Sesamin induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential

Shasha Yang,Xiangdan Li,Haowen Dou,Yulai Hu,Chengri Che,Dongyuan Xu 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.3

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

참깨의 리그난 화합물의 항염증 효과

이화정 ( Hwa Jeong Lee ),손동주 ( Dong Ju Son ),강명화 ( Myung Hwa Kang ),이범천 ( Bum Chun Lee ),홍진태 ( Jin Tae Hong ) 대한화장품학회 2006 대한화장품학회지 Vol.32 No.3

참깨(Sesamum indicum L.)는 1년생 초본식물로서 볶은 참깨나 참기름은 우리나라 식단에서 아주 중요한 조미용 양념 및 식용유지로서 이용되고 있다. 약효로는 동맥경화, 고혈압 및 노화 예방 등으로 알려져 왔으나, 참깨에 함유되어 있는 어떤 성분이, 이들 약효에 관여하고 있는지의 과학적인 규명이 미흡한 실정이다. 본 연구에서는 천연물 유래의 새로운 노화방지제를 개발하기 위해 참깨의 리그난 화합물(sesamin, sesamol, sesaminol, sesaminol diglucosides (SDG), sesaminol triglucosides (STG))의 항염증 활성을 검색하고, 그 중에서 항염증 효과가 가장 높게 나타난 sesamin을 전처치 방법과 동시처치 방법으로 NO 생성억제효과, 세포독성, inducible nitric oxide synthase (iNOS) 및 cyclooxygenases-2 (COX-2) 발현에 미치는 영향을 탐색하고 작용기작을 규명하고자 하였다. 리그난 화합물의 NO 생성억제효과를 탐색한 결과, sesamol, sesaminol, sesamin에서 NO 생성에 미치는 억제율이 높았으나, sesamol, sesaminol은 세포독성이 나타났다. 하지만 sesamin ($IC_{50}: 64{\mu}M$)은 세포독성은 없으면서 농도의존적으로 NO 생성을 억제시켰으며, iNOS 발현에서도 억제 효과를 보여주었다. 결론적으로 sesamin은 피부노화에 원인 중 하나이며 체내 염증반응의 중요 매개인자인 NO의 생성을 억제하는 항염증 물질로서 이와 같은 연구 결과는 향후 임상에서 항염증과 관련된 새로운 항노화 전략으로 개발하기 위해 기초자료로 응응될 수 있음을 시사한다. Sesame (Sesamum indicum L.), one of the oldest oilseed crops, has been known to posses antioxidative and inflammatory effects. This seed contains lignan compounds such as sesamin, sesamol, sesaminol, sesaminol diglucosides (SDG), and sesaminol triglucosides (STG). Sesamin, a major lignan in sesame, displayed several biological activities including a protective effects against oxidative damage in the skin. In the present study, we investigated the effect of sesamin, sesamol, sesaminol, SDG, and STG, on nitric oxide (NO) induction and inducible nitric oxide synthane (iNOS) and cyclooxygenases-2 (COX-2) expression in lipopolysaccharides (LPS)-treated RAW 264.7 cells. The results showed that sesamol and sesaminol significantly inhibited NO generation but they were also cytotoxicity however, sesamin effectively inhibited NO production ($IC_{50}: 64{\mu}M$) without my cytotoxic effect in LPS-stimulated macrophage RAW 264.7 cells. In further study, it was founded that sesamin inhibited the expression of inducible nitric oxide synthase but not COX-2 expression. These results suggest that sesamin may be useful for improvements of the inflammatory diseases.

Sesamin Attenuates Obesity-Associated Nonalcoholic Steatohepatitis in High-Fat and High-Fructose Diet-Fed Mice

Yang-Yang,Jing Yu,Jiayao Huo,Yaping Yan 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.3

This study explored the effects of sesamin on nonalcoholic steatohepatitis (NASH). High-fat and high-fructose diet-fed mice supplemented with or without sesamin. The results suggested that sesamin-treated mice lost body weight and fat tissue weight, had lower levels of serum metabolic parameters, and insulin resistance was mitigated. Histological examinations showed that sesamin treatment mitigated the progression of hepatic steatosis, and inflammation. In addition, sesamin enhanced hepatic antioxidant capacity, and decreased the activations of hepatic c-jun N-terminal kinase, inhibitor of kappa B kinase α, and insulin receptor substrate 1 as well as hepatic interleukin-6 and tumor necrosis factor-alpha levels. Further experiments indicated that sesamin treatment downregulated GRP78 and phospho-inositol-requiring enzyme 1 (IRE1) expression, and upregulated x-box binding protein 1 (XBP1) expression in hepatic tissue. The aforementioned results suggest that sesamin alleviates obesity-associated NASH, which might be linked to the effect of sesamin on the regulation of the hepatic endoplasmic reticulum stress-IRE1/XBP1 pathway. Thus, sesamin may be a good food functional ingredient in the treatment of obesity-associated NASH.

