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| 1 | Schisandra sphenanthera extract(Wuzhi Tablet)protects against chronic-binge and acute alcohol-induced liver injury by regulating the NRF2-ARE pathway in mice显示文摘Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available.Wuzhi Tablet(WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepatoprotective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ andthe target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway. | Xuezhen Zeng Xi Li Chenshu Xu Fulin Jiang Yufei Mo Xiaomei Fan Yaoting Li Yiming Jiang Dongshun Li Min Huang Huichang Bi | 2017 | Acta Pharmaceutica Sinica B2017，7，5： | 13 |
| 2 | Lipidomics reveals carnitine palmitoyltransferase 1C protects cancer cells from lipotoxicity and senescence显示文摘Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C(CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene m RNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence. | Huizhen Zhang Yongtao Wang Lihuan Guan Yixin Chen Panpan Chen Jiahong Sun Frank J.Gonzalez Min Huang Huichang Bi | 2021 | Journal of Pharmaceutical Analysis2021，11，3： | 3 |
| 3 | Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially via yes-associated protein activation显示文摘The constitutive androstane receptor(CAR, NR3 I1) belongs to nuclear receptor superfamily.It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein(YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration.TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wildtype(WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy(PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice.Hepatocytes enlargement around central vein(CV) area was observed, meanwhile hepatocytesproliferation was promoted as evidenced by the increased number of KI67+cells around portal vein(PV)area. The protein levels of YAP and its downstream targets were upregulated in TCPOBOP-treated mice and YAP translocation can be induced by CAR activation. Co-immunoprecipitation results suggested a potential proteineprotein interaction of CAR and YAP. However, CAR activation-induced hepatomegaly can still be observed in liver-specific YAP-deficient(Yape/e) mice. In summary, CAR activation promotes hepatomegaly and liver regeneration partially by inducing YAP translocation and interaction with YAP signaling pathway, which provides new insights to further understand the physiological functions of CAR. | Yue Gao Shicheng Fan Hua Li Yiming Jiang Xinpeng Yao Shuguang Zhu Xiao Yang Ruimin Wang Jianing Tian Frank JGonzalez Min Huang Huichang Bi | 2021 | Acta Pharmaceutica Sinica B2021，11，3： | 2 |
| 4 | Effects of flavonoids derived from Taxus yunnanensis on p-glycoprotein and cytochrome P450 3A4显示文摘The intestinal uptake of paclitaxel is hampered by trans-membrane efflux transporters such as P-glycoprotein(P-gp),and paclitaxel is mainly metabolized by cytochrome P4503A4(CYP3A4)presented in the liver.Our previous results demonstrated that flavonoids extracted from Taxus yunnanensis could improve the oral absorption of paclitaxel.The current study was purposed to investigate the effects of the flavonoid extracts on P-gp and CYP3A4 in vitro.The expression and activity of P-gp were detected by western blotting and intracellular rhodamine 123 accumulation assay in Caco-2 cells treated with the flavonoids extract.The expression of CYP3A4 was investigated by western blotting in mouse primary hepatocytes and the activity of CYP3A4 was detected by LC-MS/MS method using rat liver microsomes.Our results showed that the flavonoid extracts from T.yunnanensis could inhibit P-gp activity and concurrently decrease the expression and activity of CYP3A4.In conclusion,activity of P-gp and CYP3A4 could be inhibited by flavonoids extracted from T.yunnanensis which might be potential candidates for development of oral formulation of paclitaxel. | Jifu Li Dake Cai Huichang Bi Jing Jin Min Huang | 2013 | Asian Journal of Pharmaceutical Sciences2013，8，3： | 2 |
| 5 | YAP regulates the liver size during the fasting-refeeding transition in mice显示文摘Liver is the central hub regulating energy metabolism during feeding-fasting transition.Evidence suggests that fasting and refeeding induce dynamic changes in liver size,but the underlying mechanisms remain unclear.Yes-associated protein(YAP)is a key regulator of organ size.This study aims to explore the role of YAP in fasting-and refeeding-induced changes in liver size.Here,fasting significantly reduced liver size,which was recovered to the normal level after refeeding.Moreover,hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting.Conversely,refeeding promoted hepatocyte enlargement and proliferation compared to fasted state.Mechanistically,fasting or refeeding regulated the expression of YAP and its downstream targets,as well as the proliferation-related protein cyclin D1(CCND1).Furthermore,fasting significantly reduced the liver size in AAV-control mice,which was mitigated in AAV Yap(5SA)mice.Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation.Besides,the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice.Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation.In summary,this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition,which provides new evidence for YAP in regulating liver size under energy stress. | Xuan Li Shicheng Fan Chenghui Cai Yue Gao Xinhui Wang Yifei Zhang Hangfei Liang Huilin Li Jie Yang Min Huang Huichang Bi | 2023 | Acta Pharmaceutica Sinica B2023，13，4： | 1 |
| 6 | Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation显示文摘 | Yiming Jiang Xiaomei Fan Ying Wang Huasen Tan Pan Chen Hang Zeng Min Huang Huichang Bi | 2015 | Chemico-Biological Interactions2015，，： | 1 |
| 7 | Small molecule-based immunomodulators for cancer therapy显示文摘Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized. | Yinrong Wu Zichao Yang Kui Cheng Huichang Bi Jianjun Chen | 2022 | Acta Pharmaceutica Sinica B2022，12，12： | 1 |
