Table 3.

Pharmacological studies on anti-inflammation effects of cinnamon.

No	Extract /Main component	Part used	Model	design	Dosage/ duration of treatment	Mechanism/outcome	Ref
1	Ethanolic and water extracts /E-cinnamaldehyde and o-methoxy cinnamaldehyde	bark	In vitro	LPS and IFN-γ activated RAW 264.7 macrophages	–	1.LPS + IFN-γ induced NO, and TNF-α production was inhibited. 2.Potent activity in regards to inhibition of TNF-α production was observed. 3.Most of the inflammatory activity of cinnamon was caused by E-cinnamaldehyde and o-methoxy cinnamaldehyde.	[17]
2	polyphenol fraction	bark	In vivo/in vitro	Male Wistar rats or Swiss albino mice/ ConA-stimulated lymphocytes	50, 100, and 200 mg/kg/10 days	1.Serum TNF-α concentration was reduced. 2.Cytokines (IL-2, IL-4, and IFN-γ) release was inhibited. 3.Prostaglandin was inhibited.	[51]
3	Polyphenol Extract	–	In vitro	Mouse 3T3-L1 preadipocytes	–	1.TTP mRNA was induced 2.VEGF mRNA was reduced 3.The expression of multiple genes in adipocytes was regulated.	[52]
4	type-A procyanidin polyphenols	bark	In vivo	Adult male Wistar rats	10, 30 and 100 mg/kg/ 7 days	The inflammatory cell infiltration was reduced in lung tissue.	[53]
5	type-A procyanidin polyphenols	bark	In vivo	Carrageenan-induced rat paw edema in Wistar rats	4, 8 and 25 mg/kg/ Single dose	1.Serum C-reactive protein level was reduced. 2.Serum turbidity was reduced. 3.Anti-inflammatory and anti-arthritic effects in animal models without ulcerogenicity potential was exerted.	[54]
6	polyphenolic fraction	bark	In vivo	normal and cyclophosphamide-induced immune-compromised mice	10, 25, and 50 mg/kg p.o./ 7 days	1.Effect on body weights, HA titer, DTH responses, resident peritoneal macrophages, phagocytic activity, and resistance to E. coli induced abdominal sepsis was exerted. 2.Immunomodulatory activity on multiple arms of immunity was exerted.	[55]
7	cinnamaldehyde	bark	In vitro	RBL-2H3 cells and human mast cells isolated from intestinal tissue	–	1.Degranulation and mRNA expression was inhibited. 2.Mediator release was reduced. 3.Cytokine expression was reduced, but not the expression of proteases. 4.Activation of ERK and PLCγ1 was inhibited. 5.No apoptotic effect was observed. 6.Release and expression of pro-inflammatory mast cell mediators were decreased.	[56]
8	hydroalcoholic extract/ type-A procyanidins polyphenols	bark	In vivo	in ovalbumin-induced experimental allergic rhinitis in BALB/c mice	3, 10 and 30 μg/kg in nostril/ twice daily for 8 days	1.Alterations of the nasal, biochemical markers (serum IgE and histamine), hematological, morphological, and histopathological parameters were attenuated. 2.Anti-allergic efficacy in an animal model of allergic rhinitis was observed.	[57]
9	alcohol extract/ pentameric procyanidin type A polyphenol polymer (IND0)	bark	In vitro	Human leukemia monocytic THP-1 cells	–	1.The attachment of THP-1 cells or neutrophils to TNF-α-activated HUVECs or E-selectin/ICAM-1 was reduced. 2.The binding of E-, L- and P-selectins with sialosides was reduced. 3.Interacting with sialosides and blocking the binding of selectins and leukocytes with sialic acids were observed.	[58]
10	Type-A procyanidin polyphenols	Bark	In vitro	isolated rat peritoneal mast cells	–	1.The number of degranulated cells and levels of markers (histamine, β-HEX, and IL-4) was decreased in a dose-dependent manner. 2.Mast cell was stabilized, and the allergic markers such as histamine, IL-4, and β-HEX in an IgE-mediated manner were inhibited.	[59]
11	ethyl alcohol and methyl alcohol extracts	bark	In vivo	collagen-induced arthritic BALB/c mice	1,2 and 4 mg/Kg body weight/ 2 weeks	1.Swelling in the spleen was reduced along with the generation of free radicals by lymphocytes. 2.NFATc3, TNF-a, CAII, and mCalpain, all proteins involved in RA was inhibited.	[60]
12	essential oil blends	NM	In vitro	validated human cell cultures	–	1.Effects on the levels of protein biomarkers that are critically involved in inflammation, immune modulation, and tissue remodeling processes were exhibited. 2.Signaling pathways such as mitotic roles of the polo-like kinase canonical pathway were affected. 3.The role of CHK proteins in the cell cycle checkpoint control pathway related to inflammation function was affected. 4.BRCA1 was downregulated. 5.Anti-inflammatory and immune-modulating properties were observed due to the inhibitory effect on protein biomarkers. 6.Global gene expression was modulated.	[61]
13	Essential Oil	bark	In vitro	human dermal fibroblast system, a model of chronic inflammation and fibrosis	–	1.Vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, IFN-γ - induced protein 10, T-cell alpha chemoattractant, and monokine were decreased. 2.Epidermal growth factor receptors, MMP-1, and PAI-1 were decreased. 3.M-CSF was inhibited. 4.Global gene expression was modulated, and signaling pathways, which are essential in inflammation, were altered. 5.Anti-inflammatory effects were observed.	[62]
14	aqueous-alcoholic extraction/ polyphenol extract	NM	In vivo	Hepatic transcription factors expressions including SREBP-1c and LXR-a in rats fed a high-fat diet	100 mg/kg body weight/ 12 weeks	1.Bodyweight, visceral fat, liver weight, serum glucose, insulin concentrations, liver antioxidant enzymes, and lipid profile were decreased. 2.Reduction of serum and liver MDA 3.The hepatic SREBP-1c, LXR-a, ACLY, FAS, and NF-kB p65 expressions were suppressed 4.The PPARa, IRS-1, Nrf2, and HO-1 expressions were enhanced. 5.The reduction of hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathways was reduced.	[63]
15	Ethanolic extracts	bark	In vitro	THP-1 monocytes and HeLa-TLR4 transfected reporter cells	–	1.TLR4 and TLR2 signaling pathways were mitigated. 2.NF-κB translocation was inhibited. 3.The highest anti-inflammatory potential, up to complete inhibition of pro-inflammatory cytokine production, was observed.	[64]
16	70% aqueous ethanolic extract	bark	In vitro	toll-like receptors TLR2 and TLR4	–	1.The phosphorylation of Akt and IκBα was mitigated. 2.The LPS-dependent IL-8 secretion in THP-1 monocytes was reduced dose-dependently. 3.Any toxic effects were excluded due to the High viability of the cells.	[65]
17	essential oil	bark	In vivo	Acute pneumonitis mouse model	6 oil drops (0.15 mL)/ 90 min	1.The Vanilloid 1 or Ankyrin 1 ion channels were mediated. 2.Inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters were reduced.	[66]
18	70% aqueous ethanol	bark	In vitro/in vivo	monocyte-derived mature dendritic cells /immunized- BALB/c mice with ovalbumin	1 mL/kg body weight/every other day/ 23 days	1.DC maturation and subsequent allergen-specific T cell proliferation and Th1 and Th2 cytokine production were inhibited. 2.Sulphidoleukotriene release and CD63 expression by basophils were diminished. 3.The shift from OVA-specific IgE towards IgG2a production and to potent inhibition of OVA-specific proliferation was observed. 4.Calcipotriol-induced atopic dermatitis-like inflammation was prevented.	[67]
19	Cinnamic aldehyde	NM	In vitro	Articular Chondrocyte and Human Osteoarthritis	–	1.The expression levels of IL-1b, IL-6, TNF-a, MMP13, and ADAMTS-5 were decreased by inhibiting the NF-kB signaling pathway. 2.LPS-stimulated NF-kB activation was suppressed.	[68]
20	aqueous extracts and methanolic extracts	bark	In vitro	mouse macrophage and human chondrosarcoma cell lines as well as in human primary chondrocytes	–	1.NO, PGE2, LTB4, and MMP production were suppressed. 2.Anti-inflammatory activity was observed more in C. zeylanicum compared to C.cassia.	[69]
21	polyphenol-rich standardized extract of cinnamon bark extract	bark	Clinical trial	A randomized, double-blind placebo-controlled study	200 µg/100 µL/day/ 8 days	1.The onset of allergic inflammation was modulated by acting directly on immune cells. 2.the severity of the symptoms of SAR was decreased 3.General activity impairment was reduced along with a corresponding improvement in quality of life and work productivity.	[70]

