Adthapanyawanich Kannika, Aitsarangkun Na Ayutthaya Kanyakorn, Kreungnium Siriporn, Mark Peter J, Nakata Hiroki, Chen Wai, Chinda Kroekkiat, Amatyakul Patcharada, Tongpob Yutthapong
Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
Centre of Excellence in Medical Biotechnology (CEMB), Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
Nutrients. 2025 Jan 13;17(2):273. doi: 10.3390/nu17020273.
High-fat diet (HFD)-induced obesity represents a significant challenge to male reproductive health, affecting approximately 13% of the global adult population. This comprehensive review synthesizes current evidence regarding mulberry ( L.) fruit extract's therapeutic potential for HFD-induced male reproductive dysfunction. Through comprehensive analysis of the peer-reviewed literature from multiple databases (PubMed, Web of Science, Scopus, and Google Scholar; 2005-2024), we evaluated mulberry extract's effects on testicular morphology, spermatogenesis, sperm parameters, and the underlying molecular mechanisms. Mechanistic studies reveal that standardized mulberry extract mediates protective effects through multiple pathways: enhanced antioxidant enzyme activities (SOD: +45%, Catalase: +38%, GPx: +35%), reduced inflammatory markers (TNF-α: -64%, IL-6: -58%), and modulated NF-κB signaling (-42.3%). These effects are facilitated by mulberry's rich phytochemical profile, particularly anthocyanins (2.92-5.35 mg/g dry weight) and polyphenols (4.23-6.38 mg/g). The extract demonstrates particular efficacy in preserving seminiferous tubule integrity and maintaining blood-testis barrier function, with treated groups maintaining up to 85% of normal tubular architecture compared to HFD controls. Key molecular mechanisms include AMPK/SIRT1 pathway activation (2.3-fold increase), enhanced mitochondrial function (67% increase in mtDNA copy number), and epigenetic regulation of metabolic pathways. Temporal analysis indicates optimal therapeutic effects after 28 days of treatment, with initial improvements observable within 14 days. While current evidence is promising, limitations include predominant reliance on rodent models and lack of standardized extraction protocols. Future research priorities include well-designed human clinical trials, standardization of preparation methods, and investigation of potential synergistic effects with other therapeutic agents. This comprehensive review indicates that mulberry extract is a promising therapeutic candidate for obesity-related male infertility, warranting further clinical investigation.
高脂饮食（HFD）诱导的肥胖对男性生殖健康构成重大挑战，影响着全球约13%的成年人口。这篇综述综合了关于桑（L.）果提取物对HFD诱导的男性生殖功能障碍的治疗潜力的现有证据。通过对多个数据库（PubMed、Web of Science、Scopus和谷歌学术；2005 - 2024年）的同行评审文献进行全面分析，我们评估了桑提取物对睾丸形态、精子发生、精子参数以及潜在分子机制的影响。机制研究表明，标准化的桑提取物通过多种途径介导保护作用：增强抗氧化酶活性（超氧化物歧化酶：+45%，过氧化氢酶：+38%，谷胱甘肽过氧化物酶：+35%），降低炎症标志物（肿瘤坏死因子-α：-64%，白细胞介素-6：-58%），并调节核因子-κB信号传导（-42.3%）。这些作用得益于桑丰富的植物化学成分，特别是花青素（2.92 - 5.35毫克/克干重）和多酚（4.23 - 6.38毫克/克）。该提取物在保持生精小管完整性和维持血睾屏障功能方面显示出特别的功效，与HFD对照组相比，治疗组可维持高达85%的正常小管结构。关键分子机制包括AMPK/SIRT1途径激活（增加2.3倍）、增强线粒体功能（线粒体DNA拷贝数增加67%）以及代谢途径的表观遗传调控。时间分析表明，治疗28天后具有最佳治疗效果，14天内即可观察到初步改善。虽然目前的证据很有前景，但局限性包括主要依赖啮齿动物模型以及缺乏标准化的提取方案。未来的研究重点包括精心设计的人体临床试验、制备方法的标准化以及与其他治疗药物潜在协同作用的研究。这篇综述表明，桑提取物是肥胖相关男性不育症的一种有前景的治疗候选物，值得进一步的临床研究。
