Journal of Translational Medicine

Table 2 Spice derived compounds and their mechanism of actions against different chronic diseases

From: Chronic diseases, inflammation, and spices: how are they linked?

Compound	Chronic diseases	Mechanism of action	References
1,8-cineole	Alzheimer’s disease	↓NOS-2, ↓COX-2, ↓NF-κB	[67]
	Bronchial asthma	↓PGE2, ↓LTB4	[186]
	Colitis	↓Myeloperoxidase	[38]
	COPD	–	[69]
	Pancreatitis	↓NF-κB	[66]
	Ulceration	↓Myeloperoxidase	[38]
6-gingerol	Allergic rhinitis	↓T cell activity	[75]
	Alzheimer’s disease	↑Nrf2	[72]
	Colorectal cancer	↑NAG-1	[70]
	Diabetes	↓VEGF	[71]
	Osteoporosis	↓TNF-α	[187]
	Steatohepatitis	↓NF-κB, ↓TNF-α, ↓IL-6	[73]
α-Pinene	Acute pancreatitis	↓TNF-α, ↓IL-1β, ↓IL-6	[78]
	Arthritis	↓JNK, ↓iNOS, ↓MMP-1, ↓MMP-13	[188]
	Rhinitis	↓IKK-β, ↓Caspase-1	[76]
Allicin	Ankylosing spondylitis	↓IL-6, ↓IL-8, ↓TNF-α	[189]
	Alzheimer’s disease	↑Nrf2	[190]
	Chronic kidney disease	↑Nrf2	[191]
	Gastric cancer	↑G2/M arrest, ↑ER stress	[192]
	Glioblastoma multiforme	↓ERK	[193]
	Hypercholesterolemia	↓TNF-α, ↓NF-κB	[194]
	Recurrent aphthous ulcer	↓TNF-α	[195]
	Type 1 diabetes	–	[196]
	Ulcerative colitis	↓IL-6, ↓STAT3	[18]
Anethole	Breast cancer	↓NF-κB	[197]
Anethole	Bronchial dysplasia	–	[198]
Capsaicin	Atherosclerosis	↑TRPV1	[199]
	Alzheimer’s disease	↑Synapsin I; ↑PSD93	[112]
	Bladder cancer	↓FOXO3a	[110]
	Cholangiocarcinoma	↑PI3K/Akt/mTOR	[200]
	Colon cancer	↑Caspase-8, -9, -3	[201]
	Gastrointestinal disorders	–	[202]
	Lung cancer	↓E2F	[114]
	Cardiac hypertrophy and fibrosis	↑TRPV1	[199]
	Pancreatitis	↓ERK, ↓c-Jun, ↓Hedgehog	[203]
	Prostate cancer	↓p27	[113]
Carvacrol	Arthritis	↓Myeloperoxidase	[204]
	Asthma	↓IL-4, ↓TGF-β, ↓IL-17	[205]
	Atherosclerosis	↓MAPK	[206]
	Colon cancer	↓iNOS, ↓IL-1β	[207]
	COPD	↑IL-8	[31]
	Gastric ulcers	↓Prostanoids	[208]
	Intestinal mucositis	↑TRPA1 receptor	[209]
	Pancreatitis	↓AST, ↓ALT, ↓LDH	[210]
	Periodontitis	↓Myeloperoxidase	[211]
Cardamom	Colon cancer	↓COX-2, ↓iNOS	[212]
Cardamom	Forestomach cancer	↑GSH, ↓LDH	[213]
Carnosol	Brain damage by chronic stress	↑MDA	[214]
	Colon cancer	–	[215]
	Lymphoma	–	[215]
