TABLE 2.

Preclinical pharmacological activities of Cinnamomum genus.

Pharmacological activity	Cinnamum plant/extracts/fractions	Methods	Models cellular lines (in vitro)/animal (in vivo)	Effects/underlying mechanisms	Ref
Antimicrobial	Cinnamomum altissimum/stem bark/EOs	Disk diffusion	MRSA	IC50 = 12.0 mm	Buru et al. (2014)
				↓bacterial growth
		Microdilution	MRSA	IC50 = 156.25 μg/ml
				↓ bacterial growth
	Cinnamom umbejolghota/leaves/EOs	Disk diffusion	Escherichia coli	19.5 mm	Wannissorn et al. (2005)
			Salmonella saintpaul	17.5 mm
			Salmonella derby	16.5 mm
			Salmonella gallinarum	34 mm
			Salmonella schwarzergrund	16.5 mm
			Salmonella mbandaka	18 mm
			Salmonella monterideo	16.5 mm
	Cinnamom umburmanni Leaves/EOs	Microdilution	Staphylococcus aureus	IC50 > 2,500 μg/ml	Shan et al. (2007)
			Listeria monocytogenes	IC50 > 2,500 μg/ml
			Salmonella anatum	IC50 > 2,500 μg/ml
			Escherichia coli	IC50 > 2,500 μg/ml
	Cinnamomum cassia leaves/EOs	Microdilution	Pseudomonas putida	IC50 = 500 mg/L	Oussalah et al. (2006)
	Cinnamomum cassia leaves/EOs	Microdilution	Bacillus cereus	IC50 = 500 mg/L	Turgis et al. (2012)
			Escherichia coli	IC50 = 500 mg/L not determined
			Staphylococcus aureus
	Cinnamomum cassia/shoots/methanol	Disk diffusion	Escherichia coli	13 mm	Kim et al. (2004)
		Microdilution		IC50 = 250–500 μg/ml
	Cinnamomum cassia bark/EOs	Disk diffusion	Listeria monocytogenes	22.4 mm	de Oliveira et al. (2012)
		Microdilution		IC50 = 0.03 μg/ml
		Agar disc diffusion	Bacillus subtilis	21.1 mm	(Huang et al., 2014)
			Salmonella typhimurium	14.5 mm
			Staphylococcus aureus	27.5 mm
		Microdilution	Staphylococcus aureus	IC50 = 2.5–5 mg/ml
		Microdilution assay	Bacillus subtilis	IC50 = 10 mg/ml
			Salmonella typhimurium	IC50 = 20 mg/ml
			Escherichia coli	IC50 = 10 mg/ml
		Permeability of cell membrane	Staphylococcus aureus	↑ permeability of wall cell
			Escherichia coli
	Cinnamomum chemungianum leaves/EOs	Disk diffusion	Staphylococcus aureus	7 mm	Rameshkumar et al. (2007)
			Bacillus subtilis	8 mm
			Salmonella typhi	9 mm
			Escherichia coli	12 mm
			Pseudomonas fluorescens	7 mm
			Proteus vulgaris	7 mm
			Klebsiella pneumoniae	11 mm
	Cinnamomumim pressicostatum stem bark/VO	Disk diffusion	MRSA	14.5 mm	Buru et al. (2014)
		Microdilution		IC50 = 156.3 μg/ml
	Cinnamomum iners stem bark/VO	Disk diffusion	MRSA	10.5 mm	Buru et al. (2014)
		Microdilution		IC50 = 625.0 μg/ml
	Cinnamomum longepaniculatum leaves/VO	Microdilution	Escherichia coli	IC50 = 3.1 μL/ml	Li et al. (2014)
			Salmonella enteritidis	IC50 = 6.3 μL/ml
			Staphylococcus aureus	IC50 = 6.3 μL/ml
	Cinnamomummicranthum leaves/EOs	Diffusion method	Vibrio parahemolyticus	2 mm	Yeh et al. (2009)
			Vibrio alginolyticus	3 mm
			Vibrio alginolyticus	3 mm
