Fitoterapia最新文献

{"title":"From waste to value: evaluation of chemical composition and anti-inflammatory activity of Cannabis sativa stem extracts","authors":"Ernesto Gargiulo ,&nbsp;Benedetta Romano ,&nbsp;Carmen Formisano ,&nbsp;Nunzio Fiorentino ,&nbsp;Fabio Somma ,&nbsp;Daniela Claudia Maresca ,&nbsp;Giuseppe Ercolano ,&nbsp;Angela Ianaro ,&nbsp;Giuseppina Chianese","doi":"10.1016/j.fitote.2025.106894","DOIUrl":"10.1016/j.fitote.2025.106894","url":null,"abstract":"<div><div><em>Cannabis sativa</em> L. is a chemically diverse plant historically valued for its nutritional, textile, and medicinal properties. While the pharmacological relevance of inflorescences and seeds is well-established, the stems are commonly considered waste. In this study, we investigated the chemical composition and anti-inflammatory activity of stem extracts from fiber hemp (<em>C. sativa</em>, Felina 32), cultivated under saline irrigation at different electrical conductivities (0, 2.0, 4.0, and 6.0 dS m⁻¹). LC-HRMS analysis revealed the presence of diverse secondary metabolites, predominantly flavonoid glycosides and alkaloids, with minimal phytocannabinoid content. Extracts exhibited differential metabolomic profiles influenced by salinity, with higher phenolic content under high salinity, suggesting stress-induced biosynthetic responses. Functional assays in J774A.1 macrophages demonstrated that all stem extracts significantly suppressed inflammatory responses, reducing IL-6 expression, calcium flux, iNOS and COX2 expression, and secretion of NO and PGE2. These findings highlight the potential of <em>C. sativa</em> stem by-products as sustainable sources of bioactive compounds with anti-inflammatory properties, promoting their revaluation within circular economy models.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106894"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157020","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":"Integrated metabolomics and network pharmacology to reveal the mechanism of Wenxiao Jieyu capsule in the treatment of depression","authors":"Xiangli Yan ,&nbsp;Siqi Quan ,&nbsp;Linzhe Su ,&nbsp;Pan Su ,&nbsp;Xiuhui Guo ,&nbsp;Ming Bai ,&nbsp;Baoying Wang ,&nbsp;Erping Xu ,&nbsp;Yucheng Li","doi":"10.1016/j.fitote.2025.106903","DOIUrl":"10.1016/j.fitote.2025.106903","url":null,"abstract":"<div><div>This study aimed to explore Wenxiao Jieyu Capsule's (WJC) antidepressant mechanisms via serum pharmacochemistry, network pharmacology, metabolomics, and experimental validation. Serum pharmacochemistry and network pharmacology were employed to predict the biological processes and pathway regulated by WJC. Chronic unpredictable mild stress (CUMS)-induced rat model of depression was to explore the antidepressant mechanisms of WJC. A total of 20 prototype compounds were identified. Network pharmacology identified 283 overlapping targets, showing significant enrichment in purine metabolism and the NOD-like receptor protein 3 (NLRP3) inflammasome pathway. In vivo, WJC improved serum profiles, attenuated CUMS-induced depression-like behaviors and neuronal injury in the prefrontal cortex (PFC). Furthermore, WJC downregulated the expression of purinergic receptors P₂X purinoceptor 7 (P₂X₇R) and adenosine A_2A receptor (A_2AR), upregulated adenosine A₁ receptor (A₁R) expression, and inhibited the activation of the NLRP3 inflammasome, as evidenced by decreased protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cysteine-aspartic acid protease-1 (Caspase-1). Collectively, these findings indicate that WJC alleviating neuroinflammation in CUMS-induced depressive rats by modulating purine metabolism and suppressing NLRP3 inflammasome activation. It offering a foundation for further research and clinical applications.