Article
Pharmacology & Pharmacy
Tobias Laue, Ulrich Baumann
Summary: Systemic reduction of bile acids with the aim of preventing inflammation, and thus liver remodeling, is a novel, promising, therapeutic concept. However, early diagnosis and treatment of BA should still be emphasized to minimize liver remodeling before medical intervention can be initiated. IBAT inhibitors may offer additional medical options in limiting disease progression in BA.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Microbiology
Masahiro Matsui, Shinya Fukunishi, Takashi Nakano, Takaaki Ueno, Kazuhide Higuchi, Akira Asai
Summary: In this study, the effects of an IBATi on NAFLD were investigated by modulating the gut microbiota in mice. Treatment with IBATi significantly improved NAFLD in HFD mice, and fecal microbiome transplantation from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. These findings suggest a potential therapeutic strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.
Article
Gastroenterology & Hepatology
Ryo Yamauchi, Hidetoshi Takedatsu, Keiji Yokoyama, Eri Yamauchi, Motoko Kawashima, Takahiro Nagata, Yotaro Uchida, Takanori Kitaguchi, Tomotaka Higashi, Hiromi Fukuda, Naoaki Tsuchiya, Kazuhide Takata, Takashi Tanaka, Daisuke Morihara, Yasuaki Takeyama, Satoshi Shakado, Shotaro Sakisaka, Fumihito Hirai
Summary: The results of the study indicated that elobixibat can improve NASH-related histopathology, reduce cytokine expression, and normalize the intestinal microbial composition in MCD-fed mice.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
Qiaoling Wang, Huibin Lin, Chongrong Shen, Minchun Zhang, Xingyu Wang, Miaomiao Yuan, Mingyang Yuan, Sheng Jia, Zhiwen Cao, Chao Wu, Banru Chen, Aibo Gao, Yufang Bi, Guang Ning, Weiqing Wang, Jiqiu Wang, Ruixin Liu
Summary: The gut microbiota regulates the release of postprandial GLP-1 through microbial metabolites, highlighting the essential interaction between gut microbiota and host in maintaining intestinal function and health.
Article
Chemistry, Medicinal
Meng-ying Chen, Qin Wang, Zhao-jun Meng, Wei-jie Men, Ju-yang Huang, Bin Yu, Kun Zhou
Summary: In this study, it was found that psoralen treatment induced liver injury in mice, especially in male mice. Further analysis showed that psoralen disrupted the balance of bile acid metabolism by inhibiting the expression of efflux transporter, leading to liver damage.
PHYTOTHERAPY RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Qiong Pan, Guanyu Zhu, Ziqian Xu, Jinfei Zhu, Jiafeng Ouyang, Yao Tong, Nan Zhao, Xiaoxun Zhang, Ying Cheng, Liangjun Zhang, Ya Tan, Jianwei Li, Chengcheng Zhang, Wensheng Chen, Shi-Ying Cai, James L. Boyer, Jin Chai
Summary: OATP1B3 is a significant transporter for hepatic bile acid uptake and can partially compensate for the uptake of conjugated bile acids by the NatHorn/taurocholate cotransporter. Downregulation of hepatic OATP1B3 is an adaptive protective response against cholestasis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Pharmacology & Pharmacy
Satoko Yoshinobu, Nao Hasuzawa, Ayako Nagayama, Shimpei Iwata, Junichi Yasuda, Rie Tokubuchi, Masaharu Kabashima, Mizuki Gobaru, Kento Hara, Kenta Murotani, Yoshinori Moriyama, Kenji Ashida, Masatoshi Nomura
Summary: This study assessed the metabolic effects of elobixibat in patients with type 2 diabetes mellitus (T2DM)-related constipation. The results showed that elobixibat treatment improved glucose metabolism, lowered serum LDL-C and AA levels, and alleviated constipation symptoms.
CLINICAL THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Masaaki Miyata, Tomoyuki Tanaka, Kazuho Takahashi, Akihiro Funaki, Yoshimasa Sugiura
Summary: Research using animal models has shown that taurine can reduce cholesterol levels, possibly by altering bile acid composition and reducing ileal FXR signaling. This study explored the mechanisms underlying the cholesterol-lowering effect of taurine in mice, revealing its potential role in modulating FXR signaling and bile acid composition to lower cholesterol levels.