| 8 | Simultaneous determination of metformin and gliclazide in human plasma by liquid chromatography - tandem mass spectrometry : application to a bioequivalence study of two formulations in healthy volunteers显示文摘 | ZHONG Guoping BI Huichang ZHOU Shufeng | 2005 | Journal of Mass Spectrometer2005，40，11： | 1 |
| 9 | Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats显示文摘 | Deng Ying Bi Huichang Huang Min | 2008 | Xenobiotica2008，38，5： | 1 |
| 10 | Induction of Cytochrome P450 3A by the Ginkgo biloha Extract and Bilobalides in Human and Rat Primary Hepatocyte显示文摘 | Deng Ying Bi Huichang Huang Min | 2008 | Drug Metab Letters2008，2，： | 1 |
| 11 | Potential herb-drug interactions between anti-COVID-19 drugs and traditional Chinese medicine显示文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide.Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence,hospitalization,and mortality.At present,antiviral drugs including Nirmatrelvir/Ritonavir(Paxlovid^(TM)),Remdesivir,and Molnupiravir have been authorized to treat COVID-19 and become more globally available.On the other hand,traditional Chinese medicine(TCM)has been used for the treatment of epidemic diseases for a long history.Currently,various TCM formulae against COVID-19 such as Qingfei Paidu decoction,Xuanfei Baidu granule,Huashi Baidu granule,Jinhua Qinggan granule,Lianhua Qingwen capsule,and Xuebijing injection have been widely used in clinical practice in China,which may cause potential herb-drug interactions(HDIs)in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines.However,information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking,and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19,and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters.These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects. | Ling Ye Shicheng Fan Pengfei Zhao Chenghua Wu Menghua Liu Shuang Hu Peng Wang Hongyu Wang Huichang Bi | 2023 | Acta Pharmaceutica Sinica B2023，13，9： | 1 |
| 12 | Malignant transformation by oncogenic K-ras requires IDH2-mediated reductive carboxylation to promote glutamine utilization显示文摘Dear Editor,Oncogenic K-ras mutation plays a major role in malignant transformation and induces significant alterations in cancer cell metabolism[1–4].However,the major molecular players mediating metabolic alterations during K-ras-driven cancer development remain elusive.The observations that tumorigenesis often requires multiple hits suggest that K-ras mutation likely needs the coordination of other molecular events that enable adaptive cellular metabolism for a full malignant transformation.Based on our previous study on the impact of K-ras onmitochondrial metabolism[1,5]and our recent findings that mitochondrial isocitrate dehydrogenase 2(IDH2)could promote the“reverse”flow of the tricarboxylic acid(TCA)cycle fromα-KG to isocitrate and enhance the survival and proliferation of acute myeloid leukemia cells[6],we investigated the potential role of IDH2 in metabolic adaptation during K-ras-driven tumorigenesis. | Rui Liu Panpan Liu Huichang Bi Jianhua Ling Huiqin Zhang Mingquan Zhang Yumin Hu Paul J Chiao Peng Huang Jinyun Liu | 2023 | Cancer Communications2023，43，2： | 0 |
| 13 | Nuclear receptors and non-alcoholic fatty liver disease:An update显示文摘Non-alcoholic fatty liver disease(NAFLD)has become the leading cause of chronic liver disease in adults and children worldwide.The symptoms of NAFLD range from simple steatosis and non-alcoholic stea-tohepatitis(NASH)to hepatic fibrosis or cirrhosis,even ultimately develops to hepatocellular carcinoma.Nuclear receptors(NRs)are a superfamily of ligand-activated transcription factors,most of which are ligand-activated that control cellular homeostasis in the liver and other tissues.A growing number of studies demonstrated the important role of NRs in NAFLD.In this review,the current findings on the role of NRs in NAFLD are summarized and future perspectives to target NRs for NAFLD are discussed. | Xiao Yang Frank J.Gonzalez Min Huang Huichang Bi | 2020 | Liver Research2020，4，2： | 0 |
| 14 | Use of recombinant microRNAs as antimetabolites to inhibit human non-small cell lung cancer显示文摘During the development of therapeutic microRNAs(miRNAs or miRs),it is essential to define their pharmacological actions.Rather,miRNA research and therapy mainly use miRNA mimics synthesized in vitro.After experimental screening of unique recombinant miRNAs produced in vivo,three lead antiproliferative miRNAs against human NSCLC cells,miR-22-3p,miR-9-5p,and miR-218-5p,were revealed to target folate metabolism by bioinformatic analyses.Recombinant miR-22-3p,miR-9-5p,and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells.Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs,inhibition of glucose uptake by miR-22-3p,and reduction of serine biosynthesis from glucose by miR-9-5p and-218-5p in NSCLC cells.With greater activities to interrupt NSCLC cell respiration,glycolysis,and colony formation than miR-9-5p and-218-5p,recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity.These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine,which shall provide insight into developing antimetabolite RNA therapies. | Yixin Chen Mei-Juan Tu Fangwei Han Zhenzhen Liu Neelu Batra Primo N.Lara Hong-Wu Chen Huichang Bi Ai-Ming Yu | 2023 | Acta Pharmaceutica Sinica B2023，13，10： | 0 |
| 15 | Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies显示文摘Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders. | Xiaopeng Peng Zhihao Hu Limei Zeng Meizhu Zhang Congcong Xu Benyan Lu Chengpeng Tao Weiming Chen Wen Hou Kui Cheng Huichang Bi Wanyi Pan Jianjun Chen | 2024 | Acta Pharmaceutica Sinica B2024，14，2： | 0 |
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