Healing the Blood-Brain Barrier: Natural Compounds Show Promise

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The blood-brain barrier is a critical gatekeeper for neurological health, but when disrupted it can contribute to devastating diseases like Alzheimer's, Multiple Sclerosis, Parkinson's, and stroke. Can natural compounds come to the rescue by protecting and even healing this essential barrier? A dive into GreenMedInfo.com's research database reveals compelling evidence for the potential of nutrients and phytochemicals to safeguard the blood-brain interface.

The blood-brain barrier (BBB) is a selectively permeable interface between the peripheral circulation and the central nervous system. Consisting of specialized endothelial cells, astrocyte end-feet, and pericytes, the BBB tightly regulates transport into and out of the brain, providing a defense against toxins and pathogens.1 However, disruption and breakdown of the BBB is a known feature of several neurological disorders, from Alzheimer's disease and multiple sclerosis to brain trauma and stroke.2

While the BBB is a challenging therapeutic target, compelling research suggests that natural compounds may hold the key to both protecting and restoring this critical boundary. A search of the GreenMedInfo.com database for the keyword Blood-Brain-Barrier, which contains over 90,000 abstracts on natural medicine, reveals a number of promising substances that may buttress barrier integrity. Here's what the science says:


A class of flavonoid pigments found in blue, purple, and red foods like berries and grapes, anthocyanins have attracted attention for their neuroprotective properties. In a 2015 in vitro study, researchers found that a mixture of anthocyanins and anthocyanidins protected against oxidative stress and mechanisms implicated in Alzheimer's disease, leading them to suggest these compounds "could target multiple mechanisms involved in the etiology of AD and could be useful in preventing and treating AD."3 They further noted the ability of these phytonutrients to cross the BBB, a key factor in their therapeutic potential.


Found in foods like parsley, celery, and chamomile tea, apigenin has been shown to protect the BBB in the context of brain injury. In a rat model of subarachnoid hemorrhage, treatment with apigenin attenuated BBB disruption and reduced brain edema by suppressing inflammation.4 The researchers proposed that apigenin "could provide a new therapeutic agent for the treatment of subarachnoid hemorrhage."

Cannabidiol (CBD)

Growing interest surrounds the cannabis compound cannabidiol (CBD) for its anti-inflammatory and neuroprotective properties. A 2015 in vitro study on human brain endothelial cells found that CBD reduced permeability and prevented damage to the BBB under ischemic conditions, leading the authors to suggest this mechanism could represent "an as yet unrecognized mechanism of CBD-induced neuroprotection in ischemic stroke."5


Primarily known as a sleep hormone, melatonin also acts as a potent antioxidant and anti-inflammatory agent. Animal research indicates that melatonin may protect against BBB hyperpermeability due to inflammationand reduce "excitotoxic BBB breakdown" in neonatal rats.7


A phenolic compound found in extra virgin olive oil, oleocanthal has been identified as a potential therapy for Alzheimer's disease. In a 2015 study using both mouse models and cultured human brain endothelial cells, oleocanthal prevented the breakdown of tight junction proteins that maintain BBB integrity.8 "Oleocanthal could reduce Aβ load in the brain by enhancing the clearance across the BBB, which in turn may slow down the progression of AD," the researchers concluded.

Beyond isolated compounds, other approaches may support BBB health by enabling the delivery of protective agents. For example, a human study reported that pulsed ultrasound safely and temporarily opens the BBB to facilitate the passage of drugs or other substances.9

A nutritional factor that may contribute to increasing permeability in the blood brain barrier is wheat lectin, as extensively documented in the essay: The Critical Role of Wheat Lectin in Human Disease. Additionally, chemicals like bisphenol A appear to accumulate in the human brain, indicating they are able to pass through the blood brain barrier, and may even contribute to increasing permeability there.

While more research is needed to translate these findings into clinical applications, they provide an intriguing look at how natural compounds may promote resilience and healing of the blood-brain barrier, and how certain nutritional and environmental factors contribute to degrading it. By defending the integrity of this critical interface, these phytochemicals and nutrients hold potential as part of an integrative strategy for neurological health.

Learn more on our Blood Brain Barrier database here.


1: Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004 Jun;16(1):1-13. doi: 10.1016/j.nbd.2003.12.016. PMID: 15207256.

2: Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Blood-Brain Barrier: From Physiology to Disease and Back. Physiol Rev. 2019 Jan 1;99(1):21-78. doi: 10.1152/physrev.00050.2017. PMID: 30280653; PMCID: PMC6335100.

3: Belkacemi A, Ramassamy C. Anthocyanins and Anthocyanidins as Potential Neuroprotective Agents: Possible Effects on Alzheimer's Disease. Cent Nerv Syst Agents Med Chem. 2015 Jul 30. doi: 10.2174/1871524915666150730112517. PMID: 26238538.

4: Zhang T, Su J, Guo B, Wang K, Li X, Liang G. Apigenin attenuates blood-brain barrier disruption in a rat model of middle cerebral artery occlusion. Aging (Albany NY). 2014 Jul;6(7):550-63. doi: 10.18632/aging.100673. PMID: 25063764; PMCID: PMC4132943.

5: Hind WH, England TJ, O'Sullivan SE. Cannabidiol protects an in vitro model of the blood-brain barrier from oxygen-glucose deprivation via PPARγ and 5-HT1A receptors. Br J Pharmacol. 2016 Mar;173(5):815-25. doi: 10.1111/bph.13368. PMID: 26497782; PMCID: PMC4761095.

6: Alluri H, Wilson RL, Anasooya Shaji C, Wiggins-Dohlvik K, Patel S, Liu Y, Peng X, Beeram MR, Davis ML, Huang JH, Tharakan B. Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition. PLoS One. 2016 May 6;11(5):e0154427. doi: 10.1371/journal.pone.0154427. PMID: 27152411; PMCID: PMC4859531.

7: Moretti R, Zanin A, Pansiot J, Spiri D, Manganozzi L, Kratzer I, Favero G, Vasiljevic A, Rinaldi VE, Pic I, Massano D, D'Agostino I, Baburamani A, La Rocca MA, Rodella LF, Rezzani R, Ek J, Strazielle N, Ghersi-Egea JF, Gressens P, Titomanlio L. Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats. Neuroscience. 2015 Nov 19;311:382-97. doi: 10.1016/j.neuroscience.2015.10.044. PMID: 26542996.

8: Qosa H, Batarseh YS, Mohyeldin MM, El Sayed KA, Keller JN, Kaddoumi A. Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model. ACS Chem Neurosci. 2015 Nov 18;6(11):1849-59. doi: 10.1021/acschemneuro.5b00190. PMID: 26348065; PMCID: PMC4653736.

9: Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C, Karachi C, Leclercq D, Lafon C, Chapelon JY, Capelle L, Cornu P, Sanson M, Hoang-Xuan K, Delattre JY, Idbaih A. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016 Jun 15;8(343):343re2. doi: 10.1126/scitranslmed.aaf6086. PMID: 27306666.

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