Archives of Pharmacal Research最新文献

{"title":"Osteogenic effect of an adiponectin-derived short peptide that rebalances bone remodeling: a potential disease-modifying approach for postmenopausal osteoporosis therapy","authors":"Swati Rajput,&nbsp;Chirag Kulkarni,&nbsp;Shivani Sharma,&nbsp;Manendra Singh Tomar,&nbsp;Shamima Khatoon,&nbsp;Arvind Gupta,&nbsp;Sabyasachi Sanyal,&nbsp;Ashutosh Shrivastava,&nbsp;Jimut Kanti Ghosh,&nbsp;Naibedya Chattopadhyay","doi":"10.1007/s12272-024-01509-x","DOIUrl":"10.1007/s12272-024-01509-x","url":null,"abstract":"<div><p>Adiponectin, an adipokine, regulates metabolic processes, including glucose flux, lipid breakdown, and insulin response, by activating adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). We have previously shown that globular adiponectin (gAd), an endogenous form of adiponectin, has osteoanabolic and anti-catabolic effects in rodent models of postmenopausal osteopenia. Moreover, we reported the identification of a 13-mer peptide (ADP-1) from the collagen domain of adiponectin, which exhibited significant adiponectin-mimetic properties. Since the clinical development of gAd is constrained by its large size, here, we investigated the osteogenic property of ADP-1. ADP-1 induced osteoblast differentiation more potently than gAd. ADP-1 elicited osteoblast differentiation through two downstream pathways that involved the participation of adiponectin receptors. Firstly, it enhanced mitochondrial biogenesis and OxPhos, leading to osteoblast differentiation. Secondly, it activated the Akt-glycogen synthase kinase 3β-Wnt pathway, thereby increasing osteoblast differentiation. Additionally, ADP-1 suppressed the production of receptor–activator of nuclear kappa B ligand from osteoblasts, enabling it to act as a dual-action molecule (suppressing osteoclast function besides promoting osteoblast function). In osteopenic ovariectomized rats, ADP-1 increased bone mass and strength and improved trabecular integrity by stimulating bone formation and inhibiting bone resorption. Furthermore, by increasing ATP-producing intermediates within the tricarboxylic acid cycle in bones, ADP-1 likely fueled osteoblast function. Given its dual-action mechanism and high potency, ADP-1 offers a unique opportunity to address the unmet clinical need to reset the aberrant bone remodeling in osteoporosis to normalcy, potentially offering a disease-modifying impact.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 8-9","pages":"736 - 755"},"PeriodicalIF":6.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E3 ubiquitin ligase RNF180 mediates the ALKBH5/SMARCA5 axis to promote colon inflammation and Th17/Treg imbalance in ulcerative colitis mice","authors":"Kailing Wang,&nbsp;Fan Liu,&nbsp;Budumu Muchu,&nbsp;Jiawen Deng,&nbsp;Jing Peng,&nbsp;Yan Xu,&nbsp;Fujun Li,&nbsp;Miao Ouyang","doi":"10.1007/s12272-024-01507-z","DOIUrl":"10.1007/s12272-024-01507-z","url":null,"abstract":"<div><p>SMARCA5, a protein in the SWI/SNF family, has been previously implicated in the development of ulcerative colitis (UC) through methylation. However, the specific molecular mechanisms by which SMARCA5 contributes to colonic inflammation and the imbalance between Th17 and Treg cells remain unclear. This study was designed to explore these molecular mechanisms. A UC mouse model was established using dextran sulfate sodium induction, followed by measurements of mouse weight, disease activity index (DAI) score, colon length, pathological changes in the colon, and FITC-dextran concentration. The levels of IL-17a, IFN-γ, IL-6, TNF-α, TGF-β, and IL-10 were measured, along with the protein expression of ZO-1 and Occludin. Flow cytometry was used to assess the presence of IL-17 + CD4 + (Th17 +) cells and FOXP3 + CD25 + CD4 + (Treg +) cells in the spleen and mesenteric lymph nodes of UC mice. We observed that SMARCA5 and RNF180 were increased, while ALKBH5 was downregulated in UC mouse colon tissue. SMARCA5 or RNF180 knockdown or ALKBH5 overexpression ameliorated the colon inflammation and Th17/Treg cell imbalance in UC mice, shown by increased body weight, colon length, FOXP3 + CD25 + CD4 + T cells, and the levels of ZO-1, Occludin, TGF-β, IL-10, and FOXP3. It decreased DAI scores, IL-17 + CD4 + T cells, and levels of IL-17a, IFN-γ, IL-6, TNF-α, and ROR-γt. ALKBH5 inhibited SMARCA5 expression via m6A modification, while RNF180 reduced ALKBH5 expression via ubiquitination. Our findings indicate that RNF180 aggravated the colon inflammation and Th17/Treg cell imbalance in UC mice by regulating the ALKBH5/SMARCA5 axis.