Table 1.
Summary of the tested dosages and effects of purified phlorotannins and phlorotannin-rich extracts in published in vivo rodent studies.
| Category | Substance | Min. effective dose | Timing | Route | Animal model | Stimulus | Outcome | Reference |
|---|---|---|---|---|---|---|---|---|
| Memory | Dieckol | 1 mg/kg | Once daily for 7 days | Oral | ICR mice | Ethanol 3 g/kg (38% v/v solution in water) - acute alcohol intoxication | Prevention of memory loss during retention phase (passive avoidance test) | Myung et al. (2005) |
| Memory | PFF-A | 0.2 mg/kg | Once daily for 7 days | Oral | ICR mice | Ethanol 3 g/kg (38% v/v solution in water) - acute alcohol intoxication | Prevention of memory loss during retention phase (passive avoidance test) | Myung et al. (2005) |
| Learning, memory | NX42 (20.1% phlorotannin) | 100 mg/kg | Once daily for 4 weeks | Oral | ICR mice | Electric shocks, 15 times daily for 7 days during learning phase | Improved performance during learning and retention phases (water maze test) | Lee and Stein (2004) |
| AD | Phloroglucinol | 1.2 μmol | Once | Bilateral stereotaxic injection into hippocampus | 5XFAD mice | - | Rescued spontaneous alternation behavior in spontaneous alteration T-maze test at 12–13 days post-injection. Faster spatial learning in Morris water maze test at 7 days post-injection. | Yang et al. (2015) |
| AD | Phloroglucinol | 100 mg/kg per day | Freely administered in drinking water for 2 months | Oral | 5XFAD mice | - | Recovered spontaneous alternation ratio in spontaneous alternation T-maze and Y-maze; reductions in Aβ plaques and BACE1 protein, lipid peroxidation, Iba-1, and GFAP levels; rescued density of stubby and mushroom spines in the hippocampus CA1 subfield | Yang et al. (2018) |
| PD | Phloroglucinol | 6 μmol | Once | Stereotaxic injection with 6-OHDA | SD rats | 6-OHDA via unilateral injection | Preserved motor performance in the rotarod test; preserved number of TH+ cells in the SNpc; preserved TH and synaptophysin protein levels in the midbrain; suppressed apomorphine-induced rotation behavior | Ryu et al. (2013) |
| Movement | Dieckol | 5 mg/kg | Once immediately before test | Oral | Swiss albino mice | - | Decreased locomotion (open field test) | Li et al. (2021) |
| Stroke | Polyphenol-rich extract of Ecklonia cava (98.5% PGE) | 10 mg/kg | Half of final dose injected 30 min before and after surgery | I.p. injection | SD rats | Middle cerebral artery occlusion-induced transient focal ischemia | Reduced apoptosis at 10 mg/kg; reduced infarct size and brain water content at 50 mg/kg | Kim et al. (2012) |
| Seizure | Enzymatic extract of E. cava (98.4 mg/g PGE) | 1,000 mg/kg | 45 min before picrotoxin administration | Oral | SD rats | Picrotoxin (7 mg/kg)-induced clonic seizure | Increased latency to seizure onset | Cho et al. (2012) |
| Sleep | Dieckol | 100 mg/kg | 24 h after baseline recording in a 48-h study | Oral | C57BL/6 N mice | - | Reduced sleep latency and increased time spent in NREMS at 100 mg/kg; increased frequency of transitions from wake to NREMS at 150 mg/kg | Yoon et al. (2020) |
| Sleep | Ethanol extract of E. cava | 250 mg/kg | 12 h after baseline recording in a 24-h study | Oral | C57BL/6 N mice | - | Reduced sleep latency and increased sleep duration at 250 mg/kg; decreased time spent awake and increased time spent in NREMS at 500 mg/kg | Yoon et al. (2014) |
| Sleep | Ethanol extract of E. cava Kjellman (138.5 mg/g PGE) | 1,000 mg/kg | 45 min before pentobarbital administration | Oral | ICR mice | Pentobarbital (30 mg/kg [sub-hypnotic dose] and 45 mg/kg [hypnotic dose])-induced sedation | Reduced sleep latency and increased sleep duration | Cho et al. (2012) |
| Sleep | Polyphenol-rich extract of E. cava (630.2 mg/g PGE) | 50 mg/kg | 45 min before pentobarbital administration | Oral | SD rats | Pentobarbital (30 mg/kg [sub-hypnotic dose] and 45 mg/kg [hypnotic dose])-induced sedation | Reduced sleep latency and increased sleep duration | Cho et al. (2012) |
| Pain | Dieckol | 5 mg/kg | 30–60 min before pain stimulus | Oral | Swiss albino mice | - | Increased reaction latency to hot plate at 5 mg/kg (when supplemented with morphine); increased reaction latency to tail immersion at 10 mg/kg | Li et al. (2021) |
The minimum effective dose indicates the lowest dosage (mg/kg) of the tested substance that elicited a significant change in a parameter (p < 0.05). mg/g PGE indicates the total polyphenol content in phloroglucinol equivalents. AD, Alzheimer’s disease; PD, Parkinson’s disease; Aβ, amyloid beta; PFF-A, phlorofucofuroeckol A; PGE, phloroglucinol equivalents; i.p., intraperitoneal; NREMS, non-rapid eye movement sleep; SD, Sprague Dawley; GFAP, glial fibrillary acidic protein; SNpc, substantia nigra pars compacta; TH, tyrosine hydroxylase.