Search Our Scientific Publications & Authors

Acta Pharmacol Sin 2020 Jun 2. Epub 2020 Jun 2.

Department of Pharmacology, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China.

Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood-brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which is derived from Herba Epimedii, attenuates cerebral I/R injury by inhibiting the GSK-3β-mediated activation of autophagy both in vitro and in vivo. However, the effect of ICS II on the BBB remains unclear. Read More

Acta Pharmacol Sin 2020 May 28. Epub 2020 May 28.

Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences Henan University, Kaifeng, 475004, China.

Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, their therapeutic success can be limited by the presence of the blood-brain barrier (BBB). Furthermore, unique immune functions within the CNS provide novel target mechanisms for the amelioration of CNS diseases. Read More

Acta Pharmacol Sin 2020 May 28. Epub 2020 May 28.

CStone Pharmaceuticals (Suzhou) Co., Ltd, Shanghai, 201203, China.

The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents. Read More

Acta Pharmacol Sin 2020 May 28. Epub 2020 May 28.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China.

Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Read More

Acta Pharmacol Sin 2020 May 28. Epub 2020 May 28.

Department of Pharmaceutics, Ghent University, Ghent, Belgium.

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Previous studies have shown that baicalin, an active ingredient of the Chinese traditional medicine Huangqin, attenuates LPS-induced inflammation by inhibiting the activation of TLR4/NF-κBp65 pathway, but how it affects this pathway is unknown. It has been shown that CD14 binds directly to LPS and plays an important role in sensitizing the cells to minute quantities of LPS via chaperoning LPS molecules to the TLR4/MD-2 signaling complex. In the present study we investigated the role of CD14 in the anti-inflammatory effects of baicalin in vitro and in vivo. Read More

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in functions of Langerhans cells and atopic dermatitis. In this study, we investigated the roles of S1P receptor type 2 (S1P) in a mouse model of atopic dermatitis, which was induced by topical application of 2,4-dinitrochlorobenzene (DNCB) on ventral skin on D0, followed by repeated DNCB challenge on both ears from D7 to D49. Wild-type mice with atopic dermatitis displayed severe inflammation and mast cell accumulation in ear tissues and elevated IgE levels in serum. Read More

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism, China Pharmaceutical University, Nanjing, 210009, China.

Programmed cell death (PCD), including apoptosis, apoptotic necrosis, and pyroptosis, is involved in various organ dysfunction syndromes. Recent studies have revealed that a substrate of caspase-3, gasdermin E (GSDME), functions as an effector for pyroptosis; however, few inhibitors have been reported to prevent pyroptosis mediated by GSDME. Here, we developed a class of GSDME-derived inhibitors containing the core structure of DMPD or DMLD. Read More

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Atherosclerosis (AS) is the main pathological cause of coronary heart disease (CHD). Current clinical interventions including statin drugs can effectively reduce acute myocardial infarction and stroke to some extent, but residual risk remains high. The current clinical treatment regimens are relatively effective for early atherosclerotic plaques and can even reverse their progression. Read More

Acta Pharmacol Sin 2020 May 26. Epub 2020 May 26.

Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Read More

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, 100050, China.

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, but there is no effective drug available for GBM. Avasimibe is a potent inhibitor of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1), which was used to treat atherosclerosis. Experimental evidence and bioinformatics have shown that avasimibe has anticancer activity. Read More

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

Department of Pharmacology and Biochemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China.

High infiltration of M2-polarized macrophages in the primary tumor indicates unfavorable prognosis and poor overall survival in the patients with triple-negative breast cancer (TNBC). Thus, reversing M2-polarized tumor-associated macrophages in the tumors has been considered as a potential therapeutic strategy for TNBC. Sphingomyelin synthase 2 (SMS2) is the key enzyme for sphingomyelin production, which plays an important role in plasma membrane integrity and function. Read More

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

Department of Chemistry, Washington State University, Pullman, WA, 99164, USA.

We have recently developed an enzyme-directed immunostimulant (EDI) prodrug motif, which is metabolized to active immunostimulant by cancer cells and, following drug efflux, activates nearby immune cells, resulting in immunogenicity. In this study, we synthesized several EDI prodrugs featuring an imidazoquinoline immunostimulant resiquimod (a Toll-like receptor 7/8 agonist) covalently modified with glycosidase enzyme-directing groups selected from substrates of β-glucuronidase, α-mannosidase, or β-galactosidase. We compared the glycosidase-dependent immunogenicity elicited by each EDI in RAW-Blue macrophages following conversion to active immunostimulant by complementary glycosidase. Read More

Acta Pharmacol Sin 2020 May 25. Epub 2020 May 25.

Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

The advent of immunotherapy is a game changer in cancer therapy with monoclonal antibody- and T cell-based therapeutics being the current flagships. Small molecule immunotherapeutics might offer advantages over the biological drugs in terms of complexity, tissue penetration, manufacturing cost, stability, and shelf life. However, small molecule drugs are prone to rapid systemic distribution, which might induce severe off-target side effects. Read More

Acta Pharmacol Sin 2020 May 18. Epub 2020 May 18.

Laboratory of Nano and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Cancer immunotherapy has received extensive attention due to its ability to activate the innate or adaptive immune systems of patients to combat tumors. Despite a few clinical successes, further endeavors are still needed to tackle unresolved issues, including limited response rates, development of resistance, and immune-related toxicities. Accumulating evidence has pinpointed the tumor microenvironment (TME) as one of the major obstacles in cancer immunotherapy due to its detrimental impacts on tumor-infiltrating immune cells. Read More

Acta Pharmacol Sin 2020 May 18. Epub 2020 May 18.

Department of Cardiology, Daping Hospital, Army Medical University, Chongqing, 400042, China.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. Read More

Acta Pharmacol Sin 2020 May 15. Epub 2020 May 15.

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.

Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Read More

Acta Pharmacol Sin 2020 May 13. Epub 2020 May 13.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

In general, anti-inflammatory treatment is considered for multiple liver diseases despite the etiology. But current drugs for alleviating liver inflammation have defects, making it necessary to develop more potent and safer drugs for liver injury. In this study, we screened a series of (dihydro-)stilbene or (dihydro-)phenanthrene derivatives extracted from Pholidota chinensis for their potential biological activities. Read More

Acta Pharmacol Sin 2020 May 13. Epub 2020 May 13.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Hsp90 is a potential therapeutic target for tumor, as it maintains the stability of a variety of proteins related to tumor development and progression. Autophagy is a self-degradation process to maintain cellular homeostasis and autophagy inhibitors can suppress tumor growth. In this study, we identified DCZ5248, a triazine derivative, was a dual inhibitor of both Hsp90 and late-autophagy with potent antitumor activity against colon cancer cells in vitro and in vivo. Read More

Acta Pharmacol Sin 2020 May 13. Epub 2020 May 13.

Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of non-small cell lung cancer (NSCLC). HKB99 is a novel allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1) that preferentially suppresses cell proliferation and induces more apoptosis in acquired erlotinib-resistant HCC827ER cells compared with its parental HCC827 cells. In this study we identified the molecular biomarkers for HKB99 response in erlotinib-resistant HCC827ER cells. Read More

Acta Pharmacol Sin 2020 May 12. Epub 2020 May 12.

High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.

Glioblastoma (GBM) patients have extremely poor prognoses, and currently no effective treatment available including surgery, radiation, and chemotherapy. MAPK-interacting kinases (MNK1/2) as the downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells. Research has shown that targeting MNKs may be an effective strategy to treat GBM. Read More

Acta Pharmacol Sin 2020 May 12. Epub 2020 May 12.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Dipeptidyl peptidase 4 (DPP4), a ubiquitously expressed protease that cleaves off the N-terminal dipeptide from proline and alanine on the penultimate position, has important roles in many physiological processes. In the present study, experimental colitis was induced in mice receiving 3% dextran sulfate sodium (DSS) in drinking water. We found that mice with DSS-induced colitis had significantly increased intestinal DPP activity and decreased serum DPP activity, suggesting a probable correlation of DPP4 with experimental colitis. Read More

Acta Pharmacol Sin 2020 May 12. Epub 2020 May 12.

Institute of Pediatrics of Children's Hospital and Biomedical Science, Fudan University, Shanghai, 200032, China.

Cancer immunotherapy is rapidly changing the paradigm of cancer care and treatment by evoking host immunity to kill cancer cells. As clinical approval of checkpoint inhibitors (e.g. Read More

Acta Pharmacol Sin 2020 May 11. Epub 2020 May 11.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1-10 μM) concentration-dependently prevented HO-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Read More

Acta Pharmacol Sin 2020 May 4. Epub 2020 May 4.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capacity. After pulsing with cancer antigens in various ways, the matured DCs are administrated back into the patient. Read More

Acta Pharmacol Sin 2020 Apr 30. Epub 2020 Apr 30.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610064, China.

