1.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
2.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
3.Association between dietary patterns and overweight and obesity among primary and middle school students
JIANG Nan ; TANG Xiaomin ; SUN Wentao
Journal of Preventive Medicine 2025;37(3):228-232
Objective:
To explore the association between dietary patterns and overweight and obesity among primary and middle school students, so as to provide the guidance of diet balance and obesity prevention for students.
Methods:
Students from 11 primary and middle schools in Tongzhou District, Beijing Municipality, were selected using the stratified cluster sampling method. Demographic information was collected through a general questionnaire, and dietary intake types and frequencies over the past week were assessed using a food frequency questionnaire. Dietary patterns were determined using factor analysis, and the dietary pattern factor scores were divided into Q1, Q2, Q3, and Q4 groups based on quartiles. Height and weight were collected through physical examinations, and Z-scores of body mass index adjusted for gender and age were calculated to assess overweight and obesity. The association between dietary patterns and overweight and obesity was analyzed using a multivariable logistic regression model.
Results:
A total of 1 485 students were surveyed, including 745 males (50.17%) and 740 females (49.83%). The mean age was (12.87±2.86) years. Three dietary patterns were identified: animal and plant protein dietary pattern, high-fat and high-sugar dietary pattern, and vegetable-fruit-dairy dietary pattern. The detection rates of overweight and obesity were 42.57%, 48.42%, and 34.75%, respectively, with statistically significant differences (P<0.05). Multivariable logistic regression analysis showed that compared with the vegetable-fruit-dairy dietary pattern, the animal and plant protein dietary pattern (OR=1.406, 95%CI: 1.084-1.823) and the high-fat and high-sugar dietary pattern (OR=2.137, 95%CI: 1.643-2.779) were associated with a higher risk of overweight and obesity among primary and middle school students. Compared with the Q1 group of dietary pattern factor scores, the Q3 group (OR=1.631, 95%CI: 1.206-2.208) and Q4 group (OR=1.965, 95%CI: 1.446-2.671) of the high-fat and high-sugar dietary pattern had an increased risk of overweight and obesity, while the Q4 group of the vegetable-fruit-dairy dietary pattern (OR=0.551, 95%CI: 0.406-0.747) had a reduced risk of overweight and obesity. There was no statistical association between factor scores of animal and plant protein dietary pattern and overweight and obesity (all P>0.05).
Conclusions
The animal and plant protein dietary pattern and the high-fat and high-sugar dietary pattern are associated with a higher risk of overweight and obesity among primary and middle school students. Within the same dietary pattern, the more inclined students are to the high-fat and high-sugar dietary pattern, the higher their risk of overweight and obesity, while the more inclined they are to the vegetable-fruit-dairy dietary pattern, the lower their risk of overweight and obesity.
4.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
5.Cost-effectiveness of Fractional Flow Reserve Versus Intravascular Ultrasound to Guide Percutaneous Coronary Intervention: Results From the FLAVOUR Study
Doyeon HWANG ; Hea-Lim KIM ; Jane KO ; HyunJin CHOI ; Hanna JEONG ; Sun-ae JANG ; Xinyang HU ; Jeehoon KANG ; Jinlong ZHANG ; Jun JIANG ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Sung Gyun AHN ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Hyo-Soo KIM ; Seung-Jea TAHK ; JianAn WANG ; Tae-Jin LEE ; Bon-Kwon KOO ;
Korean Circulation Journal 2025;55(1):34-46
Background and Objectives:
The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea.
Methods:
A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D.
Results:
From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis.
Conclusions
Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.
6.Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial
Jung-Hee LEE ; Sung Gyun AHN ; Ho Sung JEON ; Jun-Won LEE ; Young Jin YOUN ; Jinlong ZHANG ; Xinyang HU ; Jian’an WANG ; Joo Myung LEE ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Myeong-Ho YOON ; Seung-Jea TAHK ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Doyeon HWANG ; Jeehoon KANG ; Hyo-Soo KIM ; Bon-Kwon KOO
Korean Circulation Journal 2024;54(8):485-496
Background and Objectives:
Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions.
Methods:
This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months.
Results:
The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCAFFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479).Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294).
Conclusions
The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months.
