Tang Dan-Dan, Li Mei-Yan, He Cheng-Xun, Xia Qing, Peng Wei, Wu Chun-Jie
School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, P. R. China.
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China.
J Food Sci. 2025 Sep;90(9):e70500. doi: 10.1111/1750-3841.70500.
Zanthoxylum bungeanum Maxim., a traditional Chinese cash crop, produces pericarps (huajiao) that are widely used as condiments and herbal medicines. Zanthoxylum bungeanum Maxim. essential oil (HEO), one of the primary bioactive components, has potential antidepressant properties, but faces challenges in pharmaceutical development due to its instability and low oral bioavailability. To address these limitations, this study developed a nanostructured lipid carrier encapsulating HEO (HEO-NLC) via a melt-ultrasonic method. The critical formulation parameters were systematically optimized through single-factor analysis and response surface methodology. Biocompatibility assessments, including histopathological evaluation, confirmed the safety profile of HEO-NLCs in vivo. Compared with HEO, HEO-NLC demonstrated superior antidepressant efficacy in a chronic unpredictable mild stress (CUMS) model. Mechanistic studies revealed that HEO-NLCs enhanced the systemic absorption and blood‒brain barrier penetration of linalool, a key bioactive terpene, as evidenced by 3.29-fold and 2.07-fold increases in the serum and brain concentrations, respectively. Furthermore, HEO-NLCs attenuated neuronal apoptosis by modulating the Bcl-2/Bax balance and suppressing caspase-3 activation. These findings establish HEO-NLCs as promising nanoformulations to overcome the pharmaceutical limitations of herbal essential oils, providing a foundation for developing oral antidepressants with enhanced stability and bioavailability. PRACTICAL APPLICATIONS: This technology enables the creation of stable, natural antidepressant supplements using encapsulated Zanthoxylum bungeanum essential oil. The improved formulation can be developed into oral capsules or liquid drops, offering a longer-lasting and more effective option for mood support than traditional herbal extracts, with reduced digestive discomfort. The enhanced shelf life of these NLCs under refrigerated conditions makes it suitable for commercial production and distribution.
花椒（Zanthoxylum bungeanum Maxim.）是一种中国传统经济作物，其果实（花椒）被广泛用作调味品和草药。花椒精油（HEO）是其主要生物活性成分之一，具有潜在的抗抑郁特性，但由于其稳定性差和口服生物利用度低，在药物开发中面临挑战。为了解决这些局限性，本研究通过熔融超声法制备了包封HEO的纳米结构脂质载体（HEO-NLC）。通过单因素分析和响应面法系统优化了关键配方参数。包括组织病理学评估在内的生物相容性评估证实了HEO-NLC在体内的安全性。与HEO相比，HEO-NLC在慢性不可预测轻度应激（CUMS）模型中表现出优异的抗抑郁效果。机制研究表明，HEO-NLC增强了关键生物活性萜类化合物芳樟醇的全身吸收和血脑屏障穿透，血清和脑浓度分别增加了3.29倍和2.07倍。此外，HEO-NLC通过调节Bcl-2/Bax平衡和抑制caspase-3激活来减轻神经元凋亡。这些发现确立了HEO-NLC作为有前景的纳米制剂，以克服草药精油的药物局限性，为开发具有更高稳定性和生物利用度的口服抗抑郁药提供了基础。实际应用：该技术能够使用包封的花椒精油制备稳定的天然抗抑郁补充剂。改进后的配方可开发成口服胶囊或液滴，与传统草药提取物相比，为情绪支持提供更持久、更有效的选择，同时减少消化不适。这些NLC在冷藏条件下延长的保质期使其适合商业生产和分销。
