• Toxicological Research
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• 제8권2호
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• pp.191-203
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• 1992

The immunosuppressive effects of safrole were studied in female BALB/c mouse. Mice were given 100,200and 400mg safrole/kg daily for 14days and evaluated on day 15. The day 4 immunogloblin-M antibody response to T-dependent antigen, sheep red blood cells (SRBC) was inhibited dose-dependently in all doses studied. In vitro antibody response to polyclonal antigen, lipopolysaccharide (LPS) by spleen cell suspensions from safrole-treated mice were also significantly inhibited. When safrole was treated for 14days to mice, and mitogen-induced proliferation of splenocytes were assayed on day 15, there were significant suppression of responses to B-cell mitogen, LPS and T-cell mitogen concanavalin A(Con A) at a dose of 400mg safrole/kg. Direct addition of safrole on the splenocyte culture also produced a dose dependent suppression on in vitro antibody response to LPS, and mitogen-induced lymphoproliferatin at doses of 100,200,400 and 800${\mu}M$ safrole. The role of metabolic activation in safrole-induced suppression of in vitro antibody response was studied using splenocyte-hepatocyte coculture system. The suppression of in vitro antibody respose to LPS by safrole was not altered when safrole were incubated in the splenocyte-hepatocyte system for 4hr as compared with direct addition of safrole in splenocytes culture. Neither the addition of salicylamide, sulfotransferase inhibitor, nor the addation of inorganic sulfate, sulfation cofactor to the splenocyte-hepatocyte coculture, altered the suppression of antibody response by safrole. These results suggest that the immunosuppression by safrole may not by produced by the reactive metabolites which are mediated in carcinogenesis of safrole.

• 한국환경성돌연변이발암원학회지
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• 제23권3호
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• pp.99-102
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• 2003

IARC classified areca quid as a human carcinogen. Areca quid chewed in Taiwan includes Piper betle inflorescence, which contains high concentrations of safrole (15 mg/fresh weight). Safrole is a documented rodent hepatocarcinogen, and chewing areca quid may contribute to human exposure (420 $\mu$m in saliva). The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. Using human liver microsomes and Escherichia coli membranes expressing bicistronic human P450s, CYP2E1 and CYP2C9 were identified as the main P450s involved in the activation of safrole. We have demonstrated the presence of stable safrole-dGMP adducts in human oral tissues following areca quid chewing using $^{32}$ P-postlabeling and HPLC mass spectrometry methods. By studying 88 subjects with a known AQ chewing history and 161 matched controls, we have demonstrated that the presence of safrole-DNA adducts in peripheral blood cells was correlated to AQ chewing, and CYP2E1 seemed to play an important role in the modulation of safrole-DNA adduct formation. We have also shown that safrole can form stable safrole-DNA adducts as well as oxidative damages in rodent liver. However, the stable safrole-DNA adducts may represent a more significant initial lesion as compared to the rapidly repaired safrole-induced 8-hydroxy-2'-deoxyguanosine. This oxidative DNA damage is mediated through the formation of hydoryxchavicol, the major safrole metabolite in human urine. Hydroxychavicol may have gone through two-electron oxidation to the o-quinone; then via one-electron reduction to semiquinone radicals to generate oxidative DNA damage. However, these reactive metabolites can be efficiently conjugated by GSH. These data suggest that safrole may contribute to the initiation of oral carcinogenesis through safrole-DNA adduct and not oxidative DNA damage. In addition, CYP2E1 may modulate this adduct formation.

• Toxicological Research
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• 제17권
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• pp.139-144
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• 2001

Chewing betel quid is associated with an increased risk of oral cancer. The betel quid chewed in Taiwan includes the inflorescence of Piper betle, which contains high concentrations of safrole (15 mg/fresh weight). Piper betle leaf is also used in betel quid; however, the concentration of safrole in betel leaf has not been documented. Chewing betel quid may contribute to safrole exposure in man (420 mm in saliva). Using $a^{32}$P-postlabeling method, we have recently demonstrated the presence of stable safrole-like DNA adducts in human oral tissues following betel quid chewing. Safrole is a rodent hepatocar-cinogen, and the real nature of safrole-DNA adducts in human tissues beside oral has not been elucidated. In this paper, we tested the safrole DNA adducts forming potential in human hepatic and oral derived cells by the ${32}^P$-postlabeling technique. The results suggest that oral cancer derived cell OC-2 alone is not able to form safrole-DNA adduct. However, safrole DNA adducts can be detected following I'-hydroxysafrole, a proximate safrole metabolite, treatment. In addition, pretreament of cytochrome P450 inducers also enhanced the formation of previously undetectable safrole DNA adducts. This finding couples with our previous results suggest that oral may serve as a target tissue for safrole, and safrole may be involved in oral carcinogenesis.