7.Inhibiting effect of epigallocatechin gallate(EGCG)on retinal oxidative damage in a rat model with dry age-related macular degeneration induced by sodium iodate
Peilin WU ; Lu WANG ; Jiaojiao JIANG ; Suqing LU ; Jianhui ZENG ; Xiaomin ZHANG ; Meiyuan QIU
Recent Advances in Ophthalmology 2024;44(11):863-867
Objective To investigate the inhibitory effect of epigallocatechin gallate(EGCG)on oxidative damage to the retina in a rat model of dry age-related macular degeneration(AMD)induced by sodium iodate.Methods A total of 36 male specific pathogen-free Sprague-Dawley rats were randomly divided into the blank control group,sodium iodate group and sodium iodate+EGCG group,with 12 rats in each group.Rats in the sodium iodate group and the sodium io-date+EGCG group were given 50 mg-kg·1 sodium iodate by tail vein injection by weight to build dry AMD models,while rats in the blank control group were administered with an equal volume of normal saline.Following the modeling proce-dure,rats in the sodium iodate+EGCG group received an intravitreal injection of 4 μL EGCG(0.5 g·L-1)into their right eyes,while the right eyes of rats in both the blank control and sodium iodate groups were treated with the same volume of normal saline.After 21 days,the rats were sacrificed,and ocular samples were collected for detection.Histopathological changes of the retinal tissues in each group were examined using hematoxylin and eosin(HE)staining.Additionally,the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)in the retinal tis-sues were quantified.Western blot analysis was conducted to assess the protein expression levels of nuclear factor ery-throid-2-related factor 2(Nrf2),NADPH quinone oxidoreductase 1(NQO1),and heme oxygenase-1(HO-1)in the retinas.Furthermore,real-time quantitative polymerase chain reaction was performed to evaluate the relative messenger ribonucleic acid(mRNA)expression levels of Nrf2,NQO1 and HO-1 in the retinas of the rats.Results HE staining revealed that,in comparison to the blank control group,the entire retinal layer in the sodium iodate group exhibited injury,characterized by noticeable injury of the retinal pigment epithelial cells and disordered outer nuclear layer with wavy transformation.The so-dium iodate+EGCG group demonstrated ameliorated retinal injury across all layers compared to the sodium iodate group.Compared to the blank control group,the levels of SOD and GSH-Px were significantly reduced(both P<0.01),while the level of MDA was significantly elevated(P<0.01)in the sodium iodate group.Compared with the sodium iodate group,the sodium iodate+EGCG group showed a significant increase in the levels of SOD and GSH-Px(both P<0.01),along-side a substantial decrease in the content of MDA(P<0.01).Western blot analyses demonstrated that compared with the blank control group,the protein expression levels of Nrf2,NQO1 and HO-1 were significantly elevated in the sodium iodate group(all P<0.01);compared with the sodium iodate group,the sodium iodate+EGCG group exhibited relatively higher protein expression levels of Nrf2,NQO1 and HO-1(all P<0.05).The results from real-time quantitative polymerase chain reaction indicated that the relative mRNA expression levels of Nrf2,NQO1 and HO-1 in the retinas of rats in the sodium io-date group were significantly greater than those in the blank control group(all P<0.05);compared with the sodium iodate group,the sodium iodate+EGCG group showed a significant increase in the relative mRNA expression levels of Nrf2,NQO1 and HO-1(all P<0.05).Conclusion EGCG can improve the capacity to scavenge oxygen free radicals by promo-ting the upregulation of Nrf2 expression.This activation subsequently enhances the expression of downstream products such as NQO1 and HO-1,leading to increased levels of SOD and GSH-Px while simultaneously reducing the MDA level.Consequently,this process inhibits oxidative damage to the retina in rats with dry AMD induced by sodium iodate.
8.Discordance Between Angiographic Assessment and Fractional Flow Reserve or Intravascular Ultrasound in Intermediate Coronary Lesions: A Post-hoc Analysis of the FLAVOUR Trial
Jung-Hee LEE ; Sung Gyun AHN ; Ho Sung JEON ; Jun-Won LEE ; Young Jin YOUN ; Jinlong ZHANG ; Xinyang HU ; Jian’an WANG ; Joo Myung LEE ; Joo-Yong HAHN ; Chang-Wook NAM ; Joon-Hyung DOH ; Bong-Ki LEE ; Weon KIM ; Jinyu HUANG ; Fan JIANG ; Hao ZHOU ; Peng CHEN ; Lijiang TANG ; Wenbing JIANG ; Xiaomin CHEN ; Wenming HE ; Myeong-Ho YOON ; Seung-Jea TAHK ; Ung KIM ; You-Jeong KI ; Eun-Seok SHIN ; Doyeon HWANG ; Jeehoon KANG ; Hyo-Soo KIM ; Bon-Kwon KOO
Korean Circulation Journal 2024;54(8):485-496
Background and Objectives:
Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions.
Methods:
This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months.
Results:
The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCAFFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479).Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294).
Conclusions
The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months.