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 7","pages":"645 - 658"},"PeriodicalIF":6.9,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor activity of Polygonatum sibiricum polysaccharides","authors":"Weiwei Lai,&nbsp;Qian Ning,&nbsp;Guihua Wang,&nbsp;Yuan Gao,&nbsp;Shuxian Liao,&nbsp;Shengsong Tang","doi":"10.1007/s12272-024-01511-3","DOIUrl":"10.1007/s12272-024-01511-3","url":null,"abstract":"<div><p>Cancer is a global public health problem. Natural polysaccharides have been shown to enhance the effectiveness of cancer treatments. <i>Polygonatum sibiricum</i> (PS) has been used for millennia to treat diverse diseases. PS comprises numerous active constituents, including saponins, peptides, volatile oils, polysaccharides, and lectins. Many studies have highlighted the crucial role of polysaccharides in PS. Modern studies have shown that <i>Polygonatum sibiricum</i> polysaccharide (PSP) exhibits diverse pharmacological activities, including immunomodulatory, antitumor, antioxidant, and anti-aging effects. However, further study of the antitumor mechanisms is difficult because the activities of PSP are closely associated with its complex structural features and the different molecular weights of its components. Therefore, this review focuses on the research background and the extraction and purification of PSP. Studies related to the mechanism of the antitumor effects of PSP constituents of different molecular weights are also summarized, and perspectives on PSP research are presented.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 8-9","pages":"696 - 708"},"PeriodicalIF":6.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pentacyclic triterpenes, potential novel therapeutic approaches for cardiovascular diseases","authors":"Dewei Peng,&nbsp;Aizan Wang,&nbsp;Wei Shi,&nbsp;Li Lin","doi":"10.1007/s12272-024-01510-4","DOIUrl":"10.1007/s12272-024-01510-4","url":null,"abstract":"<div><p>Cardiovascular diseases (CVDs) involve dysfunction of the heart and blood vessels and have become major health concerns worldwide. Multiple mechanisms may be involved in the occurrence and development of CVDs. Although therapies for CVDs are constantly being developed and applied, the incidence and mortality of CVDs remain high. The roles of natural compounds in CVD treatment are being explored, providing new approaches for the treatment of CVD. Pentacyclic triterpenes are natural compounds with a basic nucleus of 30 carbon atoms, and they have been widely studied for their potential applications in the treatment of CVDs, to which various pharmacological activities contribute, including anti-inflammatory, antioxidant, and antitumor effects. This review introduces the roles of triterpenoids in the prevention and treatment of CVDs, summarizes their potential underlying mechanisms, and provides a comprehensive overview of the therapeutic potential of triterpenoids in the management of CVDs.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 8-9","pages":"709 - 735"},"PeriodicalIF":6.9,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-phycocyanin reinforces autophagy to block pulmonary fibrogenesis by inhibiting lncIAPF biogenesis","authors":"Wenjie Hu,&nbsp;Yujie Wang,&nbsp;Huiling Yang,&nbsp;Leiming Zhang,&nbsp;Bo Liu,&nbsp;Yunxia Ji,&nbsp;Xiaodong Song,&nbsp;Changjun Lv,&nbsp;Songzi Zhang","doi":"10.1007/s12272-024-01508-y","DOIUrl":"10.1007/s12272-024-01508-y","url":null,"abstract":"<div><p>Pulmonary fibrosis is a chronic and irreversible progressive lung disease caused by various factors, such as age and environmental pollution. With countries stepping into an aging society and the seriousness of environmental pollution caused by global industrialization, the incidence of pulmonary fibrosis is annually increasing. However, no effective drug is available for pulmonary fibrosis treatment. C-phycocyanin (C-PC), extracted from blue-green algae, has good water solubility and antioxidation. This