Cancer immunotherapy, with an aim to enhance host immune responses, has been recognized as a promising therapeutic treatment for cancer. A diversity of immunomodulatory agents, including tumor-associated antigens, adjuvants, cytokines and immunomodulators, has been explored for their ability to induce a cascading adaptive immune response. Nanoscale metal-organic frameworks (nMOFs), a class of crystalline-shaped nanomaterials formed by the self-assembly of organic ligands and metal nodes, are attractive for cancer immunotherapy because they feature tunable pore size, high surface area and loading capacity, and intrinsic biodegradability. Read More

Acta Pharmacol Sin 2020 Apr 27. Epub 2020 Apr 27.

The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China.

SUMOylation is one of the posttranslational modifications that mediate cellular activities such as transcription, DNA repair, and signal transduction and is involved in the cell cycle. However, only a limited number of small molecule inhibitors have been identified to study its role in cellular processes. Here, we report a Förster resonance energy transfer (FRET) high-throughput screening assay based on the interaction between E2 Ubc9 and E3 PIAS1. Read More

Acta Pharmacol Sin 2020 Apr 27. Epub 2020 Apr 27.

Center of Drug Metabolism and Pharmacokinetics, College of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.

Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Read More

Acta Pharmacol Sin 2020 Apr 27. Epub 2020 Apr 27.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.

Mechanisms of cardiomyopathy caused by obesity/hyperlipidemia are complicated. Obesity is usually associated with chronic low-grade inflammation and may lead to the onset and progression of myocardial fibrosis and remodeling. TLR4/MyD88 signaling pathway, as a key regulator of inflammation, plays an important role in the pathogenesis of obesity-induced cardiomyopathy. Read More

Acta Pharmacol Sin 2020 Apr 23. Epub 2020 Apr 23.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering Research, Shanghai, 200011, China.

Keloid is a benign skin tumor characterized by its cell hyperproliferative activity, invasion into normal skin, uncontrolled growth, overproduction and deposition of extracellular matrices and high recurrence rate after various therapies. Nintedanib is a receptor tyrosine kinase inhibitor targeting VEGF, PDGF, FGF, and TGF-β receptors with proved efficacy in anti-angiogenesis and in treating various types of cancers. In this study, we investigated the effects of nintedanib on keloid fibroblasts in both in vitro and ex vivo models. Read More

Acta Pharmacol Sin 2020 Apr 21. Epub 2020 Apr 21.

Department of Emergency, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

In patients with sepsis, lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria triggers cardiac dysfunction and heart failure, but target therapy for septic cardiomyopathy remains unavailable. In this study we evaluated the beneficial effects of cardamonin (CAR), a flavone existing in Alpinia plant, on endotoxemia-induced cardiac dysfunction and the underlying mechanisms with focus on oxidative stress and apoptosis. Adult mice were exposed to LPS (4 mg/kg, i. Read More

Acta Pharmacol Sin 2020 Apr 21. Epub 2020 Apr 21.

Key Laboratory of Drug Research & Centre of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Current cancer immunotherapy has limited response rates in a large variety of solid tumors partly due to the low immunogenicity of the tumor cells and the immunosuppressive tumor microenvironment (ITM). A number of clinical cancer treatment modalities, including radiotherapy, chemotherapy, photothermal and photodynamic therapy, have been shown to elicit immunogenicity by inducing immunogenic cell death (ICD). However, ICD-based immunotherapy is restricted by the ITM limiting its efficacy in eliciting a long-term antitumor immune response, and by severe systemic toxicity. Read More

Acta Pharmacol Sin 2020 Apr 16. Epub 2020 Apr 16.

Department of Nephrology, Yanbian University Hospital, Yanji, 133000, China.

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and HO-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7. Read More

Acta Pharmacol Sin 2020 Apr 16. Epub 2020 Apr 16.

Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, 266021, China.

Sorafenib is currently the standard chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC). But its efficacy requires improvement, it is imperative to seek therapeutic strategies that combine sorafenib with other anticancer agents. In this study we investigated the synergistic anticancer effect of combining sorafenib and artesunate, an anti-malaria drug derivative, against HCC in vitro and in vivo. Read More

Acta Pharmacol Sin 2020 Apr 13. Epub 2020 Apr 13.

Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Louisville, KY, 40202, USA.

Cadmium (Cd) is an important environmental pollutant and long-term Cd exposure is closely related to autoimmune diseases, cancer, cardiovascular diseases (CVD), and hepatic dysfunction. Zinc (Zn) is an essential metal that plays key roles in protein structure, catalysis, and regulation of their function. Numerous studies have shown that Zn can reduce Cd toxicity; however, the underlying mechanisms have not been extensively explored. Read More

Acta Pharmacol Sin 2020 Apr 7. Epub 2020 Apr 7.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China.

