Loganin Inhibits α-MSH and IBMX-induced Melanogenesis by Suppressing the Expression of Tyrosinase in B16F10 Melanoma Cells

Hee Jin Jung(정희진),EunJin Bang(방은진),Byeong Moo Kim(김병무),Seong Ho Jeong(정성호),Gil Han Lee(이길한),Hae Young Chung(정해영) 한국생명과학회 2019 생명과학회지 Vol.29 No.11

Loganin은 Corni fructus의 주요 iridoid glycoside이며 항염증, 항당뇨 그리고 뇌신경보호 효과 등이 보고되었다. 본 연구에서는 α-MSH와 IBMX처리된 B16F10세포에서 loganin의 melanogenesis억제효과의 신호전달 경로를 조사하였다. Loganin의 미백 활성을 확인하기 위해 B16F10세포에서 1 μM에서 20 μM사이의 농도를 처리하여 세포독성 실험을 수행한 결과 최대 20 μM농도에서 독성을 나타내지 않았다. 또한 loganin은 α-MSH와 IBMX처리된 B16F10세포에서 농도-의존적으로 멜라닌 생성을 감소시키는 것을 확인하였다. 또한 loganin의 멜라닌 생성을 억제하는 신호전달 경로를 Western blotting을 실시하여 조사하였다. Western blot결과에 따르면 loganin은 α-MSH와 IBMX 처리된 B16F10세포에서 증가된 CREB인산화(Ser133)와 MITF 발현 및 tyrosinase의 유전자 발현을 감소시켰고 ERK의 인산화를 증가시켜 melanin 생성을 억제하였다. 결론적으로 loganin은 α-MSH와 IBMX에 의해 유도된 과도한 멜라닌 합성을 CREB인산화와 MITF 및 tyrosinase의 유전자 발현을 억제하고 ERK의 활성화를 통해 멜라닌 합성을 감소됨을 확인하였다. 따라서 loganin은 과색소 침착과 관련된 피부질환의 보호제로서 활용될 가능성을 가지는 것으로 사료된다. Ultraviolet radiation exposure is a major cause of extrinsic skin aging, which leads to skin hyperpigmentation. Loganin, a major iridoid glycoside obtained from Corni fructus, has anti-inflammatory, anti-diabetic, and neuroprotective effects. In this study, we investigated the mechanisms underlying the anti-melanogenic effects of loganin in B16F10 melanocytes treated with α-melanocyte stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX). Anti-melanogenic activity was measured by treating cells with loganin at concentrations between 1 and 20 μM. Cell viability assays confirmed that doses of loganin up to 20 μM were not cytotoxic. Loganin significantly and dose-dependently decreased intracellular melanin production. We also investigated potential molecular signaling pathways for the anti-melanogenesis effects of loganin. Western blotting showed that treatment with α-MSH and IBMX increased the phosphorylation of cAMP response element-binding protein (CREB) and the gene expressions of microphthalmia-associated transcription factor (MITF) and tyrosinase. Addition of loganin suppressed these increases, while promoting the phosphorylation of extracellular signal regulated kinase (ERK) and the anti-melanogenesis response. Our data therefore indicated that loganin could attenuate the increased melanin synthesis induced by α-MSH and IBMX treatment of B16F10 melanocytes. This attenuation appears to occur by downregulation of CREB phosphorylation and MITF and tyrosinase gene expression and upregulation of ERK phosphorylation. These finding suggests that loganin could be a valuable candidate for treatment of skin diseases related to hyperpigmentation.

재배 지역에 따른 산수유의 Loganin 함량과 분석법 검증

장다은 ( Da Eun Jang ),이상훈 ( Sang Hoon Lee ),황인국 ( In Guk Hwang ),송진 ( Jin Song ),황경아 ( Kyung A Hwang ) 한국산업식품공학회 2016 산업 식품공학 Vol.20 No.2

The aim of this study was to investigate the method validation for the determination of loganin content in Cornus officinalis (CO). This medicinal plant reportedly mainly included loganin. The specificity, linearity, precision, accuracy, limit of detection (LOD), and quantification (LOQ) were measured by HPLC/DAD. Our results showed that high linearity in the coefficient of calibration correlation (R2) for loganin standard was 1. LOD and LOQ for loganin were 0.007 and 0.026 mg/mL, respectively. The recovery rate of loganin was revealed to be in the high range of 95.14-105.45%. The relative standard deviation of intra- and inter-day precision of loganin in CO was 1.8% and 2.3%, respectively. The loganin content of CO from Gurye, Uiseng, Ichoen, and China were 7.81, 3.41, 7.42, and 6.52 mg/g, respectively. In conclusion, these methods were validated for the detection of loganin in CO.

