barrier

Rutin (Quercetin 3-O-rutinoside), a flavonoid, has a variety of biological activities including antiallergic, anti-inflammatory, antiproliferative, and anticarcinogenic properties.

L-DOPA (Levodopa) is an amino acid precursor of dopamine with antiparkinsonian properties. It is a prodrug converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. In the brain, levodopa is decarboxylated to dopamine, stimulating dopaminergic receptors and compensating for depleted endogenous dopamine in Parkinson's disease. To ensure adequate concentrations reach the central nervous system, levodopa is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, reducing peripheral decarboxylation and increasing CNS dopamine delivery.

Physostigmine, a parasympathomimetic alkaloid, is a reversible cholinesterase inhibitor. It extracts from the Calabar bean.

Emodin 6-O-β-D-glucoside (Glucoemodin) can protect barrier integrity and inhibit HMGB1-mediated inflammatory responses, which suggests a potential use as a therapy for sepsis or septic shock. Emodin 6-O-beta-D-glucoside has anti-inflammatory activities and also may have significant therapeutic benefits against diabetic complications and atherosclerosis.

Salvianolic acid A (Dan Phenolic Acid A) is a natural product and an inhibitor of matrix metalloproteinase 9 (MMP-9). Salvianolic acid A has antioxidant and anti-inflammatory activity and protects the blood-brain barrier.

Rutin hydrate (Sophorin), a kind of glycoside, widely exists in many plants including citrus fruit.

Ursodeoxycholic acid sodium (Sodium Ursodeoxycholate) is a naturally occurring secondary bile acid with anti-inflammatory and cytoprotective activities. Ursodeoxycholic acid sodium acts as signaling molecule, exerting its effects by interacting with bile acid activated receptors,

Dimethyl fumarate (DMF) is an Nrf2 activator with oral activity and blood-brain barrier permeability. Dimethyl fumarate has antimicrobial, anti-inflammatory, and immunomodulatory activities and has been used in the study of multiple sclerosis.

Ursodeoxycholic acid (UDCA) can be used to dissolve gallstones and reduce cholesterol absorption.

Tramiprosate (Alzhemed) is an orally active, blood-brain-barrier-crossing, naturally occurring amino acid found in a variety of red seaweeds that binds soluble Aβ and maintains it in a non-protofibrillar form.It is a GABA analog with neuroprotective, anticonvulsant, and antihypertensive activity.

sn-Glycero-3-phosphocholine (Choline glycerophosphate) is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have a potential for the treatment of Alzheimer's disease and dementia. sn-Glycero-3-phosphocholine rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of the acetylcholine neurotransmitter. It is a non-prescription drug in most countries due to its Generally Recognised As Safe (GRAS) status [1]. Studies have investigated its efficacy for cognitive disorders including stroke and Alzheimer's disease. An Italian multicentre clinical trial on 2, 044 patients suffering from recent stroke were supplied Glycerylphosphorylcholine in doses of 1, 000 mg day for 28 days and 400 mg three times per day for the five ensuing months. The trial confirmed the therapeutic role of alpha-GPC on the cognitive recovery of patients based on four measurement scales, three of which reached statistical significance [2].

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

3-Indoleacrylic acid is a metabolite of tryptophan produced by Peptostreptococcus species. 3-Indoleacrylic acid has a beneficial effect on intestinal epithelial barrier function and mitigates inflammatory responses by immune cells.

Vicenin 2 is an angiotensin-converting enzyme (ACE) inhibitor (IC50=43.83 μM) from the aerial parts of Desmodium styracifolium. Vicenin 2 is an inhibitor of α-glucosidase, PTP1B, and RLAR. Vicenin 2 has hepatoprotective, anti-cancer, antioxidant and anti-inflammatory activities, and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer. Vicenin 2 might be a useful lead for the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-associated complications. Vicenin 2 could act as a UV light barrier to protect the plants.

1. Orientin (Luteolin-8-glucoside) may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway. 2. Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. 3. Orientin has neuroprotection effect by the intracellular mediation of caspase activity; may alleviate cognitive deficits and oxidative stress in AD mice; can exert antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity.

7α-Hydroxy-4-cholesten-3-one is an intermediate in bile acid synthesis from cholesterol, a PXR agonist, and a biomarker for bile acid loss and diseases related to defective bile acid biosynthesis. It is also the physiological substrate for [CYP8B1].

Thalifendine is one of the main products of Berberine demethylation catalyzed by CYP51 (secreted by intestinal flora), which has anti-inflammatory effects, reduces intestinal inflammation, improves intestinal barrier function, and reduces the production of inflammatory factors.

Masticadienonic acid is a compound derived from Chios mastic gum, with potential anti-inflammatory and anti-cancer activities. It alleviates colitis in mice by modulating inflammatory responses, gut barrier integrity, and the microbiome. Masticadienonic acid is a potential protein tyrosine phosphatase 1B (PTP1B) inhibitor and can be used for research on diabetes.

3-Acetyldeoxynivalenol is a trichothecene mycotoxin deoxynivalenol acetylated derivative and a blood-brain barrier (BBB) permeable mycotoxin.

Enniatin B1, a Fusarium mycotoxin, crosses the blood-brain barrier, decreases the activation of ERK (p44 p42), and inhibits moderately TNF-α-induced NF-κB activation. Furthermore, it inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity, exhibiting an IC50 of 73 μM in rat liver microsome enzyme assays.

Acivicin (AT-125), a chlorinated amino acid antibiotic produced by Streptomyces porcineus, is a γ-glutamyl transpeptidase (GGT) inhibitor that crosses the blood-brain barrier, exhibits anticancer and antiparasitic activity, and is used in the study of visceral leishmaniasis.

Lactacystin is a natural non-peptide proteasome inhibitor and highly specific anticancer drug that controls the UPS of cellular protein turnover and inhibits alkaline cell proliferation, and is able to be used as a model for studying dementia, induces neurite outgrowth and transiently elevated levels of cAMP, inhibits angiogenesis, triggers apoptosis in glioma cells, and can penetrate the blood-brain barrier (BBB).

Forsythoside B binds to LPS and reduces the biological activity of serum LPS, and inhibits NF-κB activation. Forsythoside B inhibits the inflammatory response and has antioxidant properties. Potent neuroprotective effects with a favorable therapeutic time

C20 Ceramide (N-Arachidoyl-D-sphingosine) is a 20:0 ceramide found in the brain that crosses the blood-brain barrier to activate microglia and induce depressive-like behavior.