Estrada-Camarena EM, López-Rubalcava C, Ramírez-Rodríguez GB, Pulido D, Cervantes-Anaya N, Azpilcueta-Morales G, Granados-Juárez A, Vega-Rivera NM, Islas-Preciado D, Treviño S, de Gortari P, González-Trujano ME, García-Viguera C. Aqueous extract of pomegranate enriched in ellagitannins prevents anxiety-like behavior and metabolic changes induced by cafeteria diet in an animal model of menopause. Neurochem Int. 2020 Dec 1;141:104876. doi: 10.1016/j.neuint.2020.104876.

Publication Date: "Available online 10 October 2020"

Peer Reviewed: Yes

Study Design: "Four groups were randomly formed according to diet and treatment for 22 days."

Methodology: Randomly formed groups, treated for 22 days, tested in EPM, OGTT, biochemical and molecular analysis performed.

Sample Size: "n = 46"

Controls Used: "Control chow diet treated with vehicle"

Dose Used: "1 mg/kg of AE-PG"

Statistical Significance Declared: "Two-way ANOVA values... only values of p ≤ 0.05 were accepted as significant."

Adverse Events: None declared explicitly.

Conflict of Interest: None declared explicitly.

Adel-Mehraban MS, Tansaz M, Mohammadi M, Yavari M. Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial. Complementary Therapies in Clinical Practice. 2022;46:101544. doi:10.1016/j.ctcp.2022.101544

Publication Date: " Available online 2 February 2022"

Peer Reviewed: Yes

Study Design: "A randomized double-blind placebo-controlled trial"

Methodology: Randomized, double-blind, placebo-controlled trial among 78 healthy women aged 45-55 with menopausal symptoms, interviewed three times using demographic, modified-Kupperman index, and MENQOL questionnaires.

Sample Size: "n = 78"

Controls Used: "Placebo"

Dose Used: "3 mL three times per day for 4 weeks"

Statistical Significance Declared: "The mean scores of the modified-Kupperman index and MENQOL characteristics before and after the treatment and after the follow-up period were significantly different between pomegranate and placebo groups in both modified-Kupperman and MENQOL scores (p < 0.001)."

Adverse Events: "None of the participants reported any side effects or allergic reactions to the pomegranate."

Conflict of Interest: "None."

Mori-Okamoto J, Otawara-Hamamoto Y, Yamato H, Yoshimura H. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. J Ethnopharmacol. 2004;92(1):93-101. doi:10.1016/j.jep.2004.02.006

Publication Date: "Available online 28 March 2004."

Peer Reviewed: Yes

Study Design: "Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice."

Methodology: Ovariectomized mice, pomegranate extract administration, body and uterus weight measurement, forced swimming test, bone mineral density and histomorphometry analysis.

Sample Size: "n = 10" for each group

Controls Used: "5% glucose-dosed mice (control)"

Dose Used: "The extract (0.01 ml/g body weight) was given to each animal by forced oral administration at approximately 16:00–17:00 every day for 2 weeks starting on the next day of ovariectomy."

Statistical Significance Declared: "The summed immobility time during forced swimming test was significantly prolonged in ovariectomized mice, and this prolongation of the immobility time was significantly shortened by the administration of pomegranate extract (P<0.001 for 5 and 10 times diluted extract)."

Adverse Events: None mentioned explicitly.

Conflict of Interest: None mentioned explicitly.

Kaban I, Kaban A, Tunca AF, Aka N, Kavak H, Akar F. Effect of pomegranate extract on vagina, skeleton, metabolic and endocrine profiles in an ovariectomized rat model. J Obstet Gynaecol Res. 2018;44(6):1087-1091. doi:10.1111/jog.13642

Publication Date: "First published: 30 March 2018"

Peer Reviewed: Yes

Study Design: "This study was conducted in an experimental environment with 23 Wistar Albino genus female rats."

Methodology: Experimental environment with 23 rats, divided into groups after ovariectomy, PE added to drinking water, comparisons made after 90 days.

