Ameliorative effect of quercetin on pancreatic damage in rodent: a meta-analysis

Figures & data

Figure 1. Quercetin chemical structure.

Figure 2. Selection and evaluation of articles related to quercetin effect on pancreatic damage according to PRISMA. **Indicate how many records were excluded by automation tools.

Table 1. Collected studies included into the meta-analysis.

No	Author	Year	Inducer (mg/kgBW)	Strain/sex	Weight (g)	N	Quercetin doses (mg/kgBW.day)	Parameters
1	Abdou [15]	2022	STZ (35 i.p.), HFD	SD/m	160–180	25	0–50	Serum: glucose, insulin, glucagon; Pancreatic tissue: TBARS, AGE, GSH, SOD, CAT, GPx, GLUT2, GLUT4, glucokinase, hexokinase, G6p, F16bp, 6PGD, G6PDH, TNFα, IL−6, Casp3_gene, IL−1b_gene
2	Adewole [16]	2007	STZ (75 i.p)	Wistar/m	200–250	30	0–25	Serum: glucose, insulin; Pancreatic tissue: insulin, TBARS, GSH, SOD, CAT, GPx
3	Arya [17]	2014	STZ (45 i.p.)	SD/m	200–225	36	0–100	Serum: glucose, insulin
4	Carvalho [18]	2010	Cerulein (250 i.p.)	Swiss/m	25–30	40	0–100	Pancreatic tissue: pancreas weight, TBARS
5	Coskun [19]	2005	STZ (50 i.p.)	Wistar/m	200–250	30	0–15	Serum: glucose, insulin; Pancreatic tissue: insulin, TBARS, SOD, CAT, GPx
6	El-Far [20]	2020	D- galactose (120 s.c.)	Wistar/m	120–160	45	0–100	Pancreatic tissue: vacuolation, necrosis, glucagon, insulin, SOD, BCL2, Ki67, p53, p21, IL−6, NF-kB, Casp3_gene
7	El-Rahman [21]	2017	STZ (60 i.p.)	albino/m	170	48	0–20	Serum: glucose
8	Junyuan [22]	2018	Taurocholate Na (35 i.p.)	SD/m	160–180	18	0–150	Pancreatic tissue: TNFα, IL−6, IL−1b_gene
9	Kaharaman [23]	2017	Cerulein (50 i.p.)	SD/f	250–300	32	0–100	Pancreatic tissue: vacuolation, amylase, lipase, TBARS, GSH, TNFα, IL−6
10	Kalailingam [24]	2013	STZ (40 i.p.)	Wistar/m	150–200	30	0–1.6	Serum: glucose, insulin
11	Li [25]	2013	fructose 10% (ad libitum drink)	SD/m	250–280	40	0–50	Serum: glucose
12	Lin [26]	2016	STZ (65 i.p.), fructose	Wistar/f	100–200	48	0–0.01	Serum: glucose, insulin; Pancreatic tissue: BCL2, Casp3_gene, IL−1b_gene
13	Nur Syimal’ain [27]	2017	STZ (60 i.p.)	SD/m	150–200	24	0–40	Serum: glucose, insulin
14	Omar [28]	2016	HFD (ad libitum), Sucrose	Wistar/no info	100–120	30	0–50	Serum: glucose, insulin
15	Oyedemi [29]	2019	STZ (40 i.p.), fructose	Wistar/m	200	20	0–50	Serum: glucose; Pancreatic tissue: pancreas weight, TBARS, GSH, SOD, CAT
16	Rasheed [30]	2022	HFD (ad libitum)	albino/m	150–180	40	0–50	Pancreatic tissue: pancreas weight, necrosis, BCL2
17	Rifaai [31]	2012	STZ (75 i.p.)	albino/m	200–250	45	0–25	Serum: glucose; Pancreatic tissue: islets number, beta cell number
18	Vessal [32]	2003	STZ (40 iv)	SD/m	210	40	0–15	Serum: glucose; Pancreatic tissue: islets number
19	Zheng [33]	2016	Cerulein (100 i.p.), HFD	SD/m	100–110	30	0–200	Pancreatic tissue: necrosis, TNFα, IL−6, NF-kB, IL−1b_gene, IRE1

Abbreviations: HFD = high fat diet, SD = Sprague Dawley, STZ = streptozotocin, TBARS = thiobarbituric acid reactive substances, AGE = advanced glycation end product, GSH = glutathione, SOD = superoxide dismutase, CAT = catalase, GPx = glutathione peroxidase, GLUT2/4 = glucose transporter−2/4, G6p = glucose 6 phosphate, F16bp = Fructose 1,6-bisphosphate, 6PGD = 6-Phosphogluconate dehydrogenase, G6PDH = Glucose−6-phosphate dehydrogenase, TNFα = tumor necrosis factor alfa, IL−6 = interleukin 6, Casp3 = caspase−3

Figure 3. Review authors’ judgments about each Risk of Bias of included articles according to SYRCLES’s risk of bias tool.