study elucidated that C-PC reinforces autophagy to block pulmonary fibrogenesis by inhibiting long noncoding RNA (lncRNA) biogenesis in vivo and in vitro. Cleavage under targets and release using nuclease (CUT &amp; RUN)-PCR, co-immunoprecipitation (Co-IP), and nuclear–cytoplasmic separation experiments clarified that C-PC blocked the nuclear translocation of activating transcription factor 3 (ATF3) to prevent the binding between ATF3 and transcription factor Smad3, thereby hindering lncIAPF transcription. Human antigen R (HuR) truncation experiment and RNA binding protein immunoprecipitation (RIP) were then performed to identify the binding domain with lncIAPF in the 244–322 aa of HuR. lncIAPF exerted its profibrogenic function through the binding protein HuR, a negative regulator of autophagy. In summary, C-PC promoted autophagy via down-regulating the lncIAPF–HuR-mediated signal pathway to alleviate pulmonary fibrosis, showing its potential as a drug for treating pulmonary fibrosis. Exploring how C-PC interacts with biological molecules will help us understand the mechanism of this drug and provide valuable target genes to design new drugs.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 7","pages":"659 - 674"},"PeriodicalIF":6.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual roles of myeloid-derived suppressor cells in various diseases: a review","authors":"Mahesh Raj Nepal,&nbsp;Sajita Shah,&nbsp;Kyu-Tae Kang","doi":"10.1007/s12272-024-01504-2","DOIUrl":"10.1007/s12272-024-01504-2","url":null,"abstract":"<div><p>Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that originate from bone marrow stem cells. In pathological conditions, such as autoimmune disorders, allergies, infections, and cancer, normal myelopoiesis is altered to facilitate the formation of MDSCs. MDSCs were first shown to promote cancer initiation and progression by immunosuppression with the assistance of various chemokines and cytokines. Recently, various studies have demonstrated that MDSCs play two distinct roles depending on the physiological and pathological conditions. MDSCs have protective roles in autoimmune disorders (such as uveoretinitis, multiple sclerosis, rheumatoid arthritis, ankylosing spondylitis, type 1 diabetes, autoimmune hepatitis, inflammatory bowel disease, alopecia areata, and systemic lupus erythematosus), allergies, and organ transplantation. However, they play negative roles in infections and various cancers. Several immunosuppressive functions and mechanisms of MDSCs have been determined in different disease conditions. This review comprehensively discusses the associations between MDSCs and various pathological conditions and briefly describes therapeutic approaches.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 7","pages":"597 - 616"},"PeriodicalIF":6.9,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of inflammatory cell death-PANoptosis in health and disease","authors":"Hyun Bae,&nbsp;Yeonseo Jang,&nbsp;Rajendra Karki,&nbsp;Joo-Hui Han","doi":"10.1007/s12272-024-01506-0","DOIUrl":"10.1007/s12272-024-01506-0","url":null,"abstract":"<div><p>Regulated cell death (RCD) pathways, such as pyroptosis, apoptosis, and necroptosis, are essential for maintaining the body’s balance, defending against pathogens, and eliminating abnormal cells that could lead to diseases like cancer. Although these pathways operate through distinct mechanisms, recent genetic and pharmacological studies have shown that they can interact and influence each other. The concept of “PANoptosis” has emerged, highlighting the interplay between pyroptosis, apoptosis, and necroptosis, especially during cellular responses to infections. This article provides a concise overview of PANoptosis and its molecular mechanisms, exploring its implications in various diseases. The review focuses on the extensive interactions among different RCD pathways, emphasizing the role of PANoptosis in infections, cytokine storms, inflammatory diseases, and cancer. Understanding PANoptosis is crucial for developing novel treatments for conditions involving infections, sterile inflammations, and cancer.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 7","pages":"617 - 631"},"PeriodicalIF":6.