• 한국식품과학회지
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• 제36권3호
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• pp.398-402
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• 2004

신소재로 각광 받고 있는 chitosan의 낮은 수용성을 극복하기 위하여 chitosan 유도체인 safrolechitosan(SaCs) 및 eugenolchitosan(EuCs)을 제조하고, Ubbelohde 점도계를 사용하여 이들의 점도평균분자량을 측정한 결과, chitosan 및 chitosan유도체인 EuCs와 SaCs의 경우 각각 $1.2{\times}10^{5}\;Da,\;7.8{\times}10^{5}\;Da$ 및 $7.5{\times}10^{5}\;Da$인 것으로 확인되었다. Chitosan과 chitosan유도체의 구조분석을 위한 IR spectrum에서 SaCs의 경우, safrole의 공유결합에 의한 chitosan내 amine기와의 반응으로 인하여 순수 chitosau보다 amide II 흡수띠가 $1,553cm^{-1}$으로 이동함을 알 수 있었는데, 이것은 chitosan내의 1차 amine기와 safrole의 이중결합이 반응하여 공유결합을 형성함으로써 흡수띠의 이동현상이 나타난 결과이다. 또한, safrole이 반응하면서 safrole내의 vinyl기를 의미하는 특징적인 peak인 C=C 및 $H_{2}C=$의 $1,611cm^{-1}$와 $1,442cm^{-1}$에서의 흡수띠가 사라졌으며, EuCs의 경우에도 반응물질로 사용된 eugenol내의 vinyl기를 나타내는 $1,612cm^{-1}$ 및 $1,434cm^{-1}$에서의 흡수띠가 사라짐을 확인하였다. 또한 $^{1}H-NMR\;spectrum$을 확인한 결과, 합성유도체의 경우 safrole과 eugenol 간량체의 5.7-6.0ppm에서 나타난 이중결합($H_{2}C=CH-$) peak가 사라지고, SaCs는 2.1-2.2ppm에서, 그리고 EuCs는 1.9와 2.2ppm에서 단일결합($-CH_{2}-CH_{2}-$)의 peak가 생성됨을 알 수 있었으며, safrole과 eugenol이 chitosan에 그라프트된 후 safrole과 eugenol의 영향으로 chitosan내의 $H_{3}-H_{6}$의 수소 숫자가 상대적으로 감소하여 3.1-3.9ppm에서 나타나는 peak의 크기가 작아짐도 확인하였다. 이상의 결과들을 종합해 볼때, SaCs 및 EuCs를 합성하기 위한 그라프트 반응이 정상적으로 일어났음을 알 수 있었다.

• Journal of Applied Biological Chemistry
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• 제58권4호
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• pp.295-301
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• 2015

Five phenylpropanoids (1-5), a benzofuran neolignan (6), two 8-O-4'-neolignans (7-8), and five tetrahydrofuran lignans (9-13) were isolated from a methanol extract of Myristica fragrans seeds. The structures of 1-13 were determined by $^1H$- and $^{13}C$-NMR spectroscopic data analyses and a comparison with the literature data. Compound 3 was isolated for the first time from this plant. All the isolated compounds were evaluated for their inhibitory activity against tyrosinase. Among them, safrole (1) showed significant inhibitions against both the monophenolase ($IC_{50}=32.11{\mu}M$) and diphenolase ($IC_{50}=27.32{\mu}M$) activities of tyrosinase. The kinetic analysis shows that safrole (1) is competitive inhibitors for both monophenolase and diphenolase. The apparent inhibition constant ($K_i$) for safrole (1) binding with free enzyme was determined to be 16.05 and $13.66{\mu}M$ for monophenolase and diphenolase, respectively.

