Chinese Medicine
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2025
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IF 5.7
Ruiyu Wu,Runping Liu,Ranyun Chen,Yijie Li,Xiaoyong Xue,Yinhao Zhang,Fanghong Li,Jiaorong Qu,Lingling Qin,Chen Wang,Xiaojiaoyang Li
Background Obesity is frequently linked to chronic systamic inflammation and presents significant challenges to public health. Aurantio-obtusin (AO) boosted the brown adipose tissue (BAT) thermogenesis in diet-induced obesity. However, the specific mechanisms by which injured mitochondria-related damage signals derived from overwhelmed BAT can transmit to liver and exacerbate metabolic disorders and whether AO can reverse this process remain unknown. Materials and methods After applying high-fat diet and glucose-fructose water (HFHS)-induced obesity mice, different BAT transplant procedures and primary BAT adipocytes, we investigated the anti-obesity effects and mechanism of AO through RNA sequencing and biology techniques. Results AO improved whole-body lipid accumulation, mitochondrial metabolism in BAT and hepatic inflammation in HFHS-induced obesity mice. Interscapular transplant of BAT-derived from obese donor mice triggered hepatic inflammation of chow diet-fed recipient mice, which was protected by AO. Furthermore, the transplantation of BAT-derived from AO-treated mice protected hepatic inflammation in obese mice. In vivo and in lipid-challenged primary BAT adipocytes, AO decreased kexin type 9 (PCSK9), prevented mPTP opening and mitochondrial DNA (mtDNA) release in extracellular vesicles (EVs) manner by inhibiting the acetylation of cyclophilin D associated with adenine nucleotide translocase, suppressing oligomerization of voltage-dependent anion channel 1 and activating mitophagy. Ultimately, AO inhibited mtDNA-containing EVs-induced cyclic GMP-AMP synthase/stimulator of interferon genes (STING) activation and hepatic inflammation, which was confirmed by Sting −/− mice. Conclusion AO not only improves thermogenesis and mitochondrial function of BAT but also prevents liver inflammation by repairing mitochondrial function and blocking the transfer of mtDNA from BAT to the liver. Graphic abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13020-025-01097-y.
研究领域:
医学
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分子生物学
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代谢研究
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2023
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IF 8.2
Li Yi-jie,Wu Rui-yu,Liu Run-ping,Wu Kai-yi,Ding Ming-ning,Sun Rong,Gu Yi-qing,Zhou Fei,Wu Jian-zhi,Zheng Qi,Duan Shu-ni,Li Rong-rong,Zhang Yin-hao,Li Fang-hong,Li Xiaojiaoyang
Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.
研究领域:
药理学
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代谢学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2026
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IF 3.6
Yilin Wang,Shenglai Zhou,Xiaopeng Yu,Junfeng Cui,Tengfei Wu
Emerging evidence suggests that triggering ferroptosis could be a promising approach for combating breast cancer. Here, we investigated the role of aurantio-obtusin (AO), a key bioactive compound sourced from Cassiae semen, in the treatment of breast cancer. Cell viability and death were determined via a CCK-8 assay and propidium iodide (PI) staining. Ferroptosis was determined by the levels of Fe2+, lipid ROS, and GSH. Autophagy was assessed by immunofluorescence staining. An MDA-MB-231 cell transplantation tumor model was established in vivo. AO inhibited breast cancer cell growth in a concentration-dependent manner while promoting cell death. Ferroptotic changes, including blockage of the GSH–GPX4 antioxidation system, massive iron release, and lipid ROS accumulation, were evident in AO-treated breast cancer cells. Antioxidant N -acetylcysteine (NAC) treatment markedly restored GSH content and suppressed lipid ROS overproduction to relieve AO-triggered ferroptosis. The introduction of the iron scavenger deferoxamine or the ferroptosis inhibitor ferrostatin-1 weakened AO-induced ferroptosis in breast cancer cells. Moreover, AO treatment promoted autophagosome formation in breast cancer cells via the mTOR-ULK1 pathway. AO-induced autophagy and ferroptosis were both reversed by Atg7 knockdown or mTOR activator MHY1485 treatment. Network pharmacology and molecular docking investigations suggested that EGFR was a potential target of AO in breast cancer and that its protein expression was suppressed by AO. Selective EGFR inhibitor gefitinib exacerbated AO-mediated ferroptosis and autophagy, while genetic overexpression of EGFR completely reversed these AO-mediated phenotypes. In vivo assays confirmed the antitumor effects of AO. Our study revealed that AO facilitated autophagy-dependent ferroptosis in breast cancer cells through the downregulation of EGFR. This work provides a new perspective on the antitumor activity of AO, which is valuable for further investigations of the practical application of AO in breast cancer.
