Crocin from Saffron Shows Promising Longevity and Health Benefits Through the DAF-16/FOXO Pathway

Crocin from Saffron Shows Promising Longevity and Health Benefits Through the DAF-16/FOXO Pathway

Recent scientific research continues to highlight the potential health benefits of natural bioactive compounds derived from traditional medicinal plants. A study published in the journal Food & Function by researchers from Chengdu University of Traditional Chinese Medicine demonstrated that crocin, a key carotenoid compound extracted from Crocus sativus, can significantly extend lifespan in Caenorhabditis elegans by alleviating oxidative stress and regulating lipid metabolism through the DAF-16/FOXO signaling pathway. Beyond longevity effects, crocin has also been associated with neuroprotective, antidepressant, metabolic, and vision-protective properties. These findings highlight the growing potential of crocin as a natural functional ingredient for health promotion and disease prevention.

Crocin May Extend Lifespan

Last year, researchers from Chengdu University of Traditional Chinese Medicine published a research paper on crocin in the journal Food & Function. The study found that crocin can alleviate oxidative stress and regulate lipid metabolism through the DAF-16/FOXO pathway, thereby extending lifespan.

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In this study, the researchers analyzed the effects of crocin on the lifespan of Caenorhabditis elegans and explored its potential molecular mechanisms. The results showed that crocin enhanced the antioxidant capacity of both young and aged nematodes and significantly improved their resistance to heat stress and oxidative stress. Crocin treatment significantly increased the survival rate of nematodes under high-temperature stress. At concentrations of 100, 200, and 400 μM, the survival rate increased by 64.74%, 171.56%, and 69.04%, respectively.

Antioxidant capacity of crocin in Caenorhabditis elegans

A hallmark of aging is persistent oxidative stress and dysregulated lipid metabolism. The study further found that crocin significantly extended the average lifespan of nematodes, with the best lifespan-extending effect observed at a concentration of 200 μM, where the mean lifespan increased by 15.46%. This effect was comparable to that of Resveratrol, which is known for its anti-aging properties, at the same concentration. In addition, treatment with 100 μM and 200 μM crocin significantly reduced the accumulation of lipofuscin. These results suggest that crocin can effectively reduce age-related oxidative damage and promote longevity, with 200 μM crocin showing the optimal effect.

Crocin extended the lifespan of Caenorhabditis elegans

Mechanistically, crocin activated DAF-16, the Caenorhabditis elegans homolog of human FOXO, leading to the upregulation of key antioxidant genes (gst-4, sod-3, and hsp-16.2). Notably, in daf-16 mutants, the lifespan-extending effect of crocin was abolished, indicating that DAF-16/FOXO plays a crucial role in crocin-mediated lifespan extension.

Furthermore, crocin reduced fat accumulation and upregulated the expression of genes involved in lipid mobilization in aged nematodes (lipl-3, lipl-4, atgl-1, and acs-2) as well as genes involved in unsaturated fatty acid synthesis (fat-6 and elo-2). GC-MS analysis further showed that crocin treatment increased the levels of unsaturated fatty acids (C18:1n9, C20:4n-6, C20:4n-3, and C20:5n-3). This effect was completely abolished when daf-16 was knocked down. These findings suggest that crocin extends the lifespan of Caenorhabditis elegans by alleviating oxidative stress and regulating lipid metabolism through the DAF-16/FOXO pathway.

Saffron and Crocin

Crocus sativus, commonly known as saffron and also called “Zang Hong Hua” or “Fan Hong Hua” in Chinese, is a perennial herb belonging to the Iridaceae family. Saffron originated in Spain, Greece, Southern Europe, and Iran, and was later introduced to China via India. Today it is cultivated in regions such as Jiangsu, Zhejiang, and northern China. In Iran, saffron is known as “Red Gold” and is considered the world’s most expensive cultivated herb as well as the most expensive traditional spice.

Saffron flowers are light purple, and their most distinctive feature is the presence of three red thread-like stigmas (25–30 mm long). These stigmas can be used both as a spice and as a natural coloring agent. Commercial saffron consists of dried red stigmas along with a small portion of the pale yellow style attached to them. Approximately 36,000 flowers are required to produce one pound of stigmas, and more than 200,000 dried stigmas yield about 500 grams of pure saffron.

