The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, 840, Taiwan; Chinese Medicine Department, E-DA Hospital, Kaohsiung, 824, Taiwan; 1PT Biotechnology Co., Ltd., Taichung, 433, Taiwan.
Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan.
J Ethnopharmacol. 2021 Jan 10;264:113297. doi: 10.1016/j.jep.2020.113297. Epub 2020 Aug 22.
The Fructus (Alpinia oxyphylla MIQ) known as Yi Zhi Ren in Chinese medicine has been used as a food and herbal medicinal substance in China for centuries; in the year 2015 Chinese Pharmacopoeia Commission reported water extracts of Alpinia oxyphyllae Fructus (AoF) as a popular medication for aging-related diseases in the form of tonic, aphrodisiac, and health-care food in south China.
Adipose mesenchymal stem cells are physiologically and therapeutically associated with healthy vascular function and cardiac health. However aging conditions hinder stem cell function and increases the vulnerability to cardiovascular diseases. In this study, the effect of the anti-aging herbal medicine AoF to enhance the cardiac restorative function of adipose-derived mesenchymal stem cells (ADMSCs) in aging condition was investigated.
Low dose (0.1 μM) Doxorubicin and D-galactose (150 mg/kg/day for 8 weeks) were used to respectively induce aging in vitro and in vivo. For In vivo studies, 20 week old WKY rats were divided into Control, Aging induced (AI), AI + AoF, AI + ADMSC, AI + AoF Oral + ADMSC, and AI + AoF treated ADMSC groups. AoF (100 mg/kg/day) was administered orally and ADMSCs (1 × 10 cells) were injected (IV).
AoF preconditioned ADMSC showed reduction in low dose Dox induced mitochondrial apoptosis and improved DNA replication in H9c2 cardiomyoblasts. In vivo experiments confirmed that both a combined treatment with AoF-ADMSCs and with AoF preconditioned ADMSCs reduced aging associated cardiac damages which was correlated with reduction in apoptosis and expression of senescence markers (P21 and β-gal). Survival and longevity markers were upregulated up on combined administration of AoF and ADMSCs. The cardiac performance of the aging-induced rats was improved significantly in the treatment groups. AoF along with ADMSCs might activate paracrine factors to restore the performance of an aging heart.
Hence, we propose that ADMSCs combined with AoF have promising therapeutic properties in the treatment of healthy aging heart.
在中国，中药中的益智仁（Alpinia oxyphylla MIQ）作为一种食品和草药已有数百年的历史；2015 年，中国药典委员会报告称，水提益智仁（AoF）作为一种流行的药物，以滋补、壮阳和保健品的形式在中国南方用于治疗与衰老相关的疾病。
脂肪间充质干细胞与健康血管功能和心脏健康在生理和治疗上密切相关。然而，衰老会阻碍干细胞功能，增加患心血管疾病的风险。在这项研究中，我们研究了抗衰老草药 AoF 对增强衰老条件下脂肪来源间充质干细胞（ADMSCs）的心脏修复功能的影响。
低剂量（0.1μM）阿霉素和 D-半乳糖（150mg/kg/天，持续 8 周）分别用于体外和体内诱导衰老。在体内研究中，将 20 周龄 WKY 大鼠分为对照组、衰老诱导组（AI）、AI+AoF 组、AI+ADMSC 组、AI+AoF 口服+ADMSC 组和 AI+AoF 处理的 ADMSC 组。AoF（100mg/kg/天）口服给药，ADMSCs（1×10 个细胞）静脉注射（IV）。
AoF 预处理的 ADMSC 显示减少了低剂量阿霉素诱导的线粒体凋亡，并改善了 H9c2 心肌细胞的 DNA 复制。体内实验证实，AoF-ADMSC 联合治疗和 AoF 预处理的 ADMSC 联合治疗均能减轻与衰老相关的心脏损伤，这与凋亡和衰老标志物（P21 和β-gal）表达的减少有关。联合给予 AoF 和 ADMSCs 后，存活和长寿标志物上调。衰老诱导大鼠的心脏功能在治疗组中得到显著改善。AoF 与 ADMSCs 联合使用可能会激活旁分泌因子，从而恢复衰老心脏的功能。
因此，我们提出 ADMSCs 联合 AoF 在治疗健康衰老心脏方面具有有前景的治疗特性。