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106903"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157022","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":"HPLC-guided isolation and characterization of monoterpene glycosides from the dried roots bark of Paeonia × suffruticosa Andr","authors":"Lan Chen ,&nbsp;Yan-gang Cao ,&nbsp;Yan-ling Liu ,&nbsp;Xu Chen ,&nbsp;Di Lu ,&nbsp;Bing-xian Zhao ,&nbsp;Ying Niu ,&nbsp;Xiao-ke Zheng ,&nbsp;Wei-sheng Feng","doi":"10.1016/j.fitote.2025.106900","DOIUrl":"10.1016/j.fitote.2025.106900","url":null,"abstract":"<div><div>Three undescribed monoterpene glycosides (<strong>1</strong>–<strong>3</strong>), along with seventeen known analogues (<strong>4</strong>–<strong>20</strong>), were isolated from the dried roots bark of <em>Paeonia</em> × <em>suffruticosa</em> Andr. based on high-performance liquid chromatography (HPLC) analysis and small molecule accurate recognition technology (SMART). Their structures were assigned by spectroscopic techniques, and the absolute configurations of compounds <strong>1</strong>–<strong>3</strong> were elucidated by comparing the computed and experimental electronic circular dichroism (ECD) spectra. Additionally, compound <strong>2</strong> exhibited moderate inhibitory effect on acetylcholinesterase (AChE) with the IC₅₀ value of 18.54 ± 2.60 μM. Compound <strong>13</strong> showed significantly activity on DPPH with the IC₅₀ value of 9.04 ± 2.33 μM.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106900"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174402","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":"Discovery of new dammarane saponins from Actinostemma lobatum: C-3 monoglucosylation governs α-glucosidase inhibition","authors":"Wei Li,&nbsp;Zhenlin Liu,&nbsp;Huiyu Li,&nbsp;Minjie Wang,&nbsp;Yue Dai,&nbsp;Jinliandi Zhang,&nbsp;Chao Wen,&nbsp;Wenqiang Guo,&nbsp;Qiugui Zhou,&nbsp;Lijuan Zheng,&nbsp;Guilan Wang,&nbsp;Yun Tang","doi":"10.1016/j.fitote.2025.106898","DOIUrl":"10.1016/j.fitote.2025.106898","url":null,"abstract":"<div><div>Four new dammarane saponins, named actinostemmosides L-O (<strong>1</strong>–<strong>4</strong>), together with five known analogues (<strong>5</strong>–<strong>9</strong>), were isolated from the whole plant of <em>Actinostemma lobatum</em>. Their structures were established by HR-ESI-MS, exhaustive 1D/2D-NMR, and chemical methods. All nine saponins exhibited <em>α</em>-glucosidase inhibitory activity (IC₅₀ 40.3–150.9 μM), with actinostemmoside L (<strong>1</strong>) exhibiting an IC₅₀ of 40.3 μM—twice the potency of acarbose (84.6 μM)—while <strong>5</strong> and <strong>6</strong> were equipotent with the drug. These results expand the chemical space of dammarane saponins and establish <em>A. lobatum</em> as a renewable source of <em>α</em>-glucosidase inhibitors.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106898"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157019","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":"An overview of the phytochemical and biological activities of the genus “Jacaranda”, family Bignoniaceae (1976–2024)","authors":"Sara Abd-Eltawab Makhlouf Mohammad ,&nbsp;Miada F. Abdelwahab ,&nbsp;Mamdouh Nabil Samy ,&nbsp;Ashraf N.E. Hamed","doi":"10.1016/j.fitote.2025.106896","DOIUrl":"10.1016/j.fitote.2025.106896","url":null,"abstract":"<div><div><em>Jacaranda</em> is a genus belonging to family Bignoniaceae and comprises about 49 species. <em>Jacaranda</em> plants are frequently employed in traditional medicine for skin ailments, venereal infections, leishmaniasis, colds, rheumatism and gastrointestinal disorders. Numerous studies have stated that <em>Jacaranda</em> species constitutes a rich source of various classes of secondary metabolites primarily dominated by flavonoids, followed by phenylethanoid glycosides, triterpenoids, hydroquinones, organic acids, sterols, and others. Additionally, different extracts from various <em>Jacaranda</em> species as well as many isolated phytoconstituents displayed a variety of biological effects, particularly antioxidant, cytotoxic, antimicrobial and anti-inflammatory activities in addition to the antiprotozoal and insecticidal potentials. The present review summarizes all the secondary metabolites purified from the genus <em>Jacaranda</em> besides the relevant biological activities of the different extracts, fractions and/or compounds. We are, herein, updating the earlier published reviews and highlighting the most recent published data, covering the period from 1976 to 2024, and over 109 publications have been reviewed. The study recommended that some species of the genus <em>Jacaranda</em> require more pharmacological and phytochemical attention in order to discover new natural drug leads.