Sirtuin 6 (SIRT6) has been reported to play a key role in cognitive function and mood regulation, yet its role in mood disorders is not completely understood. Here, we confirmed that knockdown of hippocampal SIRT6 alleviated depression-like behaviors induced by chronic unpredictable stress (CUS) in mice. Our in vitro data showed that SIRT6 negatively regulated protein kinase B (AKT) signaling by deacetylating histone 3 at Lys9 and Lys56. Read More

Acta Pharmacol Sin 2020 Apr 7. Epub 2020 Apr 7.

Department of Pharmacology, Second Military Medical University / Naval Medical University, Shanghai, 200433, China.

Dyslipidemia is a risk factor for cardiovascular diseases and type 2 diabetes. Several adipokines play important roles in modulation of blood lipids. Metrnl is a recently identified adipokine, and adipose Metrnl participates in regulation of blood triglyceride (TG). Read More

Acta Pharmacol Sin 2020 Apr 2. Epub 2020 Apr 2.

Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, Albuquerque, NM, 87108, USA.

Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. Read More

Acta Pharmacol Sin 2020 Apr 1. Epub 2020 Apr 1.

Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Wnt/β-catenin signaling in Dox-induced cardiotoxicity. Read More

Acta Pharmacol Sin 2020 Apr 1. Epub 2020 Apr 1.

Pharmaceutical College, Dalian Medical University, Dalian, 116044, China.

Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg · d, ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. Read More

Acta Pharmacol Sin 2020 Mar 31. Epub 2020 Mar 31.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China.

Alflutinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) inhibitor that inhibits both EGFR-sensitive mutations and T790M mutations. Previous study has shown that after multiple dosages, alflutinib exhibits nonlinear pharmacokinetics and displays a time- and dose-dependent increase in the apparent clearance, probably due to its self-induction of cytochrome P450 (CYP) enzyme. In this study, we investigated the CYP isozymes involved in the metabolism of alflutinib and evaluated the enzyme inhibition and induction potential of alflutinib and its metabolites. Read More

Acta Pharmacol Sin 2020 Mar 31. Epub 2020 Mar 31.

The National Center for Drug Screening and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China.

Relaxin/insulin-like family peptide receptor 4 (RXFP4) is a class A G protein-coupled receptor (GPCR), and insulin-like peptide 5 (INSL5) is its endogenous ligand. Although the precise physiological role of INSL5/RXFP4 remains elusive, a number of studies have suggested it to be a potential therapeutic target for obesity and other metabolic disorders. Since selective agonists of RXFP4 are scarcely available and peptidic analogs of INSL5 are hard to make, we conducted a high-throughput screening campaign against 52,000 synthetic and natural compounds targeting RXFP4. Read More

Acta Pharmacol Sin 2020 Mar 24. Epub 2020 Mar 24.

The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Mitophagy is a degradative pathway that mediates the degradation of the entire mitochondria, and defects in this process are implicated in many diseases including cancer. In mammals, mitophagy is mediated by BNIP3L (also known as NIX) that is a dual regulator of mitochondrial turnover and programmed cell death pathways. Acute myeloid leukemia (AML) cells with deficiency of BNIP3L are more sensitive to mitochondria-targeting drugs. Read More

Acta Pharmacol Sin 2020 Mar 19. Epub 2020 Mar 19.

Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in PINP. Because the nuclear factor erythroid-2-related factor 2 (Nrf2) has been considered as the critical regulator of endogenous antioxidant defense, we here explored whether activation of Nrf2 could attenuate PINP. Read More

Acta Pharmacol Sin 2020 Mar 18. Epub 2020 Mar 18.

Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha, 410208, China.

The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Read More

Acta Pharmacol Sin 2020 Apr 18;41(4):523-534. Epub 2020 Mar 18.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Ginsenoside Rg1 is one of the most active ingredients in ginseng, which has been reported to protect dopaminergic neurons and improve behavioral defects in MPTP model, 6-OHDA model and rotenone model. However, it is unclear whether Rg1 exerted neuroprotection in LPS-induced sub-acute PD model. In this study, we investigated the neuroprotective effect of Rg1 in the sub-acute PD mouse model and explored the related mechanisms. Read More

Acta Pharmacol Sin 2020 Mar 18. Epub 2020 Mar 18.

Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin, 150086, China.

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. Read More

Acta Pharmacol Sin 2020 Mar 18. Epub 2020 Mar 18.

Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Ji-nan, 250000, China.

Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr). Read More

Acta Pharmacol Sin 2020 Mar 18. Epub 2020 Mar 18.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

Various lipids and lipid metabolites are bound to and modify the proteins in eukaryotic cells, which are known as 'protein lipidation'. There are four major types of the protein lipidation, i.e. Read More