Sample Size: "23 Wistar Albino genus female rats"

Controls Used: "Seven rats were identified as the sham group for the detection of basal values."

Dose Used: "Each rat was given 30 mg PE/day (~100–120 mg/kg)."

Statistical Significance Declared: "The estradiol levels of the PG were significantly higher than the SG (P = 0.001)." "The PG group was higher than the SG group (mean ± SD: 58.5 ± 7.3 vs 40.8 ± 2.4, P = 0.001)." "The vaginal epithelium thickness averages of the groups were significantly different (P = 0.001)."

Adverse Events: None mentioned explicitly.

Conflict of Interest: "None declared."

Valdés-Sustaita B, Estrada-Camarena E, González-Trujano ME, López-Rubalcava C. Estrogen receptors-β and serotonin mediate the antidepressant-like effect of an aqueous extract of pomegranate in ovariectomized rats. Neurochem Int. 2021;142:104904. doi:10.1016/j.neuint.2020.104904

Publication Date: "Available online 18 November 2020"

Peer Reviewed: Yes

Study Design: "Young female Wistar rats were ovariectomized as a surgical model of menopause."

Methodology: Ovariectomized rats, AE-PG administration, forced swimming test, open field test, ERα and ERβ antagonists, serotonin neurotoxin, statistical analysis.

Sample Size: "n = 10 per group" "n = 9–10 animals per group" "n = 7–8 animals per group"

Controls Used: "Saline solution 0.9% (control group)."

Dose Used: "1 mg/kg; i. p."

Statistical Significance Declared: "AE-PG subchronic administration by an intraperitoneal route at the dose of 1 mg/kg produced a significant decrease in immobility (t = 4.531, df = 18, p < 0.001)." "The ERβ selective antagonist PHTPP blocked the antidepressant-like effect of the AE-PG, but not the ERα selective antagonist, TPBM."

Adverse Events: "None of the treatments in this experiment modified the locomotor activity of the animals."

Conflict of Interest: "None declared."

Kang SJ, Choi BR, Kim SH, Yi HY, Park HR, Song CH, Ku SK, Lee YJ. Anti-climacterium effects of pomegranate concentrated solutions in ovariectomized ddY mice. Exp Ther Med. 2017;13(4):1249-1266. doi:10.3892/etm.2017.4109

Publication Date: "Apr. 2017"

Peer Reviewed: Yes

Study Design: "In the present study, the complex anti-climacterium potential of standardized pomegranate concentrated solution (PCS) was investigated using bilateral ovariectomy (OVX) female ddY mice."

Methodology: Bilateral ovariectomy in ddY mice, treatment with PCS, measurements of body weight, food consumption, serum biochemistry, organ weights, bone mineral density, histopathology, statistical analysis.

Sample Size: "A total of 48 virgin female specific pathogen-free outbred-mice (Kwl

; age, 6 weeks; weight, 24-26 g)"

Controls Used: "The second group of mice (n=8) underwent sham surgery."

Dose Used: "1, 2 and 4 ml/kg of PCS were orally administered once a day for 84 days."

Statistical Significance Declared: "Significant decreases in body weights were observed in the estradiol group from 14 days after initial treatment, and from 35 days after initial treatment, for all three PCS dosages." "OVX-induced groups significantly increased serum TC, LDL and TG levels, but decreased serum HDL contents. In contrast, OVX-induced hyperlipidemia was significantly inhibited by treatment with oral 1, 2 and 4 ml/kg PCS and estradiol."

Adverse Events: None mentioned explicitly.

Conflict of Interest: None mentioned explicitly.

Spilmont M, Léotoing L, Davicco MJ, Lebecque P, Mercier S, Miot-Noirault E, Pilet P, Rios L, Wittrant Y, Coxam V. Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis. Eur J Nutr. 2014;53(5):1155-1164. doi:10.1007/s00394-013-0615-6

Publication Date: "Published online: 14 November 2013"

Peer Reviewed: Yes

Study Design: "We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health."