Article
Biochemistry & Molecular Biology
Hana Lastuvkova, Fatemeh Alaei Faradonbeh, Jolana Schreiberova, Milos Hroch, Jaroslav Mokry, Hana Faistova, Zuzana Nova, Radomir Hyspler, Ivone Cristina Igreja Sa, Petr Nachtigal, Alzbeta Stefela, Petr Pavek, Stanislav Micuda
Summary: Atorvastatin modulates bile acid metabolomics significantly by altering their intestinal processing and liver synthesis in control and NASH mice, improving liver conditions and reducing steatosis and inflammation in NASH animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Petar D. Petrov, Polina Soluyanova, Sonia Sanchez-Campos, Jose Castell, Ramiro Jover
Summary: Treatment of beta-lactamase positive bacterial infections with amoxicillin and clavulanic acid combination can cause idiosyncratic drug-induced liver injury in patients, particularly leading to intrahepatic cholestasis. Clavulanic acid, in particular, downregulates key biliary transporters by modulating NRF2 and FXR signaling pathways, potentially exacerbating intrahepatic cholestasis along with increased ROS production and GSH depletion.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Review
Gastroenterology & Hepatology
Frans Stellaard, Dieter Luetjohann
Summary: Regulation of bile acid metabolism involves maintaining a constant pool size through synthesis to compensate for intestinal loss. Bile acids cycle through the enterohepatic circulation after meals, with processes involving feedback inhibition of synthesis. A biphasic diurnal expression pattern of bile acid synthesis has been observed in humans, but details of synthesis inhibition and activation mechanisms remain unknown.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bhargavi Nallamothu, Kaushik Kuche, Rohan Ghadi, Dasharath Chaudhari, Sanyog Jain
Summary: This study examines the impact of charge and chain length of bile salts in bilosomes on the oral bioavailability of insulin and verifies the results by examining their uptake via ASBT. The results indicate that anionic bilosomes are more efficiently taken up by ASBT than cationic bilosomes, thereby improving the oral bioavailability of insulin in bilosomes. Additionally, the developed bilosomes are able to provide superior protection in biological fluids while maintaining the integrity of the loaded drug.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Pharmacology & Pharmacy
Chunlin Li, Siyu Yu, Xiaoxiao Li, Ying Cao, Meng Li, Guang Ji, Li Zhang
Summary: The HZRG formula has been shown to alleviate non-alcoholic steatohepatitis (NASH) by improving hepatic steatosis, reducing inflammation, and modulating the bile acid profile and gut dysbiosis. It enhances fecal bile acid excretion by inhibiting bile acid transporters, and improves the intestinal environment through the modulation of tight junction proteins.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Feiyang Deng, Kyoung Sub Kim, Jiyoung Moon, You Han Bae
Summary: Bile acid-modified nanoparticles can improve oral bioavailability of poorly permeable drugs by interacting with bile acid transporters. This study investigates the transport of glycocholic acid (GCA)-conjugated polystyrene nanoparticles (GCPNs) in Caco-2 cell models and identifies a new pathway correlated with both apical sodium-dependent bile acid transporter (ASBT) and chylomicron pathways. The study also reveals that the higher uptake of GCPNs does not result in higher transcytosis compared to unmodified nanoparticles (CPNs). Pharmacological and genomics analysis indicate that GCA conjugation alters endocytosis mechanisms and downregulates cellular response, leading to higher cellular retention of GCPNs.
Article
Health Care Sciences & Services
Henriette Kreimeyer, Katharina Vogt, Tobias Goetze, Jan Best, Oliver Goetze, Jochen Weigt, Alisan Kahraman, Mustafa Oezcueruemez, Julia Kaelsch, Wing-Kin Syn, Svenja Sydor, Ali Canbay, Paul Manka
Summary: The prevalence of NAFLD and NASH is increasing globally, but there is currently no approved medical treatment. This study found that interfering with bile acid metabolism through UDCA treatment can improve liver function in NASH patients with elevated GGT, especially in those with bile acid gene polymorphisms. However, there was no difference in fibrosis or clinical outcomes using non-invasive tests.
JOURNAL OF PERSONALIZED MEDICINE
(2023)