A Natural Composition with Multi-Target Neuroprotective Effects for Alzheimer’s

Scientists now believe that for most people, Alzheimer’s disease is caused by a combination of factors that affect the brain over time. Many health, environmental, and lifestyle risk factors have been implicated in causing harm and death of brain cells and Alzheimer’s. Because of the multifactorial nature, drug development for Alzheimer’s by approaches of focusing on single biomarkers, such as Aβ or tau, has not been successful. Instead, a natural approach with multi-target, neuroprotective, memory and cognition improving effects could offer a safe and effective alternative for Alzheimer’s disease.

An adult human brain uses largely the same brain cells or neurons from his or her birth. In most part of human brain, brain cells will not regrow if they are lost. Only recently, scientists confirmed new cells continue to grow in specific area like hippocampus, an area important for memory formation and cognitive functions1. However, if brain loses large number of brain cells and new cells cannot make up the loss, it leads to cognitive and memory impairments, and development of Alzheimer’s. External and internal risk factors can cause harm and death of brain cells. As we age, our blood brain barrier gets disrupted and the brain is more liable to the harms of various external risk factors. For instance, studies have linked alcohol, stroke, sleep disorders, bacteria in the mouth, and traumatic brain injury to higher risk of Alzheimer’s. Other risk factors include CVD, diabetes, hypertension, chronic stress, smoking, drugs, toxins, depression, unhealthy diet, social and physical isolation, etc. All these risk factors potentially induce inflammation, heighten levels of oxidative radicals, Aβ, tau protein and a series of toxic events in the brain that lead to damage, loss of connection, and death of brain cells. Therefore, a product or therapy capable of protecting brain cells against multiple risk factors, reducing toxic events in the brain, and increasing growth of brain cells is most likely a feasible approach for prevention and treatment of Alzheimer’s.

Advancements in natural product research and medical imaging have resulted in new discoveries of plants and its constituents having potential in prevention and treatment of Alzheimer’s. Especially, a few active constituents from spices and edible plants have been found with multi-target and neuroprotective effects. They were indicated as external neuroprotectors and brain cell growth enhancers that potentially increase new brain cell growth for better memory2.

Crocin, the main active constituent of Saffron (Crocus sativus), has been found in recent animal and human clinical studies as a unique natural agent with antioxidant, anti-inflammation, multi-target neuroprotective and memory/cognition improving effects3.

Highlights of Crocin/Saffron Studies:

  • Human clinical studies demonstrated effects of crocin in: 1) reducing DNA damage, inflammation, and oxidative stress in patients with multiple sclerosis4; 2) suppressing edema and inflammation in patients with diabetic maculopathy5; 3) lowering serum TC, TG and increasing HDL-C in patients with hyperlipidemia6; 4) reducing pro-oxidant–anti-oxidant balance in patient with metabolic syndrome7; 5) improving depression and quality of life in patients with depression8, metabolic syndrome 9 and coronary artery disease10; and 6) improving quality of life and recovery in patients with acute ischemic stroke11.
  • Among many human clinical studies supporting effects of saffron in various health conditions, at least 8 clinical studies of saffron or its combination with other herb components were reported to improve memory and cognitive impairments in patients with mild cognitive impairment (MCI), mild-moderate and moderate-severe Alzheimer’s, vascular dementia (VaD) and major neurocognitive disorders. In a one-year study12, treatment with 125mg saffron per day in patients with MCI resulted better cognitive performance while the control group became worse. A small volume increase near hippocampal area in the brain was observed by MRI in saffron treated patients, likely a result of increased brain cell growth. At the same time, improved brain activation was measured by a HD-EEG.
  • Crocin was shown in multiple animal models to prevent or improve memory and cognitive impairments caused by alcohol, aged, Aβ, ischemia, chronic stress, toxins, and drugs such as scopolamine, streptozotocin, morphine, ketamine, etc3.
  • Pre-clinical studies demonstrated crocin and saffron tighten and maintain integrity of blood-brain barrier and lower Aβ levels in the brain, crocin also act to reducing total tau and tau phosphorylation13-15.
  • Crocin exhibited neuroprotective effects in preventing brain cells from injury and death against inflammation, infection, oxidative stress, drugs, chemicals or toxins in dozens of animal and cell studies.
  • Animal studies indicated crocin reduce other Alzheimer’s associated risk factors, including brain injury, depression, sleep disorder, diabetes, heart disease, obesity, etc.

