Pharmacology & Therapeutics最新文献

{"title":"Mechanistic insights into medulloblastoma relapse","authors":"Kendell Peterson ,&nbsp;Maria Turos-Cabal ,&nbsp;April D. Salvador ,&nbsp;Isabel Palomo-Caturla ,&nbsp;Ashley J. Howell ,&nbsp;Megan E. Vieira ,&nbsp;Sean M. Greiner ,&nbsp;Thibaut Barnoud ,&nbsp;Jezabel Rodriguez-Blanco","doi":"10.1016/j.pharmthera.2024.108673","DOIUrl":"10.1016/j.pharmthera.2024.108673","url":null,"abstract":"<div><p>Pediatric brain tumors are the leading cause of cancer-related deaths in children, with medulloblastoma (MB) being the most common type. A better understanding of these malignancies has led to their classification into four major molecular subgroups. This classification not only facilitates the stratification of clinical trials, but also the development of more effective therapies. Despite recent progress, approximately 30% of children diagnosed with MB experience tumor relapse. Recurrent disease in MB is often metastatic and responds poorly to current therapies. As a result, only a small subset of patients with recurrent MB survive beyond one year. Due to its dismal prognosis, novel therapeutic strategies aimed at preventing or managing recurrent disease are urgently needed. In this review, we summarize recent advances in our understanding of the molecular mechanisms behind treatment failure in MB, as well as those characterizing recurrent cases. We also propose avenues for how these findings can be used to better inform personalized medicine approaches for the treatment of newly diagnosed and recurrent MB. Lastly, we discuss the treatments currently being evaluated for MB patients, with special emphasis on those targeting MB by subgroup at diagnosis and relapse.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"260 ","pages":"Article 108673"},"PeriodicalIF":12.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725824000937/pdfft?md5=4beb186973f7f1f12b001d2538e954b9&pid=1-s2.0-S0163725824000937-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mithramycin and its analogs: Molecular features and antitumor action","authors":"José Portugal","doi":"10.1016/j.pharmthera.2024.108672","DOIUrl":"10.1016/j.pharmthera.2024.108672","url":null,"abstract":"<div><p>The antitumor antibiotic mithramycin A (MTA) binds to G/C-rich DNA sequences in the presence of dications. MTA inhibits transcription regulated by the Sp1 transcription factor, often enhanced during tumor development. It shows antitumor activity, but its clinical use was discontinued due to toxic side effects. However, recent observations have led to its use being reconsidered. The MTA biosynthetic pathways have been modified to produce mithramycin analogs (mithralogs) that encompass lower toxicity and improved pharmacological activity. Some mithralogs reduce gene expression in human ovarian and prostate tumors, among other types of cancer. They down-regulate gene expression in various cellular processes, including Sp1-responsive genes that control tumor development. Moreover, MTA and several mithralogs, such as EC-8042 (DIG-MSK) and EC-8105, effectively treat Ewing sarcoma by inhibiting transcription controlled by the oncogenic EWS-FLI1 transcription factor.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"260 ","pages":"Article 108672"},"PeriodicalIF":13.5,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the reciprocal regulation of m6A modification with non-coding RNAs and its therapeutic application in acute myeloid leukemia","authors":"Jiawang Yang ,&nbsp;Feng Liang ,&nbsp;Fenglin Zhang ,&nbsp;Hailong Zhao ,&nbsp;Qihai Gong ,&nbsp;Ning Gao","doi":"10.1016/j.pharmthera.2024.108671","DOIUrl":"10.1016/j.pharmthera.2024.108671","url":null,"abstract":"<div><p>N⁶-methyladenosine (m⁶A) is one of the most common modifications of RNA in eukaryotic cells and is involved in mRNA metabolism, including stability, translation, maturation, splicing, and export. m⁶A also participates in the modification of multiple types of non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, thereby affecting their metabolism and functions. Increasing evidence has revealed that m⁶A regulators, such as writers, erasers, and readers, perform m⁶A-dependent modification of ncRNAs, thus affecting cancer progression. Moreover, ncRNAs modulate m⁶A regulators to affect cancer development and progression. In this review, we summarize recent advances in understanding m⁶A modification and ncRNAs and provide insights into the interaction between m⁶A modification and ncRNAs in cancer. We also discuss the potential clinical applications of the mechanisms underlying the interplay between m⁶A modifications and ncRNAs in acute myeloid leukemia (AML). Therefore, clarifying the mutual regulation between m⁶A modifications and ncRNAs is of great significance to identify novel therapeutic targets for AML and has great clinical application prospects.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108671"},"PeriodicalIF":13.