Activation of Nrf2/HO-1 antioxidant signaling correlates with the preventive effect of loganin on oxidative injury in ARPE-19 human retinal pigment epithelial cells

Choi Yung Hyun 한국유전학회 2023 Genes & Genomics Vol.45 No.3

Background Loganin, a type of iridoid glycoside derived from Corni Fructus, is known to have beneficial effects various chronic diseases. However, studies on mechanisms related to antioxidant efficacy in human retinal pigment epithelial (RPE) cells have not yet been conducted. Objectives This study was to investigate whether loganin could inhibit oxidative stress-mediated cellular damage caused by hydrogen peroxide (H2O2) in human RPE ARPE-19 cells. Methods The preventive effect of loganin on H2O2-induced cytotoxicity, reactive oxygen species (ROS) generation, DNA damage and apoptosis was investigated. In addition, immunofluorescence staining and immunoblotting analysis were applied to evaluate the related mechanisms. Results The loss of cell viability and increased ROS accumulation in H2O2-treated ARPE-19 cells were significantly abrogated by loganin pretreatment, which was associated with activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased expression of heme oxygenase-1 (HO-1). Loganin also markedly attenuated H2O2-induced DNA damage, ultimately ameliorating apoptosis. In addition, H2O2-induced mitochondrial dysfunction was reversed in the presence of loganin as indicated by preservation of mitochondrial integrity, decrease of Bax/Bcl-2 expression ratio, reduction of caspase-3 activity and suppression of cytochrome c release into the cytoplasm. However, zinc protoporphyrin, a selective inhibitor of HO-1, remarkably alleviated the preventive effect offered by loganin against H2O2-mediated ARPE-19 cell injury, suggesting a critical role of Nrf2-mediated activation of HO-1 in the antioxidant activity of loganin. Conclusion The results of this study suggest that loganin-induced activation of the Nrf2/HO-1 axis is at least involved in protecting at least ARPE-19 cells from oxidative injury.

Loganin protects against pancreatitis by inhibiting NF-κB activation

Kim, M.J.,Bae, G.S.,Jo, I.J.,Choi, S.B.,Kim, D.G.,Shin, J.Y.,Lee, S.K.,Kim, M.J.,Shin, S.,Song, H.J.,Park, S.J. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.765 No.-

<P>Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which, in its most severe form, is associated with multi-organ failure and death. Loganin, a major iridoid glycoside obtained from Corni fructus, has been shown to have anti-inflammatory and anti-shock effects. However, the effects of loganin on AP have not been determined. Pre-treatment of loganin reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by (1) a reduction in several biochemical parameters (pancreatic weight to body weight ratio, myeloperoxidase activity, and level of amylase) and (2) production of pro-inflammatory cytokines such as interleukin (IL)-1 beta and tumor necrosis factor (INF)-alpha. However, post-treatment of loganin failed to improve pancreatic damage and biochemical parameters of AP, but could inhibit the AP-induced elevation of IL-1 beta and TNF-alpha significantly. In addition, cerulein-induced activation of nuclear factor (NF)-kappa B was inhibited in the pancreas by administration of loganin. In conclusion, these results suggest that loganin exhibits an anti-inflammatory effect in cases of AP and its pulmonary complications through inhibition of NF-kappa B activation. (C) 2015 Elsevier B.V. All rights reserved.</P>

시중에 유통되고 있는 산수유 음료의 Morroniside, Loganin 및 Cornin 함량과 이화학적 특성

박수진(Su-Jin Park),정지숙(Ji-Suk Jeong),정재훈(Jae-Hun Jeong),박노진(No-Jin Park),손병길(Byeong-Gil Son) 한국식품영양과학회 2017 한국식품영양과학회지 Vol.46 No.8

