Table 2.

Methods for preparing an aqueous extract of cinnamon, its effects, and significant bioactive compounds present in the extract.

Aqueous extraction methods	Concentrations used	Cinnamon species and the plant part used	Results	Major bioactive compounds identified/tested	References
Ground cinnamon extracted in hot water extractor for 3 h, supernatant freeze-dried after sterile filtration	Concentration (in vivo study)-10 mg/dose (400 μg/g of body weight)	C. cassia (bark)	Study demonstrates the role of aqueous cinnamon extract as an anticancer agent	Not stated	Kwon et al. [65]
	Concentrations (in vitro study)-0.3 and 0.5 mg/mL		Treatment with the aqueous cinnamon extract resulted in decreased neovascularization and increased cytolytic activity of CD8+ T cells in a mouse melanoma model
Ground cinnamon (5 g) was added to 50 mL nanopure water at 40°C (round bottom flask in a mineral oil bath at 40°C), stirred rapidly for 10 min. Centrifuged (10 min at 12,000 ×g, 4°C), placed in a prechilled beaker in an ice bath, and again stirred for 30 min. Filtered, flash-frozen, and then lyophilized. Yield was approx. 7% of the starting material	Concentrations (in vitro studies)-up to 0.22 mg/mL of cinnamon extract, up to 100 μM of a-linked proanthocyanidin trimer and cinnamaldehyde	C. zeylanicum	Study demonstrates the role of the aqueous extract of cinnamon in inhibition of the aggregation of human tau in vitro (a critical process in Alzheimer's disease)	A-linked proanthocyanidin trimer and cinnamaldehyde	Peterson et al. [55]
50 mg/1 mL aqueous solution of cinnamon powder, heated at 15 PSI and 121°C for 20 min. The resulting extract was centrifuged (10,000 rpm for 10 min), and the supernatant was filter sterilized and stored at −80°C	Concentrations (in vitro studies)-up to 1.28 mg/mL of cinnamon extract and up to 320 μM of cinnamaldehyde	C. zeylanicum (bark)	Study demonstrates the role of aqueous cinnamon extract as an anticancer agent	Polyphenols and cinnamaldehyde	Singh et al. [66]
Ground cinnamon extracted in hot water extractor for 3 h, supernatant freeze-dried after sterile filtration	Cinnamon water extract concentration (in vivo study)-10 mg/dose (400 μg/g of mouse weight)	C. cassia (bark)	Study demonstrates the role of aqueous cinnamon extract as an anticancer agent focusing on the induction of apoptosis	Not stated	Kwon et al. [56]
	Concentrations (in vitro study)-0.3 and 0.5 mg/mL		Observed effects were a reduction in NFκB and AP1 expression and downstream antiapoptotic genes
Ground cinnamon powder resuspended in sterile water and heated at 70°C for 1 h, centrifuged, and used after filtration	Cinnamon water extract concentrations (in vitro study)-up to 75 μg/ml	C. zeylanicum	Study demonstrates the role of aqueous cinnamon extract as an anticancer agent via inhibition of angiogenesis	Procyanidin oligomers	Lu et al. [67]
			Focus on VEGF inhibitors present in the aqueous cinnamon extract
Ground cinnamon was extracted (1 : 16 ratio of cinnamon to water) in a hot water extractor, centrifuged at 13000 rpm for 15 min, and used after sterile filtration	Cinnamon water extract concentrations (in vitro study)-up to 80 μg/ml	C. cassia (bark)	Study demonstrates the role of the aqueous cinnamon extract as an anticancer agent	Not stated	Koppikar et al. [68]
			Observed effects were decreased growth rate of SiHa cells, decreased expression of MMP-2, and downregulation of Her-2 expression in SiHa cells
A 400 g bark was soaked in an equal volume of water (overnight), sonicated for 1 h, filtered, and freeze-dried at −70°C. The dried material was reconstituted in phosphate-buffered saline and sterile filtered before use. Yield was 0.7% of the starting material weight	Cinnamon water extract concentrations (ex vivo study)-up to 200 μg/ml	C. cassia (bark)	Study demonstrates the role of the aqueous extract of cinnamon in inflammatory disorders	Not stated	Lee et al. [69]
	Cinnamon water extract concentrations (in vivo study)-up to 1 g/kg of body weight		Observed effects were downregulation of IFN-γ expression and inhibition of downstream signaling pathways such as p38, JNK, and STAT4
Ground cinnamon soaked in one volume of water (48 h at room temperature), sonicated (1 h), filtered, and freeze-dried at −70°C. Yield was approximately 3.62%	Cinnamon water extract concentrations (in vitro study)-up to 100 μg/ml	C. cassia (bark)	Study demonstrates the role of the aqueous extract of cinnamon as an anti-inflammatory agent	Polyphenols	Hong et al. [70]