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroartemisinin inhibits follicular helper T and B cells: implications for systemic lupus erythematosus treatment","authors":"Xiaoyi Shi,&nbsp;Tao Liao,&nbsp;Ye Chen,&nbsp;Jingrong Chen,&nbsp;Yan Liu,&nbsp;Jun Zhao,&nbsp;Junlong Dang,&nbsp;Qipeng Sun,&nbsp;Yunfeng Pan","doi":"10.1007/s12272-024-01505-1","DOIUrl":"10.1007/s12272-024-01505-1","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis mainly involves the aberrant activation of B cells through follicular helper T (Tfh) cells to produce pathogenic antibodies, which requires more effective and safe treatment methods. Dihydroartemisinin (DHA) is the main active ingredient of artemisinin and has immunosuppressive effects. In this study, in vitro experiments confirmed that DHA inhibited Tfh cell induction and weakened its auxiliary function in B cell differentiation; furthermore, DHA directly inhibited B cell activation, differentiation, and antibody production. Furthermore, a mouse model of SLE was established, and we confirmed that DHA significantly reduced the symptoms of SLE and lupus nephritis, and decreased serum immunoglobulin (Ig)G, IgM, IgA, and anti-dsDNA levels. Moreover, DHA reduced the frequencies of total Tfh cells, activated Tfh cells, and B cell lymphoma 6, and interleukin (IL)-21 levels in Tfh cells from the spleen and lymph nodes, as well as the levels of B cells, germinal center B cells, and plasma cells in the spleen, lymph nodes, and kidneys. Additionally, DHA inhibited Tfh cells by blocking IL-2-inducible T cell kinase (ITK) signaling and its downstream nuclear factor (NF)-κB, nuclear factor of activated T cell, and activating protein-1 pathways, and directly inhibited B cells by blocking Bruton’s tyrosine kinase (BTK) signaling and the downstream NF-κB and Myc pathways. Overall, our results demonstrated that DHA inhibited Tfh cells by blocking ITK signaling and also directly inhibited B cells by blocking BTK signaling. Therefore, reducing the production of pathogenic antibodies might effectively treat SLE.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 7","pages":"632 - 644"},"PeriodicalIF":6.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities","authors":"Ritwik Maiti,&nbsp;Bhumika Patel,&nbsp;Nrupesh Patel,&nbsp;Mehul Patel,&nbsp;Alkesh Patel,&nbsp;Nirav Dhanesha","doi":"10.1007/s12272-024-01502-4","DOIUrl":"10.1007/s12272-024-01502-4","url":null,"abstract":"","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 7","pages":"675 - 675"},"PeriodicalIF":6.9,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and opportunities of developing small-molecule therapies for age-related macular degeneration","authors":"Xiang Fei,&nbsp;Sooyun Jung,&nbsp;Sangil Kwon,&nbsp;Jiweon Kim,&nbsp;Timothy W. Corson,&nbsp;Seung-Yong Seo","doi":"10.1007/s12272-024-01503-3","DOIUrl":"10.1007/s12272-024-01503-3","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is the leading cause of vision loss in senior adults. The disease can be categorized into two types: wet AMD and dry AMD. Wet AMD, also known as exudative or neovascular AMD, is less common but more severe than dry AMD and is responsible for 90% of the visual impairment caused by AMD and affects 20 million people worldwide. Current treatment options mainly involve biologics that inhibit the vascular endothelial growth factor or complement pathways. However, these treatments have limitations such as high cost, injection-related risks, and limited efficacy. Therefore, new therapeutic targets and strategies have been explored to improve the outcomes of patients with AMD. A promising approach is the use of small-molecule drugs that modulate different factors involved in AMD pathogenesis, such as tyrosine kinases and integrins. Small-molecule drugs offer advantages, such as oral administration, low cost, good penetration, and increased specificity for the treatment of wet and dry AMD. This review summarizes the current status and prospects of small-molecule drugs for the treatment of wet AMD. These advances are expected to support the development of effective and targeted treatments for patients with AMD.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 6","pages":"538 - 557"},"PeriodicalIF":6.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}