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| 1 | Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage显示文摘Ischemic stroke and ischemia/reperfusion(I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species(ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier(BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine(TCM)has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases.In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica,and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. | Kai Sun Jingyu Fan Jingyan Han | 2015 | Acta Pharmaceutica Sinica B2015，5，1： | 85 |
| 2 | HIF-1α pathway: role, regulation and intervention for cancer therapy显示文摘Hypoxia-inducible factor-1(HIF-1) has been recognized as an important cancer drug target.Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia(low O_2 levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway. | Georgina N.Masoud Wei Li | 2015 | Acta Pharmaceutica Sinica B2015，5，5： | 132 |
| 3 | Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes:current perspectives and future challenges显示文摘Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed. | Dinh Ha Ningning Yang Venkatareddy Nadithe | 2016 | Acta Pharmaceutica Sinica B2016，6，4： | 104 |
| 4 | The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb显示文摘Licorice is a common herb which has been used in traditional Chinese medicine for centuries.More than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. Recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral,antimicrobial, anti-inflammatory, antitumor and other activities. This paper provides a summary of the antiviral and antimicrobial activities of licorice. The active components and the possible mechanisms for these activities are summarized in detail. This review will be helpful for the further studies of licorice for its potential therapeutic effects as an antiviral or an antimicrobial agent. | Liqiang Wang Rui Yang Bochuan Yuan Ying Liu Chunsheng Liu | 2015 | Acta Pharmaceutica Sinica B2015，5，4： | 64 |
| 5 | Approaches to establish Q-markers for the quality standards of traditional Chinese medicines显示文摘Traditional Chinese medicine(TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic 'multicomponent and multitarget' feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine. However, TCM is investigated essentially as'herbal medicine' or 'natural product', and the pharmacopoeia quality monographs are actually chemicalmarkers-based, which can ensure the consistency only in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. A concept of 'quality marker'(Q-marker), following the 'property-effect-component' theory, is proposed. The establishment of Q-marker integrates multidisciplinary technologies like natural products chemistry, analytical chemistry, bionics, chemometrics,pharmacology, systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and multicomponent determination conduce to the construction of more scientific quality control system of TCM.This review delineates the background, definition, and properties of Q-marker, and the associated technologies applied for its establishment. Strategies and approaches for establishing Q-marker-based TCM quality control system are presented and highlighted with a few TCM examples. | Wenzhi Yang Yibei Zhang Wanying Wu Luqi Huang Dean Guo Changxiao Liu | 2017 | Acta Pharmaceutica Sinica B2017，7，4： | 51 |
| 6 | Bile acid nuclear receptor FXR and digestive system diseases显示文摘Bile acids(BAs) are not only digestive surfactants but also important cell signaling molecules,which stimulate several signaling pathways to regulate some important biological processes. The bileacid-activated nuclear receptor, farnesoid X receptor(FXR), plays a pivotal role in regulating bile acid,lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles ofFXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases. | Lili Ding Li Yang Zhengtao Wang Wendong Huang | 2015 | Acta Pharmaceutica Sinica B2015，5，2： | 47 |
| 7 | Discovery of direct inhibitors of Keap1–Nrf2 protein–protein interaction as potential therapeutic and preventive agents显示文摘The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1–Nrf2PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1's cysteine residues. The electrophilicity of these indirect inhibitors may cause 'off-target' side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1–Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1–Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions. | Dhulfiqar Ali Abed Melanie Goldstein Haifa Albanyan Huijuan Jin Longqin Hu | 2015 | Acta Pharmaceutica Sinica B2015，5，4： | 46 |
| 8 | Mechanisms of resistance to EGFR tyrosine kinase inhibitors显示文摘Since the discovery that non-small cell lung cancer(NSCLC) is driven by epidermal growth factor receptor(EGFR) mutations, the EGFR tyrosine kinase inhibitors(EGFR-TKIs, e.g., ge fi tinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation(T790M), activation of alternative pathways(c-Met, HGF, AXL), aberrance of the downstream pathways(K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway(BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette(ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies. | Lihua Huang Liwu Fu | 2015 | Acta Pharmaceutica Sinica B2015，5，5： | 42 |
| 9 | Cancer metastases: challenges and opportunities显示文摘Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been signi fi cantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs(predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment(such as extracellular matrix structure,growth factors, chemokines, matrix metalloproteinases) plays a signi fi cant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention. | Xiangming Guan | 2015 | Acta Pharmaceutica Sinica B2015，5，5： | 43 |
| 10 | Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways显示文摘Acute lung injury(ALI) or acute respiratory distress syndrome(ARDS) is a severe, lifethreatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide(trade name: Xi-Yan-Ping Injection), on lipopolysaccharide(LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid(BALF) and serum were reduced by andrographolide sulfonate administration. m RNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase(MAPK) as well as p65 subunit of nuclear factor-κB(NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders. | Shuang Peng Nan Hang Wen Liu Wenjie Guo Chunhong Jiang Xiaoling Yang Qiang Xu Yang Sun | 2016 | Acta Pharmaceutica Sinica B2016，6，3： | 38 |
