Table 2. Effects of marine bioactive substances against periodontitis through in vivo studies

Publication year	Kind of sample	Sample	Kind of source	Organisms	Model	Outcomes	Ref
2019	Application	CMC-Na gel containing Stichopus herrmanni powder	Echinodermata	S. herrmanni	Periodontitis diabetes rat model induced by Porphyromonas gingivalis administration	↓ Expression of IL-1β and IL-10	Mulawarmanti et al., 2019a
2019	Application	CMC-Na gel containing S. herrmanni powder	Echinodermata	S. herrmanni	Periodontitis mice model induced by P. gingivalis administration	↑OPG expression↑Number of osteoblast↓ Number of osteoclast	Mulawarmanti et al., 2019b
2019	Extract	Sulfated polysaccharides	Rhodophyta	Gracilaria caudata	Ligature-induced periodontitis rat model	↓ GBI and PPD↓ MPO activity↓ MDA concentration and GSH level in liver↓ Histopathological alteration in liver tissue	da Silva et al., 2019
2019	Extract	ECE	Phaeophyceae	Ecklonia cava	Ligature-induced periodontitis rat model	↓ GI and TM↓ Distance between CEJ and ABC↓ Proliferation and erosion of periodontal epithelial cell↓ Bone resorption↓ mRNA expression of IL-1β, MMP-2, MMP-9, and RANKL/OPG	Kim et al., 2019b
2020	Compound	Bromoageliferin	Porifera	Agelas dilatata	Pseudomonas aeruginosa-infected Galleria mellonella model	Anti-survival effect	Pech-Puch et al., 2020
2020	Compound	M101	Annelida	Arenicola marina	P. gingivalis-induced subcutaneous calvarial abscess mice model	↓ Clinical abscess size↓ Inflammatory cell infiltration↓ Inflammatory score↑Quantity and quality of bone↓ TRAP-positive cell number	Batool et al., 2020
2020	Compound	Omega-3 polyunsaturated fatty acid	Unknown	Unknown	Ligature-induced periodontitis rat model	↓ Serum level of IL-1β, IL-6, and TNF-α	Jalal et al., 2020a
2020	Compound	Omega -3 polyunsaturated fatty acid	Unknown	Unknown	Ligature-induced periodontitis rat model	↑Bone formation↓ Inflammatory cell infiltration↓ Periodontal damage score	Jalal et al., 2020b
2020	Extract	Fish oil	Chordata	Unknown	Hypercholesterolemic rat model with ligature-induced periodontitis	↓ Bone loss↑Bone trabeculae↑LBV/TLV%↑Substitution of saturated fat↑PBS	Antona et al., 2020
2020	Extract	Nannochloropsis oculata extract	Ochrophyta	N. oculata	A. actinomycetemcomitans infected periodontitis rat model	↓ TNF-α expression↑Expression of OPG and IL-10	Revianti et al., 2020
2021	Application	Ginsenoside Rg1 and amelogenin-loaded injectable glycol chitosan/aldehyde-modified hyaluronic acid hydrogel	Unknown	Unknown	Periodontitis rat model induced by periodontium defect	Nearly completed periodontium regeneration↓ Distance between CEJ and ABC↓ BMD, bone volume fraction (BV/TV), and Tb. Th↓ Infiltration of inflammatory cells↓ Optical density of IL-1, TGF-β, and TNF-α	Guo et al., 2021
2021	Application	Minocycline-loaded chitosan/cyclodextrin mouthwash	Unknown	Unknown	Ligature-induced periodontitis rat model	Antiplaque biofilm activity↓ GBI and ABL↓ Distance between CEJ and ABC	Li et al., 2021
2021	Extract	ECE	Phaeophyceae	E. cava	Ligature-induced periodontitis rat model	↓ ABL and bone height↓ mRNA expression of RANKL/OPG	Jung et al., 2021
2021	Extract	Spirulina maxima extract	Cyanophyta	S. maxima	P. gingivalis inoculated periodontitis rat model	↓ MPO activity↓ TRAP-positive cell number↑OPG/RANKL expression ratio↓ Distance between CEJ and ABC↑Osteoblast number↓ mRNA expression of IL-1β, IL-4, IL-6, NF-κB, and TNF-α↓ mRNA expression of MMP-8 and MMP-13↑Protein expression OPN, OSX, and Type I COL↑Activation of BMP-2/Smad pathway	Kang et al., 2021
2022	Application	Hydroxyapatite-loaded chitosan gel	Unknown	Unknown	Femoral defect rat model	↑BMP-2 expression↓ IL-1 expression	Gani et al., 2022
2022	Compound	M101	Annelida	A. marina	P. gingivalis soaked ligature-induced periodontitis mice model	Augmentation in the FA↓ EA↑AL and bone contour and quality↓ Expression of HIF-1α, NF-κB, and MMP-9↓ Number of TRAP positive cell	Batool et al., 2022
2022	Extract	S. herrmanni extract	Echinodermata	S. herrmanni	Femoral defect guinea pig model	↑OCN expression↑Number of osteoblast	Adam et al., 2022

CMC-Na, sodium carboxymethylcellulose; OPG, osteoprotegerin; ECE, Ecklonia cava ethanol extract; GBI, gingival bleeding index; PPD, probing pocket depth; MPO, myeloperoxidase; MDA, malondialdehyde; GSH, glutathione; GI, gingival index; TM, tooth mobility; CEJ, cementoenamel junction; ABC, the crest of the alveolar bone; IL, interleukin; MMP, matrix metalloproteinase; RANKL, receptor activator of nuclear factors κB ligand; TRAP, tartrate resistant acid phosphatase; TNF-α, tumor necrosis factor alpha; LBV, lower bone volume; TLV, total lower volume; PBS, periodontal bone support; BMD, bone mineral density; BV, bone volume; TV, tissue volume; Tb. Th, trabecular thickness; TGF, transforming growth factor; ABL, alveolar bone loss; OPN, osteopontin; OSX, osterix; COL, collagen; BMP, bone morphogenetic protein; FA, fibrous connective tissue attachment; EA, epithelial attachment; AL, attachment level; HIF, hypoxia inducible factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells.