Mellow Yellow: Saffron Ingredient Supports Cognitive Health

Stress can be a major bummer and build up with time, hastening the aging process. In particular, this excess stress can affect cognitive health and aging.

Research shows that an ingredient in saffron—alluded to in Donovan’s megahit “Mellow Yellow,”—called crocin supports cognitive health in stressed mice. Crocin significantly benefits learning, memory, and social interaction in stressed mice. This saffron ingredient that provides the yellowish-red pigmentation regulates an enzyme that produces NMN, the direct precursor to the vital molecule NAD+. The results were published in the journal Neurochemistry International and suggest that crocin may support cognitive health and aging in the face of stress.

The Crux of Cognitive Crumbling

The prefrontal cortex (PFC) is a crucial cortical region that plays an essential role in many brain functions, including cognitive processes like regulation of emotion, motivation, sociability, self-awareness, and the ability to interpret behaviors (desires, intention, and beliefs). So, perhaps it’s not surprising that numerous experiments have provided evidence of the importance of keeping the PFC healthy to keep cognition sharp.

Neurons use signaling molecules called neurotransmitters to send signals to any brain region, including the PFC. The cell receiving the signal could be another neuron but could also be a gland or muscle cell. The nervous system uses several neurotransmitters to segregate different brain programs. For example, dopamine is involved in movement, coordination, and feelings of pleasure and reward, and serotonin is involved in emotions and affects digestion and metabolism. Generally, changes in neurotransmitters are closely related to poor neural and cognitive health.

When we are subjected to stress, our adrenal glands secrete hormones that affect our entire body. One of these hormones, cortisol, enables us to adapt physically and mentally to the stimulus. Following major or repeated stress, adrenal glands pump out cortisol in significant quantities, sometimes over a long period. This hypersecretion has damaging effects on the individual, to the point of accelerating aging.

Crocin & Clear Cognition

In this article, researchers from Hangzhou Medical College in China tested the effects of crocin on the cognition of stressed mice. Crocin has advantages in that the critical metabolized product can penetrate the blood-brain barrier (BBB)—the protective barrier preventing pathogens and other particles from reaching the CNS.

Not surprisingly, stressed mice exhibited significantly higher levels of cortisol. However, crocin administration reversed this trend. Cortisol is released in response to stress and serves many vital functions, while dysregulation is associated with cognitive and memory impairment. Specifically, there’s an inverse correlation between cortisol levels with cognitive health; when cortisol levels skyrocket, cognitive health plummets.

Several neurotransmitters are altered by stress in mice. The present study showed relatively low dopamine and serotonin contents in stressed mice, while crocin treatment significantly increased the two neurotransmitters. Interestingly, crocin appeared to be as effective in regulating neurotransmitters as sertraline, a common medication for mood disorders. This SSRI (selective serotonin receptor inhibitor) works by increasing serotonin levels. 

Nudging NAD+ to Nullify Nerves

Another class of important molecules used by neurons is neurotrophins—small proteins that typically support neuron growth and maturation. BDNF—the most abundant neurotrophin—is critical for maintaining various brain functions, and reduced BDNF has been associated with poor cognitive health. The present study revealed a significant decline in BDNF in the stressed mice, while crocin treatment markedly reversed this reduction.

So, what’s controlling these changes in neurotransmitters and neurotrophins? Previous research has shown that disruptions of SIRT1, the NAD+-dependent enzyme, and NAMPT, the NAD+ precursor generating enzyme, lead to poor neural development and cognitive health. Interestingly, NAD+, SIRT1, and NAMPT were all decreased in stressed mice. The present study showed that NAMPT, SIRT1, and NAD+ were significantly downregulated in stressed mice, while crocin and sertraline treatment upregulated the levels of all three factors in the PFC.

Overall, these results demonstrated that crocin could support cognitive health during stress by regulating levels of cortisol and neurotransmitters. Interestingly, crocin appears to provide similar effects as other NAD+ precursors, which increases NAD+ levels and SIRT1 activity. What is unclear is whether crocin can boost levels of NAD+ as much as NAD+ precursors like NMN. It would be interesting to compare these molecules because it is possible that they could work synergistically, especially if crocin has other effects beyond those attributed to the NAD+ pathway.

References:

Zhang F, Zhu X, Yu P, Sheng T, Wang Y, Ye Y.  Neurochem Int. 2022;157:105343. doi:10.1016/j.neuint.2022.105343