본 연구는 산수유 음료 개발에 기초자료로 활용하고자 시중에 유통 중인 산수유 파우치 형태 액상제품 18종의 제품을 수거하여 기능성 성분 함량 및 이화학적 품질특성을 조사하였다. 가장 많이 함유되어 있는 유효물질은 morroniside였으며, 다음으로 loganin, cornin 순이었다. 구례 지역 생산산수유 제품의 1 · 2차 평균 유효물질 morroniside, loganin 및 cornin의 함량이 각각 89.55, 66.04, 12.91 mg/100 g으로 전체 평균 77.22, 45.51, 8.16 mg/100 g보다 유의적으로 높게 측정되었다. Morroniside가 전체 평균보다 높은 제품은 각각 7개 및 7개였으며, loganin은 6개 및 4개, cornin은 8개 및 1개였다. 또한, cornin이 전혀 검출되지 않은 제품도 1차 및 2차에서 각각 1개 및 4개 있었다. 지역별 유효성분 차이는 구례지역이 타 지역에 비해 morroniside 함량 2차 분석을 제외하고 모든 유효성분 함량이 높았다. 그러나 대부분 제품의 유효물질 함량이 유의적인 차이를 나타내었다(P<0.05). 이상의 결과를 종합해보면 품질이 우수한 산수유 음료를 생산하기 위해서는 원료의 표준화와 추출조건과 같은 추출공정의 표준화 연구가 필요할 것으로 판단된다. The present study collected 18 kinds of commercially circulated liquid Sansuyu (Corni fructus) in pouch form and conducted comparative analysis on markings and physicochemical characteristics in order to utilize this information as a base material for the development of Sansuyu liquid products. The most abundant valid substance was morroniside, followed by loganin and cornin, in that order. Total concentration of valid substances in Cornus fruit products produced in the Gurye region was 168.50 mg/100 g, which was significantly higher than the overall average of 130.89 mg/100 g. There were seven (1st) and seven (2nd) kinds that contained more morroniside than the overall average, six (1st) and four (2nd) kinds with more loganin than the overall average, and eight (1st) and one (2nd) kinds with more cornin than the overall average. There were also five types in which no loganin was detected. There were significant differences in the valid substances of most products according to production period. Overall, these results show that processing method standardization research on extraction conditions is needed to produce liquid Sansuyu products of excellent quality.

산수유 추출조건에 따른 Loganin 함량 분석 및 활성 평가

임소연 ( So Yeon Im ),정경옥 ( Kyoung Ok Jeong ),이정호 ( Jeong Ho Lee ) 한국키틴키토산학회 2020 한국키틴키토산학회지 Vol.25 No.3

산수유는 인체 건강에 유익하여 전북지역에서 재배가 증가하고 있어 기능성식품을 개발하고자 loganin의 함량과 항산화, 항당뇨 및 항염 활성, 일반성분을 분석하였다. 산수유에 함유된 loganin 함량을 분석한 결과 3시간, 100℃ 추출물에서 7.68 ± 0.06 mg/g, 9시간 100℃ 추출물에서 7.88 ± 0.04 mg/g 분석되었으며, 추출시간 및 추출온도가 증가함에 따라 loganin 함량도 증가하였다. 산수유 100oC 3시간 추출물 1,000 μg/mL에서 DPPH 라디칼 소거활성은 53.58 ± 3.35%, ABTS 라디칼 소거활성은 18.22 ± 0.62%, SOD 효소 활성은 69.6 ± 7.42%으로 측정되었으며, 추출물의 처리농도가 증가함에 따라 항산화 활성도 증가하였다. 세포 독성은 나타나지 않았으며, NO 생성 저해 활성은 1 μg/mL에서 12.88 ± 0.24, 10 μg/mL 12.89 ± 0.96으로 저해되었다. α-Glucosidase 저해 활성은 1,000 μg/mL에서 98.9 ± 5.95%, 500 μg/mL에서 91.9 ± 5.28%으로 분석되었다. 일반 성분은 열량 344.94 kcal/100 g, 탄수화물 80.83% 조단백질 3.29%, 조지방 0.94%, 총당 347.61 mg/g으로 분석되었다. 산수유에는 loganin이 함유되어 있고 항산화, 항암, 항당뇨 활성이 있어 기능성 소재로 개발이 가능할 것으로 판단된다. The aim of this study was to investigate the potential of Cornus officinals as a content of protocatechuic acid and physiological activities. The analyzed the content of protocatechuic acid of Cornus officinals water extracts according to different extract temperature and time for extraction. It was analyzed as 7.68 ± 0.06 mg/g in the extract at 100℃ for 3 h. Protocatechuic acid content increased as extraction time and temperature increased. The activity of the Cornus officinals water extract at 100℃ for 3 h was measured. Antioxidant activity against the concentration of Cornus officinals water extract 1,000 μg/mL was measured. DPPH radical scavenging activity was measured at 53.58 ± 3.35%, ABTS radical scavenging activity at 18.22 ± 0.62%, and SOD activity at 69.6 ± 7.42%, antioxidant activity also increased as the processing concentration of extracts increased. Cell viability was shown for RAW 264.7 cells, and nitric oxide(NO) production was also inhibited. The α-Glucosidase inhibitory activity was determined to be 98.9 ± 4.45% at concentration of 1000 μg/mL. The nutritional components were analyzed to be 344.94 kcal/100g of calories, 80.83% of carbohydrates, 3.29% of crude protein, 0.94% of crude fat, and 347.61 mg/g of total sugars. Cornus officinals is thought to be developed as a functional food material because it contains protocatechuic acid and has antioxidant activity, anti-inflammatory and antidiabetic activity.

