Antidepressant, analgesic activity and SAR studies of substituted benzimidazoles

Purpose. Benzimidazole class of compound is found to have diverse biological properties. From the literature study, it is observed that depression is a severe mental disease affecting a huge population and pain is affecting about 20% of world population. In continuation of our previous research work, we selected benzimidazole pharmacophore to further explore its pharmacological activities. Methods. Forced swim test and Thermal stimulus test were used to assess the antidepressant and analgesic activity of synthesized benzimidazole analogs. Results. The antidepressant activity results showed that compound 3j was found most potent having Mean ± SEM value 21.6 ± 0.8 for treated group. Furthermore, in the analgesic test, 3b, 3j, and 3o showed Mean ± SEM values; 1.8 ± 0.10, 2.3 ± 0.10 and 2.2 ± 0.10, respectively. The study results suggested that these compounds could be explored further for the development of better antidepressant and analgesic agents. Conclusion. From the present study, it may be concluded that these active benzimidazole derivatives have been found to possess potential antidepressant and analgesic activit

Effect of different drying treatments and different extraction methods on α-glucosidase inhibitory activities of S. zalacca fruit

Introduction: Salacca zalacca (Gaertn Voss), commonly known as snake fruit and belongs to the Arecaceae family and natives of Southeast Asia. This fruit is edible and have certain medicinal values. Objectives: The aim of this study was to compare the α-glucosidase inhibitory activities of different drying and extraction methods. Material and methods: Flesh of this fruit was subjected to two different drying methods namely; oven dried (OD) and freeze dried (FD) and extracts were prepared using soxhlet (SX), sonication (SC) and maceration (MC) techniques. The α-glucosidase inhibitory activity of extracts were evaluated using α-glucosidase enzyme . Results: The S. zalacca fruit extracts obtained through SC and MC demonstrated better α-glucosidase inhibitory activity as compared to SX method, specifically, the FD extracts showed higher activity compared to the OD extracts. Analysis of α-glucosidase inhibitory activity of the OD S. zalacca fruit extract indicates that extract obtained through SC method possesses significantly higher activity (IC50 79.42 µg/mL) than that of SX extracted sample which displayed IC50 at 125.73 µg/mL. Considering the effects of both methods (drying and extraction) on the α-glucosidase inhibitory activity of S. zalacca fruit extracts, extract obtained through SC of the FD fruits demonstrated the highest activity (IC50 19.40 µg/mL) Meanwhile, extracts obtained via OD and different extraction methods such as SX, MC and SC showed the least inhibition with IC50 125.73, 87.23 and 79.42 µg/mL, respectively. Conclusion: This study suggests that S. zalacca fruit has the potential for nutraceutical enhancement and as ingredient in medicinal preparation

Correlation of FT-IR fingerprint and α-glucosidase inhibitory activity of Salak (Salacca zalacca) fruit extracts utilizing orthogonal partial least square

Salak fruit (Salacca zalacca), commonly known as snake fruit, is used indigenously as food and for medicinal applications in Southeast Asia. This study was conducted to evaluate the α-glucosidase inhibitory activity of salak fruit extracts in correlation to its Fourier transform infrared spectroscopy (FT-IR) fingerprint, utilizing orthogonal partial least square. This calibration model was applied to develop a rapid analytical method tool for quality control of this fruit. A total of 36 extracts prepared with different solvent ratios of ethanol–water (100, 80, 60, 40.20, 0% v/v) and their α-glucosidase inhibitory activities determined. The FT-IR spectra of ethanol–water extracts measured in the region of 400 and 4000 cm−1 at a resolution of 4 cm−1. Multivariate analysis with a combination of orthogonal partial least-squares (OPLS) algorithm was used to correlate the bioactivity of the samples with the FT-IR spectral data. The OPLS biplot model identified several functional groups (C–H, C=O, C–N, N–H, C–O, and C=C) which actively induced α-glucosidase inhibitory activity

Cat's whiskers tea (orthosiphon stamineus) extract inhibits growth of colon tumor in nude mice and angiogenesis in endothelial cells via suppressing VEGFR phosphorylation