NM: not mentioned, LPS: Lipopolysaccharides, NF-kB: Nuclear factor- kappaB, TNF-a: tumor necrosis factor-a, IL: interleukin, PGE2: prostaglandin E2, HO: heme- oxygenase, NRF2: Nuclear factor erythroid 2-related factor 2, Th: T helper, IFN: Interferon, TTP: Tristetraprolin, VEGF: Vascular endothelial growth factor, ERK: extracellular signal-regulated kinases, NO: nitric oxide, IκBα: inhibitor of nuclear factor kappa B, MDA: Malondialdehyde, M-CSF: Macrophage-colony stimulating factor, HA: Haemagglutination, DTH: delayed-type hypersensitivity, PLCγ1: Phospholipase Cγ1, ConA: Concanavalin A, IgE: Immunoglobulin E, HUVECs: Human umbilical vein endothelial cells, ICAM-1: Intercellular Adhesion Molecule 1, β-HEX: Bet-hexosaminidase CAII: Carbonic anhydrase-II, BRCA1: breast cancer 1, PAI-1: Plasminogen activator inhibitor-1, SREBP-1: sterol regulatory element-binding protein 1, LXRs: liver X receptors, ACLY: ATP-citrate lyase, FAS: fatty acid synthase, PPARα: peroxisome proliferator-activated receptor α, DC: dendritic cells, OVA: ovalbumin, ADAMTS-5: A disintegrin and metalloproteinase with thrombospondin motifs 5, LTB4: Leukotriene B4, NFATc3: Nuclear Factor Of Activated T Cells 3, CHK: checkpoint kinase, MMPs: Matrix metalloproteinases, TLR: Toll-like receptor