| 11 | Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment显示文摘Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field. | Ruixiang Li Yuwei He Shuya Zhang Jing Qin Jianxin Wang | 2018 | Acta Pharmaceutica Sinica B2018，8，1： | 36 |
| 12 | Targeting ERK,an Achilles' Heel of the MAPK pathway,in cancer therapy显示文摘The mitogen-activated protein kinases(MAPK) pathway, often known as the RAS-RAFMEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors. However, the clinical benefits of these inhibitors are compromised by the frequently occurring acquired resistance due to cancer heterogeneity and genomic instability. This review briefly introduces the key protein kinases involved in this pathway as well as their activation mechanisms. We also generalize the correlations between mutations of MAPK members and human cancers, followed by a summarization of progress made on the development of small molecule MAPK kinases inhibitors. In particular, this review highlights the potential advantages of ERK inhibitors in overcoming resistance to upstream targets and proposes that targeting ERK kinase may hold a promising prospect for cancer therapy. | Feifei Liu Xiaotong Yang Meiyu Geng Min Huang | 2018 | Acta Pharmaceutica Sinica B2018，8，4： | 40 |
| 13 | Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes显示文摘The objective was to investigate the effect of kinsenoside(Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis(OA) progression.RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction(q RT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium(CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection(ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB(NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases(MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages,promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment. | Feng Zhou Jingtian Mei Xiuguo Han Hanjun Li Shengbing Yang Minqi Wang Linyang Chu Han Qiao Tingting Tang | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 35 |
| 14 | Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis显示文摘Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3 K/AKT in fibrotic processes is increasingly prominent, with PI3 K/AKT inhibitors currently under clinical evaluation in IPF. Therefore,PI3 K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3 K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3 K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future. | Jincheng Wang Kaili Hu Xuanyan Cai Bo Yang Qiaojun He Jiajia Wang Qinjie Weng | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 31 |
| 15 | Targeting calcium signaling in cancer therapy显示文摘The intracellular calcium ions(Ca^(2+)) act as second messenger to regulate gene transcription,cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca^(2+)homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis,progression and metastasis. Targeting derailed Ca^(2+)signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca^(2+)channels, transporters and Ca^(2+)-ATPases,which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca^(2+)channels/transporters or Ca^(2+)-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for researchinto the understanding of cellular mechanisms underlying the regulation of Ca^(2+)signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca^(2+)channels or transporters. | Chaochu Cui Robert Merritt Liwu Fu Zui Pan | 2017 | Acta Pharmaceutica Sinica B2017，7，1： | 32 |
| 16 | Mesoporous silica nanoparticles for drug and gene delivery显示文摘Mesoporous silica nanoparticles(MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume,selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly,the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted. | Yixian Zhou Guilan Quan Qiaoli Wu Xiaoxu Zhang Boyi Niua Biyuan Wu Ying Huang Xin Pan Chuanbin Wu | 2018 | Acta Pharmaceutica Sinica B2018，8，2： | 31 |
| 17 | Targeting the untargetable KRAS in cancer therapy显示文摘RAS is one of the most well-known proto-oncogenes. Its gain-of-function mutations occur in approximately 30% of all human cancers. As the most frequently mutated RAS isoform, KRAS is intensively studied in the past years. Despite its well-recognized importance in cancer malignancy,continuous efforts in the past three decades failed to develop approved therapies for KRAS mutant cancer. KRAS has thus long been considered to be undruggable. Encouragingly, recent studies have aroused renewed interest in the development of KRAS inhibitors either directly towards mutant KRAS or against the crucial steps required for KRAS activation. This review summarizes the most recent progress in the exploration of KRAS-targeted anticancer strategies and hopefully provides useful insights for the field. | Pingyu Liu Yijun Wang Xin Li | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 33 |
| 18 | Regulation of multidrug resistance by microRNAs in anti-cancer therapy显示文摘Multidrug resistance(MDR) remains a major clinical obstacle to successful cancer treatment.Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood.Micro RNAs(mi RNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression.Accumulating evidence shows that mi RNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of mi RNAs in regulating MDR in cancer treatment. | Xin An Cesar Sarmiento Tao Tan Hua Zhu | 2017 | Acta Pharmaceutica Sinica B2017，7，1： | 29 |
| 19 | Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters显示文摘Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster. | Lulu Sun Yuanyuan Pang Xuemei Wang Qing Wu Huiying Liu Bo Liu George Liu Min Ye Wei Kong Changtao Jiang | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 29 |
| 20 | Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed. | Danyu Du Chan Liu Mengyao Qin Xiao Zhang Tao Xi Shengtao Yuan Haiping Hao Jing Xiong | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 27 |
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