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106896"},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157021","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":"Erratum to \"Ethnobotanical and alkaloid composition with their cytotoxicity of Tabernaemontana polyneura: A review with in silico ADMET analysis\" [Fitoterapia 186 (2025) 106851].","authors":"Wen Xin Toh, Sin Yee Tang, Kae Shin Sim, Siew Huah Lim, Chun Hoe Tan","doi":"10.1016/j.fitote.2025.106869","DOIUrl":"10.1016/j.fitote.2025.106869","url":null,"abstract":"","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":" ","pages":"106869"},"PeriodicalIF":2.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112244","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":"Identification of a novel ACLY inhibitor proanthocyanidin B2 from grape seeds with lipid-lowering effect in vitro","authors":"Yao Wang ,&nbsp;Pan Wang ,&nbsp;Fangfang Xu ,&nbsp;Han Zhou ,&nbsp;Xiaomin Xie ,&nbsp;Tao Hou ,&nbsp;Fengbin Luo ,&nbsp;Yuchang Sun ,&nbsp;Yanfang Liu ,&nbsp;Jixia Wang ,&nbsp;Dongmei Fu","doi":"10.1016/j.fitote.2025.106874","DOIUrl":"10.1016/j.fitote.2025.106874","url":null,"abstract":"<div><div>ATP citrate lyase (ACLY) is a crucial enzyme in glycolipid metabolism. To date, only its one prodrug bempedoic acid has been approved. The discovery of direct ACLY inhibitors is important for developing new lipid-lowering drugs. Grape seeds, used in functional foods and medicines, have lipid-lowering efficacy. However, it remains unknown whether their components directly inhibit ACLY. To investigate it, a multi-component screening method was used and proanthocyanidin B2 was identified as a novel ACLY inhibitor with an IC₅₀ value of 2.73 μM. Differential scanning fluorimetry confirmed its directly binding to ACLY. Proanthocyanidin B2 acted as a noncompetitive inhibitor in kinetic studies and bound stably with ACLY in molecular dynamics simulations. <em>In vitro</em>, proanthocyanidin B2 reduced lipid accumulation <em>via</em> inhibiting key transcription factors associated with ACLY. This study revealed a novel ACLY inhibitor contributing to lipid-lowering efficacy of grape seeds and provided a unique scaffold for ACLY drug design.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106874"},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112361","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":"Pharmacodynamic effects and mechanism of Pueraria lobata-Schisandra chinensis combination in the treatment of alcoholic liver disease","authors":"Shihao Zhang ,&nbsp;Ding Liu ,&nbsp;Dongyan Guo ,&nbsp;Chongbo Zhao ,&nbsp;Yajun Shi ,&nbsp;Junbo Zou ,&nbsp;Huanxian Shi ,&nbsp;Jiangxue Cheng ,&nbsp;Jing Sun ,&nbsp;Xiaofei Zhang","doi":"10.1016/j.fitote.2025.106873","DOIUrl":"10.1016/j.fitote.2025.106873","url":null,"abstract":"<div><div>With the increasing consumption of alcohol and alcoholic beverages, liver injury may occur. This has become an important cause endangering human health. As edible herbal medicines, <em>Pueraria lobata</em> (PL) and <em>Schisandra chinensis</em> (SC) are often used in combination to treat alcohol-related diseases and have a long-standing history in China. In this study, we demonstrated that the PL-SC drug pair (P<img>S) could mitigate ethanol-induced liver injury through the construction of both in – vivo and in - vitro models. Pharmacodynamic results showed that P<img>S attenuated liver injury by lowering aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It increases alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) levels and relieves alcohol-suppressed nervous system excitability. P<img>S is more effective compared to PL or SC alone. The chemical components of the P<img>S combination were identified using UPLC-Q-TOF-MS. By integrating transcriptome sequencing, network pharmacology, and molecular docking techniques, it was discovered that Puerarin, Daidzein, Schisandrol A, and Schisandrin A in P<img>S could act on key targets in the PI3K/AKT pathway, thus treating ALD. Metabolomic analysis revealed that dysregulation of Arachidonic acid (AA) metabolic pathways exacerbated inflammatory responses and oxidative stress, subsequently mediating pathological changes in ALD and exacerbating liver damage.