イソピムピネリン（1）はフラノクマリン類の一種で，セロリやパセリなどのセリ科や，ライムやグレープフルーツなどの柑橘類の植物に含まれる成分です¹⁾。ベルガモッチンなどの多くのフラノクマリン類は虫などの草食動物に対する防御機構の一つとして産生されており²⁾，光線過敏を引き起こす原因とされていますが，1には光毒性はありません³⁾。しかしながら，防カビ作用や駆虫作用，昆虫摂食阻害作用があることが報告されています⁴⁾。 一方，1を含む漢方生薬としてセリ科のオカゼリの成熟果実である蛇床子が知られており，その止痒性作用が確認されています⁵⁾。また，1は肝臓の解毒酵素であるシトクロムP450を調節することで，多環芳香族炭化水素（PAHs）の代謝物による腫瘍発生を阻害することも報告されています⁶⁾。

[1] The natural coumarins: occurrence, chemistry and biochemistry

J. B. Harborne, Plant Cell Environ. 1982, 5, 435.

[2] Furanocoumarin induction in wild parsnip: Evidence for an induced defense against herbivores

A. R. Zangerl, Ecology 1990, 71, 1926.

[3] (a) Furocoumarins of Heracleum Laciniatum: isolation, phototoxicity, absorption and action spectra studies

G. Kavli, J. Raa, B. E. Johnson, G. Volden, S. Haugsbo, Contact Dermatitis 1983, 9, 257.

(b) Isopimpinellin is not phototoxic in a chick skin assay

G. W. Ivie, R. C. Beier, Photochem. Photobiol. 1996, 63, 306.

[4] (a) Antifungal activity of coumarins

C. Montagner, S. M. de Souza, C. Groposo, F. D. Monache, E. F. A. Smania, A. Smania Jr., Z. Naturforsch. 2008, 63c, 21. [PDF]

(b)”Insecticidal effect of phthalides and furanocoumarins from Angelica acutiloba against Drosophila melanogaster”

M. Miyazawa, T. Tsukamoto, J. Anzai, Y. Ishikawa, J. Agric. Food Chem. 2004, 52, 4401. DOI: 10.1021/jf0497049

Insecticidal activity of Angelica acutiloba extract and its constituents was investigated and compared with that of rotenone. Bioassay-guided isolation of the chloroform extract of A.acutiloba against larvae of Drosophila melanogaster afforded two phthalides, (Z)-butylidenephthalide (1) and (Z)-ligustilide (2), and two furanocoumarins, xanthotoxin (3) and isopimpinellin (4). The structures of these compounds were established by spectroscopic analysis. The isolated compounds 1, 2, 3, and 4 exhibited LC50 values of 0.94, 2.54, 3.35, and 0.82 μmol/mL of diet concentration against larvae of D. melanogaster, respectively. Against both sexes (males/females, 1:1) of adults (5−7 days old), compound 1 showed the most potent activity with a LD50 value of 0.84 μg/adult. Compound 1 is a more active insecticide than rotenone (LD50 = 3.68 μg/adult) and has potential as a novel insect control agent. However, compound 2 was inactive against adults. The structure−activity relationship of phthalides isolated indicated that the aromaticity appeared to play an important role in the activity of both larvae and adults. To determine the insecticide mode of action for acute adulticidal activity, acetylcholinesterase (AChE) inhibitory activity was also investigated in vitro, and the result indicated that the acute adulticidal activity of compounds 3 and 4 was due to the inhibition of AChE.

(c) “Osthol and isopimpinellin from Fructus cnidii for the control of Dactylogyrus intermedius in Carassius auratus”

G. Wang, Z. Zhou, C. Cheng, J. Yao, Z. Yang, Vet. Parasitol. 2008, 158, 144.　DOI: 10.1016/j.vetpar.2008.07.034

(d) “Phloroglucinol-type furocoumarins, a group of potent naturally-occurring insect antifeedants”

T. Yajima, K. Munakata, Agric. Biol. Chem. 1979,, 43, 1701. DOi: 10.1271/bbb1961.43.1701

[5] (a) “Inhibition of itch-scratch response by fruits of Cnidium monnieri in mice”

P. Basnet, I. Yasuda, N. Kumagai, C. Tohda, H. Nojima, Y. Kuraishi, K. Komatsu, Biol. Pharm. Bull. 2001, 24, 1012. DOI: 10.1248/bpb.24.1012

We previously screened the anti-itching activities of 33 herbal medicines in substance P (SP)-induced itching model mice. One of the most potent antipruritogenic extracts, the methanol extract of fruits of Cnidium monnieri (Cnidii Fructus) was studied further. The chloroform-soluble fraction of the methanol extract markedly inhibited SP-induced scratching. Among 10 subfractions of the chloroform-soluble fraction, the CS-3 fraction had the most potent inhibitory effect on scratching. Each of 3 subfractions of CS-3 showed significant anti-scratching activities. However, inhibitory potencies were not different among the three and weaker than that of CS-3 itself at a same dose. These 3 subfractions of CS-3 mainly contained xanthotoxin, isopimpinellin, bergapten, imperatorin and osthol. Single administration of osthol did not inhibit SP-induced scratching, and imperatorin very weakly subsided scratching. These results suggest that the strong antipruritic action was focused on the CS-3 fraction of the C. monnieri methanol extract, and it might result from the combined effects of these coumarin derivatives, or by undetermined minor compounds.

(b) “Antipruritic effect of Cnidii Monnieri Fructus (fruits of Cnidium monnieri Cusson)”

H. Matsuda, Y. Ido, A. Hirata, Y. Ino, S. Naruto, T. Amamiya, M. Kubo, Biol. Pharm. Bull. 2002, 25, 260. DOI: 10.1248/bpb.25.260

Antipruritic effects of 70% ethanol extract (CM-ext) of Cnidii Monnieri Fructus (dried fruits ofCnidium monnieri Cusson, Umberifferae) were investigated. In mice, an oral administration of CM-ext (200 and 500 mg/kg) inhibited compound 48/80-induced scratching behavior without influence on spontaneous locomotion. Isopimpinellin (3) and osthol (1), coumarin derivatives isolated from CM-ext, showed an inhibitory effect on compound 48/80-induced scratching behavior.

[6] (a) Inhibition and inactivation of murine hepatic ethoxy- and pentoxyresorufin O-dealkylase by naturally occurring coumarins

Y. Cai, D. Bennett, R. V. Nair, O. Ceska, M. J. Ashwood-Smith, J. DiGiovanni, Chem. Res. Toxicol. 1993, 6, 872.

(b) Oral administration of the citrus coumarin, isopimpinellin, blocks DNA adduct formation and skin tumor initiation by 7,12-dimethylbenz[α]anthracene in SENCAR mice

H. E. Kleiner, S. V. Vulimiri, M. F. Starost, M. J. Reed, J. DiGiovanni, Carcinogenesis 2002, 23, 1667.

(c) Effects of naturally occurring coumarins on hepatic drug metabolizing enzymes in mice

H. E. Kleiner, X. Xia, J. Sonoda, J. Zhang, E. Pontius, J. Abey, R. M. Evans, D. D. Moore, J. DiGiovanni, Toxicol. Appl. Pharmacol. 2008, 232, 337.

 

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