9.Exploring the mechanism of acute liver injury induced by Cortex dictamni based on network pharmacology and in vivo experiments
Wenkai HU ; Xiaomin XU ; Xin JIANG ; Jiameixue WO ; Suxia JIA ; Shumin LIU ; Fang LU
China Pharmacist 2024;27(7):1089-1098
Objective To explore the mechanism of acute liver injury induced by Cortex dictamni through network pharmacology and in vivo experiment in animal.Methods The chemical constituents and targets of Cortex dictamni were retrieved from TCMSP,TCMIP and SwissTargetPrediction databases,and the related targets of liver injury diseases were identified through GeneCards and CTD databases.The protein interaction network of the intersection targets was analyzed by STRING database and the core targets were selected.The GO function and KEGG pathway enrichment analysis were completed by DAVID database,and the multi-level association network diagram of"drug-component-target"was constructed by Cytoscape software.In the animal study,Cortex dictamni was administered to mice at a dosage of 92.7 g/(kg·d)via intragastric administration,and the biological samples were collected after 7 days.The pathological changes of liver were observed by hematoxylin-eosin(HE),Masson and Oil Red O staining.The expression levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and lactate dehydrogenase(LDH)in serum,as well as malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin(IL)-1β in liver tissues,were quantified using enzyme-linked immunosorbent assay(ELISA).The expressions of protein kinase B1(AKT1),IL-6,TNF-α,tumor protein p53(TP53),cystatin 3(CASP3),and IL-1β mRNA in liver tissues were determined using real-time quantitative reverse transcription PCR(qRT-PCR).Molecular docking was employed to verify the binding affinity of potentially toxic components to their respective targets.Results A total of 14 chemical constituents,244 predicted targets and 202 intersection targets with liver injury were obtained.The GO biological process analysis mainly involved positive regulation of gene expression,negative regulation of apoptosis process.KEGG pathway enrichment analysis mainly included cancer pathway and PI3K-Akt,TNF,IL-17 signaling pathways.The pathological sections revealed severe hemorrhage,a considerable amount of hepatocyte necrosis,nuclear fragmentation or dissolution in the liver tissues of mouse with HE staining after the administration of Cortex dictamni.Masson staining showed evident fibrosis in the liver tissues,while Oil Red O staining indicated a substantial production of lipid droplets.Compared with the control group,the ELISA results demonstrated a significant increase in serum AST,ALT,ALP,LDH levels,as well as hepatic MDA,TNF-α,and IL-1β levels(P<0.05),and a decrease in hepatic SOD levels(P<0.05)in the treated group.The qRT-PCR results indicated a significant elevation in the expression levels of relevant mRNAs in the liver tissues of the treated mice(P<0.05).Molecular docking showed that the potentially toxic components of obacunone,dictamnine and fraxinellon had good binding affinity to AKT1,IL-6,TNF-α,TP53,CASP3 and IL-1β.Conclusion Obacunone,dictamnine,fraxinellon,and limonin might be the potential toxic components of acute liver injury induced by Cortex dictamni in mice.Cortex dictamni could act on the liver by changing the expressions of AKT1,IL-6,TNF-α,TP53,CASP3,IL-1β and other proteins,affecting energy metabolism,cell differentiation,inflammation,oxidative stress and immunity,leading to liver injury.
10.Research progress on chemical constituents,pharmacological effects and toxicity of Dictamni cortex
Wenkai HU ; Xiaomin XU ; Xin JIANG ; Jiameixue WO ; Suxia JIA ; Shumin LIU ; Fang LU
China Pharmacist 2024;28(10):252-267
Dictamni cortex is the root bark of Rutaceae plants.It is the main medicinal part and the key drug of 'Zhuhuang Fengbi'.It has the effects of clearing heat and detoxifying,dispelling wind and drying dampness,and relieving itching.Dictamni cortex mainly contains 228 chemical components such as alkaloids,sesquiterpenes,limonoids,fatty acids,volatile oils,flavonoids,steroids,etw.Its pharmacological activities in vivo and in vitro include antibacterial activity,anti-inflammatory activity,hepatoprotective activity,cardiovascular protection activity,insecticidal activity,anticancer activity,anti-allergic activity,and improvement of gastrointestinal activity.It has been reported that Dictamni cortex also has potential hepatotoxicity,among which dictamnine,fraxinellone and limonin compounds are potential hepatotoxic components.In this paper,the chemical constituents,pharmacological effects and toxicity of Dictamni cortex are reviewed by consulting domestic and foreign literature,to provide theoretical support for the clinical rational application and related product development of Dictamni cortex.


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