In 2019, saffron was officially included in China’s list of substances that are both food and medicine. Crocin is a water-soluble carotenoid compound extracted from saffron and is the primary active and pigment component of saffron. It has been reported to exhibit neuroprotective, antidepressant, antihypertensive, lipid-lowering, antithrombotic, and anti-atherosclerotic effects.

Beyond Anti-Aging: Additional Health Benefits of Crocin

 

1) Neuroprotection / Cognitive improvement: 

Alzheimer's disease (AD) is characterized by degeneration of the central nervous system, and abnormal aggregation of Aβ plays a crucial role in its pathogenesis. Studies have shown that crocin can alleviate Aβ-induced spatial learning and memory deficits and hippocampal neuronal damage. Crocin also effectively suppresses Aβ-induced inflammation in mice and activates the PI3K/AKT pathway. By activating the PI3K/AKT signaling pathway, crocin inhibits neuroinflammation and improves cognitive dysfunction in Alzheimer’s disease mouse models.

In addition, crocin can prevent cognitive decline in rats exposed to acute high-altitude hypoxia by promoting mitochondrial biogenesis, alleviating oxidative stress damage, and reducing neuronal apoptosis.

2) Antidepressant effects:

Crocin, as a natural medicinal component, exhibits rapid-acting antidepressant effects. Studies have confirmed that crocin can reduce neurotoxicity induced by rotenone in Parkinson’s disease rats by inhibiting PI3K/Akt-mediated inflammation and improve depressive symptoms associated with chronic obstructive pulmonary disease. Crocin can also reduce depressive behaviors in mice with corticosterone-induced depression by inhibiting hippocampal neuroinflammation (IL-1β) and oxidative stress, and alleviate depression-like behaviors in mice subjected to chronic restraint stress by regulating the microbiota–gut–brain axis. In addition, studies have shown that crocin exerts antidepressant-like effects by increasing the levels of P-CREB and brain-derived neurotrophic factor (BDNF) and by regulating classical antidepressant signaling pathways such as the GHSR-PI3K pathway.

3) Anti-diabetic and kidney protection:

Crocin can alleviate oxidative stress and inflammatory responses in mice with diabetic nephropathy (DN), showing significant anti-inflammatory and antioxidant effects. Crocin treatment can upregulate the decreased levels of CYP4A11 and phosphorylated PPARγ in the kidneys of DN mice while reducing the elevated levels of TGF-β1 and phosphorylated Smad2/3. The therapeutic mechanism of crocin may be associated with the regulation of biotin, riboflavin, and arachidonic acid metabolism in the kidney, activation of the CYP4A11/PPARγ pathway, and inhibition of the TGF-β/Smad pathway.

4) Vision protection:

Crocin has potential for improving vision. Crocin treatment significantly increased the protein level of brain-derived neurotrophic factor (BDNF) in the mouse retina, thereby promoting the relocalization of cone opsins and restoring visual acuity (VA) and visual contrast sensitivity function (VCSF) at high spatial frequencies. Components rich in crocin may be used for eye health to enhance functional vision and protect retinal tissue.

According to market data from Grand View Research, the global crocin market size was estimated at USD 4.54 billion in 2022, with a projected compound annual growth rate (CAGR) of 5.14% from 2023 to 2030. Today, consumer preference for natural ingredients is driving the application of crocin in dietary supplements for immune support, mood improvement, and eye health (such as relieving visual fatigue), and the crocin market may enter a new stage of rapid growth.

References
[1] https://doi.org/10.1039/D5FO01157D
[2] Wenwen Su, Yanbo Wang, Sen Shao, Xiaojun Ye. Crocin ameliorates neuroinflammation and cognitive impairment in mice with Alzheimer's disease by activating PI3K/AKT pathway. Brain Behav. 2024 May 22;14(5):e3503. doi:10.1002/brb3.3503
[3] Yan Wang, Sixu Zhou, Xujiao Song, Shanshan Ding, Baogui Wang, Jiangfeng Wen, Chunlin Chen. Study on Antidepressant Effect and Mechanism of Crocin Mediated by the mTOR Signaling Pathway. Neurochem Res. 2022 Jul 8;47(10):3126–3136. doi:10.1007/s11064-022-03668-z
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