Angelicin

Angelicin is a naturally occurring, photoreactive furocoumarin (molecular formula: C₁₁H₆O₃; molar mass: 186.16 g/mol) of plant origin. It forms the basic structure of the so-called angelicins (angular furocoumarins). Its structural isomer is psoralen, the basic structure of linear furocoumarins.

The molecule consists of a coumarin backbone to which a furan ring is condensed at an angle. This angular arrangement distinguishes angelicin from the linearly structured psoralens. The lack of, or severely limited ability to, cross-link DNA is the most important photochemical characteristic of angelicin.

Natural occurrence:

Angelicin is found primarily in plants of the families

• Apiaceae (umbellifers),
• Fabaceae (legumes), and
• Moraceae (mulberry family)

. It has been detected, among others, in species of the genera:

• Angelica (see below:Angelicae radix)
• Pastinaca,
• Heracleum,
• Psoralea, and Bituminaria.

It is found, for example, in parsnips, celery species, and various angelica species. The content and composition of furocoumarins can vary considerably depending on the plant part, stage of development, damage, fungal infestation, and environmental conditions.

Angelicin belongs to the class of plant phytoalexins, or defense compounds. It protects the plant from herbivores, microorganisms, and other biological stressors. Its photochemical activation enhances its toxic effect on exposed pests. In plants, angelicin is usually present alongside other furocoumarins, some of which are more phototoxic. Therefore, phytophotodermatitis triggered by contact with plants usually cannot be attributed to a single substance.

When exposed to UVA radiation, angelicin is photosensitizing, phototoxic, DNA-damaging, and potentially photomutagenic. Although the predominant formation of reparable monoadducts suggests lower genotoxicity than that of cross-linking psoralens, angelicin should not be considered harmless. The risk depends largely on concentration, skin contact, penetration depth, UVA dose, and the presence of other furocoumarins.

Angelicin absorbs ultraviolet radiation, particularly in the UVA range. After photoactivation, it can:

insert itself between the base pairs of DNA,

covalently bind to pyrimidine bases—especially thymine,

form predominantly monofunctional DNA photoadducts,

impair DNA replication and transcription,

activate DNA repair mechanisms, particularly nucleotide excision repair.

Due to its bent molecular structure, a second photoreaction with the opposite DNA strand is largely ruled out spatially. Angelicin therefore—unlike 8-methoxypsoralen—normally does not produce pronounced interstrand crosslinks (Kaye J et al. 1980). In addition, photoactivated angelicins can react with proteins and membrane lipids and induce reactive oxygen species and lipid peroxidation processes.

Angelicin has demonstrated anticancer properties against several cell lines (I-Hsiao C et al. 2023), acting via both intrinsic and extrinsic apoptotic pathways, and it has also demonstrated the ability to inhibit tubulin polymerization to a greater extent than psoralen. Furthermore, angelicin exhibited anti-inflammatory activity through the inhibition of the MAPK/NF-κB signaling pathway (Liu F et al. 2013). Angelicin also exhibited osteogenic and chondrogenic effects on osteoblasts and prechondrocytes, respectively (Mahendra CK et al. 2020).

Following skin contact and subsequent exposure to sunlight or UVA radiation, angelicin may contribute to phototoxic dermatitis. Clinically, the following symptoms may occur:

• well-defined edematous erythema and a burning sensation. Blistering may occur depending on the intensity of exposure. Subsequent hyperpigmentation, which may be long-lasting in some cases, may also occur.

Pharmacological Significance

Angelicin and synthetic angelicin derivatives have been studied as photosensitizers and pharmacological model compounds. Experimental studies have described, among other things:

• antiproliferative, antitumor, antimicrobial, anti-inflammatory, bone metabolism-modulating, and neuroprotective effects.

Some derivatives, particularly 4,5′-dimethylangelicin, have been investigated as potential photosensitizers for photochemotherapeutic procedures. Angelicin itself, however, has no established role as a standard drug; the published pharmacological effects are based primarily on cell culture and animal experiments (Mahendra et al. 2020)

1. I-Hsiao C et al. (2023) Angelicin inhibits the growth and migration of triple-negative breast cancer cells. Pak J Pharm Sci 36:51-57.
2. Kaye J et al. (1980) DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin. Cancer Res 40:696–702.
3. Liu F et al. (2013) Angelicin regulates LPS-induced inflammation by inhibiting MAPK/NF-κB pathways. J Surg Res 185:300–309.
4. Mahendra CK et al. (2020) Angelicin-A: A Furocoumarin Compound With Vast Biological Potential. Front Pharmacol 11:366