Table 2. Effect of quercetin administration on status of pancreatic damage in animal model.

Parameter	Unit	Model	N	Intercp.	SE Int.	Slope	SE Slope	p-value	RMSE	AIC	Trend
Serum glucose	mg/dL	Q	47	295.129	31.597	−6.098	1.569	0.0004	79.869	581.0	Minimum
						0.055	0.019	0.0057
pancreatic necrosis	%	L	10	24.167	5.340	−0.150	0.056	0.0301	9.834	82.5	Negative
pancreatic TBARS	nmol/g tissue	L	18	21.201	4.882	−0.097	0.032	0.0116	3.236	126.9	Negative
pancreatic TNFa	pg/g tissue	L	13	120.362	45.104	−0.342	0.089	0.0050	14.374	129.3	Negative
pancreatic IL6	pg/g tissue	L	17	44.445	8.309	−0.164	0.040	0.0016	7.206	139.8	Negative
pancreatic NFkB	fold	L	8	4.081	1.595	−0.024	0.006	0.0068	0.739	39.5	Negative
pancreatic insulin	mU/g protein	L	8	3.248	1.717	0.079	0.025	0.0292	1.513	47.4	Positive
pancreatic GSH	nmol/g tissue	L	12	32.494	5.753	0.184	0.053	0.0085	4.229	89.4	Positive
pancreatic SOD	U/g tissue	L	15	5.572	0.765	0.058	0.021	0.0176	2.147	78.7	Positive
serum insulin	mU/L	L	30	36.564	4.341	0.146	0.115	0.2177	14.035	257.8	Positive
pancreas relative weight	g/gBW	L	9	0.700	0.340	0.000	0.000	0.2689	0.017	1.0	Negative
pancreatic islets number	n/cm2	L	5	43.065	85.076	7.180	2.526	0.1037	33.916	50.4	Positive
pancreatic vacuolation	fold	L	7	2.474	0.642	−0.016	0.007	0.1007	0.666	32.7	Negative
Pancreatic CAT	U/g tissue	L	11	28.842	4.800	0.361	0.198	0.1011	11.300	89.7	Positive
Pancreatic GPx	U/g tissue	L	8	5.662	0.958	0.047	0.047	0.3521	1.957	44.6	Positive
Pancreatic BCl2	%	L	11	23.846	15.833	0.117	0.132	0.4039	8.793	93.8	Positive
Casp3 gene	fold	L	13	7.277	4.608	−0.068	0.076	0.3921	5.886	96.6	Negative
IL1b gene	fold	L	13	6.212	3.475	−0.030	0.033	0.3898	5.113	93.9	Negative

Q = quadratic model, L = Linear model, N = Sample size, RMSE = Root means square error, AIC = Akaike information criterion, TBARS = thiobarbituric acid reactive species.

Figure 4. Quercetin effect on tissue antioxidant status. (Abbr.: SOD = superoxide dismutase, O₂ = oxygen, H2O2 = hydrogen peroxide, Fe = iron, CAT = catalase, GPx = glutathione peroxidase, GR = glutathione reductase, GSH = glutathione, GSSG = glutathione disulfide).

Figure 5. Quercetin inhibit further inflammation by neutralizing ROS, and in consequence inactivate NF-Kb and Casp3 signaling. (Abbr.: ROS = reactive oxygen species, Casp3 = caspase − 3, PARP = Poly [ADP-ribose] polymerase, IKK = IκB kinase, IκB = Inhibitor of NF-κB, NF-κB = Nuclear factor-kappa B, TNF-α = Tumor necrosis factor alpha, IL = interleukin).

Abdou HM, Hamaad FA, Ali EY, et al. Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats. Biomed Pharmacother. 2022;149:112838. doi: 10.1016/j.biopha.2022.112838

 PubMed Web of Science ®Google Scholar

Adewole S, Caxton-Martins E, Ojewole J. Protective effect of quercetin on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats. Afr J Tradit Complement Altern Med. 2007;4:64–74. doi: 10.4314/ajtcam.v4i1.31196

 Web of Science ®Google Scholar

Arya A, Jamil Al-Obaidi MM, Shahid N, et al. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study. Food Chem Toxicol. 2014;71:183–196. doi: 10.1016/j.fct.2014.06.010

 PubMed Web of Science ®Google Scholar

Carvalho KMMB, Morais TC, de Melo TS, et al. The natural flavonoid quercetin ameliorates cerulein-induced acute pancreatitis in mice. Biol Pharm Bull. 2010;33:1534–1539. doi: 10.1248/bpb.33.1534

 PubMed Web of Science ®Google Scholar

Coskun O, Kanter M, Korkmaz A, et al. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol Res. 2005;51:117–123. doi: 10.1016/j.phrs.2004.06.002

