Table 3.

Summary of mechanisms implicated in the impact of diet on depression symptoms with confirmed effects in preclinical rodent studies.

Herricium erinaceus
Biological effect	Neuroprotective effect	Effects in preclinical in vivo studies	Reported effects in clinical studies
Anti-inflammatory	Erinacine-A promotes neuronal survival in mouse hippocampus via BDNF and NFκB increase in response to LPS [78].	Reduction in passive stress-coping induced by LPS [78]. Decrease in plasma proinflammatory cytokines: TNFα [77,78], and Il-6 [78]. Increase of plasma anti-inflammatory cytokine Il-10 [77].	Reduction in self-reported depression [80,81] and anxiety symptoms [80]. Higher noradrenaline turnover [82]. Modulation of gut microbiota [75].
Antioxidative	Neuroprotective against DEHP [72] and high corticosterone levels [73] via antioxidative and antiapoptotic activity in vitro.	no data
Gut microbiota	no data	Polysaccharides regulate inflammation in the gut via microbiota [74].
HPA axis	Neuroprotective against high corticosterone levels in vitro [73].	Reversal of passive stress-coping induced by repeated restraint stress in mice [78]. Prevents a decrease in noradrenaline, serotonin and dopamine in hippocampi of stressed mice [78].
Mitochondria protection	Neuroprotective against DEHP-induced mitochondrial dysfunction in vitro [72].	no data
Neurogenesis and BDNF	Erinacine-A increases proliferation of hippocampal progenitors in the subgranular zone of the dentate gyrus [79] and increases via BDNF and NFκB signaling [78].	Reduction in passive stress-coping compared to non-supplemented mice [79].
Cordyceps militaris
Biological effect	Neuroprotective effect	Effects in preclinical in vivo studies	Reported effects in clinical studies
Anti-inflammatory	no data	Cordycepin normalized hippocampal IL-6 and TNFα levels increased by chronic stress in mice [93], and serum IL-1β in chronically stressed rats [94]	no data
Antioxidative	no data	Increase in brain antioxidant levels in rats [94].
HPA axis	no data	Reversal of passive stress-coping and consummatory anhedonia induced by chronic unpredictable mild stress in mice [93] and rats [94,95]. Recovery of noradrenalin, dopamine, serotonin and glucocorticoid receptor levels in the hypothalamus of chronically stressed rats [95].
Neurogenesis and BDNF	no data	Cordycepin slightly upregulated hippocampal BDNF levels decreased by chronic stress in mice [93].
Ganoderma lucidum
Biological effect	Neuroprotective effect	Effects in preclinical in vivo studies	Reported effects in clinical studies
Anti-inflammatory	no data	Polysaccharides normalized hippocampal proinflammatory (Il-6, TNFα) and anti-inflammatory (Il-10) cytokine levels increased by chronic stress in mice [96].	Improvement [97] or worsening [98] of self-reported fatigue and improvement of well-being [96,98]. Reduction [99] or no change [98] in depression and anxiety symptoms.
HPA axis	Polysaccharides are neuroprotective against high corticosterone levels in vitro [100].	Polysaccharides reverse passive stress-coping and consummatory anhedonia induced by chronic unpredictable mild stress in mice [97,100].
Neurogenesis and BDNF	Triterpenes promote neuronal survival via NGF and BDNF signaling in vitro [101].	Polysaccharides restore hippocampal [97] and frontal cortex [100] BDNF levels decreased by chronic stress in mice.