Cinnamon	Arthritis	↓IL-2,-4, ↓IFNγ	[120]
	Alzheimer’s disease	↑p21rac	[121]
	Colitis	↓COX-2	[216]
	Diabetes	↓AP-1	[217]
	Hyperglycemia	↑PPARγ	[218]
	Inflammatory disorders	↓p38, ↓JNK, ↓ERK1/2, ↓STAT4	[219]
	Melanoma	↓AP-1	[217]
	Multiple sclerosis	↑Tregs	[119]
	Parkinson’s disease	↓ Aβ polypeptide	[122]
Coriander	Alzheimer’s disease	↓Aβ42-induced ROS, ↓ERK	[220, 221]
	Atherosclerosis	–	[222]
	Colitis	–	[223]
	Dermatitis	↓IgE, ↓TNF-α, ↓INFγ, ↓IL-1,-4,-13	[224]
	Diabetes	↑Insulin release	[225]
	Rheumatism	–	[226]
Crocin	Alzheimer’s disease	↓Aβ peptide	[227]
	Asthma	↓p-ERK, ↓p-JNK, ↓p-p38	[228]
	Colitis	↓INFγ, ↓COX-2	[16]
	Diabetes	↓TNF-α, ↓IL-1β	[229]
	Liver cancer	↓NF-κB, ↓TNF-α, ↓IL-6, -10	[230]
	Rheumatoid arthritis	↓iNOS, ↓TNF-α, ↓IL-1β, -6	[231]
Curcumin	Alzheimer’s disease	↑PI3K, ↑Akt	[87]
	Asthma	↑Nrf2/HO-1	[89]
	Atherosclerosis	↓IL-1β, -6, ↓TNF-α, ↑PPARγ	[232]
	Cancer	↓Multiple pathways	[160, 161]
	Chagas myocarditis	↓NFAT/COX-2/PGE2	[233]
	COPD	↓p66Shc	[234]
	Colitis	↓STAT3	[235]
	Diabetes	↓NF-κB, ↓NO	[236]
	Epilepsy	↓IL-1β, ↓IL-6, ↓TNF-α	[237]
	Gastric ulcer	↓Acetylation of histone H3	[238]
	Hepatitis	↓PGC-1α	[239]
	Irritable bowel disease	↓p38 MAPK, ↓IL-1β, -10	[240]
	Lupus nephritis	↓IgG1, ↓IgG2a	[241]
	Oral lichen planus	–	[240]
	Psoriasis	↓TNF-α, ↓IFN-γ, ↓IL-2, -12, -22,	[242]
	Prostatitis	↓IL-8, ↓TNF-α	[88]
	Ulcerative proctitis	–	[240]
	Uveitis	–	[240]
Diallyl sulphide	Asthma	↑Nrf2	[79]
	Colon cancer	–	[82]
	Prostate cancer	↑Caspases-3,-9,-10, ↓Bcl-2	[84]
	Osteoarthritis	↓MMP-1,-3,-13, ↓IL-1β	[81]
	Skin cancer	↑Apoptosis	[83]
Diosgenin	Alzheimer’s disease	↑1,25D3-MARRS	[243]
	Breast cancer	↓Vav2	[93]
	Chronic myeloid leukemia	↓PI3K/Akt/mTOR	[94]
	Diabetes	–	[244, 245]
	Graves’ disease	↓IGF-1, ↓NF-κB, ↓cyclin D1, ↓PCNA	[246]
	Hepatitis C	↓STAT3	[96]
	Liver cancer	↑Caspase-3, -8,-9	[97]
	Osteoarthritis	↓IL-1β	[95]
	Osteoporosis	↓RANKL, ↑OPG	[247]
	Prostate cancer	↓PI3K/Akt/mTOR	[98]
Eugenol	Asthma	↓NF-κB	[101]
	Atherosclerosis	↓ALP, ↓LDH, ↓HMG-CoA	[248]
	Breast cancer	↓E2F1/survivin	[103]
	Cervical cancer	↓Bcl-2, ↓COX-2, ↓IL-1β	[102]
	Depression	↑MTT-III	[249]
