{"doi":"10.1002/ptr.7822","title":"Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota‐host co‐metabolism of branched‐chain amino acid","abstract":"<jats:title>Abstract</jats:title><jats:p>Elevations in circling branched‐chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). <jats:italic>Morus alba</jats:italic> L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co‐metabolism modulated by host and gut microbiota. Tissue‐specific expressions of BCAA‐catabolizing enzymes were detected by RT‐PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high‐throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as <jats:italic>Anaerovorax</jats:italic>, <jats:italic>Bilophila</jats:italic>, <jats:italic>Blautia</jats:italic>, <jats:italic>Colidextribacter</jats:italic>, <jats:italic>Dubosiella</jats:italic>, <jats:italic>Intestinimonas</jats:italic>, <jats:italic>Lachnoclostridium</jats:italic>, <jats:italic>Lachnospiraceae_NK4A136</jats:italic>, <jats:italic>Oscillibacter</jats:italic>, and <jats:italic>Roseburia</jats:italic>. Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue‐specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ‐free‐mimic T2DM mice. Those results indicated that MLE improving T2DM‐related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue‐specific expression of BCAAs catabolic enzyme.</jats:p>","journal":"Phytotherapy Research","year":2023,"id":638313,"datarank":0.5375278407684165,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.0,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1657830,"name":"Ding‐xiang Li","orcid":null,"position":1,"is_corresponding":false},{"id":1657832,"name":"Ya‐ting Li","orcid":null,"position":2,"is_corresponding":false},{"id":1657833,"name":"Yu‐lang Chen","orcid":null,"position":3,"is_corresponding":false},{"id":1657834,"name":"Yan‐lin Zhao","orcid":null,"position":4,"is_corresponding":false},{"id":1657076,"name":"Shuai Ji","orcid":null,"position":5,"is_corresponding":false},{"id":1657835,"name":"Meng‐zhe Guo","orcid":null,"position":6,"is_corresponding":false},{"id":84733,"name":"Yan Du","orcid":"0000-0001-9931-4197","position":7,"is_corresponding":false},{"id":1657836,"name":"Dao‐Quan Tang","orcid":"0000-0002-5443-4619","position":8,"is_corresponding":false},{"id":1657828,"name":"Xiao‐xiao Zheng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota‐host co‐metabolism of branched‐chain amino acid","abstract":"<jats:title>Abstract</jats:title><jats:p>Elevations in circling branched‐chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). <jats:italic>Morus alba</jats:italic> L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co‐metabolism modulated by host and gut microbiota. Tissue‐specific expressions of BCAA‐catabolizing enzymes were detected by RT‐PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high‐throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as <jats:italic>Anaerovorax</jats:italic>, <jats:italic>Bilophila</jats:italic>, <jats:italic>Blautia</jats:italic>, <jats:italic>Colidextribacter</jats:italic>, <jats:italic>Dubosiella</jats:italic>, <jats:italic>Intestinimonas</jats:italic>, <jats:italic>Lachnoclostridium</jats:italic>, <jats:italic>Lachnospiraceae_NK4A136</jats:italic>, <jats:italic>Oscillibacter</jats:italic>, and <jats:italic>Roseburia</jats:italic>. Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue‐specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ‐free‐mimic T2DM mice. Those results indicated that MLE improving T2DM‐related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue‐specific expression of BCAAs catabolic enzyme.</jats:p>","is_dataset_classified":null,"base_score":3.58351893845611,"endowment":3.58351893845611,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37013717","pmcid":null,"openalex_id":"https://openalex.org/W4362520757","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"82204708","title":null},{"funder_name":"Natural Science Foundation of Xuzhou City of China","grant_id":"KC21204","title":null},{"funder_name":"Natural Science Foundation of Jiangsu Higher Education Institutions of China","grant_id":"22KJD360004","title":null},{"funder_name":"Traditional Chinese Medicine Scientific and Technological Development of Jiangsu Province of China","grant_id":"YB2020050","title":null},{"funder_name":"Traditional Chinese Medicine Scientific and Technological Development of Jiangsu Province of China","grant_id":"ZT202212","title":null},{"funder_name":"Natural Science Foundation of Xuzhou City of China","grant_id":"KC22146","title":null}],"total_grants":6,"fwci":3.2566,"citation_percentile":0.93384706,"influential_citations":0,"citation_trend":[{"year":2023,"count":3},{"year":2024,"count":11},{"year":2025,"count":14},{"year":2026,"count":7}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ptr.7822","host_type":"publisher"},{"url":"https://doi.org/10.1002/ptr.7822","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37013717","host_type":"repository"}],"fields_of_study":["Gut microbiota and health","Ginger and Zingiberaceae research","Mangiferin and Mango Extracts"],"mesh_terms":["Gastrointestinal Microbiome","Amino Acids, Branched-Chain","Animals","Diabetes Mellitus, Type 2","Insulin Resistance","RNA, Ribosomal, 16S","Plant Leaves","Morus","Mice"],"keywords":["Gut flora","Metabolism","Host (biology)","Type 2 diabetes","Biology","Bacteria","Chemistry","Microbiology","Biochemistry","Diabetes mellitus","Endocrinology","Genetics","Insulin resistance","Type 2 diabetes mellitus","Gut Microbiota","Branched-chain Amino Acid","Morus Alba Leaf Water Extract"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T20:28:44.568000Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}