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercellular pathways of cancer treatment-related cardiotoxicity and their therapeutic implications: the paradigm of radiotherapy","authors":"Stella Logotheti ,&nbsp;Athanasia Pavlopoulou ,&nbsp;Hamid Khoshfekr Rudsari ,&nbsp;Anne-Marie Galow ,&nbsp;Yağmur Kafalı ,&nbsp;Efthymios Kyrodimos ,&nbsp;Aris I. Giotakis ,&nbsp;Stephan Marquardt ,&nbsp;Anastasia Velalopoulou ,&nbsp;Ioannis I. Verginadis ,&nbsp;Constantinos Koumenis ,&nbsp;Thorsten Stiewe ,&nbsp;Jerome Zoidakis ,&nbsp;Ilangko Balasingham ,&nbsp;Robert David ,&nbsp;Alexandros G. Georgakilas","doi":"10.1016/j.pharmthera.2024.108670","DOIUrl":"10.1016/j.pharmthera.2024.108670","url":null,"abstract":"<div><p>Advances in cancer therapeutics have improved patient survival rates. However, cancer survivors may suffer from adverse events either at the time of therapy or later in life. Cardiovascular diseases (CVD) represent a clinically important, but mechanistically understudied complication, which interfere with the continuation of best-possible care, induce life-threatening risks, and/or lead to long-term morbidity. These concerns are exacerbated by the fact that targeted therapies and immunotherapies are frequently combined with radiotherapy, which induces durable inflammatory and immunogenic responses, thereby providing a fertile ground for the development of CVDs. Stressed and dying irradiated cells produce ‘danger’ signals including, but not limited to, major histocompatibility complexes, cell-adhesion molecules, proinflammatory cytokines, and damage-associated molecular patterns. These factors activate intercellular signaling pathways which have potentially detrimental effects on the heart tissue homeostasis. Herein, we present the clinical crosstalk between cancer and heart diseases, describe how it is potentiated by cancer therapies, and highlight the multifactorial nature of the underlying mechanisms. We particularly focus on radiotherapy, as a case known to often induce cardiovascular complications even decades after treatment. We provide evidence that the secretome of irradiated tumors entails factors that exert systemic, remote effects on the cardiac tissue, potentially predisposing it to CVDs. We suggest how diverse disciplines can utilize pertinent state-of-the-art methods in feasible experimental workflows, to shed light on the molecular mechanisms of radiotherapy-related cardiotoxicity at the organismal level and untangle the desirable immunogenic properties of cancer therapies from their detrimental effects on heart tissue. Results of such highly collaborative efforts hold promise to be translated to next-generation regimens that maximize tumor control, minimize cardiovascular complications, and support quality of life in cancer survivors.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"260 ","pages":"Article 108670"},"PeriodicalIF":12.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The endocrine FGFs axis: A systemic anti-fibrotic response that could prevent pulmonary fibrogenesis?","authors":"Mada Ghanem ,&nbsp;Gabrielle Archer ,&nbsp;Bruno Crestani ,&nbsp;Arnaud A. Mailleux","doi":"10.1016/j.pharmthera.2024.108669","DOIUrl":"10.1016/j.pharmthera.2024.108669","url":null,"abstract":"<div><p>Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which therapeutic options are limited, with an unmet need to identify new therapeutic targets. IPF is thought to be the consequence of repeated microlesions of the alveolar epithelium, leading to aberrant epithelial-mesenchymal communication and the accumulation of extracellular matrix proteins. The reactivation of developmental pathways, such as Fibroblast Growth Factors (FGFs), is a well-described mechanism during lung fibrogenesis. Secreted FGFs with local paracrine effects can either exert an anti-fibrotic or a pro-fibrotic action during this pathological process through their FGF receptors (FGFRs) and heparan sulfate residues as co-receptors. Among FGFs, endocrine FGFs (FGF29, FGF21, and FGF23) play a central role in the control of metabolism and tissue homeostasis. They are characterized by a low affinity for heparan sulfate, present in the cell vicinity, allowing them to have endocrine activity. Nevertheless, their interaction with FGFRs requires the presence of mandatory co-receptors, alpha and beta Klotho proteins (KLA and KLB). Endocrine FGFs are of growing interest for their anti-fibrotic action during liver, kidney, or myocardial fibrosis. Innovative therapies based on FGF19 or FGF21 analogs are currently being studied in humans during liver fibrosis. Recent data report a similar anti-fibrotic action of endocrine FGFs in the lung, suggesting a systemic regulation of the pulmonary fibrotic process. In this review, we summarize the current knowledge on the protective effect of endocrine FGFs during the fibrotic processes, with a focus on pulmonary fibrosis.