	Diabetes	↓AST, ↓ALT, ↓LDH, ↓ALP	[100]
	Gastric cancer	↓NF-κB	[104]
	Hepatic steatosis and fibrosis	↓SREBP1	[250]
	Hyperglycemia	↓Glycogen phosphorylase b	[251]
	Skin cancer	↓NF-κB, ↓iNOS, ↓IL-6, ↓TNF-α, ↓PGE2	[252]
Garcinol	Allergy	↓STAT3	[106]
	Breast cancer	↓Caspase-3, ↓NF-κB	[125]
	Cardiovascular diseases	↓STAT3	[106]
	Colon cancer	↓PK 1/2, PI3K/Akt/p70 ribosomal S6 kinase	[123]
	Diabetes	↓STAT3	[106]
	Head and neck cancer	↓STAT3, ↓NF-κB	[126]
	Lung cancer	↓p38-MAPK	[127]
	Oral squamous cell carcinoma	↓NF-κB	[116]
	Pancreatic cancer	↓Wnt/β-catenin, ↓miR-200s	[128]
	Prostate cancer	↑mTOR, ↑Akt	[253]
Limonene	Asthma	↓IL-5, -13, ↓MCP-1	[254]
	Breast cancer	–	[255]
	Colitis	↓NF-κB	[256]
	Colorectal cancer	–	[255]
	Skin cancer	↓Ras-ERK	[257]
Linalool	Diabetes	↓TGF-β1	[258]
	Skin cancer	↓IL-6, ↓COX-2, ↓VEGF, ↓Bcl-2	[259]
	Leukemia	↑p53, ↑p21, ↑p27, ↑p16, ↑p18	[260]
	Cervical cancer	↑p53, ↑p21, ↑p27, ↑p16, ↑p18	[260]
	Colon cancer	↑Hydroxy radical	[261]
Menthol	Pancreatic cancer	↓Focal-adhesion kinase	[262]
	Depression	↑IL-1β,-6, ↑TNF-α	[263]
	Skin cancer	↓NF-κB, ↓ERK, ↓p38	[264]
	Napkin dermatitis	–	[265]
	Neuropathic pain	↑TRPM8	[266]
Macelignan	Alzheimer’s disease	–	[267]
	Asthma	↓IL-4, ↓GATA3	[268]
	Type 1 allergy	↓Akt, ↓TNF-α, ↓MAPK, ↓c-Jun	[269]
Piperine	Alzheimer’s disease	–	[270]
	Arthritis	↑IL-10	[151]
	Asthma	↓IL-4, -5, ↓NF-κB	[150]
	Breast cancer	↑p53, ↓MMP-9,-2, ↓c-Myc, ↓VEGF	[271]
	Chronic gastritis	↓IL-1β, ↓IFN-γ, ↓IL-6, ↓iNOS	[272]
	Colorectal cancer	–	[273]
	Depression	↑BDNF	[274]
	Endometritis	↓NF-κB, ↓MAPK	[148]
	Fibrosarcoma	↓MMP-9	[275]
	Gastric cancer	↓STAT3	[154]
	Parkinson’s disease	↓IL-1β, ↓TNF-α	[276]
	Triple negative breast cancer	↓Survivin, ↓p65	[277]
	Ulcerative colitis	–	[278]
Quercetin	Arthritis	↓NF-κB, ↓1β, ↓MCP	[139]
	Atherosclerosis	↑Akt	[147]
	Atopic dermatitis	↓JAK-STAT	[142]
	Breast cancer	↓Twist	[140]
	Diabetes mellitus	–	[143]
	Hepatitis	↑Nrf2	[138]
	Inflammatory bowel disease	↑GSH	[141]
	Periodontitis	↓IL-1β, ↓TNF-α, ↓RANKL, ↓iCAM-1	[279]
	Psoriasis	–	[144]
Rosmarinic acid	Asthma	↓ERK, ↓JNK, ↓p38MAPK	[19]
	Amyotrophic lateral sclerosis	↓HNE	[280]