A few other spice or plant constituents, including curcumin of turmeric and phenolic components of green tea, have also been indicated in animal and human studies having multi-target and neuroprotective effects. Combination of these active constituents could provide synergistic, multi-target, neuroprotective, memory and cognition improving effects that a drug is unable to deliver. Based on clinical and pre-clinical findings, a composition containing crocin and other natural active components with multi-target, neuroprotective, memory and cognition enhancing effects, could offer an effective alternative for Alzheimer’s disease.

Reference:

  1. Tobin MK, et al. (2019), Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients. Cell Stem Cell, 2019, 24: 974–982.
  2. Sadoughi D. (2019) The effect of crocin on apoptotic, inflammatory, BDNF, Pt, and Aβ40 indicators and neuronal density of CA1, CA2, and CA3 regions of hippocampus in the model of Alzheimer suffering rats induced with trimethyltin chloride. Comp Clin Pathol. 2019, https://doi.org/10.1007/s00580-019-02981-4.
  3. Finley JW & Gao S. (2017) Perspective on Crocus sativus L. (Saffron) Constituent Crocin: A Potent Water-Soluble Antioxidant and Potential Therapy for Alzheimer’s Disease. Agric. Food Chem. 2017, 65, 1005−1020.
  4. Ghiasian M, et al. (2019) Effects of crocin in reducing DNA damage, inflammation, and oxidative stress in multiple sclerosis patients: A double‐blind, randomized, and placebo‐controlled trial. J Biochem Mol Toxi. 2019, 33(12), e22410.
  5. Sepahi et al. (2018) Effects of Crocin on Diabetic Maculopathy: A Placebo-Controlled Randomized Clinical Trial. Am J Ophthalmol. 2018, 190: 89-98.
  6. Qian Z (2009) The Experiment and Clinical Study on The Hypolipidemic Effect of Crocin. China Licensed Pharmacist. 2009, 6(2): 6-9.
  7. Nikbakht-Jam I, et al (2016) Effect of crocin extracted from saffron on pro-oxidant–anti-oxidant balance in subjects with metabolic syndrome: A randomized, placebo-controlled clinical trial. Eur J Interg Med. 2016, 8(3): 307-312.
  8. Talaei A, et al (2015) Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. Journal of Affective Disorders. 2015, 174: 51–56.
  9. Jam IN, et al. (2017) The effects of crocin on the symptoms of depression in subjects with metabolic syndrome. Adv Clini Exp Med. 2017, 26: 925–930
  10. Abedimanesh N et al. (2017) Effects of Saffron Aqueous Extract and Its Main Constituent, Crocin, on Health-Related Quality of Life, Depression, and Sexual Desire in Coronary Artery Disease Patients: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Iran Red Crescent Med J. 2017, 19(9): e13676. doi: 10.5812/ircmj.13676.
  11. Asadollahi , et al. (2019) Protective properties of the aqueous extract of saffron (Crocus sativus L.) in ischemic stroke, randomized clinical trial. J Ethnopharmacol. 2019, 238: 111833.
  12. Tsolaki M, et al. (2016) Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. Journal of Alzheimer’s Disease. 2016, 54: 129–133.
  13. Batarseh YS, et al. (2017) Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice. ACS Chem Neurosci. 2017; 8(8): 1756-1766.
  14. Zhang X, et al. (2017) Crocin protects against cerebral- ischemia-induced damage in aged rats through maintaining the integrity of blood-brain barrier. Restorative Neurology and Neuroscience, 2017; 35(1): 65-75.
  15. Chalatsa I, et al (2019) The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models. Neurosci., 26 March 2019, https://doi.org/10.3389/fnins.2019.00249

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