Table 4.

Experimental data for antidiabetic activity of cinnamon oil and some of its main constituents.

Study Product	Study Type	Dosage	Effect	Reference
Cinnamon oil	Animal (Rat), KK-Ay	25, 50, 100 mg/kg b.w.	Significant decrease in fasting blood glucose, plasma C-peptide, serum triglyceride, total cholesterol, and blood urea nitrogen levels, with significant increase in high-density lipoprotein after 35 days. Glucose tolerance was improved and pancreatic islet β-cells showed increased immunoreactivity.	Ping, Zhang, and Ren (2010) [7]
Cinnamon oil (encapsulated emulsion)	Animal (Rat), STZ	200 or 400 mg/kg b.w.	Both doses improved levels of glucose, insulin, SOD, GSH, amylase, lipid profile, and hepatic MDA. Gene expression was modulated to favor antidiabetic outcomes. Positive histological changes seen in liver and pancreas.	Mohammed, Ahmed, Sharaf, El-Nekeety, Abdel-Aziem, Mehaya, Abdel-Wahhab (2020) [35]
Cinnamon oil (encapsulated)	Animal (Rat), STZ	200 or 400 mg/kg b.w.	Treatment with encapsulated cinnamon oil showed improvement in all diabetes-related markers in STZ-treated rats, including liver and kidney function, insulin and glucose levels, lipid profile, and antioxidant enzymes.	Mohammed (2020) [36]
Cinnamon oil	Animal (Rat), Alloxan	5, 10, 20 mg/kg b.w., i.p.	Decreases in fasting blood glucose, total cholesterol, markers of kidney damage and glutathione were observed in treated animals. Histological studies of kidney showed reduced glomerular expansion and tubular dilatations.	Mishra, Bhatti, Singh, Ishar (2010) [37]
Cinnamon oil	Animal (Rat), STZ	100, 200, or 400 mg/kg b.w.	Treatment with cinnamon oil showed significant improvement in histopathology of testicular organs compared to untreated diabetic rats.	Budiastuti, Safitri, Plumeriastuti, Srianto, Effendi (2020) [38]
Cinnamon oil	Human	400 mg/day	Fasting blood glucose levels and insulin levels, along with Quality-of-Life measures, showed improvement after treatment with cinnamon oil, although results were not statistically significant. Pharmacokinetic data indicated low bioavailability.	Stevens (2020) [28]
Cinnamon oil	Animal (Mouse), Balb C	0.2 and 1.0 μL/cage, inhalation	Docking simulations showed interaction of cinnamon oil constituents with leptin receptor in olfactory bulb. In vivo studies confirmed interaction with leptin receptor resulting in decreased appetite and lower weight gain in treated mice.	Kusmardi, Tedjo, Fadilah, Arsianti, Paramita (2018) [39]
Cinnamon oil	Animal (Rat), STZ	5% cinnamon oil in commercial chow	Treatment with cinnamon oil resulted in decreased blood glucose, triglycerides, LDL-cholesterol, and ALT, while levels of HDL-cholesterol were increased compared to diabetic rats.	Zari, Al-Logmani (2009) [40]
Cinnamon oil	Animal (Rat), Alloxan	5, 10, 20 mg/kg b.w., i.p.	Cinnamon oil significantly ameliorated blood glucose levels and thermal hyperalgesia compared to untreated diabetic controls.	Bhatti, Kaur, Singh, Ishar (2009) [41]
Cinnamaldehyde	In vitro (HEK293 and 3T3-L1)	--	Cinnamaldehyde induced expression of peroxisome proliferator-activated (PPAR) genes in 3T3-L1 adipocytes and increased target mRNA expression in HEK293- derived cells.	Li, Futakawa, Yamamoto, Kasahara, Tagami, Liu, and Moriyama (2015) [42]
Cinnamaldehyde	Animal (Mouse), DIO-mice	250 mg/kg/day	Cinnamaldehyde induced significant reduction in cumulative food intake, gastric emptying rates, and ghrelin. Upregulation of genes involved in fatty-acid oxidation was observed in adipose tissue, and mice showed improved glucose tolerance over 5 weeks.	Camacho, Michlig, de Senarclens-Bezencon, Meylan, Meystre, Pezzoli, Markram, le Coutre (2015) [43]