	Concentrations (in vivo study)-up to 500 mg/kg of body weight		In an in vivo study using a mouse model, treatment with an aqueous extract of cinnamon decreased TNF-α and IL-6 release in serum when stimulated with LPS. IκBα degradation and MAPK activation were observed in LPS-stimulated macrophages in vitro
A total of 5 g ground cinnamon was soaked in 50 mL water, incubated for 5 h at 40°C, the extract centrifuged (7000 ×g for 10 min), and the supernatant stored at −20°C after lyophilization	Cinnamon water extract and proanthocyanidins concentrations (in vitro study)-up to 82 μg/ml	C. zeylanicum (bark)	Role of aqueous extract of cinnamon in managing type 2 diabetes mellitus	Proanthocyanidins, cinnamic acid, coumarin, and cinnamaldehyde	Jiao et al. [71]
			The aqueous extract inhibited the aggregation of human islet amyloid polypeptide (hIAPP), which is one of the causes of type 2 diabetes mellitus
Ground cinnamon was added to distilled water (10 mL/g), incubated, and stirred for 4 h, followed by boiling for 2 h, centrifuging (7500 ×g for 30 min), filtering, and lyophilizing	Cinnamon water extract concentrations (in vitro study)-up to 8 mg/ml	Not available	This study demonstrated the anticancer activity of the aqueous extract of cinnamon on transformed cell lines (HeLa, MCF-7, and MDA-MB234)	Not available	Ariaee-Nasab et al. [72]
A total of 100 g of ground cinnamon was soaked in one liter of water (48 h at room temperature), sonicated (1 hour), filtered, and lyophilized	Cinnamon water extract concentrations (in vitro study)-up to 100 μg/ml	C. cassia (bark)	This study demonstrated the role of the aqueous extract of cinnamon in preventing the development of atherosclerotic lesions and associated inflammation	Cinnamon, cinnamyl alcohol, cinnamic acid, cinnamaldehyde, coniferyl aldehyde, coumarin polyphenols, catechin, and epicatechin	Kang et al. [73]
			The aqueous extract interfered with monocyte differentiation (decreasing the expression of CD11b, CD36) and macrophage scavenger activity
A total of 100 mg of ground cinnamon was dissolved in 1000 mL water, boiled (100°C for 30 min), centrifuged, filtered, and lyophilized. Dissolved in DMSO after lyophilization	Cinnamon water extract concentrations (in vitro study)-up to 50 μg/ml	C. cassia (bark)	This study demonstrated the role of the aqueous extract of cinnamon against chemotherapeutic-induced toxicity	Phenylpropanoids, phenols, β-cadinene, α-murolene, α-cadinene, and hydrocarbons	ElKady and Ramadan [74]
			The aqueous extract prevented the activation of various cellular mechanisms mediating apoptosis without compromising the anticancer efficiency of cis-diamine-dichloro platinum (CDDP)
A total of 80 g of dried cinnamon powder was added to 400 mL water (stirred on a magnetic stirrer at 80°C for 15 h), filtered, and stored in a −80°C freezer until completely frozen. Freeze-dried for one week, weighed, and stored at room temperature. Yield was 2.54%	Cinnamon water extract concentrations (in vitro study)-up to 6.25 mg/ml	C. zeylanicum (bark)	This study demonstrated the role of the aqueous extract of cinnamon as an anticancer agent	Cinnamaldehyde, cinnamyl alcohol, eugenol, methoxy cinnamaldehyde, hexadecenal, and hexadecenoic acid	Abd Wahab and Adzmi [41]
			Cytotoxic effect of the aqueous extract towards MCF-7 cell line
Cinnamon powder (500 g) was dissolved in distilled water (500 ml, boiled for 3 h, filtered, and freeze-dried (in a vacuum evaporator). Sterilized by radiation	Cinnamon water extract concentrations (in vivo study)-500 mg of cinnamon/kg body mass/day	C. cassia (bark)	This study demonstrated the role of the aqueous extract of cinnamon as an anticancer agent	Not available	Ezzat et al. [75]
			The study focused on the effect of the aqueous extract of cinnamon in preventing oral carcinogenesis induced by 7,12-di-methylbenz[a]anthracene (DMBA) hamster cheek pouch (HCP) mucosa
Powdered cinnamon was extracted in water (1 : 16 w/v) in a hot water extractor. The extract was centrifuged (13000 rpm for 15 min), and the filter sterilized	Cinnamon water extract concentrations (in vitro study)-up to 80 μg/ml	C. cassia (bark)	This study demonstrated the inhibitory potential of the aqueous extract of cinnamon against histone deacetylase family member 8 (HDAC8), which is linked with various cancers	Cinnamaldehyde, cinnamic acid, cinnamyl alcohol	Raina et al. [76]
			The potency of aqueous extract was much better than individual bioactive components, indicating that these components might be working synergistically to induce inhibition
Cinnamon powder was dissolved in water (70°C, 1 h), centrifuged (13,000 rpm, 10 min), filtered, and lyophilized under vacuum	Cinnamon water extract concentrations (in vitro study) - up to 32 μg/ml	C. zeylanicum	Role of aqueous extract of cinnamon as anticancer and antiangiogenic agent	Cinnamaldehyde and procyanidins	Zhang et al. [77]
	Cinnamon water extract concentrations (in vivo study in mice) -0.3 mg of cinnamon extract/g body weight		Cinnamon aqueous extract suppressed HIF-1α gene expression and protein synthesis resulting in inhibition of VEGF production in the cancer cells. Treatment also inhibited the expression and phosphorylation of downstream signal transduction molecules such as STAT3 and AKT
Five grams of ground cinnamon were added to 25 mL of water and kept in a water bath (55°C for 3 h), vortexed (every 30 min), followed by centrifugation (6300 ×g for 15 min). Supernatant filtered and stored	Cinnamon water extract concentrations (in vitro study)-up to 25 mg/ml	Not available	Role of aqueous cinnamon extract and one of its bioactive components, procyanidinB2 (PCB2), in inhibiting the proteasome activity and suppression of prostate cancer cell growth	procyanidinB2 (PCB2)	Gopalakrishnan et al. [62]
			The aqueous treatment resulted in a decrease in markers involved in the survival of cells
A total of 10 g of the dried powdered soaked in 100 mL water and boiled (2 h), filtered. Filtrate dried by heating overnight at 80°C in an oven	Cinnamon water extract concentrations (in vivo study in rats) -400 mg/kg orally once a day for 15 days	C. zeylanicum (bark)	Role of aqueous extract of cinnamon in as an antioxidant	Cinnamaldehyde, cinnamic acid, and eugenol	Abdeen et al. [78]
			Results showed that when rats were pretreated with the aqueous cinnamon extract, it led to decreased acetaminophen-induced cellular alterations and apoptosis in healthy cells
Ground cinnamon (30g) was added to water (1 : 10, w/v) and extracted using a subcritical water extraction device at 110°C for 40 minutes, with a pressure of 50 bar. The extract was centrifuged at 4°C (11 000 ×g for 5 min), filtered, and lyophilized	Cinnamon subcritical water extract concentrations (in vitro study)-up to 100 μg/ml	C. japonicum (bark)	Role of aqueous extract of cinnamon in cellular intestinal inflammation model	Cinnamic acid and cinnamaldehyde	Kim and Kim [79]
			Significant downregulation of the PGE2, TNF-α, cytokines, and NFkB activity was reported
Ground cinnamon soaked in water (1 : 20, w/v for 48 h), filtered, placed in rotary devices (3-4 h), condensed extracts obtained were centrifuged (10,000 rpm, 15 min), the supernatant was sterile filtered and stored at −80°C	Cinnamon water extract concentrations (in vitro study)-up to 1.3 mg/ml	Not available	Role of the aqueous cinnamon extract as an anticancer agent in treating oral squamous cell carcinoma	Not available	Dehghani Nazhvani et al. [9]
An aqueous solution of 10 mg/mL of ground cinnamon was prepared and kept at 4°C in the dark after filtering	Cinnamon water extract concentrations (in vitro study)-up to 500 μg/ml	C. burmannii (bark) commercialized as Cinnulin® PF	Role of aqueous cinnamon extract as an antiinflammatory agent to treat periodontal diseases	Phenolic acids, flavonoids (flavanols, anthocyanins, flavan-3-ols), and procyanidins, cinnamon fraction, cinnamic acid was the most abundant phenolic acid	Ben Lagha et al. [37]
			The polyphenolic fraction of aqueous cinnamon extract reduced IL-6, IL-8, and TNF-α secretion
The aqueous solution was prepared at 10%, boiled for 2 h at 100°C, and dried overnight (80°C) after filtering. Yield was 20% w/w	Cinnamon water extract concentrations (in vivo study in rats)-300 mg/kg daily for 15 days	C. zeylanicum (bark)	Role of the aqueous extract of cinnamon anti-inflammatory and antioxidant agent	Phenols, flavonoids, and tannins	Elshopakey and elazab 2021 [61]
			Aqueous extract of cinnamon protected against diclofenac sodium (DFS) and oxytetracycline (OTC) toxicity in a rat model