Antioxidative Activity of Cornus officianalis Extracts Obtained by Four Different Extraction Techniques

Eun-Bi Park(박은비),Hye-Sun Kim(김혜선),So-Yun Shin(신소연),In-Ae Ji(지인해),Ji-Hyun Kim(김지현),Sung-Goo Kim(김성구),Byung Hong Yoo(유병홍),Byung-Woo Kim(김병우),Inseok Kwak(곽인석),Moon-Moo Kim(김문무),Kyung Tae Chung(정경태) 한국생명과학회 2012 생명과학회지 Vol.22 No.11

산수유는 다양한 생리적 기능을 가지는 것으로 보고되어 있으며 또한 최근에 관심의 증가로 산수유로부터 유효성분의 추출 방법 개발은 산업적으로 매우 중요하며, 유효성분의 존재 여부를 분석하는 것은 산업적 상품의 진위와 품질을 판정하는데 중요한 수단이 된다. 본 연구는 loganin을 지표 물질로 하여 산수유로부터 유효성분을 추출하는 여러 방법을 비교 분석하였으며, 각 방법에 따라 추출한 시료의 기능성의 차이를 항산화 작용으로 분석하였다. 산수유로부터 항산화 성분을 추출하기 위하여 네 가지 방법을 적용하였다. 추출된 유효성분 지표물질로 loganin의 함량을 HPLC로 분석하였을 때 열수를 사용한 추출 방법이 알코올 추출 또는 효소 처리 방법 보다효율적인 결과를 보여 주었다. 각 추출 시료의 항산화 기능은 DPPH radical 소거능, hydrogen peroxide scavenging assay, reducing power 측정으로 분석하였다. 추출 방법에 따라 항산화 기능이 차이가 있었으며, 열수 추출 시료가 DPPH radical 소거능과 hydrogen peroxide scavenging 효과가 우수하였고, 효소 처리 추출 시료는 reducing power가 우수하게 나타났다. 추출 방법에 따라 시료에 함유된 성분의 차이가 항산화 기능이 차이와 연관이 있다고 생각된다. 이 연구에서 얻은 결과는 산수유는 대조군으로 사용한 vitamin C에 준하는 항산화 성분을 함유하고 있으며, 이들 성분은 열수 추출 방법으로 효율적으로 추출되었으며, 열수 추출 방법은 산업적으로 응용 될 수 있음을 제시하고 있다. Oxidative stress leads to damage in all components of the cell, including proteins, lipids, and DNA due to imbalance between reactive oxygen species production and cellular detoxification. Phytochemicals are well-known to contain antioxidants, and their physiological role has been intensively studied. The fruit of Cornus officianalis has been used in oriental medicine and has been reported to have many functions. In this study, four different extraction techniques were applied to extract functional components from the fruit of Cornus officianalis, and the content of loganin, which is an antioxidant having DPPH radical and hydrogen peroxide scavenging activity and reducing power, was analyzed in each extract. Extraction techniques employed in this study were heat extraction by water, 70% ethanol extraction, enzyme treatment, and combination of enzyme treatment and heat extraction by water. All extracts contained 11.8-18.0 mg/g loganin and showed antioxidation function assayed by measuring DPPH radical and hydrogen peroxide scavenging activity and reducing power. Among them, heat extraction was the most effective technique, showing a maximum amount of loganin (18.0 mg/g) and antioxidative activity at 100 mg/ml concentration. Each extract showed very low cytotoxicity up to at 500 mg/ml but 10-20% cytotoxicity at 1,000 mg/ml by in vitro MTT assay.

인체 섬유아세포에서 인동덩굴 추출물의 MMP-1 생성 억제효과

정연수 ( Yeon Su Jeong ),이진영 ( Jin Young Lee ),고재영 ( Jaeyoung Ko ) 대한화장품학회 2020 대한화장품학회지 Vol.46 No.1

본 연구에서는 사람 피부 섬유아세포에서 콜라겐을 파괴하는 matrix metalloproteinase-1 (MMP-1)을 억제하는 새로운 항노화 천연물을 얻고자 하였다. 50 여종의 생약추출물을 스크리닝 한 후 그 중 인동덩굴 추출물을 선정하여 본 연구를 수행하였다. 인동 줄기를 70% 에탄올로 추출한 후 헥산, 에틸아세테이트, 부탄올 차례로 용매 분획을 하였다. 에틸아세테이트층 50 μg/mL와 부탄올층 200 μg/mL 농도에서 유의적으로 MMP-1 생성을 억제하였다. 이 효능 성분들을 모두 포함하는 분획을 얻기 위해 HP20 레진 컬럼 크로마토그래피를 통해 80% 에탄올 분획을 얻었다(LJ F80). LJ F80과 지표성분 loganin은 농도의존적으로 MMP-1 생성을 억제하였으며 그 활성을 비교하였을 때 같은 농도에서 LJ F80이 더 억제효과가 높게 나타났다. 이 분획에 대한 안정도를 각각 4 ℃, 상온, 40 ℃에 보관하면서 HPLC로 분석하여 16 주간 평가하였다. Loganin을 기준으로 하여 초기값 대비 ± 10%내외의 안정도를 유지하였다. 따라서 인동의 LJ F80은 피부주름개선효과를 나타내는 유효 화장품 원료로 사용될 수 있을 것으로 생각된다. In this study, we attempted to obtain an active ingredient that inhibits the production of matrix metalloproteinase-1 (MMP-1) that breaks down collagen in human skin fibroblasts. More than 50 plant extracts were screened, and Lonicera japonica was selected for this study. The stem of L. japonica was extracted with 70% ethanol and fractions with solvents in the order of hexane, ethyl acetate, and butanol. MMP-1 production were significantly inhibited at the concentration of 50 μg/mL of the ethyl acetate layer and 200 μg/mL of the butanol layer. To get a fraction containing all of these effective components, 80% ethanol fraction (LJ F80) was obtained through HP20 resin column chromatography. The reference substance, loganin and LJ F80 inhibited dose-dependently MMP-1 production. At the same concentration, LJ F80 showed a higher inhibitory effect than loganin. The stability of this fraction was analyzed with HPLC while kept storing at 4 ℃, room temperature, and 40 ℃, for 16 week. The stability was maintained as ± 10% of initial value with reference loganin. Therefore, it is thought that LJ F80 of L. japonica may be used to improve wrinkles.

산수유로 건조과육 가공 시 건조 시간, 데치는 온도 및 시간에 따른 건조과육의 품질 특성 변화

정지숙(Ji-Suk Jeung),김한모(Han-Mo Kim),강석원(Seuk-Wan Kang),김은하(Eun-Ha Kim),손병길(Byeong-Gil Son),박노진(No-Jin Park) 한국식품영양과학회 2019 한국식품영양과학회지 Vol.48 No.3