Cinnamaldehyde	Animal (Mouse), db/db	0.02% added to normal chow diet	Treatment with cinnamaldehyde improved aortic tone and function and normalized elevated kidney markers. Treatment also ameliorated glomerular fibrosis and renal dysfunction. Authors suggest a protective effect against vascular dysfunction by inhibiting oxidative stress via Nrf2 signaling pathway activation.	Wang, Yang, Wang, Yang, Wan, Liu, Zhou, Yang (2020) [44]
Cinnamaldehyde	Animal (Rat), STZ	20 mg/kg b.w.	Oral administration led to insulinotropic effects, with increased glucose uptake through GLUT4 receptors and improved function of pyruvate kinase and phosphoenolpyruvate carboxykinase.	Anand, Murali, Tandon, Murthy, Chandra (2010) [45]
Cinnamaldehyde	Animal (Rat), FSD/STZ	20 mg/kg b.w.	Gestating rats treated with cinnamaldehyde showed numerous improvements in health markers compared to diabetic controls, including improved lipid panels and glucose tolerance, more viable fetuses, and improved fetal glucose and insulin levels.	Hosni, Abdel-Moneim, Abdel-Reheim, Mohamed, Helmy (2017) [46]
Cinnamaldehyde	Animal (Rat), FSD/STZ	20 mg/kg b.w.	In rats with gestational diabetes, treatment with cinnamaldehyde prevented development of placental vasculopathy and fetal hypoxia while also alleviating maternal and fetal hyperglycemia.	Hosni, El-Twab, Abdul- Hamid, Prinsen, AbdElgwad, Abdel-Moneim, Beemster (2021) [47]
Cinnamaldehyde	Animal (Mouse), STZ	20 mg/kg/day	Treated mice showed significantly improved insulin sensitivity and glucose metabolism, as well as positive changes in gut microbiota. Authors suggest that modulating host metabolomics may directly or indirectly affect expression levels of genes related to glucose metabolism.	Zhao, Wu, Duan, Liu, Zhu, Zhang, Wang (2021) [48]
Cinnamaldehyde	Animal (Rat), STZ	20 mg/kg/day	Treatment with cinnamaldehyde prevented development of hyperglycemia and insulin resistance following STZ administration.	El-Bassossy, Fahmy, Dadawy (2011) [49]
Cinnamaldehyde	Animal (Rat), STZ	10, 20, 40 mg/kg b.w., p.o.	Rats treated with cinnamaldehyde showed reduced blood glucose levels and amelioration of neurochemical and behavioral deficits seen in diabetic rats. Reductions in IL-2 and TNF-⍺ levels were also noted.	Jawale, Datusalia, Bishnoi, Sharma (2016) [50]
Cinnamaldehyde	Rat	125, 250, 500 mg/kg b.w.	Pharmacokinetic determination of Cmax in rats administered 125, 250, and 500 mg/kg b.w. cinnamaldehyde was 249, 121, and 82 ng/mL serum, respectively. Estimated half-life of cinnamaldehyde was 6.2–6.9 h.	Zhao, Xie, Yang, Cao, Tu, Cao, Wang (2014) [51]
Eugenol	Animal (Mouse), STZ	100 mg/kg b.w. i.p., 2× per week for 2 weeks	Significant reduction in advanced glycation end-products (AGE) and blood glucose levels.	Singh et al. (2014) [52]
Eugenol	Animal (Rat), STZ		Treatment with eugenol produced lower blood glucose, decrease in serum glycosylated hemoglobin (HbA1C), lipase, and angiotensin-converting enzyme. Lipid panel levels were also positively affected.	Mnafgui et al. (2013) [53]
Eugenol	Animal (Rat), STZ	2.5, 5, 10 mg/kg b.w.	Eugenol improved blood glucose and HbA1C levels in diabetic rats and returned glucose metabolism enzyme levels to near normal. Body weight and liver function also improved.	Srinivasan et al. (2013) [54]
Eugenol	Animal (Rat), FSD/STZ	10 mg/kg b.w.	Levels of fasting blood glucose, insulin, triglyceride, cholesterol, and low-density lipoprotein were all improved. Glutathione levels were increased, as were GLUT4 and AMPK levels in skeletal muscle. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower in rats treated with eugenol compared to diabetic controls.	Al-Trad, Alkhateeb, Alsmadi, Al-Zoubi (2019) [55]