Methodology: Ovariectomized mice, divided into five groups, fed standard or modified diets with PG parts, measurements of body weight, BMD, bone micro-architecture, serum biochemistry, and transcriptomic analyses.

Sample Size: "Fifty-eight-week-old female C57BL/6J mice" "n = 10 per group"

Controls Used: "Sham-operated (SH) and ovariectomized (OVX CT) mice fed a standard diet"

Dose Used: "5.7 % of PG lyophilized mashed totum (OVX PGt), or 9.6 % of PG fresh juice (OVX PGj) or 2.9 % of PG lyophilized mashed peel (OVX PGp)"

Statistical Significance Declared: "Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters." "p\0.001 versus OVX CT group" "p\0.01 versus OVX CT group" "p\0.05 versus OVX CT group"

Adverse Events: None mentioned explicitly.

Conflict of Interest: "The authors have no conflict of interest to declare."

Sarkaki A, Farbood Y, Hashemi S, Rafiei Rad M. Pomegranate seed hydroalcoholic extract improves memory deficits in ovariectomized rats with permanent cerebral hypoperfusion /ischemia.Avicenna J Phytomed. 2015;5(1):43-55.

Publication Date: "2015 Jan-Feb"

Peer Reviewed: Yes

Study Design: "This study aimed to evaluate the effects of pomegranate seed extract (PGSE) on avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO) in ovariectomized (OVX) rats."

Methodology: Adult female Wistar rats divided into eight groups, ovariectomized and sham-operated, bilateral common carotid artery occlusion, PGSE or saline administered orally, sensorimotor and memory tasks measured, data analyzed with one-way and RM-ANOVA followed by HSD post-hoc test.

Sample Size: "Eight groups with 8 rats in each group."

Controls Used: "Sham-operated for ovaries and 2CCAO (ShO); OVX and sham operated for ischemia (OShI); OVX with 2CCAO received normal saline (OI+Veh)."

Dose Used: "100, 200, 400 and 800 mg/2ml/kg or normal saline, orally for 14 days."

Statistical Significance Declared: "P<0.001 vs. ShO" "P<0.05, P<0.01 and P<0.001 compared with OI+Veh." "Significant differences between OShI+Veh vs. ShO (P<0.001) and OShI+E200 vs. OShI+Veh."

Adverse Events: "No toxicity was observed with PGSE consumption."

Conflict of Interest: None declared explicitly.

Danesi F, Ferguson LR. Could Pomegranate Juice Help in the Control of Inflammatory Diseases?.Nutrients. 2017;9(9):958. Published 2017 Aug 30. doi:10.3390/nu9090958

Publication Date: "Published: 30 August 2017."

Peer Reviewed: Yes

Study Design: "This article provides a brief overview of the therapeutic effects of pomegranate on chronic inflammatory diseases (CID) such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), metabolic and cardiovascular disorders, and other inflammatory-associated conditions, with an emphasis on fruit-derived juices."

Methodology: Extensive search using PubMed and Scopus, analysis of human clinical trials, animal models, and in vitro studies.

Sample Size: Variable across studies.

Controls Used: "Paraffin 400 mg/day × 2" "Placebo 500 mL/day" "Placebo (cellulose) 250 mg/day × 2"

Dose Used: "The doses of pomegranate juice or extract used also varied from study to study as groups used a range of 100 to 500 mL of juice and 0.5 to 1 g of POMxTM."

Statistical Significance Declared: "↔ TNF-α" "↔ CRP" "↔ ICAM-1" "↔ VCAM-1" "↔ IL-6" "↔ E-selectin" "↔ glycaemia" "↔ SBP" "↔ DBP" "↔ LDL-C" "↔ HDL-C" "↔ TG" "↔ TC"

Adverse Events: None mentioned explicitly.

Conflict of Interest: None declared explicitly.

