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Fulltext Antihyperglycemic Effect of Methanol Extract of Syzygium polyanthum (Wight.) Leaf in Streptozotocin-Induced Diabetic Rats

Widyawati T, Yusoff NA, Asmawi MZ, Ahmad M

Nutrients, 2015 Sep;7(9):7764-80.
PMID: 26389944 DOI: 10.3390/nu7095365

Syzygium polyanthum (S. polyanthum), a plant belonging to Myrtaceae, is widely used in Indonesian and Malaysian cuisines. Diabetic patients in Indonesia also commonly use it as a traditional medicine. Hence, this study was conducted to investigate the antihyperglycemic effect of the methanol extract (ME) of S. polyanthum leaf and its possible mechanisms of action. To test for hypoglycemic activity, ME was administered orally to normal male Sprague Dawley rats after a 12-h fast. To further test for antihyperglycemic activity, the same treatment was administered to glucose-loaded (intraperitoneal glucose tolerance test, IPGTT) and streptozotocin (STZ)-induced diabetic rats, respectively. Hypoglycemic test in normal rats did not show significant reduction in blood glucose levels (BGLs) by the extract. Furthermore, IPGTT conducted on glucose-loaded normal rats also did not show significant reduction of BGLs. However, repeated administration of metformin and three doses of ME (250, 500 and 1000 mg/kg) for six days caused significant reduction of fasting BGLs in STZ-induced diabetic rats. The possible mechanisms of action of S. polyanthum antihyperglycemic activity were assessed by measurement of intestinal glucose absorption and glucose uptake by isolated rat abdominal muscle. It was found that the extract not only inhibited glucose absorption from the intestine but also significantly increased glucose uptake in muscle tissue. A preliminary phytochemical qualitative analysis of ME indicated the presence of tannins, glycosides, flavonoids, alkaloids and saponins. Additionally, Gas Chromatography-Mass Spectrometry (GC-MS) analysis detected squalene. In conclusion, S. polyanthum methanol leaf extract exerts its antihyperglycemic effect possibly by inhibiting glucose absorption from the intestine and promoting glucose uptake by the muscles.
Fulltext Bioactivity-Guided Fractionation and Identification of Antidiabetic Compound of Syzygium polyanthum (Wight.)'s Leaf Extract in Streptozotocin-Induced Diabetic Rat Model

Widyawati T, Yusoff NA, Bello I, Asmawi MZ, Ahmad M

Molecules, 2022 Oct 12;27(20).
PMID: 36296407 DOI: 10.3390/molecules27206814

(1) Background: An earlier study on the hypoglycemic activity of S. polyanthum (Wight.) leaf methanol extract identified squalene as the major chemical compound. The present study was conducted to assess the hypoglycemic effect of fractions and subfractions of the methanol extract of S. polyanthum compared to the squalene using a bioassay-guided in vivo study. (2) Methods: The methanol extract was fractionated using the liquid−liquid fractionation method. Streptozotocin-induced type 1 diabetic rat was used to study the hypoglycemic effect. (3) Results: The findings showed that chloroform fraction significantly (p < 0.05) lowered blood glucose levels of diabetic rats as compared to the control. Further fractionation of chloroform fraction yielded subfraction-1 and -2, whereby subfraction-1 exhibited a higher blood-glucose-lowering effect. The lipid profile test showed that the total cholesterol level of subfraction-1 and squalene-treated groups decreased significantly (p < 0.05). An immunohistochemistry study revealed that none of the treatments regenerated pancreatic β-cells. Gas chromatography−mass spectrophotometer analysis identified the presence of squalene in the active methanol extract, chloroform fraction, and subfraction-1. In silico analysis revealed a higher affinity of squalene against protein receptors that control lipid metabolism than metformin. (4) Conclusions: Data obtained from the present work suggested the crude methanol extract exerted the highest hypoglycemic effect compared to fraction, subfraction, and squalene, confirming synergistic effect may be responsible for the hypoglycemic activity of S. polyanthum.
Fulltext Antidiabetic and antioxidant activities of Nypa fruticans Wurmb. vinegar sample from Malaysia

Yusoff NA, Yam MF, Beh HK, Abdul Razak KN, Widyawati T, Mahmud R, et al.

Asian Pac J Trop Med, 2015 Aug;8(8):595-605.
PMID: 26321511 DOI: 10.1016/j.apjtm.2015.07.015

OBJECTIVES: To study the antidiabetic and antioxidant activities of nipa palm vinegar (NPV) used in traditional Malay medicine for treating diabetes.
METHODS: NPV was extracted using liquid-liquid extraction method and the obtained samples were subjected to antidiabetic studies using normal and streptozotocin-induced diabetic rat models whereas antidoxidant activities were investigated via in vitro antioxidant tests namely 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radicals scavenging activities and the reducing power assay.
RESULTS: Single administration of NPV and its extracts were not effective in both normal and diabetic rats. In intraperitoneal glucose tolerance test, NPV and its aqueous extract showed significant blood glucose lowering effect. In the sub-acute study, compared with the diabetic control, aqueous extract of NPV showed the most notable blood glucose lowering effect (56.6%) and a significant improvement in serum insulin levels (79.8%, P
Fulltext Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats

Yusoff NA, Ahmad M, Al-Hindi B, Widyawati T, Yam MF, Mahmud R, et al.

Nutrients, 2015 Aug;7(8):7012-26.
PMID: 26308046 DOI: 10.3390/nu7085320

Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.
Fulltext Nypa fruticans Wurmb. Vinegar's Aqueous Extract Stimulates Insulin Secretion and Exerts Hepatoprotective Effect on STZ-Induced Diabetic Rats

Yusoff NA, Lim V, Al-Hindi B, Abdul Razak KN, Widyawati T, Anggraini DR, et al.

Nutrients, 2017 Aug 23;9(9).
PMID: 28832548 DOI: 10.3390/nu9090925

BACKGROUND: An aqueous extract (AE) of vinegar made from Nypa fruticans Wurmb. can improve postprandial glucose levels in normoglycaemic rats. The aim of this study was to evaluate its antihyperglycaemic activity further using in vivo and in vitro approaches.
METHODS: AE was administered to streptozotocin (STZ)-induced diabetic rats twice daily at three doses (1000, 500, and 250 mg/kg b.w.) for 12 days p.o. Several biochemical analyses and a histological study of the pancreas and liver were performed, accompanied by a cell culture assay.
RESULTS: As compared to diabetic control (DC), AE at the doses of 500 and 1000 mg/kg b.w. caused significant reduction (p < 0.05) of blood glucose, total cholesterol and triglycerides levels, with positive improvement of serum insulin levels. Interestingly, immunohistochemical staining of the pancreas suggested no β-cell regeneration, despite significant increase in insulin production. AE-treated groups, however, showed overall restoration of the hepatic histoarchitecture of STZ-induced liver damage, suggesting a possible hepatoprotective effect. The pancreatic effect of AE was further studied through RIN-5F cell culture, which revealed a positive stimulatory effect on insulin release at a basal glucose concentration (1.1 mM).
CONCLUSION: Nypa fruticans Wurmb. vinegar's aqueous extract exerts its antihyperglycaemic activity, at least in part, through insulin stimulatory and hepatoprotective effects.