			Vibrio vulnificus	2 mm
			Lactococcus garvieae	1 mm
			Debaryomyces hansenii	1 mm
			Photobacteria damsel	1 mm
			Streptococcus sp	1 mm
			Eromonas hydrophila	2 mm
	Cinnamomum micranthum twig/EOs	Diffusion method	Vibrio parahemolyticus	5 mm
			Vibrio alginolyticus	5 mm
			Vibrio alginolyticus	6 mm
			Vibrio vulnificus	5 mm
			Lactococcusgarvieae	3 mm
			Debaryomyces hansenii	4 mm
			Photobacteria damsel	7 mm
			Streptococcus sp	7 mm
			Eromonas hydrophila	1 mm
Cinnamomum osmophloeum leaves/EOs	Microdilution	Escherichia coli	IC50 = 250 μg/ml	Chang et al. (2001), Chang et al. (2008)
		Enterococcus faecalis	IC50 = 250 μg/ml
		Klebsiella pneumoniae	IC50 = 500 μg/ml
		Salmonella sp	IC50 = 500 μg/ml
		Vibrio parahemolyticus	IC50 = 250 μg/ml
		Staphylococcus epidermidis	IC50 = 250 μg/ml
		MRSA	IC50 = 250 μg/ml
		Legionella pneumophila	IC50 = 1,000 μg/ml
Cinnamomum porrectum stem bark/VO	Disk diffusion	MRSA	7.5 mm	Buru et al. (2014)
	Microdilution		IC50 = 500 μg/ml
Cinnamomum tamala stem bark/methanolic extract	Agar well diffusion	Escherichia coli	Without inhibition	Goyal et al. (2009)
		Salmonella typhi	11 mm
		Bacillus cereus	14 mm
		Bacillus subtilis	14 mm
		Staphylococcus aureus	20 mm
		Streptococcus pyogenes	13.5 mm
		Staphylococcus aureus	IC50 = 256 μg/ml
		Streptococcus pyogenes	IC50 = 4,096 μg/ml
		Bacillus subtilis	IC50 = 4,096 μg/ml
Cinnamomum verum bark/EOs	Microdilution	Staphylococcus aureus	IC50 = 0.55 mg/ml	Unlu et al. (2010)
		Streptococcus pyogenes	IC50 = 0.55 mg/ml
		Streptococcus pneumoniae	IC50 < 0.04 mg/ml
		Enterococcus faecalis	IC50 = 1.15 mg/ml
		Enterococcus faecium	IC50 = 1.12 mg/ml
		Bacillus cereus	IC50 = 0.56 mg/ml
		Acinetobacter lwoffii	IC50 < 0.04 mg/ml
		Enterobacter erogenes	IC50 = 0.56 mg/ml
		Escherichia coli	IC50 = 1.12 mg/ml
		Klebsiella pneumoniae	IC50 = 0.14 mg/ml
		Proteus mirabilis	IC50 = 0.14 mg/ml
		Pseudomonas eruginosa	IC50 = 0.28 mg/ml
		Salmonella typhimurium	IC50 = 0.14 mg/ml
		Mycobacterium smegmatis	IC50 = 0.07 mg/ml
		Clostridium perfringens	IC50 = 0.14 mg/ml
		Listeria ivanovii	IC50 = 0.56 mg/ml
		Listeria innocua	IC50 = 0.28 mg/ml
		Listeria welshimeri	IC50 = 0.56 mg/ml
		Listeria seeligeri	IC50 = 0.56 mg/ml
Cinnamomum verum bark/aqueous	Disk diffusion	Moraxella cattarhalis	11 mm	Rasheed and Thajuddin. (2011)
	Microdilution	Moraxella cattarhalis	IC50 = 120 mg/ml
Cinnamomum verum bark/EOs	Microdilution	Pseudomonas eruginosa	IC50 = 0.1125 mg/ml	Utchariyakiat et al. (2016)
Cinnamomum verum bark/methanolic	Disk diffusion	Proteus mirabilis	5 mm	Hameed et al., (2016)
		Pseudomonas eurogenosa	4 mm
		Escherichia coli	5.4 mm
		Klebsiella pneumonia	6 mm
		Staphylococcus aureus	5.2 mm
