Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Table 1 Potential novel treatments

Treatment	Biomarkers changed in desired direction	Ref.
Fluprostenol	iNOS, TNF-α, CD11c, IL-10, NF-kB, p65	[10]
Liu Shen Wan	Anti-inflammatory, IL-1β, TNF-α, IFN-γ, IL-6, TLR4, NF-kB p65, p-IkBα	[11]
Erdosteine	Anti-oxidant, anti-inflammatory, IL-1β, COX-2, iNOS, P65, ADAMTS-5, MMP1, MMP3, MMP-13, MAPK, Wnt/β-catenin	[12]
4-Octyl itaconate	Anti-inflammatory, TGF-β/Smad, NF-kB, ROS, autophagy	[13]
2 ,3-dihydro-5,6-dimethoxy-1H-inden-1-one	ROS, LDH, MDA, TAC, anti-inflammatory	[14]
Neutrophilic granule protein	TNF-α, IL-1β, NF-kB, IL-10, anti-inflammatory	[15]
Dioscorea zingiberensis	BTB integrity, ZO-1, MDA, 8-OHdG, Nrf2, NOQ1, HO-1	[16]
FCPR16	TNF-α, Caspase-3, Caspase-8, NF-kB p65, iNOS, ROS, JNK	[17]
7,8-dihydroxyflavone	GSH, nitrite, MDA, NF-kB, iNOS, caspase-3, Nrf2, HO-1, BDNF	[18]
X-inactive specific transcript	Anti-inflammatory, NF-kB, IL-6	[19]
3-[3-pyridinyl]-1-[4-pyridinyl]-2-propen-1-one	M1, autophagy, NF-kB, TNF-α, ICAM-1, VCAM-1	[20]
NMDEA	IL-1β, IL-6, p65, iNOS	[21]
Cashew gum	MPO, TER, anti-inflammatory, barrier function	[22]
Ampelopsin	ROS, NOX2, NOX4, FN, Col IV, Nrf2, HO-1, NQO-1	[23]
Esculentoside A	IL-1β, IL-6, IL-8, TNF-α, MMP -2, -3, -13, NF-kB, MAPK	[24]
Phyllanthus emblica	Antioxidant, GSH, SOD, MDA, inflammation	[25]
Anoectochilus roxburghii	Oxidative stress, SOD, GSH-PX, MDA, GPx-1, GPx-4	[26]
Ivacaftor; Tezacaftor	IL-18, IL-1β, TNF, Caspase-1, IL-10, Anti-inflammatory	[27]
Floccularia luteovirens	SOD, GSH-Px, CAT, MDA, ROS, oxidative stress	[28]
Ishige okamurae; DPHC	ROS, elastase, MMPs, NF-kB, AP-1, MAPKs	[29]
Syzygium polyanthum (Wight) walp.; Bay leaf	CRP, MPO, anti-inflammatory	[30]
Empagliflozin	LDH, total leucocytic count, IL-6, TNF-α, TLR4, TGF-β1, oxidative stress, Nrf2/HO-1	[31]
Isorhynchophylline	Antioxidant, TGF-β1, CTGF, 4-HNE, MDA, Nrf2, MAPK	[32]
Neoagarooligosaccharide	Nrf2, GSH, glutathione, ROS, inflammation, antioxidant	[33]
COMP-4; Muira puama	NO, antioxidative, apoptosis, HO-1, MPO, GSH/GSSG ratio	[34]
Quzhou fructus aurantii	Anti-inflammatory, MAPK, NF-kB, TNF, IL-6, IL-1β, IL-10	[35]
Cerevisterol	MAPK, NF-kB, AP-1, Nrf2, HO-1, anti-inflammatory	[36]
Maslinic acid	HO-1, COX-2/PGE2, STAT-1, Nrf2, IL-1, iNOS, NF-kB	[37]
Scrophularia koraiensis nakai; Scrophulariaceae	Ig-E, anti-inflammatory, NF-kB, Nrf-2, HO-1	[38]
Grateloupia lithophila	Blood glucose, TC, TGs, LDL, VLDL, HDL, SOD, GPx, MDA	[39]
Acetyl-l-carnitine	LDL, HDL, SOD, GSH-Px MDA, TNF-α, IL-1SS, iNOS, CRP	[40]
Methylseleninic acid	GPx, Nrf2, Socs3, p-JAK1, p-STAT3, NF-kB	[41]
Omentin-1	Pro-inflammatory cytokines, NF-kB, Nrf2	[42]
Dowijigi	NO, PGE2, TNF-α, IL-6, IL-1β, COX2, iNOS, NF-kB	[43]
AAL	NO, iNOS, TNF-α, IL-6, IL-1β, NF-kB	[44]
AXT and HupA	Oxidative stress, LDH, ROS, SOD, MDA	[45]
Continentalic acid (CNT)	GSH, GST, catalase, SOD, MDA, POD, MPO, NO, Nrf2, iNOS	[46]
7-Methoxyflavanone (7MF)	IL-6, TNF-α, COX-2, iNOS, ICAM-1, MCP-1, TLR4, MyD88, p-JNK, p-ERK, Nrf2, NQO-1, Iba1	[47]
Biseokeaniamide A	NO, iNOS, IL-1β, IkBα	[48]
Strigolactone GR24	NF-kB, Nrf2, PPARγ, occludin	[49]
Timosaponin BII	MDA, GSH, PS, NLRP3, IL-1β, oxidative stress	[50]
Cycloastragenol (Y006)	BAX, COX2, GSK3β, TNF-α, IFN-γ, IL-17, IL-10, IL-4	[51]
Ocellatin-K1(1-16); Ocellatin-K1(1-21)	Nitrite, MDA, SOD, GSH, ROS, NF-kB, oxidative stress	[52]
Leocarpinolide B (LB)	NO, PGE2, IL-6, TNF-α, MCP-1, COX-2, iNOS, NF-kB, ROS, HO-1, Nrf2	[53]
Enteromorpha powder	GSH-Px, MDA, lipid peroxidation	[54]
Aminooxyacetic acid (AOAA)	ATP, IL-6, TNF-α, IL-10, NLRP3, caspase-1, IL-1β	[55]
Gastrodin	ROS, 8-OHDG, MDA, GSH-Px, SOD, Nrf2, HO-1, Bcl-2, Bax, caspase-3	[56]
Cinnamtannin D1 (CTD-1)	IL-17, IL-6, IL-1β, TGF-β, IL-10, Th17, Treg, STAT5/Foxp3	[57]
ent-Kaur-15-en-17-al-18-oic acid	ROS, MDA, GSH, SOD, NF-kB, bcl-2, p53, Bax, caspase-3	[58]
Hederacoside-C (HDC)	IL-6, IL-1β, TNF-α, IL-10, TLR2, TLR4, MAPKs, NF-kB	[59]
PS-1145 dihydrochloride	IL-6, TNF-α, IL-1β, NF-kB, COX-2	[60]
Cytokine-induced apoptosis inhibitor 1 (CIAPIN1)	ROS, MAPKs, NF-kB, Bax, caspase-3, COX-2, iNOS, IL-6, TNF-α	[61]
Ruscogenin	CRP, TNF-α, IL-6, IL-1β, ICAM-1, NF-kB, NOS-1	[62]
Phascolosoma esculenta	IL-1β, TNF-α, IL-10, MDA, Nrf2, inflammation, oxidation	[63]
ALA/SFC	Anti-oxidation, RANKL, IL-6, Nrf2	[64]
Xanthoplanine	Inflammatory cytokines, ROS, STAT5	[65]
Lixisenatide	ROS, NADPH, NOX-1, TNF-α, IL-6, IL-1β, MMP -2 -9, TLR4, NF-kB	[66]
Germanium	MPO, TNF-α, IL-1β, IL-6, IL-10, NF-kB p65, p38, ERK, JNK	[67]
SDP	Permeability, ZO-1, E-cadherin, NFkB, Il-6, hydrogen peroxide, IL-10	[68]
Amomum tsaoko	IL-6, VEGF, Nh-kB, P-STAT3	[69]
Alkaline water	ROS, SOD-1, GSH, telomerase activity, telomeres length	[70]
Dihydrotestosterone	NO, PGE2, iNOS, COX-2, TNF-α, IL-1β, TLR4, NF-kB	[71]
Midazolam/Sufentanil	TNF-α, IL-1β, HMGB1, NF-kB, ROS, SOD, inflammatory	[72]
JNJ16259685	Permeability, VASP, p-VASP, occludin, AQP	[73]

