Future Perspectives of H. erinaceus Research in Depressive Disorder

Hericium erinaceus crude extract contains various hericenones, erinacines, and possibly other bioactive compounds that are still being discovered. Overall, the potent NGF-enhancing activities of H. erinacines are possibly mediated through the synergistic effects of several compounds in the crude extract. These compounds can greatly enhance adult hippocampal neurogenesis and contribute to the antidepressant-like effects. Chronic stress is known to induce an anhedonia effect that is highly associated with depression. However, the anti-anhedonia activity of H. erinaceus has not been reported yet and needs to be investigated in future studies. Furthermore, it would be interesting to examine if hericenones, erinacines, or/and other compounds of H. erinaceus can be absorbed in the blood and pass through the blood–brain barrier. The variety of bioactive compounds with potent NGF-inducing activity also supports the use of crude extract rather than pure extracts. The majority of studies on H. erinaceus bioactive compounds have focused on their NGF activities. Future studies on the antidepressant activity of these bioactive compounds need to examine their effects on the expression of BDNF. Although BDNF was found to be restored in the hippocampus after chronic administration of H. erinaceus, it is still unclear whether the increase is also reflected in peripheral BDNF expressions. The investigation of the effects on peripheral BDNF expression may provide important information for future clinical studies of depression. Moreover, as chronic administration of H. erinaceus was found to increase peripheral pro-BDNF but not BDNF, it would be interesting to examine the association of neurotrophic isoforms with depressive-like behaviors and whether H. erinaceus also affects their expression. In addition, as H. erinaceus was shown to stimulate monoaminergic modulation, it would be interesting to examine if the bioactive compounds of H. erinaceus act as agonists or inhibitors of monoamine neurotransmitter receptors. Although treatment with H. erinaceus was found to elicit an anti-inflammatory response, the detailed molecular mechanism is still unknown. These studies provide evidence that H. erinaceus possesses potential in alleviating depression, but the precise underlying mechanisms remain to be investigated. However, there is still a lack of strong and convincing evidence that H. erinaceus can effectively reduce anxiety and depression in vivo, which requires further investigation. Moreover, compounds in the extracts from the mycelium and fruiting body, as well as the method of extraction, requires further investigation to optimize the efficacy of H. erinaceus as a treatment for depressive disorders. In present investigation, majority of the studies does not include placebo or positive controls; and therefore, conventional antidepressants should be included as a positive control in future placebo-controlled research to compare their efficacy and eliminate potential placebo or non-specific effect. Furthermore, there is no concrete evidence of bioactive compounds unique to H. erinaceus that are responsible for its therapeutic effects, therefore future investigations involving selected medicinal-culinary mushrooms are highly warranted to rule out placebo and/or general effects.