Oral Glucose Tolerance Test (OGTT) Evidence for the Postprandial Anti-Hyperglycemic Property of Salacca zalacca (Gaertn.) Voss Seed Extract.

Salak seed extract (Salacca zalacca) is known for its high antioxidant content and low caffeine levels, making it a promising candidate for the development of value-added health products. However, there is a lack of scientific evidence for its anti-hyperglycemic effects. To address this, we investigated the in vitro and in vivo anti-hyperglycemic and antioxidant effects of salak seed extract. The HPLC chromatogram of salak seed extract shows a prominent peak that corresponds to chlorogenic acid. In vitro studies revealed that salak seeds inhibited α-glucosidase activity and glucose uptake in Caco-2 cells in a concentration-dependent manner, while also exhibiting antioxidant properties. The extract exhibits a non-competitive inhibition on α-glucosidase activity, with an IC50 and Ki of 16.28 ± 7.22 and 24.81 µg/mL, respectively. In vivo studies utilizing streptozotocin-nicotinamide-induced diabetic mice showed that the extract significantly reduced fasting blood glucose (FBG) levels in the oral glucose tolerance test. Continuous administration of the salak seed extract resulted in lower FBG levels by 13.8% as compared with untreated diabetic mice, although this change was not statistically significant. The estimated LD50 value of salak seed extract exceeds 2000 mg/kg, and no toxicity symptoms have been detected. Our research supports that salak seed extract has the potential to serve as a functional food or supplement that may be beneficial in reducing postprandial hyperglycemia among people with type 2 diabetes. This effect was explained by the salak's inhibitory mechanisms of glucose absorption due to inhibition of both α-glucosidase activity and intestinal glucose uptake, coupled with its antioxidant effects.

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo.

CONTEXT: Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) (Fabaceae) has traditionally been used to treat diabetes mellitus. OBJECTIVE: This study demonstrates the antidiabetic and antioxidant effects of aqueous extract of LS leaves in vivo and in vitro. MATERIALS AND METHODS: The effects of aqueous LS leaf extract on glucose uptake, sodium-dependent glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) mRNA expression in Caco-2 cells, α-glucosidase, and lipid peroxidation were evaluated in vitro. The antidiabetic effects were evaluated using an oral glucose tolerance test (OGTT) and a 28-day consecutive administration to streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic mice. RESULTS: The extract significantly inhibited glucose uptake (IC50: 236.2 ± 36.05 µg/mL) and downregulated SGLT1 and GLUT2 mRNA expression by approximately 90% in Caco-2 cells. Furthermore, it non-competitively inhibited α-glucosidase in a concentration-dependent manner with the IC50 and Ki of 6.52 ± 0.42 and 1.32 µg/mL, respectively. The extract at 1000 mg/kg significantly reduced fasting blood glucose levels in both the OGTT and 28-day consecutive administration models as compared with untreated STZ-NA-induced diabetic mice (p < 0.05). Significant improvements of serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and GLUT4 levels were observed. Furthermore, the extract markedly decreased oxidative stress markers by 37-53% reduction of superoxide dismutase 1 (SOD1) in muscle and malondialdehyde (MDA) in muscle and pancreas, which correlated with the reduction of MDA production in vitro (IC50: 24.80 ± 7.24 µg/mL). CONCLUSION: The LS extract has potent antihyperglycemic activity to be used as alternative medicine to treat diabetes mellitus.

Inhibitory effects of Triphala on CYP isoforms in vitro and its pharmacokinetic interactions with phenacetin and midazolam in rats.

Context: Direct evidence of Triphala-drug interactions has not been provided to date. Objective: This study was aimed to determine the effects of Triphala on cytochrome P450 (CYP) isoforms and P-glycoprotein (P-gp) in vitro, and to investigate pharmacokinetic interactions of Triphala with CYP-probes in rats. Materials and methods: Effects of Triphala on the activities of CYP isoforms and P-gp were examined using human liver microsomes (HLMs) and Caco-2 cells, respectively. Pharmacokinetic interactions between Triphala and CYP-probes (i.e., phenacetin and midazolam) were further examined in rats. Results: Triphala extract inhibited the activities of CYP isoforms in the order of CYP1A2>3A4>2C9>2D6 with the IC50 values of 23.6 ± 9.2, 28.1 ± 9.8, 30.41 ± 16.7 and 93.9 ± 27.5 µg/mL, respectively in HLMs. It exhibited a non-competitive inhibition of CYP1A2 and 2C9 with the K i values of 23.6 and 30.4 µg/mL, respectively, while its inhibition on CYP3A4 was competitive manner with the Ki values of 64.9 µg/mL. The inhibitory effects of Triphala on CYP1A2 and 3A4 were not time-dependent. Moreover, Triphala did not affect the P-gp activity in Caco-2 cells. Triphala, after its oral co-administration at 500 mg/kg, increased the bioavailabilities of phenacetin and midazolam by about 61.2% and 40.7%, respectively, in rats. Discussion and conclusions: Increases observed in the bioavailabilities of phenacetin and midazolam after oral co-administration of Triphala in rats provided a direct line of evidence to show Triphala-drug interactions via inhibition of CYP1A and CYP3A activities, respectively. These results, together with the lack of time-dependency of CYP 1A2 and 3A4 inhibition in vitro, suggested that the inhibitory effect of Triphala is primarily reversible.

Anti-Helicobacter pylori xanthones of Garcinia fusca.

A new geranylated xanthone derivative, fuscaxanthone I (1), along with nine xanthones (2-9 and 11), a biphenyl (10) and three biflavonoids (12-14) were isolated from the roots of Garcinia fusca Pierre. Compounds 8, 10 and 11-14 were reported from this plant species for the first time. Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR and MS. The isolated compounds were evaluated for antibacterial activity against Helicobacter pylori. Cowaxanthone (5) and fukugiside (14) exhibited stronger inhibitory activity against H. pylori DMST reference strain at MICs 4.6 and 10.8 µM, respectively, than that of the control metronidazole. Isojacareubin (8) displayed the most potent activity against H. pylori HP40 clinical isolate with MIC 23.9 µM, which was approximately two times greater than that of the standard drug amoxicillin.

Anti-tumorigenicity of dietary α-mangostin in an HT-29 colon cell xenograft model and the tissue distribution of xanthones and their phase II metabolites.

SCOPE: This study investigated the in vivo and in vitro activity of α-mangostin (α-MG), the most abundant xanthone in mangosteen pericarp, on HT-29 cell tumorigenicity, proliferation, and several markers of tumor cell activity, as well as the profile and amounts of xanthones in serum, tumor, liver, and feces. METHODS AND RESULTS: Balb/c nu/nu mice were fed either control diet or diet containing 900 mg α-MG/kg. After 1 week of acclimation to diet, mice were injected subcutaneously with HT-29 cells and fed the same diets ad libitum for an additional 2 or 4 weeks. After 2 and 4 weeks, tumor mass and the concentrations of BcL-2 and ß-catenin in tumors of mice fed diet with α-MG were significantly less than in mice fed control diet. Xanthones and their metabolites were identified in serum, tumor, liver, and feces. In vitro treatment of HT-29 cells with α-MG also inhibited cell proliferation and decreased expression of BcL-2 and ß-catenin. CONCLUSION: Our data demonstrate that the anti-neoplastic effect of dietary α-MG is associated with the presence of xanthones in the tumor tissue. Further investigation of the impact of beverages and food products containing xanthones on the prevention of colon cancer or as complementary therapy is merited.