Cat's whiskers (Orthosiphon stamineus) is commonly used as Java tea to treat kidney stones including a variety of angiogenesis-dependent diseases such as tumorous edema, rheumatism, diabetic blindness, and obesity. In the present study, antitumor potential of standardized 50% ethanol extract of O. stamineus leaves (EOS) was evaluated against colorectal tumor in athymic mice and antiangiogenic efficacy of EOS was investigated in human umbilical vein endothelial cells (HUVEC). EOS at 100 mg/kg caused 47.62 ± 6.4% suppression in tumor growth, while at 200 mg/kg it caused 83.39 ± 4.1% tumor regression. Tumor histology revealed significant reduction in extent of vascularization. Enzyme-linked immunosorbent assay showed EOS (200 mg/kg) significantly reduced the vascular endothelial growth factor (VEGF) level in vitro (211 ± 0.26 pg/ml cell lysate) as well as in vivo (90.9 ± 2 pg/g tissue homogenate) when compared to the control (378 ± 5 and 135.5 ± 4 pg, respectively). However, EOS was found to be noncytotoxic to colon cancer and endothelial cells. In vitro, EOS significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). EOS suppressed VEGF-induced phosphorylation of VEGF receptor-2 in HUVECs. High performance liquid chromatography (HPLC) analysis of EOS showed high rosmarinic acid contents, whereas phytochemical analysis revealed high protein and phenolic contents. These results demonstrated that the antitumor activity of EOS may be due to its VEGF-targeted antiangiogenicity

Antioxidant and α‐glucosidase inhibitory activities and gas chromatography–mass spectrometry pro le of salak (salacca zalacca) fruit peel extracts

Background: This study was aimed to investigate antioxidant and α‑glucosidase inhibitory activity, with a proximate analysis of total phenolic and total flavonoid content with gas chromatography–mass spectrometry (GC‑MS) profiling of salak (Salacca zalacca) fruit peel extracts. Materials and Methods: The peels extracts were prepared by maceration process at room temperature with different ratio of ethanol/water. Results: Phytochemical screening showed the presence of phenolic and flavonoid contents in all the extracts. About 100% ethanol extract shows the highest phenolic content (116.70 ± 0.764 μg/mL) while 60% ethanol extract has the lowest content 18.65 ± 1.155 μg/ml using gallic acid as a reference. 100% ethanol extract was observed to exhibit highest radical scavenging, ferric reducing antioxidant power (FRAP), and α‑glucosidaseinhibitory activities (IC50: 49.45 ± 3.87 μg/mL, 144.81 ± 3.72 μg AAE/g,IC50: 11.62 ± 0.67b μg/mL), respectively. Water extracts had the lowestFRAP, radical scavenging activity as well as α‑glucosidase activity. The phytochemical investigation on GC‑MS showed the presence of active compounds in salak fruit peel extracts. Conclusion: Salak fruit peels showed the highest antioxidant as well as α‑glucosidase inhibitory activities. Phytochemical analysis on GC‑MS confirms the presence of gallic acid, linoelaidic acid, palmitic acid, α‑tocopherol, and steric acid whichmay contribute to α‑glucosidase inhibitory activity

GC-MS analysis of metabolites from soxhlet extraction, ultrasound-assisted extraction and supercritical fluid extraction of Salacca zalacca flesh and its alpha-glucosidase inhibitory activity

ABSTRACT Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18 ±4.35%), whereas SFE_1 showed the lowest yield (0.42 ±0.08%). All extracts were evaluated for in vitro a-glucosidase inhibitory activity, measured by their IC50 values in comparison to that of quercetin, the positive control (IC50 ¼ 2.7 ±0.7 lg/mL). The lowest a-glucosidase inhibitory activity was indicated by water extract of SE (IC50 ¼ 724.3 ±42.9 lg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC50 ¼ 16.2 ± 2.4 lg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as a-glucosidase inhibitor and may attribute to the a-glucosidase inhibitory activity