Sesamin에 의한 PC12 세포중의 Dopamine 생합성 촉진작용

장민영,최현숙,이명구 한국생약학회 2010 생약학회지 Vol.41 No.3

The effects of sesamin on dopamine biosynthesis in PC12 cells were investigated. Sesamin at concentration ranges of 20-75 µM significantly increased intracellular dopamine levels and tyrosine hydroxylase (TH) activities at 24 h: 50 µM sesamin increased dopamine levels to 132% and TH activities to 128% of control levels. Sesamin (50 µM) induced the phosphorylation of TH, cyclic AMP-dependent protein kinase (PKA) and cyclic AMP-response element binding protein (CREB)for 0.5-24 h. Sesamin (50 µM) also increased the mRNA levels of TH and CREB for 3-24 h. In addition, sesamin (50 µM)associated with L-DOPA (50 and 100 µM) further increased the intracellular levels of dopamine for 24 h compared to L-DOPA alone. These results suggest that sesamin enhances dopamine biosynthesis and L-DOPA-induced increase in dopamine levels by inducing TH activity and TH gene expression, which is mediated by PKA-CREB systems in PC12 cells. Therefore, sesamin could serve as an adjuvant phytonutrient for neurodegenerative diseases.

Inhibitory effects of sesamin on human osteoclastogenesis

Orawan Wanachewin,Peraphan Pothacharoen,Prachya Kongtawelert,Thanyaluck Phitak 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.10

The promotional nature of sesamin on humanosteoblast differentiation has been proven. Here, the effectof sesamin on human osteoclasts was investigated in termsof differentiation and function in M-CSF and RANKLinduced human PBMCs. Sesamin treatment significantlydecreased the number of differentiated osteoclastsobserved by TRAP staining; however, sesamin inhibitiondid not result from the alteration of precursor cell proliferation. Sesamin did not decrease NFATc1 gene expression,which opposed the decreasing trend of CathK andTRAP expression. DC-STAMP, but not Atp6v0d2, alsosignificantly decreased in the presence of 14 lM sesamin. Expressions of CCR2b and CCR4 as chemokine receptorswere significantly down-regulated. Sesamin might mediatethe inhibition of human osteoclast differentiation, therecruitment of precursor cells and F-actin formation. Decrease in the area of the resorption pits and the collagenreleased from the bone slices under sesamin treatmentemphasized the inhibitory effects on both the differentiationand function of osteoclasts. Sesamin is a promisingphytochemical agent inhibiting osteoclast differentiationand function.

참깨 종실의 항산화 성분 정량분석 연구

柳守魯,李正日,姜三植,崔彰烈 韓國作物學會 1992 한국작물학회지 Vol.37 No.4

본 연구는 고항산화 양질 육종의 체계확립을 위해서 참깨에 있는 특수성분인 sesamin, sesamolin의 표준물질을 동정하고 그 분석기술을 개발하였는바 그 결과는 다음과 같다. 1. 한국산 참깨로부터 sesamin, sesamolin 성분을 분리하여 화학적 구조를 분광학적 방법(UV, 1 H와 13C-NMR, MS)으로 확인하여 sesamin, sesamolin의 표준물질을 동정하였다. 2. 참깨 lignan성분의 추출 및 분리에는 Unsaponifiable fration 보다 MeOH 냉온처리가 더 효과적이었다. 3. 검량선의 회귀직선의 방정식은 sesamin에서 y=53924.43+1277.93x(r=0.9993)이었고 sesamolin의 경우는 y=11034.95+1188.38x(r=0.9994)로 추정되었다. 4. 한국산 참깨의 lignan 성분함량은 단백깨의 경우 sesamin 0.42% sesamolin 0.3%로 나타났다. This study was conducted to obtain basic informations on the lignan components from sesame seed. Two major lignans, sesamin and sesamolin, were isolated and identified by means of spectral methods, and quantitative analysis was by HPLC from sesame variety Danbaeggae. Separation was achieved by isocratic elution and reversed phase chromatography Develosil ODS column. The content of the major lignan components were about 0.42% and 0.30% for sesamin and sesamolin, respectively.