Cinnamomum verum bark/EOs	Microdilution	Acinetobacter spp.	IC50 = 625 μg/ml	Guerra et al., (2012), Noudeh et al., (2010)
		Staphyllococcus aureus	IC50 = 0.2 mg/ml
		Bacillus subtilis	IC50 = 0.4 mg/ml
		Escherichia coli	IC50 = 0.1 mg/ml
		Pseudomonas eruginosa	IC50 = 0.2 mg/ml
		Agrobacterium tumefaciens	IC50 = 12.5 mg/ml
	Disk diffusion	Staphylococcus aureus	17.2 mm	Al-Bayati and Mohammed, (2009)
		Bacillus cereus	18.3 mm
		Escherichia coli	15.7 mm
		Proteus mirabilis	15.2 mm
		Klebsiella pneumonia	17.5 mm
		Pseudomonas eruginosa	14.4 mm
		Staphylococcus aureus	IC50 = 62.5 μg/ml
		Bacillus cereus	IC50 = 1.2 μg/ml
		Escherichia coli	IC50 = 62.5 μg/ml
		Proteus mirabilis	IC50 = 125.0 μg/ml
		Klebsiella pneumonia	MIC = 62.5 μg/ml
		Pseudomonas eruginosa	MIC = 125.0 μg/ml
	Membrane permeability reduction test	Escherichia coli	↓wall cell permeability	Yap et al. (2015)
	Microdilution	Pseudomonas putida	IC50 = 1 mg/ml	Oussalah et al. (2006)
Antidiabetic	In vitro studies
	Cinnamomum verum bark/aqueous	α-amylase, a-glucosidase inhibition		IC50 = 0.5, 1.25, 2.5 mg/ml	Ranilla et al. (2010)
				↓α-amylase, ↓α-glucosidase
	Cinnamomum verum bark/methanol	Yeast a-glucosidase, rat-intestinal a-glucosidase inhibition		IC50 = 5.83 μg/ml	Shihabudeen et al. (2011)
				↓yeast a-glucosidase
				IC50 = 670 μg/ml
				↓mammalian a-glucosidase
	Cinnamomum cassia (L.) J. Presl/Bark/acetone and aqueous	Glucosidase, sucrase, maltase inhibition		↓α-glucosidase inhibitory activity ↑ sucrase and maltase inhibition	Kang et al. (2014)
	Cinnamomum osmophloeum twig/aqueous	PTP1B, a-glucosidase,α-amylase inhibition		↓ a-amylase, ↓α-glucosidase ↓ PTP1B	Lin et al. (2016)
	In vivo studies
	Cinnamomum burmanni (nees and T. Nees) blume/bark/aqueous	Rats/very high fat diet induced hyperglycemia 500, 300 mg/b.w.; oral		↓FBG, dose dependent manner	Cheng et al. (2012)
	Cinnamomum cassia (L.) J. Presl/bark/aqueous	Rats/glucose 2 g/kg b.w. ip; 85.7 mg/b.w oral		↓blood glucose control: Glibenclamide	Verspohl et al. (2005)
	Cinnamomum cassia (L.) J.Presl/aqueous	Mice/STZ induced diabetes; 100 mg/kg/day; oral		↓blood glucose	Chen et al. (2013)
				↑insulin
	Cinnamomum cassia (L.) J.Presl/Bark/Methanol	Mice/STZ induced diabetes; 200 mg/b.w.; oral		↓ blood glucose	Kim et al. (2006)
	Cinnamomum cassia (L.) J. Presl bark/aqueous	Rats/alloxan induced diabetes 60 mg/b.w.; oral		↓blood glucose	Kamble and Rambhimaiah, (2015)
	Cinnamomum porrectum bark/polyphenols rich extract	Rats/STZ induced diabetes 100,200,300 mg/b.w.; oral		↓blood glucose	Jia et al. (2009)
	Cinnamomum tamala/leaves/ethanol	Rats/alloxan induced diabetes; 500 mg/b.w.; oral		↓ blood glucose	Kar et al. (2003)
	Cinnamomum tamala leaves/essential oil	Rats/STZ induced diabetes 10, 200 mg/b.w.; oral		↓ blood glucose	Kumar et al. (2012)