산수유(Corni Fructus)는 산수유나무(Cornus officinalis Siebold et Zucc.)의 열매에서 씨앗을 제거한 건조 과육을 일컫는다. 대부분 재배 농가에서 직접 가공하여 수매하는 유통구조로 제조과정은 동일하나 제조조건은 가가호호(家家戶戶) 다양하다. 본 연구는 산수유 건피 제조조건 정립을 위한 연구의 일환으로 동결건조 산수유와 45°C에서 2, 5, 7, 10, 15시간 건조한 산수유, 산수유 열매를 45°C에서 5시간 건조한 후 씨앗을 분리하기 위해 45, 65, 95°C 항온수조에서 1, 3, 5분 동안 데친 다음 씨앗이 분리된 산수유의 품질특성을 비교 조사하였다. 그 결과 산수유 과육과 씨앗을 분리할 경우 데침 온도보다 데침 시간에 영향을 받는 것으로 확인되었다. pH는 2.89~3.24, 당도는 0.85~0.97°Brix였다. 동결건조 산수유의 morroniside, loganin 및 cornin은 각각 2,226.16, 1,258.15 및 446.24 mg/100 g이었다. 산수유 열매를 5시간 건조하여 65, 95°C에서 1, 3, 5분간 데친 산수유(HD5B)의 주요 기능 물질인 morroniside는 1,769.11~1,928.09 mg/100 g, loganin은 721.83~987.36 mg/100 g 및 cornin은 223.61~395.18 mg/100 g이었다. 건조시간이 증가할수록 기능 물질 3종은 감소하였다. 그러나 7시간 이상 건조하여 씨앗을 분리한 경우 산수유의 모양이 온전하지 못하기 때문에 건조 시간은 2~5시간이 적당할 것으로 판단된다. 색도는 데침 온도보다 데침 시간에 영향을 받았으며, 데침 시간이 증가할수록 L값은 감소하고, a값과 b값은 증가하였다. 산수유 열매를 15시간 건조하여 65, 95°C에서 1, 3, 5분간 데친 산수유(HD15B)의 경우 주요물질의 함량은 높으나 외관의 크기가 작고 모양이 온전하지 못하며, 전반적인 색이 어두웠다. 이상의 연구 결과로 산수유 건피 제조조건의 범위를 설정할 수 있었으며 향후 산수유 원료의 품질기준이 될 수 있을 것으로 본다. Sansuyu (Corni Fructus, CF) usually refers to the dried flesh of the fruit of Cornus officinalis Siebold et Zucc. without seeds. The dried fruit is mostly manufactured by the growers through direct processing and then sold and distributed; however, the processing conditions differ according to the households. After eliminating the seeds from freeze-dried CF and hot air-dried CF at 45°C for 2, 5, 7, 10, and 15 hours, the CF was pre-dried at 45°C for 5, 15, and 22 hours and then blanched for 1, 3, and 5 minutes at 45, 65, and 95°C. According to the results, when the seeds were separated from CF, the blanching time had a greater influence than the blanching temperature. The morroniside, loganin, and cornin contents of freeze-dried CF were 2,226 mg/100 g, 1,258 mg/100 g, and 446 mg/100 g respectively. Regarding the main functional compounds of CF, the morroniside, loganin, and cornin contents were 1,769~2,343, 717∼1,270, and 224∼544 mg/100 g, respectively. As the drying time was increased, the concentration of the functional compounds decreased. On the other hand, the shape of CF was not well preserved when the seeds were separated after more than seven-hour drying. Therefore, two to five-hour drying appears to be appropriate. The color value is more influenced by the blanching time than by the blanching temperature, and as the blanching time increases, the L-value decreases with a concomitant increase in the a-value and b-value. These results can be used to develop the quality standards for dried Sansuyu fruit.

Dose-independent pharmacokinetics of loganin in rats: effect of intestinal first-pass metabolism on bioavailability

박휘진,Bae Sung Hun,김소희 한국약제학회 2021 Journal of Pharmaceutical Investigation Vol.51 No.6

Purpose Loganin, one of the two main iridoid glycosides in Cornus officinalis Sieb et Zucc, has been reported to exhibit many biological activities such as immune modulation, as well as anti-inflammatory and anti-shock effects. This study was designed to evaluate the pharmacokinetics of loganin, administered intravenously (5, 10, 20 and 50 mg/kg) and orally (20, 50, 100 and 200 mg/kg), in rats. Methods To evaluate its hepatic and gastrointestinal first-pass effects, loganin was administered intraportally, intragastrically and intraduodenally to rats. Results Following intravenous administration of 5–50 mg/kg loganin, a linear relationship was observed between the total area under the plasma concentration–time curve from zero to infinity (AUC) and loganin dose, with ~ 19% of the administered dose excreted in the urine. AUCs following oral administration of 20–200 mg/kg loganin were dose-independent, with the extent of absolute oral bioavailability (F) being approximately 4.87%. The AUC of loganin was significantly lower by 90.6% after intraduodenal than intraportal administration, but did not differ between intragastric and intraduodenal administration. The AUC was also significantly lower by 52.7% after intraportal, compared to intravenous, administration, suggesting that the hepatic first-pass effect on loganin after entering the portal vein was approximately 4.95% of the oral dose. Conclusion Taken together, our data suggest that the low F of loganin in rats was due exclusively to its high intestinal firstpass metabolism.