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108669"},"PeriodicalIF":13.5,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725824000895/pdfft?md5=2fa70f5ca438378a85096562c85402d7&pid=1-s2.0-S0163725824000895-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological mechanisms of botulinum neurotoxin-induced analgesia for neuropathic pain","authors":"Ana Bagues ,&nbsp;Jiaxin Hu ,&nbsp;Ishraq Alshanqiti ,&nbsp;Man-Kyo Chung","doi":"10.1016/j.pharmthera.2024.108668","DOIUrl":"10.1016/j.pharmthera.2024.108668","url":null,"abstract":"<div><p>Botulinum neurotoxins (BoNTs) are a family of neurotoxins produced by <em>Clostridia</em> and other bacteria that induce botulism. BoNTs are internalized into nerve terminals at the site of injection and cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins to inhibit the vesicular release of neurotransmitters. BoNTs have been approved for multiple therapeutic applications, including the treatment of migraines. They have also shown efficacies for treating neuropathic pain, such as diabetic neuropathy, and postherpetic and trigeminal neuralgia. However, the mechanisms underlying BoNT-induced analgesia are not well understood. Peripherally administered BoNT is taken up by the nerve terminals and reduces the release of glutamate, calcitonin gene-related peptide, and substance P, which decreases neurogenic inflammation in the periphery. BoNT is retrogradely transported to sensory ganglia and central terminals in a microtubule-dependent manner. BoNTs decrease the expression of pronociceptive genes (ion channels or cytokines) from sensory ganglia and the release of neurotransmitters and neuropeptides from primary afferent central terminals, which likely leads to decreased central sensitization in the dorsal horn of the spinal cord or trigeminal nucleus. BoNT-induced analgesia is abolished after capsaicin-induced denervation of transient receptor potential vanilloid 1 (TRPV1)-expressing afferents or the knockout of substance P or the neurokinin-1 receptor. Although peripheral administration of BoNT leads to changes in the central nervous system (e.g., decreased phosphorylation of glutamate receptors in second-order neurons, reduced activation of microglia, contralateral localization, and cortical reorganization), whether such changes are secondary to changes in primary afferents or directly mediated by trans-synaptic, transcytotic, or the hematogenous transport of BoNT is controversial. To enhance their therapeutic potential, BoNTs engineered for specific targeting of nociceptive pathways have been developed to treat chronic pain. Further mechanistic studies on BoNT-induced analgesia can enhance the application of native or engineered BoNTs for neuropathic pain treatment with improved safety and efficacy.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108668"},"PeriodicalIF":13.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered cancer metabolism and implications for next-generation CAR T-cell therapies","authors":"Rishab Ramapriyan ,&nbsp;Vivasvan S. Vykunta ,&nbsp;Gust Vandecandelaere ,&nbsp;Leland G.K. Richardson ,&nbsp;Jing Sun ,&nbsp;William T. Curry ,&nbsp;Bryan D. Choi","doi":"10.1016/j.pharmthera.2024.108667","DOIUrl":"10.1016/j.pharmthera.2024.108667","url":null,"abstract":"<div><p>This review critically examines the evolving landscape of chimeric antigen receptor (CAR) T-cell therapy in treating solid tumors, with a particular focus on the metabolic challenges within the tumor microenvironment. CAR T-cell therapy has demonstrated remarkable success in hematologic malignancies, yet its efficacy in solid tumors remains limited. A significant barrier is the hostile milieu of the tumor microenvironment, which impairs CAR T-cell survival and function. This review delves into the metabolic adaptations of cancer cells and their impact on immune cells, highlighting the competition for nutrients and the accumulation of immunosuppressive metabolites. It also explores emerging strategies to enhance CAR T-cell metabolic fitness and persistence, including genetic engineering and metabolic reprogramming. An integrated approach, combining metabolic interventions with CAR T-cell therapy, has the potential to overcome these constraints and improve therapeutic outcomes in solid tumors.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108667"},"PeriodicalIF":13.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141029508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDH2 polymorphism and myocardial infarction: From alcohol metabolism to redox regulation","authors":"Reece J. Lamb ,&nbsp;Kayleigh Griffiths ,&nbsp;Gregory Y.H. Lip ,&nbsp;Vitaly Sorokin ,&nbsp;Michael P. Frenneaux ,&nbsp;Martin Feelisch ,&nbsp;Melanie Madhani","doi":"10.1016/j.pharmthera.2024.108666","DOIUrl":"10.1016/j.pharmthera.2024.108666","url":null,"abstract":"<div><p>Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation of reactive oxygen species (ROS) during the early reperfusion phase is thought to trigger lipid peroxidation and disrupt redox homeostasis, leading to myocardial injury. Whilst the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) is chiefly recognised for its central role in ethanol metabolism, substantial experimental evidence suggests an additional cardioprotective role for ALDH2 independent of alcohol intake, which mitigates myocardial injury by detoxifying breakdown products of lipid peroxidation including the reactive aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Epidemiological evidence