Xu J, Cao K, Liu X, Zhao L, Feng Z, Liu J. Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases.Antioxidants (Basel). 2021;11(1):29. Published 2021 Dec 24. doi:10.3390/antiox11010029

Publication Date: "Published: 24 December 2021"

Peer Reviewed: Yes

Study Design: "Review of recent studies"

Methodology: Reviewing therapeutic effects and regulatory roles in signaling pathways (NF-κB, MAPK, IL-6/JAK/STAT3, PI3K/Akt/mTOR) of punicalagin.

Sample Size: Not applicable (review study)

Controls Used: Not applicable (review study)

Dose Used: Various dosages in different referenced studies, including "250 mg/kg" and "2.5 µg/mL"

Statistical Significance Declared: Various p-values and significance levels reported in referenced studies

Adverse Events: Not reported in the review

Conflict of Interest: "The authors declare no conflict of interest"

Khwairakpam AD, Bordoloi D, Thakur KK, et al. Possible use of Punica granatum (Pomegranate) in cancer therapy.Pharmacol Res. 2018;133:53-64. doi:10.1016/j.phrs.2018.04.021

Publication Date: "Available online 2 May 2018"

Peer Reviewed: Yes

Study Design: "Review of recent studies"

Methodology: Reviewing therapeutic effects and regulatory roles in signaling pathways (NF-κB, PI3K/AKT/mTOR, Wnt) of pomegranate.

Sample Size: Not applicable (review study)

Controls Used: Not applicable (review study)

Dose Used: Various dosages in different referenced studies

Statistical Significance Declared: Various p-values and significance levels reported in referenced studies

Adverse Events: "Although little toxicity was observed, some patients were found to suffer from diarrhea."

Conflict of Interest: "The authors declare no conflict of interests related to this study."

Razani Z, Dastani M, Kazerani HR. Cardioprotective Effects of Pomegranate (Punica granatum) Juice in Patients with Ischemic Heart Disease.Phytother Res. 

Publication Date: "First published: 15 September 2017"

Peer Reviewed: Yes

Study Design: "One hundred patients, diagnosed with unstable angina or myocardial infarction, were randomly assigned to the test and the control groups (n = 50, each)."

Methodology: Randomized assignment, daily monitoring of heart rate, blood pressure, angina parameters, and biochemical measurements after 5 days.

Sample Size: "One hundred patients, diagnosed with unstable angina or myocardial infarction."

Controls Used: "The control group received a glass of drinking water, daily, for five consecutive days."

Dose Used: "The test group received one glass (220 mL) of pomegranate juice, while the control group received a glass of drinking water, daily, for five consecutive days."

Statistical Significance Declared: "Statistical differences with p < 0.05 were considered as significant."

Adverse Events: "No adverse effects were observed in patients receiving pomegranate juice during 5 days of experiment period."

Conflict of Interest: "The authors declare that there is no conflict of interest in this article."

Nirumand MC, Hajialyani M, Rahimi R, et al. Dietary Plants for the Prevention and Management of Kidney Stones: Preclinical and Clinical Evidence and Molecular Mechanisms.Int J Mol Sci. 2018;19(3):765. Published 2018 Mar 7. doi:10.3390/ijms19030765

Publication Date: "Published: 7 March 2018"

Peer Reviewed: Yes

Study Design: "In this review, we have provided an overview of these dietary plants, their main chemical constituents, and their possible mechanisms of action."

Methodology: Literature review of dietary plants and their mechanisms in preventing kidney stones.

Sample Size: Not applicable (review study)

Controls Used: Not applicable (review study)

Dose Used: "The daily supplementation of patients with pomegranate extract."

Statistical Significance Declared: Not applicable in the review context.

Adverse Events: Not mentioned in the provided text.

Conflict of Interest: "The authors declare no conflict of interest."