시중 참기름에 혼입된 이종기름에 관하여

유영찬,박유신,정희선,정진일 한국식품위생안전성학회 1992 한국식품위생안전성학회지 Vol.7 No.1

근래 외국에서 참기름이 들어오고 있어 산지에 따른 성분조성을 밝히고자 sterolfb와 지방산류의 함량을 측정하였다. 일본, 중국, 대만 등에서 수입되고 있는 참깨에서 얻은 참기름과 우리 나라 산의 참기름의 성분조성을 비교할 때 유사하여, sterol 류중 campesterol은 1.00~1.29 mg/g이었으며, ${\beta}-sitosterol$의 camp.에 대한 비율은 2.39~2.99%이고, sesamin의 camp.에 대한 비율은 3032~5.46이었으며, 지방산은 palmitic acid 8.37~10.09%, stearic acid 4.61~5.50%, oleic acid 35.24~39.97%, linoleic acid 43.04~49.76%, linolenic acid 0.21~0.31% 그리고 arachidic acid 0.40~0.69% 이었다. 그러나 일부 일본제 상품에서 sesamin이 아주 적게 함유되어 있고 linoleic acid, linolenic acid가 많이 함유되어 있는 반면 oleic acid와 stearic acid가 적게 함유되어 있으므로 콩기름을 함유한 것으로 추정되는 상품이 나타나고 있으며, 이들이 동일 상품에서 나타나고 있는 것으로 보아 불법으로 제조된 상품으로 사료되었다. This study primarily attempted to establish the method for the determination of the adulteration in the sesame oil. First of all, extensive experiment was conducted to determine the composition of genuine sesame oil prepared from Korean, Japanese, Taiwanese and Chinese sesame seed. Sesamin and sterols in unsaponfiable matter were examined along with fatty acid in saponifiable fraction by Gc. There was no significant difference in the composition of sesamin and sterols in sesame oils prepared from Korean and foreign seeds. The ranges of sesamin and ${\beta}-sitosterol$ against campesterol were 3.32~5.46 and 2.39~2.99 respectively in all samples. Similiar composition of fatty acids was showed in all pure sesame oils, in which the contents were 8.37~lO.09% palmitic acid, 4.61~5.50% stearic acid, 35.24~39.97% oleic acid, 43.04~49.76% linoleic acid, O.21~O.31% linolenic acid and 0.40~O.69% arachidic acid. Among the commercial sesame oils sold in Markets, three sesame oils from Japan revealed low sesamin, high linoleic acid and linolenic acid, and low oleic acid and stearic acid, suggesting the adulteration with soybean oil.

참기름의 옥배유 혼합에 따른 이화학적 특성 및 산화안정성 비교

서정희,정윤희,이기동,권중호 한국식품위생안전성학회 1998 한국식품위생안전성학회지 Vol.13 No.1

참기름의 이종기름 함유 유무를 판단하기 위한 기초자료를 얻고자 국내산 참기름의 옥배유를 혼합한 시료와 중국산 참기름에 대하여 지방산, sesamolin 및 sesamin 함량, AOM에 의한 유도기간을 각각 조사했다. 국내산 참기름에 옥배유를 혼합할 경우, stearic acid는 옥배유를 20% 이상 혼입한 참기름에서 국내산 참기름과 뚜렷한 차이를 나타내었다. 그리고 Oleic acid와 linoleic acid에서는 10%의 혼합시에도 미약하나마 함량의 차이를 보였다. 참기름에 옥배유를 혼합하 fruddn stearic/linoleic 비율은 옥배유의 혼입된 함량과 비례하였다. 국내산 참기름에 이종기름으로 drhqodb를 30% 혼합시에는 sesamolin이 18.3%, sesamin이 21.0% 감소하였다. AOM에 의한 유도 기간은 중국산, 백배유 20% sesamolin과 sesamin의 함량 및 AOM에 의한 유도기간 측정 등이 적용하리라 생각된다. Korean sesame oil mixed with corn oil and Chinese sesame oil were subjected to instrumental determination for fatty acid composition, sesaminol and sesamin contents, and induction period by AOM test to obtain basic data for ascertaining the truth of pure sesame oil, respectively. In sesame oil mixed with corn oil, stearic acid content of sesame oil containing above 20% corn oil was remarkably discriminated from that of pure sesame oil. Oleic and linoleic acid contents of sesame oil with 10% corn oil were significantly differnt from that of pure sesame oil. Stearic/linoleic acid ratio of sesame oil mixed with corn oil dcreased in proportion to corn oil content in sesame oil. Sesamolin and sesamin contents of sesame oil containing 30% corn oil were lower 18.3% and 21.0% than those of pure sesame oil, respectively. Induction periods of sesame oil by AOM were 8.14~9.24 hrs in Chinese sesame oil and sesame oils inculding 20% and 40% corn oils, but around 16hrs in Korean pure sesame oil. Based on the above results, it is considered that the comparisons of fatty acids, sesaminol and sesamin contents, and induction period by AOM test might be one of the potential criteria in discriminating between pure sesame oil and sesame oil mixed with corn oil.

