Abstracto

Pomegranate (Punica granatum l.) in Cardio Metabolic Syndromes

Aimen Umer Khan

Background: Scientific interest in pomegranate is escalating in recent year due to its use in the treatment of diarrhea, parasitic infection, diabetes mellitus, cancer Dermatological disorders, neurodegenerative, and Depressive Disorders, hemodialysis respiratory diseases, prostate cancer, hepatocellular carcinoma, prostatic hyperplasia, rheumatoid arthritis, inflammatory bowel disease, cardiovascular disorders, and obesity have been ascribed to various diversified phytochemical constituents present in juice, peel flower, seed, and leaf. Objectives: The current review expedites the role of polyphenolic compounds and their mechanism involved in combating cardiometabolic syndromes and various pathological biomarkers involving preclinical and clinical studies and future perspective of pomegranate as a therapeutic and pharmacological agent in cardiometabolic syndrome. Methodology: The present review summarizes the data and literature taken from previously done studies from research gate, science direct, PubMed, PubMed Central, Medline, and some other scientific databases emphasizing the role of Punica granatum and besides its pharmacological, therapeutic perspective in cardiometabolic syndrome. The results obtained through this database were assembled, composed, critically elucidated and presented in explanatory and tabular form. Results: anti-obesity constituents from juice (urolithin A, EA, punicalagin,) seed (linoleic acid punicic acid) leaf (punicalin, EA) inhibited DPD-4, TGs deposition mainly via PPAR-γ, GLUT4, FABP4 NF-β expressions. The preclinical and clinical study showed leaf, and PV (AMPK phosphorylation) exerted anti-obesity effects. Antidiabetic constituents from flower (oleanolic acid, ursolic acid, gallic acid,) presented antidiabetic activity via PPAR-γ and PPAR-expression activation and improvement in sensitivity of insulin, Tricetin showed significant α- glucosidase inhibition properties. Peel and leaf showed a significant reduction in TGs, Blood glucose, TC, LDL-c alone and combined with anti-diabetic drugs. The pancreatic restoration was seen with juice in preclinical and clinical studies. JP reduced oxidative stress at lower doses, and inflammation at higher doses. Insulin resistance and fasting blood glucose was reduced. SICAM-1 and VCAM-1 did not alter. anti-atherosclerotic, anti-hyperlipidemic and antidyslipidemic constituents from juice e.g. urolithin A and D were more effective than punicalagin and ellagic acid, urolithin reduced THP-1, ICAMP-1, MCP-1, TNF-α, IL-6 and increased in PPAR- γ and anthocyanins inhibits xanthine oxidase and chelate metal ion, TNF-α, NF-қβ Arachidonic acid pathway, enhance Nrf2 expression. Leaf extract (pyrogallic acid, tannic acid, and ellagic acid) decreased intestinal, pancreatic lipases and inhibited absorption of lipids. Punicalagin and gallic acid from juice and peel of pomegranate enhanced PPAR- γ, AP-1, PON-2 eNOS expression, and NO production. PJ in pre-clinical studies decreased lipid oxidation, uptake by macrophages, triglycerides, total cholesterol, LDL-c VLDL-c, atherosclerotic size, and foam cell and increased HDL-c. Upregulation of FN-1, BdKrB1 and at/K/ eNOS pathway and downregulation of MCP-1, IL-1β, and TNF-α In Clinical studies, PJ reduced IMT and SBP. Peel significantly decreased TGs, TC and TC. Antihypertensive constituents (Quercetin, naringin, and naritutins) in seed, peel, and juice enhanced EDHF. Preclinical PJ and peel increased eNOS, NO and reduced TGβ-1, MABP, ACE, Angiotensin II. PJ increased drastically SOD, CAT, and GHS. Seed significantly decreased TSP-1. In clinical trials PJ drastically decreased SBP DBP (at a higher dose). While Peel significantly decreased hsCRP, SBP, LDL-c, TGs, and TCs at higher doses and longer duration compared to juice. In-vitro pre-clinical and clinical studies reduced drastically LDH, CK, troponin1 and increased antioxidant status in (MI) myocardial ischemia and reperfusion MI/R Conclusion: Constituents from leaf, juice, peel, seed exert protection against obesity, diabetes, hyperlipidemias, dyslipidemias, atherosclerosis, hypertension myocardial infarction (MI) myocardial ischemia and reperfusion MI/R. Studies from marine and human subjects disclosed that Pomegranate leaf, and vinegar has many promising effects against obesity these areas needed further clinical interrogations to reveal other hidden perspectives of it. According to preclinical in-vitro and in-vivo all parts possessed anti-diabetic properties but peel and leaf exerted significant antidiabetic properties. Juice produced restoration properties in the pancreas of Langerhans in preclinical and clinical studies. But clinical data is not sufficient to conclude it. Pomegranate juice and peel have many promising effects against atherosclerosis, hyperlipidemia, dyslipidemia, and hypertension. Juice at higher doses is significant against DBP and SBP but lipid profile wasn’t affected much at a higher dose and longer duration of action compared to peel which covers lipid profile in a better way at higher doses and longer duration of action. BP and ACE reduction and its relation with pomegranate juice are still in question. PJ gives protective shreds of evidence in myocardial infarction (MI) myocardial ischemia and reperfusion MI/R but some biomarkers could cover better results by the peel. Future Perspective: Pomegranate covers the wider range of satiety in cardiometabolic syndromes. If pomegranate juice and peel are combined together it could be proven as an unprecedented exemplary juice for combating Cardiometabolic syndromes