• Current Research on Agriculture and Life Sciences
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• 제5권
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• pp.173-184
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• 1987

식물에서 얻어지는 정유의 한 성분으로 화학구조가 유사한 anethole, eugenol, isoeugenol, safrole 및 isosafrole이 토끼 적출장관 운동에 미치는 영향과 그 potency를 알아 보고 또 어떤 작용 양식에 의하여 이루어 지는가를 알아보고 carbachol, pilocarpine, barium chloride 및 histamine 등과의 상호작용을 검토하였던 바 다음과 같은 결론을 얻었다. 1. 화학구조가 유사한 다섯가지 정유들을 단독 투여하였던 바 각각 억제 정도에 차이는 있었으나 모두 토끼 적출장관 운동을 억제시켰으며 그 potency는 isoeugenol>isosafrole>eugenol>safrole>anethole의 순으로 그 $pD_2$값은 각각 4.22, 4.18, 4.17, 4.15 및 3.82이었다. 2. 실험에 사용한 정유 모두가 carbachol, pilocarpine, barium chloride 및 histamine에 의하여 수축된 장관을 이완시켰다. 3. Anethole에 의하여 이완된 장관은 carbachol, pilocarpine, barium chloride 및 histamine에 의하여 모두 투약전과 같은 상태로 회복하지 못하였으며 eugenol, isoeugenol, safrole 및 isosafrole에 의하여 이완된 장관은 carbachol, pilocarpine 및 barium chloride에 의하여는 투약전의 상태로 회복하였으나 histamine으로는 부분적인 회복을 나타내었다. 4. 이상의 결과로 보아서 실험에 사용한 정유들은 향신경성(neurotropic) 및 향근육성(musculotropic), 양쪽에 작용하여 토끼의 적출장관 운동을 억제시킨다고 생각된다.

• Bulletin of the Korean Chemical Society
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• 제33권11호
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• pp.3571-3575
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• 2012

A number of novel small molecules, safrole oxide derivatives 4a-c, 6a-c, 9a-h, were synthesized by the reaction of safrole oxide with anilines 3 and 5, or its alkyl allyl ether derivative 7 with alkyl bromide 8 in moderate yields. The antiproliferative effects of all the target molecules on A549 cell growth were investigated and it was found that the 14 novel compounds could suppress A549 lung cancer cell growth. Among them, compound 6b was the most effective compound in inhibiting the proliferation of A549 cells.

• 한국약용작물학회지
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• 제5권2호
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• pp.126-130
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• 1997

$^1H-NMR,\;^{13}C-NMR$, Dept. NMR의 spectrum으로 compound 1은 safrole로, compoud 2은 o-methyleugenol로 추정(推定)되었으며 처리농도별(處理濃度別) 발아억제(發芽抑制) 효과조사(效果調査)에서 발아억제 물질로 추정한 safrole은 25mg/ml의 처리에서도 발아 및 생육억제 효과를 나타내지 않았다. o-methyleugenol의 경우는 5mg/ml의 처리(處理)로 최종발아(最終發芽)는 무처리구에 비해 58% 저해하였으며, 그리고 25mg/ml에서도 92%, 생육(生育)에는 100%의 저해도(沮害度)를 나타내었다. 이상(以上)의 결과(結果)를 보면 o-methyleugenol은 세신의 강(强)한 발아저해활성 물질의 하나로 처음 확인되었으며 천연(天然) 제초제(除草劑)로서의 개발(開發) 가능성(可能性)은 추후 재검증(再檢證)해 보아야 하겠다.

• 한국자원식물학회지
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• 제12권1호
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• pp.27-30
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• 1999

야생 약초인 세신의 재배년수별 생육특성과 수량성을 구명하고 주요 정유 성분인 methyleugenol과 safrole함량 변화를 조사하여 세신의 상품적 가치를 높이고 품질의 규격화를 위한 기초자료를 얻고자 1993년부터∼1997년까지 5년간에 걸쳐 시험을 실시하였던 결과를 요약하면 다음과 같다. 1. 재배년차별 생육은 재배년수가 경과함에 따라 지하부 생육의 신장차이가 크게 나타났으며 특히 근장의 크기에 따라 수량변화에 영향을 미쳤다. 2. 10a당 건근 수량은 3년재배(127kg/10a)에 비하여 4년재배 191%, 5년재배 259% 순으로 증수되었다. 3. 재배기간별 정유함량은 재배 기간에 따라 3년 5%, 4년 4.5%, 5년은 4.3% 순이었다. 4. 주요 정유 조성성분인 methyleugenol은 재배년수가 길어질수록 증가하였으나 safrole함량은 점차 감소하여 methyleugenol과 safrole 함량은 서로 상반된 관계를 나타내었다.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 춘계학술대회
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• pp.49-53
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• 2004