Kehtari Tarlan, Tovar Diego Cardenas, Epstein Dustin, Junquera Patricia
Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, USA.
Psychiatry and Behavioral Sciences, Herbert Wertheim College of Medicine, Florida International University, Miami, USA.
Cureus. 2025 Apr 24;17(4):e82924. doi: 10.7759/cureus.82924. eCollection 2025 Apr.
Depression, anxiety, mild cognitive impairment (MCI), and Alzheimer's disease (AD) pose ongoing therapeutic challenges, particularly in aging populations. Conventional pharmacologic treatments often have delayed onset, limited efficacy, and unfavorable side effects, prompting interest in natural alternatives. Saffron ( L.), a spice long used in traditional medicine, has emerged as a promising candidate due to its multimodal neuroprotective properties. This review evaluated the clinical efficacy, safety, and mechanistic profile of saffron in the treatment of mood and cognitive disorders. A targeted literature search identified multiple double-blind randomized controlled trials (RCTs) and meta-analyses comparing saffron to standard pharmacologic agents or placebo. In depression, RCTs using 30 mg/day of saffron for six weeks showed comparable improvements in Hamilton Depression Rating Scale (HAM-D) scores to fluoxetine (20 mg/day), with significant reductions from baseline and no difference in adverse events. An adjunctive study using crocin (an active ingredient of saffron; 15 mg twice daily) also demonstrated additive effects alongside selective serotonin reuptake inhibitors (SSRIs). In cognitive disorders, saffron (30 mg/day) showed non-inferiority to donepezil (10 mg/day) and memantine (20 mg/day) in patients with mild-to-moderate and moderate-to-severe AD. Trials lasting 16 to 52 weeks demonstrated significant improvements on validated cognitive scales such as Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) and Clinical Dementia Rating - Sum of Boxes (CDR-SB), with fewer gastrointestinal side effects compared to standard treatments. Meta-analyses confirm the superiority of saffron over placebo and its equivalence to conventional drugs, with no serious adverse events. Saffron represents a safe, well-tolerated, and culturally integrated intervention with growing evidence for use in psychiatric and neurologic disorders. Larger, multicenter trials with biomarker validation and standardized extract formulations are needed to confirm its role in clinical practice.
抑郁症、焦虑症、轻度认知障碍（MCI）和阿尔茨海默病（AD）带来了持续的治疗挑战，尤其是在老年人群中。传统药物治疗往往起效延迟、疗效有限且副作用不佳，这引发了人们对天然替代疗法的兴趣。藏红花（Crocus sativus L.）是一种长期用于传统医学的香料，因其多模式神经保护特性而成为一个有前景的候选药物。本综述评估了藏红花在治疗情绪和认知障碍方面的临床疗效、安全性和作用机制。一项有针对性的文献检索确定了多项双盲随机对照试验（RCT）和荟萃分析，这些研究将藏红花与标准药物或安慰剂进行了比较。在抑郁症方面，使用每天30毫克藏红花持续六周的RCT显示，汉密尔顿抑郁量表（HAM-D）评分的改善与氟西汀（每天20毫克）相当，与基线相比有显著降低，且不良事件无差异。一项使用藏红花素（藏红花的一种活性成分；每日两次，每次15毫克）的辅助研究也证明了其与选择性5-羟色胺再摄取抑制剂（SSRI）联合使用时的增效作用。在认知障碍方面，对于轻度至中度和中度至重度AD患者，藏红花（每天30毫克）显示出与多奈哌齐（每天10毫克）和美金刚（每天20毫克）相当的效果。持续16至52周的试验表明，在诸如阿尔茨海默病评估量表 - 认知子量表（ADAS-Cog）和临床痴呆评定量表 - 方框总和（CDR-SB）等经过验证的认知量表上有显著改善，与标准治疗相比胃肠道副作用更少。荟萃分析证实了藏红花优于安慰剂且与传统药物等效，且无严重不良事件。藏红花是一种安全、耐受性良好且融入文化的干预措施，越来越多的证据表明其可用于精神和神经疾病。需要开展更大规模的、具有生物标志物验证和标准化提取物配方的多中心试验，以确认其在临床实践中的作用。