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106873"},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109896","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":"Phenylpropanoid glycosides from the fruits of Lycium chinense and their potential anti-diabetic activity","authors":"Yv-Xin Fan ,&nbsp;Yu-Guo Ma ,&nbsp;Yan-Jie Zhu ,&nbsp;Ji-Le Xin ,&nbsp;Xiang-Yang Dai ,&nbsp;Kun Du ,&nbsp;Yan-Gang Cao ,&nbsp;Yan-Jun Sun ,&nbsp;Xiao-Ke Zheng ,&nbsp;Wei-Sheng Feng ,&nbsp;Hui Chen","doi":"10.1016/j.fitote.2025.106878","DOIUrl":"10.1016/j.fitote.2025.106878","url":null,"abstract":"<div><div>Phytochemical study of the fruits of <em>Lycium chinense</em> Mill. allowed the identification of eight undescribed phenylpropanoid glycosides, namely lychinosides A-H (<strong>1</strong>–<strong>8</strong>), along with five known compounds (<strong>9</strong>–<strong>13</strong>). The structures of the new compounds were elucidated through detailed analysis of spectroscopic data (HRESIMS, 1D and 2D NMR) and acid hydrolysis experiment. Compounds <strong>1</strong>, <strong>3</strong>–<strong>6</strong>, <strong>8</strong>–<strong>10</strong>, <strong>12</strong>, and <strong>13</strong> could significantly increase the glucose consumption in insulin-resistant HepG2 cells at 50 μM, and compounds <strong>1</strong> and <strong>9</strong> could improve the glucose uptake capacity of insulin-resistant HepG2 cells and enhance the hexokinase and pyruvate kinase activities. In addition, compound <strong>9</strong> exhibited excellent inhibitory activities against <em>α</em>-glucosidase with an IC₅₀ value of 16.8 μM, comparable to that of the positive control acarbose (300.0 μM).</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106878"},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085512","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":"Bioactive 2-arylbenzofuran and chalcone derivatives from Morus mesozygia Stapf","authors":"Jackson Obegi Matundura ,&nbsp;Jackson T. Mollel ,&nbsp;Masum Miah ,&nbsp;Joanna Said ,&nbsp;Vaderament-Alexe Nchiozem-Ngnitedem ,&nbsp;Wouter A. Remmerswaal ,&nbsp;Leonidah K. Omosa ,&nbsp;Edward Trybala ,&nbsp;Tomas Bergström ,&nbsp;Luis Apaza Ticona ,&nbsp;Mate Erdelyi ,&nbsp;Abiy Yenesew","doi":"10.1016/j.fitote.2025.106871","DOIUrl":"10.1016/j.fitote.2025.106871","url":null,"abstract":"<div><div>The phytochemical investigation of the stem bark of <em>Morus mesozygia</em> afforded the fourteen known secondary metabolites moracin N (<strong>1</strong>), moracin S (<strong>2</strong>), mulberrofuran L (<strong>3</strong>), moracin C (<strong>4</strong>), moracin L (<strong>5</strong>), moracin M (<strong>6</strong>), moracin D (<strong>7</strong>), artopithecin A (<strong>8</strong>), isobavachalcone (<strong>9</strong>), morachalcone A (<strong>10</strong>), 2,2՛,4,4՛-tetrahydroxychalcone (<strong>11</strong>), 3<em>β</em>-acetoxy-urs-12-en-11-one (<strong>12</strong>), betulinic acid (<strong>13</strong>), and 4,4′-diphenylmethane-bis(methyl) carbamate (<strong>14</strong>). Their structures were elucidated by NMR spectroscopic and mass spectrometric analyzes and their cytotoxicity (CC₅₀ for HEKa, IMR-90, and HPrEC), anti-inflammatory (TNF-α, NF-κB, and NO inhibition), antibacterial (MIC), antitumor (IC₅₀), and antiviral (CPE-based and plaque reduction assays) activities were studied. Moracin D (<strong>7</strong>) showed potent anti-inflammatory activity towards the release of NF-κB (0.57 &lt; IC₅₀ &lt; 1.21 μM). 3<em>β</em>-Acetoxy-urs-12-en-11-one (<strong>12</strong>) had potent antibacterial activity towards <em>Bacillus subtilis</em> and <em>Micrococcus luteus</em>, with MIC values of 12.71 and 15.59 μM, respectively. Moracin M (<strong>6</strong>) had the highest antitumor activity (IC₅₀ = 19.80 μM) against SK-MEL-28 human melanoma cells. Isobavachalcone (<strong>9</strong>) exhibited activity against Human Rhinovirus 2 (HRV-2; IC₅₀ = 7.01 μM) with a selectivity index (SI) = 9.1 as compared to HeLa cells. None of the compounds exhibited significant antiviral activity against respiratory syncytial virus (RSV) or herpes simplex virus type 2 (HSV-2). Out of the isolated compounds, moracin D (<strong>7</strong>), isobavachalcone (<strong>9</strong>) and marsformoxide B (<strong>12</strong>), may be considered to be promising leads for the development of anti-inflammatory (NF-κB), antiviral (HRV-2), and antibacterial (<em>B. subtilis</em> and <em>M. luteus</em>) agents, respectively.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"187 ","pages":"Article 106871"},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085529","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}