Table 2 Recently identified potential inflammatory bowel disease treatments.

Treatment	Biomarkers changed in desired direction	Ref1	Ref2
Taraxasterol	ROS, MDA, Caspase-3, Bcl-2, Bax, Nrf2, HO-1, NQO-1, GPx-3	[74]	[75]
Rhodiola rosea; Salidroside	IL-6, sIL-6R, IFN-gamma, IL-17A, IL-4, Th1 cells, Th17 cells, Treg cells, JAK1, JAK2, STAT3, RORgammat	[76-78]	[79]
VAS2870	Nox2, ROS, Epithelium barrier integrity, Cell viability	[80]	[81]
Pinitol	Oxidative stress, ROS, TNF-alpha, IL-1beta, IL-6, NO, PGE2, iNOS, COX-2, IkappaBalpha, NF-kappaB, TREM2, Inflammation	[82]	[83]
TAK-242; Resatorvid	TLR4, Apoptosis, IL-1beta, Inflammation	[84]	[85]
Troxerutin	CK-mB, MDA, ROS, ATP	[86]	[87]
Vinpocetine	MAPK, NF-kB, MMP-9, AKT, ROS, Nrf2, HO-1, NQO-1, IL-1beta, TNF-alpha	[88]	[89]
Poria Cocos	ROS, MDA, SOD, LOX-1, Nrf2, HO-1, ERK, Oxidative stress	[90]	[91]
Carvacrol	Nrf2, ROS, MDA, SOD, Oxidative stress	[92]	[93]
Saururus Chinensis	NF-kB IL-6 IL-8	[94]	[95]