Eugenol	Animal (Rat), HFD	20, 40 mg/kg b.w.	Plasma glucose and insulin levels decreased in a dose-dependent manner, and hepatic gluconeogenesis was inhibited via the CAMKK-AMPK-CREB signaling pathway.	Jeong, Kim, Quan, Jo, Kim, Chung (2014) [56]
Eugenol	Animal (Rat), STZ	5, 10 mg/kg b.w.	Diabetic neuropathy parameters (both blood markers and histological changes) were ameliorated in diabetic rats treated with eugenol. Overexpression of TGF-β1 associated with diabetes was also reduced.	Garud, Kulkarni (2017) [57]
Eugenol	Animal (Rat), STZ	10 mg/kg b.w.	Diabetic rats treated with eugenol showed diminished oxidative stress markers and increased antioxidants. In the brain, levels of acetylcholinesterase and calcium were attenuated. Authors postulate that eugenol may help ameliorate diabetic complications due to oxidative stress.	Prasad, Bharath, Muralidhara (2016) [58]
Eugenol	Animal (Rat), STZ	2 mL/day of a 10% nanoemulsion	Oxidative damage was attenuated, and levels of antioxidants were returned to near-normal levels in diabetic rats compared to untreated controls.	Boroujeni, Dehkordi, Sharifi, Taghian, Mazaheri (2021) [59]
Eugenol	In vitro (Islets of Langerhans cells from male mouse)	50, 100, 200 μM	Total antioxidant capacity, superoxide dismutase, and catalase levels increased in cells treated with eugenol following exposure to hydrogen peroxide to induce oxidative stress. Eugenol can bolster antioxidant systems in islet cells that are particularly vulnerable to oxidative stress in diabetics.	Oroojan, Chenani, An’aam (2020) [60]
Eugenol	Animal (Rat), Alloxan	5, 10, 15 mg/kg b.w.	Diabetic rats treated with eugenol showed lower fasting blood glucose, and improved morphology of liver and islet of Langerhans cells.	Hamdin, Utami, Muliasari, Prasedya, Sudarma (2019) [61]
β-caryophyllene	In silico	--	β-caryophyllene showed affinity for interaction with insulin downstream signaling molecules such as IRS-1, cSrc, and Akt.	Mani, Balraj, Venktsan, Soundrapandiyan, Kasthuri, Danavel, Babu (2021) [62]
β-caryophyllene	Animal (Rat), STZ	10 mg/kg b.w.	Diabetic neuropathy was attenuated in rats treated with β-caryophyllene. Depression behavior and cytokine markers of diabetes were also reduced.	Aguilar-Ávila, Flores-Soto, Tapia-Vázquez, Pastor-Zarandona, López-Roa, Viveros-Paredes (2019) [63]
β-caryophyllene	Animal (Rat), STZ	200 mg/kg b.w.	Hyperglycemia was attenuated by treatment with β-caryophyllene, and oxidative stress was avoided through increased activity of antioxidant enzymes.	Basha, Sankaranarayanan (2016) [64]
β-caryophyllene	Animal (Rat), STZ	200 mg/kg b.w.	Plasma insulin levels were rescued to near-normal levels in diabetic rats treated with β-caryophyllene.	Basha, Sankaranarayanan (2015) [65]
β-caryophyllene	Animal (Rat), STZ	100, 200, 400 mg/kg b.w.	Administration of β-caryophyllene ameliorated STZ-induced changes in blood glucose, insulin levels, and glucose metabolism enzymes. The antidiabetic and insulinotropic effects were most pronounced at the 200 mg/kg dose.	Basha, Sankaranarayanan (2014) [66]
β-caryophyllene	Animal (Rat), HFD	30 mg/kg b.w.	Treatment with β-caryophyllene improved glycemic and lipidemic markers and reduced vascular oxidative stress and inflammation.	Youssef, El-Fayoumi, Mahmoud (2019) [67]
β-caryophyllene	In vitro (mesangial cells)	--	β-caryophyllene modulated NF-κB and Nrf pathways and exhibited anti-inflammatory and nephroprotective activity in mesangial cells under high-glucose conditions.	Li, Wang, Chen, Yang (2020) [68]
β-caryophyllene	In vitro (C2C12 myotubes)	--	β-caryophyllene significantly increased skeletal muscle uptake of glucose and glycolytic production of ATP through cannabinoid receptor-2-mediated pathways.	Geddo et al. (2021) [69]