Sesamum indicum L. Oil and Sesamin Induce Auditory-Protective Effects Through Changes in Hearing Loss-Related Gene Expression

김윤희,김은영,Isabel Rodriguez,남연희,정서율,홍빈나,정세영,강동호 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.5

Changing consumption patterns and increasing health awareness, especially in Europe, are resulting in an increased demand for sesame seeds. In 2016, Asia imported the highest quantity of sesame seeds, followed by Europe and North America. We examined, for the first time, the effects of treatment with sesame oil and sesamin in hearing impairment models. Sesame oil exhibited an ameliorative effect on auditory impairment in a hair cell line in zebrafish and mice. In ototoxic zebrafish larvae, neuromasts and otic cells increased in numbers because of sesame oil. Furthermore, auditory function in noise-induced hearing loss (NIHL) was studied through auditory brainstem response to evaluate the therapeutic effects of sesame oil. Sesame oil reduced the hearing threshold shift in response to clicks and 8, 16-kHz tone bursts in NIHL mice. Auditory-protective effect of sesame oil was seen in zebrafish and mice; therefore, we used chromatographic analysis to study sesamin, which is the major effective factor in sesame oil. To investigate its effects related to auditory function, we studied the hearing-related gene, Tecta, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) assay. Auditory cell proliferation was induced by treatment with sesame oil and sesamin using Tecta (Tectorin Alpha) regulation. The expression of Tecta increases in the apex area of the cochlear hair cells as they grow, and their activity is enhanced by sesame oil and sesamin. These results provide a novel mechanistic insight into the sesame oil activities and suggest that sesamin, the key constituent in sesame oil, is responsible for its auditory function related benefits, including protection of auditory cells and reversal of their impairments.

Quantitative Dissection of Antioxidative Bioactive Components in Cultivated and Wild Sesame Germplasm Reveals Potentially Exploitable Wide Genetic Variability

Niti Pathak,Ashwani Kumar Rai,Supradip Saha,Suresh Walia,Soumitra Kumar Sen,Kangila Venkataraman Bhat 한국작물학회 2014 Journal of crop science and biotechnology Vol.17 No.3

Sesame (Sesamum indicum L.) is one of the oldest oilseed crops grown in India and worldwide. This oilseed crop has high nutritionalvalue due to the presence of antioxidants such as lignans and tocopherols. Screening of oilseed germplasm for important nutritionalattributes is of prime importance in quality breeding programs. In the present study, the content of lignans (sesamin andsesamolin) and tocopherol homologues (α-, γ -, and δ-tocopherol) was determined using reverse phase HPLC (RP-HPLC) in 143sesame lines collected from diverse agro-ecological zones of India. Exploitable levels of sesamin, sesamolin, γ-, and δ-tocopherolwas observed in the studied sesame lines. Sesamum indicum cultivar CO 1, introgressed line MKN 9, and Sesamum malabaricumshowed high values for sesamin. Exotic and indigenous accessions of S. indicum (EC 542283 and IC 132176, IC 204681, IC 204773)showed high sesamolin contents. Cultivars, AKT 64, AKT 101, Phule til 1, and Tapi A showed high values for γ - and δ-tocopherol. The average content of sesamin and sesamolin was 0.86 and 0.50 mg g-1 seed, respectively. The average tocopherol content (292 μgg-1 seed) found in this study indicates the presence of a high amount of tocopherol in Indian sesame germplasm. Superior genotypesof sesame reported in this study could be utilized in sesame breeding programs for enhancing oil yield and nutritional attributes