	Colitis	↓NF-κB, ↓STAT3	[281]
	Colorectal cancer	↓IL-6/STAT3	[282]
	Gastric cancer	↓IL-6/STAT3	[283]
	Hepatocellular carcinoma	↓NF-κB	[284]
	Leukemia	–	[285]
	Neuropathic pain	↓COX-2, ↓PGE2, ↓IL-1β, ↓MMP-2	[286]
	Osteoporosis	↓NFATc1	[287]
	Pancreatitis	↓NF-κB	[288]
	Psoriasis	↓IL-1β, ↓IL-6, -8, ↓CCL20, ↓TNF-α	[289]
	Rhinoconjunctivitis	↓iCAM-1, ↓VCAM-1, ↓COX-2, ↓MIP-2	[290]
Sesamin	Asthma	↓IκB-α, ↓NF-κB	[291]
	Atherosclerosis	↓MCP-1, ↓IL-1α, ↓IL-6, ↓CXCL-16	[292]
	Breast cancer	↓VEGF, ↓MMP-9	[293]
	Diabetes	↓FBS, ↓HbA1C, ↓TNF-α	[294]
	Gall bladder carcinoma	↓NF-κB-IL-6-Stat3-Twist	[295]
	Osteoarthritis	↑Nrf2	[296]
	Prostate cancer	↓p38-MAPK, ↓NF-κB	[297]
Sulforaphane	Alzheimer disease	↑NLRP3	[298]
	Atherosclerosis	–	[299]
	Breast cancer	↓Bcl-2, ↑Caspase-3,-9	[158]
	Cardiovascular diseases	↑Nrf2	[155]
	Colorectal cancer	↑AP-1	[158]
	Diabetes	↓RAGE	[157]
	Lung cancer	↓Bcl-2, ↑Caspase-3, ↑Bax	[158]
	Multiple sclerosis	↑Nrf2	[159]
Tocopherol	Atherosclerosis	↓IL-6,-10, ↓MCP-1, ↓TNF-α	[300]
	Colitis	↓IL-6	[301]
	Colon cancer	↓8-HDOG, ↓γ-H2AX	[302]
	Lung cancer	↓8-HDOG, ↓γ-H2AX	[302]
	Mammary hyperplasia	↓PCNA, ↓COX-2, ↑PPARγ, ↑Nrf2	[303]
Thymol	Asthma	↓NF-κB	[304]
	Endometritis	↓TNF-α, ↑IL-1β, ↑iNOS, ↑COX-2	[305]
	Gastric ulcer	↑ PGEs, ↑ATP K(+) channels	[306]
	Mastitis	↓IκBα, ↓NF-κB, ↓ERK, ↓JNK	[307]
Thymoquinone	Allergic conjunctivitis	↓Eosinophils, ↓IgE, ↓histamine	[133]
	Asthma	↓CD31, ↓α-SMA	[131]
	Bladder cancer	↓NF-κB, ↓XIAP	[134]
	Cholangiocarcinoma	↓PI3K/Akt, ↓NF-κB	[308]
	Depression	↓TBARS, ↑GSH	[309]
	Diabetes mellitus	↓p44/42, ↓p38-MAPKs	[310]
	Gastric cancer	↓STAT3, ↓JAK2, ↓c-Src	[137]
	Lung cancer	↓PCNA, ↓CD1, ↓MMP-2, ↓ERK1/2	[135]
	Multiple myeloma	↓Ki-67, ↓VEGF, ↓Bcl-2, ↓p65	[311]
	Myeloid leukemia	↓NF-κB, ↓CD1, ↓COX-2, ↓MMP-9	[312]
	Osteoarthritis	↓IL-1β-induced MMP-1,-3,-13	[130]
	Ovarian cancer	↑pH2AX, ↓NF-κB	[136]
	Rheumatoid arthritis	↓ASK1	[132, 313]
	Rhinosinusitis	–	[314]
Ursolic acid	Asthma	↓IL-5, -13	[315]
	Colitis	↓NF-κB	[316]
	Prostate cancer	↑Caspase-3,-9, ↓ROCK/PTEN	[317]
	Rheumatoid arthritis	↓PGE2	[318]

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