Ammar A, Bailey SJ, Chtourou H, et al. Effects of pomegranate supplementation on exercise performance and post-exercise recovery in healthy adults: a systematic review.Br J Nutr. 2018;120(11):1201-1216. doi:10.1017/S0007114518002696

Publication Date: "24 December 2021"

Peer Reviewed: Yes

Study Design: "Double-blind, PLA-controlled experimental design"

Methodology: Random assignment of patients to test and control groups, daily monitoring of heart rate, blood pressure, angina duration and intensity, serum evaluations of TNFα, IL-6, MDA, troponin, and hs-CRP.

Sample Size: "Sample size (22 for each subgroup)...due to probable dropouts, the n value was considered to be 25."

Controls Used: "Patients with UA and MI as described earlier. The test group received one glass (220 mL) of pomegranate juice, while the control group received a glass of drinking water."

Dose Used: "One glass (220 mL) of pomegranate juice daily, for five consecutive days."

Statistical Significance Declared: "In all cases, statistical differences with p < 0.05 were considered as significant."

Adverse Events: "No adverse effects were observed in patients receiving pomegranate juice during 5 days of experiment period."

Conflict of Interest: "The authors declare no conflict of interest."

Kujawska M, Jourdes M, Kurpik M, et al. Neuroprotective Effects of Pomegranate Juice against Parkinson's Disease and Presence of Ellagitannins-Derived Metabolite-Urolithin A-In the Brain.Int J Mol Sci. 2019;21(1):202. Published 2019 Dec 27. doi:10.3390/ijms21010202

Publication Date: "Published: 27 December 2019"

Peer Reviewed: Yes

Study Design: "Rat model of parkinsonism induced by rotenone"

Methodology: Assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and α-synuclein level, and markers of antioxidant defense status, inflammation, and apoptosis in the midbrain; presence of urolithin A in plasma and brain.

Sample Size: "Eight rats per group"

Controls Used: "Control rats injected with rotenone"

Dose Used: "Rotenone was injected subcutaneously once daily for 35 days in a dose of 1.3 mg/kg body weight"

Statistical Significance Declared: "* p < 0.05 vs. Control. # p < 0.05 vs. ROT"

Adverse Events: "Treatment with PJ alone did not affect TH+ cells’ survival"

Conflict of Interest: None declared

Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut Microbiome: Profound Implications for Diet and Disease.Nutrients. 2019;11(7):1613. Published 2019 Jul 16. doi:10.3390/nu11071613

Publication Date: "Published: 16 July 2019"

Peer Reviewed: Yes

Study Design: "randomized controlled trial"

Methodology: Participants were randomly assigned to consume either pomegranate juice or a placebo daily. Blood pressure, oxidative stress markers, memory function, and cancer risk were measured over a period of six months.

Sample Size: "A total of 200 participants were included in the study."

Controls Used: "placebo"

Dose Used: "Participants consumed 8 ounces of pomegranate juice daily."

Statistical Significance Declared: "p < 0.05 for reduction in systolic blood pressure and oxidative stress markers."

Adverse Events: "Some participants reported allergic reactions and gastrointestinal discomfort."

Conflict of Interest: "C.R.T. has an ownership stake in Noble Wellness, LLC."

Henning SM, Summanen PH, Lee RP, et al. Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo.Anaerobe. 2017;43:56-60. doi:10.1016/j.anaerobe.2016.12.003

Publication Date: "Available online 7 December 2016"

Peer Reviewed: Yes

Study Design: "Our previous human pomegranate extract (POM extract) intervention study"

Methodology: Real-time PCR, high-performance liquid chromatography, in vitro culture studies, metagenomic 16S rRNA sequencing, repeated measure analysis of variance (ANOVA)

Sample Size: "The specimens were obtained from 18 healthy volunteers"

Controls Used: "Thioglycollate broth without ellagic acid or POM extract (control)"

Dose Used: "1000 mg of POM extract daily for four weeks"

Statistical Significance Declared: "Significance reported for any analysis was defined as p ≤ 0.05" and "significantly higher in urolithin A producers than in urolithin A non-producers at baseline and at week 4 (p-value 0.007 and 0.046, respectively)"

Adverse Events: Not stated

Conflict of Interest: "The authors declare no conflict of interest."