{"doi":"10.1038/s41598-022-18065-3","title":"The aphrodisiac potential of β-cyclodextrin–curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells","abstract":"<jats:title>Abstract</jats:title><jats:p>The water-soluble β-cyclodextrin–curcumin (CDC) is used in pharmaceutical applications and as a natural food colorant. The previous study revealed that curcumin potentially impacted the reproductive system. The present study investigated the possible roles of the CDC in testosterone secretion in Leydig cells and mice. Primary Leydig cells were treated with the CDC to determine their effect on cell proliferation, testosterone levels, the protein and mRNA expression of the transcription factor, and steroidogenic enzymes. Our data showed that CDC stimulated testosterone production via upregulating transcription factor steroidogenic factor-1 (NR5A1), cAMP-response element-binding protein (CREB), and steroidogenic enzymes steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), 17-alpha-hydroxylase/17,20-lyase (CYP17A1), 3β-/17β-hydroxysteroid dehydrogenase type 1 (3β/17β-HSD, HSD3b1/HSD17b1). CDC could significantly stimulate H89-suppressed StAR and CREB expression but not reverse melatonin-suppressed StAR expression. We further detected the hormonal activity with transgenic yeast, and CDC showed potential androgenic antagonistic activity. Meanwhile, we investigated its aphrodisiac effect on hydrocortisone-induced mice. Exposure to hydrocortisone decreased the mating ability, reproductive organs, and testosterone level and disrupted testicular histology. However, all of these effects were significantly improved by CDC treatment. In conclusion, these results indicated that mechanisms of CDC in stimulating testosterone production involve upregulating the cAMP-PKA pathway.</jats:p>","journal":"Scientific Reports","year":2022,"id":36765,"datarank":0.27178289089315527,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.03036720402804019,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.03036720402804019,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":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":185592,"name":"Shan Xue","orcid":null,"position":1,"is_corresponding":false},{"id":56852,"name":"Lin Yuan","orcid":"0000-0001-5556-0994","position":2,"is_corresponding":false},{"id":185368,"name":"Zihan Li","orcid":null,"position":3,"is_corresponding":false},{"id":118140,"name":"Haitao Hu","orcid":null,"position":4,"is_corresponding":false},{"id":185593,"name":"Yichang Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":185594,"name":"Yimei Liu","orcid":null,"position":6,"is_corresponding":false},{"id":104490,"name":"Juan Li","orcid":"0000-0003-4376-7781","position":7,"is_corresponding":false},{"id":36395,"name":"Liu Yang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35995927","pmcid":"PMC9395524","openalex_id":"https://openalex.org/W4292582384","authors":[],"funders":[{"funder_name":"Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources","grant_id":"2060302","title":null},{"funder_name":"The Opening Project of Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases","grant_id":"PT022002","title":null}],"total_grants":2,"fwci":0.2189,"citation_percentile":0.40483691,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41598-022-18065-3.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41598-022-18065-3.pdf","host_type":"GOLD"},{"url":"https://www.nature.com/articles/s41598-022-18065-3.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41598-022-18065-3","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41598-022-18065-3","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35995927","host_type":"repository"},{"url":"https://doaj.org/article/f7a121306abf4e9cbf3d68531d1ec036","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9395524","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9395524","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9395524?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Curcumin's Biomedical Applications","Aldose Reductase and Taurine","Protein Hydrolysis and Bioactive Peptides","Medicine","Chemistry","Animals","Aphrodisiacs","Cholesterol Side-Chain Cleavage Enzyme","Curcumin","Cyclic AMP Response Element-Binding Protein","Hydrocortisone","Leydig Cells","Male","Mice","Phosphoproteins","Testosterone","beta-Cyclodextrins"],"mesh_terms":["Animals","Aphrodisiacs","Cholesterol Side-Chain Cleavage Enzyme","Curcumin","Hydrocortisone","Leydig Cells","Male","Phosphoproteins","Testosterone","Cyclic AMP Response Element-Binding Protein","beta-Cyclodextrins","Mice"],"keywords":["Steroidogenic acute regulatory protein","Cholesterol side-chain cleavage enzyme","CREB","CYP17A1","Curcumin","Endocrinology","Internal medicine","Leydig cell","Testosterone (patch)","Chemistry","Steroidogenic factor 1","Biology","Hormone","Transcription factor","Gene expression","Enzyme","Pharmacology","Luteinizing hormone","Medicine","Biochemistry","Gene","Cytochrome P450"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T17:20:18.484803Z","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":[]}