	Cinnamomum verum bark/water-soluble polyphenols	Rats/STZ induced diabetes 200 mg/kg, oral		↑weight loss ↓FBG, ↓PPG	Krishnakumar et al. (2014)
	Cinnamomum verum bark/volatile oil	Rats/STZ induced diabetes 20 mg/kg; oral		↓plasma glucose	Subash Babu et al. (2007)
	Cinnamomum verum essential oil	Rats/STZ induced diabetes 20 mg/kg; oral		↓blood glucose	Al-LogmaniI and Zari, (2009)
	Cinnamomum verum stem bark/chloroform	Rats/STZ induced diabetes 20 mg/kg; oral		↑muscle glycogen	Anand et al. (2010)
				↑hepatic glycogen
				↓FBG
	Cinnamomum verum bark/volatile oil	Rats/alloxan induced diabetes 5, 10, 20 mg/kg; oral		↓FBG, dose-dependent manner	Mishra et al. (2010)
				↓cholesterol
				↓urinary protein
				↓TBARS
				↓blood urea
				↓catalase
	Cinnamomum verum bark/volatile oil	Rats/alloxan induced diabetes		↓FBG, dose-dependent manner	Rajbir et al. (2009)
		5, 10 and 20 mg/kg; oral
	Cinnamomumverum sticks/Aqueous	Rats/STZ induced diabetes		↓blood glucose, dose-dependent manner	Shen et al. (2010)
		3, 30 and 100 mg/kg; oral
	Cinnamomumverum bark/aqueous	Rats/oral glucose tolerance test		↓glycemic levels	Kannappan et al. (2006)
		0.2 ml day/rat; oral
	Cinnamomum verum/bark/methanol	Rats/STZ induced diabetes		↓ postprandial hyperglycemia	Shihabudeen et al. (2011)
		300 mg/kg; oral
Anti-inflammatory	In vitro studies
	Cinnamomum cassia/cinnamic aldehyde	RAW 264.7, LPS stimulated mice macrophages		IC50= 0, 6.25, 12.5, 25, 50 μM anti-inflammatory	Liao et al. (2012a)
	Cinnamomum camphora/total crude extract/80% methanol, hexane, ethyl acetate fractions	RAW 264.7, LPS stimulated mice macrophages		IC50= 100 μg/ml anti-inflammatory	Lee et al. (2006)
	In vivo studies
	Cinnamomum cassia bark oil/cinnamaldehyde	Rats		dose = 2–6 mg/kg bw	Chua et al. (2008)
				↓NF-kB
	Cinnamomum cassia cinnamic aldehyde	Mice/carrageenan induced paw edema		dose = 1.25, 2.5, 5 mg/kg/bw	Liao et al. (2012a)
				Anti-inflammatory
Anti-cancer	In vitro studies
	C. burmanni stem bark/methanolic	NPC/HK1, C666–1, human cancer cell lines		↑cytotoxicity	Daker et al. (2013)
				IC50 = 224.3 μg/ml
				IC50 = 6.30 μg/ml
	C. cassia bark aqueous	SiHa, human cervical carcinoma cell lines		↓growth of cancer cells	Koppikar et al. (2010)
				↑cytotoxicity
				IC50 = 80 μg/ml
	C. cassia ethanolic extract	HT 29, HCT 116, human colorectal carcinoma cell lines		↑Nrf2	Wondrak et al. (2010)
		↑antioxidant
	C. burmann stem bark/aqueous	Lymphoma, melanoma, mice cancer cell lines		↓tumor cell growth	Kwon et al. (2010)
				↑cytotoxicity
				IC50 = 0.5 mg/ml
	Cinnamomum species cinnamaldehyde	Hep G2, hepatoma cells line		↑apoptosis	Ng and Wu. (2011)
				↑p53, ↑APO-1
				↑cytotoxicity
				IC50 = 9.8 μM