 PubMed Web of Science ®Google Scholar

El-Far AH, Lebda MA, Noreldin AE, et al. Quercetin attenuates pancreatic and renal D-Galactose-induced aging-related oxidative alterations in rats. Int J Mol Sci. 2020;21:4348. doi: 10.3390/ijms21124348

 PubMed Web of Science ®Google Scholar

El-Rahman SNA, Al-Jameel SS. Synergistic effect of quercetin nanoparticles on liver and pancreas tissues and oxidative stress of streptozotocin-induced diabetic rats. Asian J Chem. 2017;29:1003–1010. doi: 10.14233/ajchem.2017.20389

 Google Scholar

Junyuan Z, Hui X, Chunlan H, et al. Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition. Pancreatology. 2018;18:742–752. doi: 10.1016/j.pan.2018.08.001

 PubMed Web of Science ®Google Scholar

Kahraman A, Vurmaz A, Koca HB, et al. The effect of quercetin on cerulein-induced acute pancreatitis. Med Express. 2017;4:1–7. doi: 10.5935/medicalexpress.2017.05.02

 Google Scholar

Kalailingam P, Balasubramanian K, Kannaian B, et al. Isolation and quantification of flavonoids from ethanol extract of Costus igneus rhizome (CiREE) and impact of CiREE on hypoglycaemic, electron microscopic studies of pancreas in streptozotocin (STZ)-induced diabetic rats. Biomed Prev Nutr. 2013;3:285–297. doi: 10.1016/j.bionut.2013.01.001

 Google Scholar

Li J-M, Wang W, Fan C-Y, et al. Quercetin preserves β -Cell Mass and function in fructose-induced hyperinsulinemia through modulating pancreatic Akt/FoxO1 Activation. Evid Based Complement Alternat Med. 2013;2013:1–12. doi: 10.1155/2013/303902

 Web of Science ®Google Scholar

Lin C-F, Kuo Y-T, Chen T-Y, et al. Quercetin-Rich Guava (Psidium guajava) Juice in combination with trehalose reduces autophagy, apoptosis and pyroptosis formation in the kidney and pancreas of type ii diabetic rats. Molecules. 2016;21:334. doi: 10.3390/molecules21030334

 PubMed Web of Science ®Google Scholar

Nur Syimal’ain A, Nooraain H, N S, et al. Effect of azadirachta excelsa and quercetin on the endocrine pancreas of the experimentally induced diabetic rats: histological and insulin secretion. Adv Nat Appl Sci. 2017;11:35+. https://go.gale.com/ps/anonymous?id=GALE%7CA601551043&v=2.1&it=r&linkaccess=abs&issn=19950772

 Google Scholar

Omar H-D, Ragaa SM, Elghaffar SKA, et al. Berberine, Quercetin and O-Coumaric acid phytochemicals ameliorate the impact of experimentally fed high-fat/high-sucrose diet on pancreas β-cells and glycemic control indices. Austin J Endocrinol Diabetes. 2016;3:1–6. https://austinpublishinggroup.com/endocrinology-diabetes/fulltext/ajed-v3-id1042.php

 Google Scholar

Oyedemi SO, Nwaogu G, Chukwuma CI, et al. Quercetin modulates hyperglycemia by improving the pancreatic antioxidant status and enzymes activities linked with glucose metabolism in type 2 diabetes model of rats: in silico studies of molecular interaction of quercetin with hexokinase and catalase. J Food Biochem. 2020;44:1–16. doi: 10.1111/jfbc.13127

 Web of Science ®Google Scholar

Rasheed RA, Elshikh MS, Mohamed MO, et al. Quercetin mitigates the adverse effects of high fat diet on pancreatic and renal tissues in adult male albino rats. J King Saud Univ - Sci. 2022;34:101946. doi: 10.1016/j.jksus.2022.101946

 Web of Science ®Google Scholar

Rifaai RA, El-Tahawy NF, Ali Saber E. Effect of quercetin on the endocrine pancreas of the experimentally induced diabetes in male albino rats: a histological and immunohistochemical study. J Diabetes Metab. 2012;3:1000182. doi: 10.4172/2155-6156.1000182

 Google Scholar

Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol - C Toxicol Pharmacol. 2003;135:357–364. doi: 10.1016/S1532-0456(03)00140-6

 PubMed Web of Science ®Google Scholar

Zheng J, Wu J, Chen J, et al. Therapeutic effects of quercetin on early inflammation in hypertriglyceridemia-related acute pancreatitis and its mechanism. Pancreatology. 2016;16:200–210. doi: 10.1016/j.pan.2016.01.005

 PubMed Web of Science ®Google Scholar

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Interested parties can contact the corresponding author via the email provided: https://docs.google.com/spreadsheets/d/11E_B7JgjLzAWmPmWktWiUqgNq1wKrdSb/edit?usp=sharing&ouid=105511364159406934633&rtpof=true&sd=true.