Abstract：
Depression is one of the most common psychiatric conditions worldwide, with an annual escalation in prevalence. The serotonin (5-Hydroxytryptamine [5-HT]) metabolism through the gut-brain axis has been revealed to be related to the development of depression. Our previous study demonstrated that Lactococcus lactis WHH2078 alleviated depression in mice by shaping the gut microbiome composition and 5-HT metabolism. However, little research has explored the synergistic effects of probiotics and natural mental health-improving products. In this study, three natural products (saffron, l-theanine, and phosphatidylserine), either individually or in combination, were orally administrated for 4 weeks in chronic restraint stress (CRS)-induced mice, and their depressive behaviors, hippocampal 5-HT, and serum corticosterone were assessed. Saffron demonstrated improvement of the depressive-like behaviors via multiple behavioral tests and reversed the declined concentration of 5-HT and increased concentration of corticosterone. Following an initial screening, saffron was chosen to be combined with WHH2078, referred to as WHHMOOD™. Furthermore, the effects of WHHMOOD were evaluated in mice with depressive-like behaviors. WHHMOOD reduced immobility time in the forced swimming test and tail suspension test, increased the time spent in the central area in open field test, and reduced the serum corticosterone level. Besides, WHHMOOD improved the CRS-induced gut microbial dysbiosis by reversing gut microbial diversity and the abundances of Ligilactobacillus, Candidatus Arthromitus, and Erysipelatoclostridium. Compared to WHH2078, WHHMOOD treatment significantly increased the travel distance and hippocampal 5-HT level in mice. In conclusion, WHHMOOD exhibited prophylactic effects on depressive-like in CRS mice, which may act as a promising agent for improving the symptoms of depression.
摘要：
抑郁症是全世界最常见的精神病之一，患病率逐年上升。5-羟色胺（5-羟色胺[5-HT]）通过肠-脑轴的代谢已被发现与抑郁症的发展有关。我们先前的研究表明，乳酸乳球菌WH2078通过塑造肠道微生物组组成和5-HT代谢来减轻小鼠的抑郁症。然而,很少有研究探索益生菌和天然精神健康改善产品的协同作用。在这项研究中,三种天然产品(藏红花，l-茶氨酸,和磷脂酰丝氨酸），无论是单独还是组合，在慢性束缚应激（CRS）诱导的小鼠中口服给药4周，和他们的抑郁行为，海马5-HT，和血清皮质酮进行评估。藏红花通过多种行为测试证明了抑郁样行为的改善，并逆转了5-HT浓度的下降和皮质酮浓度的增加。经过初步筛选,选择藏红花与WHH2078组合,称为WHMOOD™。此外，在具有抑郁样行为的小鼠中评估了WHMOOD的作用。WHMOOD减少了强制游泳测试和尾部悬挂测试中的不动时间，增加了在中部地区进行野外测试的时间，并降低血清皮质酮水平。此外,WHHMOOD通过逆转肠道微生物多样性和配体芽孢杆菌的丰度来改善CRS诱导的肠道微生物菌群失调，拟南芥,和丹毒病菌.与WHH2078相比,WHMOOD处理显著增加了小鼠的行进距离和海马5-HT水平。总之,WHMOOD对CRS小鼠的抑郁样表现出预防作用，它可以作为改善抑郁症状的有前途的药物。