	C. subavenium miq subamolide D subamolide E	SW 480, human colon adenocarcinoma cell lines A431, SCC1 human epidermoid carcinoma cells A375, human melanoma cell lines		↑DNA damage	Kuo et al. (2008); Yang et al. (2013)
				↑cytotoxicity
				IC50 = 9.12 μg/ml
				IC50 = 13.30 μg/ml
				IC50 = 17.59 μg/ml
	C. subavenium miq subamolide B, A	NTUB1, human urothelial carcinoma cell line SW480, human colon adenocarcinoma cell line		↓tyrosinase	Chen et al. (2007); Wang et al. (2011)
				↑apoptosis
	C. tenuifolium/butanolides	DU145, human prostate cancer cell line		↓mitochondrial transmembrane potential	Lin et al. (2009)
				↑cytochrome C
				↑caspase-9/caspase-3 ↑cytotoxicity
Neuroprotective	In vitro studies
	Cinnamomum species water extract/procyanidin type a trimer	C6 glial cells, OGD exposed		↓glial cell swelling	Panickar et al. (2012)
				↓glutamate uptake
	Cinnamomum cassia/extract/cinnamaldehyde	BV2 microglias, LPS activated		↓neuroinflammation	Ho et al. (2013)
				IC50 = 50 μg/ml
	In vivo studies
	Cinnamomum species trans-cinnamaldehyde	Mice/6-OHDA treated intracerebroventricular		Anti-neuroinflammatory	Pyo et al. (2013)
				Dose = 30 mg/kg
	Cinnamomum zeylanicum bark extract	Rats/SCOP treated intravenous		↑cognition dose = 100, 200, 400 mg/kg	Jain et al. (2015)
Others pharmacological activities	In vivo studies
	Cinnamomum zeylanicum/stem bark/methanol extract	Rats/l-name-induced hypertension, intravenous		Antihypertensive	Nyadjeu et al. (2011)
				dose = 5, 10, 20 mg/kg
	Cinnamomum zeylanicum/bark and leaf/EOs	Culex quinquefasciatus, Anopheles tessellatus and Aedes egypti		Mosquitocidal	Samarasekera et al. (2005)
				Bark oil
				A. essellatus
				LD50 = 0.33 μg/ml
				C. uinquefasciatus
				LD50 = 0.66 μg/ml leaf oil
				LD50 = 1.03–2.1 μg/ml
	Cinnamomum zeylanicum bark/EOs	Pediculushumanus capitis		Ovicidal, adulticidal activities	Yang et al. (2005)
				LD50 = 0.5 mg/cm2
	Cinnamomum zeylanicum bark/aqueous suspension	Rats		Anti-secretagogue	Alqasoumi. (2012)
				Antiulcer
				dose = 250, 500 mg/kg b.w
	Cinnamomum zeylanicum bark/ethanol extract	Rats		Pro-healing effect	Kamath et al. (2003); Farahpour and Habibi. (2012)
				dose = 250, 500 mg/kg b.w
	Cinnamomum zeylanicum bark/ethanol extract	Rats/CCl4-induced liver injury		↑hepatoprotective	Eidi et al. (2012)
				Dose = 0.01, 0.05, 0.1 g/kg

Abbreviations and symbols: ↑, increase; ↓, decrease; APOA-1, Apolipoprotein A-1; bw, body weight; FBG, fasting blood glucose; L-NAME, N(G)-nitro-L-arginine-methyl ester, LPS, lipopolysaccharide; p53, tumorprotein p53; PPG, postprandial plasma glucose; PTP1B, protein-tyrosine phosphatase; NF-κB, nuclear factor κB; OGD, oxygen-glucose deprivation; 6-OHDA, 6-hydroxydopamine; SCOP, scopolamine; STZ, streptozotocin; TBARS, thiobarbituric acid reactive substances.