suggests that an ALDH2 mutant variant with reduced activity that is highly prevalent in the East Asian population increases AMI risk. Additional studies have uncovered a strong association between coronary heart disease and this ALDH2 mutant variant. It appears this enzyme polymorphism (in particular, in ALDH2*2/2 carriers) has the potential to have wide-ranging effects on thiol reactivity, redox tone and therefore numerous redox-related signaling processes, resilience of the heart to cope with lifestyle-related and environmental stressors, and the ability of the whole body to achieve redox balance. In this review, we summarize the journey of ALDH2 from a mitochondrial reductase linked to alcohol metabolism, <em>via</em> pre-clinical studies aimed at stimulating ALDH2 activity to reduce myocardial injury to clinical evidence for its protective role in the heart.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108666"},"PeriodicalIF":13.5,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016372582400086X/pdfft?md5=d1ecdcb6f90f4a15f49b7d911fd0e346&pid=1-s2.0-S016372582400086X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141036078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric analysis of research progress on tetramethylpyrazine and its effects on ischemia-reperfusion injury","authors":"Mingzhu Qi,&nbsp;Xiaohui Su,&nbsp;Zhuohang Li,&nbsp;Helan Huang,&nbsp;Jingbo Wang,&nbsp;Na Lin,&nbsp;Xiangying Kong","doi":"10.1016/j.pharmthera.2024.108656","DOIUrl":"10.1016/j.pharmthera.2024.108656","url":null,"abstract":"<div><p>In recent decades, natural products have attracted worldwide attention and become one of the most important resources for pharmacological industries and medical sciences to identify novel drug candidates for disease treatment. Tetramethylpyrazine (TMP) is an alkaloid extracted from <em>Ligusticum chuanxiong Hort.</em>, which has shown great therapeutic potential in cardiovascular and cerebrovascular diseases, liver and renal injury, as well as cancer. In this review, we analyzed 1270 papers published on the Web of Science Core Collection from 2002 to 2022 and found that TMP exerted significant protective effects on ischemia-reperfusion (I/R) injury that is the cause of pathological damages in a variety of conditions, such as ischemic stroke, myocardial infarction, acute kidney injury, and liver transplantation. TMP is limited in clinical applications to some extent due to its rapid metabolism, a short biological half-life and poor bioavailability. Obviously, the structural modification, administration methods and dosage forms of TMP need to be further investigated in order to improve its bioavailability. This review summarizes the clinical applications of TMP, elucidates its potential mechanisms in protecting I/R injury, provides strategies to improve bioavailability, which presents a comprehensive understanding of the important compound. Hopefully, the information and knowledge from this review can help researchers and physicians to better improve the applications of TMP in the clinic.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108656"},"PeriodicalIF":13.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical diversity, traditional uses, and bioactivities of Rosa roxburghii Tratt: A comprehensive review","authors":"Archana Jain ,&nbsp;Surendra Sarsaiya ,&nbsp;Qihai Gong ,&nbsp;Qin Wu ,&nbsp;Jingshan Shi","doi":"10.1016/j.pharmthera.2024.108657","DOIUrl":"10.1016/j.pharmthera.2024.108657","url":null,"abstract":"<div><p><em>Rosa roxburghii</em> Tratt (RRT), known as chestnut rose, has been a subject of growing interest because of its diverse chemical composition and wide range of traditional uses. This comprehensive review aimed to thoroughly examine RRT, including its traditional applications, chemical diversity, and various bioactivities. The chemical profile of this plant is characterized by the presence of essential nutrients such as vitamin C (ascorbic acid), flavonoids, triterpenes, organic acids, tannins, phenolic compounds, polysaccharides, carotenoids, triterpenoids, volatile compounds, amino acids, and essential oils. These constituents contribute to the medicinal and nutritional value. Additionally, we explore the multifaceted bioactivities of RRT, including its potential as an anticancer agent, antioxidant, antiaging agent, antiatherogenic agent, hypoglycemic agent, immunoregulatory modulator, radioprotective agent, antimutagenic agent, digestive system regulator, anti-inflammatory agent, cardioprotective agent, and antibacterial agent, and its intriguing role in modulating the gut microbiota. Furthermore, we discuss the geographical distribution and genetic diversity of this plant species and shed light on its ecological significance. This comprehensive review provides a holistic understanding of RRT, bridges traditional knowledge with contemporary scientific research, and highlights its potential applications in medicine, nutrition, and pharmacology.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"259 ","pages":"Article 108657"},"PeriodicalIF":13.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}