Cucurbitacin S from ''Bryonia dioica''

Cucurbitacin T

* Cucurbitacin T, from the fruits of ''Citrullus colocynthis''

28/29 Norcucurbitacins

There are several substances that can be seen as deriving from cucurbita-5-ene skeleton by loss of one of the methyl groups (28 or 29) attached to carbon 4; often with the adjacent ring (ring A) becoming aromatic.

Other

Several other cucurbitacins have been found in plants.

Occurrence and bitter taste

Constituents of the colocynth fruit and leaves (''Citrullus colocynthis'') include cucurbitacins. The 2-O-β-D- glucopyranosides of cucurbitacins K and L can be extracted with ethanol from fruits of ''Cucurbita pepo'' cv ''dayangua''. Pentanorcucurbitacins A and B can be extracted with methanol from the stems of ''Momordica charantia''. Cucurbitacins B and I, and derivatives of cucurbitacins B, D and E, can be extracted with methanol from dried tubers of ''Hemsleya endecaphylla''.

Cucurbitacins impart a bitter taste in plant foods such as cucumber, zucchini, melon and pumpkin.

Research and toxicity

Cucurbitacins are under basic research for their biological properties, including toxicity and potential pharmacological uses in development of drugs for inflammation, cancer, cardiovascular diseases, and diabetes, among others.

The toxicity associated with consumption of foods high in cucurbitacins is sometimes referred to as "toxic squash syndrome". In France in 2018, two women who ate soup made from bitter pumpkins became sick, involving nausea, vomiting, and diarrhea, and had hair loss weeks later. Another French study of poisoning from bitter squash consumption found similar acute illnesses and no deaths. The high concentration of toxin in the plants could result from cross-pollination with wild cucurbitaceae species, or from plant growth stress due to high temperature and drought.

See also

* Goyaglycoside
* Hemslecin
* Mogroside
* Momordicine
* Momordicoside
* Neomogroside
* Scandenosides R1–R8, R10-R11
* Siamenoside I

References

{{Cytokine receptor modulators

Chemistry set index articles
Laxatives
Plant toxins
Steroidal glycosides
Terpenoid glycosides