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Zhou Fei,Ding Mingning,Gu Yiqing,Fan Guifang,Liu Chuanyang,Li Yijie,Sun Rong,Wu Jianzhi,Li Jianchao,Xue Xiaoyong,Li Hongjuan,Li Xiaojiaoyang
Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications.
研究领域:
药理学
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肝病学
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代谢疾病
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Xiang Chen,Mengting Li,Miaomiao Xia,Yumeng Yang,Rui Liu,Ling Ma,Mao Luo
Ethnopharmacological relevance Cassiae Semen, the dried seeds of Cassia obtusifolia L., has traditionally been used in East Asian medicine to manage metabolic disorders, including hyperglycemia and dyslipidemia. Aurantio-obtusin (AO), a bioactive anthraquinone compound, exhibits diverse pharmacological activities, derived from Cassiae Semen, a traditional herb used for metabolic disorders; however, its protective efficacy against prediabetes remains poorly understood. Aim of the study This study aimed to investigate the effects of AO on prediabetes and to elucidate the underlying mechanisms, with particular emphasis on gut microbiota-mediated regulation of metabolic homeostasis. Materials and methods Mice were subjected to prediabetes by a combination of a high-fat diet and streptozotocin. Metabolic parameters, liver function, oxidative stress, inflammatory responses, insulin signaling, and gut microbiota composition were assessed. Fecal microbiota transfer and models simulating antibiotic-induced germ-free conditions were utilized to investigate the function of gut microbiota. Results AO exhibited a marked improvement in glucose tolerance, lipid profiles, and insulin sensitivity among prediabetic mice. Furthermore, AO demonstrated a protective effect against liver damage, as suggested by the notable reductions in serum levels of alanine aminotransferase and aspartate aminotransferase. Oxidative stress was markedly suppressed, as indicated by decreased malondialdehyde levels, along with enhanced antioxidant defenses, including superoxide dismutase, catalase, and reduced glutathione. Additionally, AO preserved intestinal barrier integrity, reduced endotoxemia, and suppressed Toll-like receptor 4-mediated inflammatory signaling, accompanied by restoration of the PI3K/Akt/GLUT4 pathway. Notably, depletion of gut microbiota completely abolished the metabolic benefits of AO. Conclusion Collectively, this study substantiates the ethnomedical value of Cassiae Semen, demonstrating that AO improves prediabetes through the regulation of intestinal barrier function, oxidative stress, inflammation, and insulin signaling, which is dependent on gut microbiota.
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DOI
PubMed
高影响因子
Journal of Analytical Methods in Chemistry
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2021
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IF 2.193
Shi-han Qin,Yuan Xu,Kai-lin Li,Kai-yan Gong,Jie Peng,Si-lin Shi,Fang Yan,Wei Cai
Aurantio-obtusin (AO) is a major anthraquinone compound isolated from Cassiae Semen or Duhaldea nervosa, which possesses diverse pharmacological effects. Previous studies have shown that it has a good effect on lowering blood lipids and treating various diseases. A few studies have also reported about its metabolites. A rapid and reliable method using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry and multiple data-processing technologies was established to investigate the metabolites of AO in the plasma and various tissues of rats, including the heart, liver, spleen, lung, kidneys, and brain. Finally, a total of 36 metabolites were identified in the plasma of rats, which could be very beneficial for understanding the effective form of AO metabolites leading to new drug discovery. The result demonstrated that this strategy, especially parallel reaction monitoring, has shown a wide range of applications in the identification of metabolites.
研究领域:
药理学
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分析化学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）