Metabolomics-based profiling with chemometric approach to identify bioactive compounds in Salacca zalacca fruits extracts and in silico molecular docking

Salak (Salacca zalacca) is well-known as snake fruit and it is immensely studied for its antioxidative and antidiabetic active metabolites throughout the southeast Asian countries. However, there are many remaining unidentified metabolites due to very low abundance and natural variation, which need to be further explored. Nowadays mass spectrometry (MS/MS) facilitates the tentative identification of unknown compounds in the crude herbal extracts. This study described the metabolite profiling of hydroalcoholic extracts of S. zalacca analysed by LCQTOF- MS/MS. The 60% ethanolic extract exhibited the highest a-glucosidase inhibition and ferric reducing antioxidant power activities with IC50 of 15.94 mg/mL and 78.13 lg AAE/g, respectively. Multivariate data analysis (MVDA) by an orthogonal partial least-squares (OPLS) algorithm was conducted to correlate the a-glucosidase inhibition activity with the LC- QTOF-MS data. A total of 4 compounds were reported for first time in this fruit and identified based on the molecular mass and fragment ions. LC-QTOF-MS analysis indicated the presence of carexane I, 5-phenoxytetra zol-1-yl)-2,3,5,6-hexahydrofurofuran-3-ethylurea, 3-acetylphenoxy)-N-[(2)-1-amino-4-methyl-1-oxo pentan-2-yl]-4,5-dihydroxycyclohexene-1-carboxamide and Ethyl 4-[5-methyl-2-oxo-10,20,50,60,70,70 a-hexahydro-1H-spiro[indole-3,30-pyrrolizine]-20-ylamido] benzoate. Molecular docking of those compounds with the a–glucosidase enzyme was performed to confirm their antidiabetic potential. These bioactive compounds could be suggested as a-glucosidase inhibitors and functional food additive

Modulation of metabolic alterations of obese diabetic rats upon treatment with Salacca zalacca fruits extract using H NMR-based metabolomics

Fruit of salak (Salacca zalacca) is tradition ally used and commercialized as an an tidiabetic agent. How ever, the scientific evidence to prove this traditional use is lack ing. This re search was aimed to evaluate the metabolic changes of obese-diabetic (OBDC) rats treated with S. zalacca fruit using proton-nuclear magnetic resonance ( H NMR)-based metabolomics approach. This re search presents the first report on the in vitro antidiabetic effect of S. zalacca fruits ex tract us ing this approach. The obtained results in dicated that the administration of 400 mg/ kg bw of 60% ethanolic S. zalacca extract for 6 weeks significantly de creased the blood glucose level and normalized the blood lipid pro file of the OBDC rats. The potential biomarkers in urine were 2-oxoglutarate, alanine, leucine, succinate 3-hydroxy butyrate, taurine, betaine, allantoin, acetate, dimethylamine, creatine, creatinine, glucose, phenyl-acetyl glycine, and hippurate. Based on the data obtained, the metabolite pro files of the urine of treated rats by the 60% ethanolic extract could not be fully improved the metabolic complications of diabetic rats. The ex tract of S. zalacca fruit was able to de crease the ketones bodies as 3-hydroxy butyrate and acetoacetate. It has also improved energy metabolism, involving glucose, acetate, lactate, 2-hydroxy butyrate, 2-oxoglutarate, citrate, and succinate. More over, it decreased metabolites from gut microflora, including choline. This extract had significant effect on amino acid metabolism, metabolites from gut microflora, bile acid metabolism and creatine. The result can further support the traditional claims of S. zalacca fruits in management of diabetes. This finding might bevaluable in understanding the molecular mechanism and pharmacological properties of this medicinal plant for managing diabetes mellitus

Phytochemical constituents, a-glucosidase inhibitory activity and preliminary acute toxicity studies of the ethanol-water extracts of Salacca zalacca fruits in rats

Purpose: To evaluate the phytochemical constituent screening, α-glucosidase inhibitory activity and in vivo preliminary toxicity study of ethanol and water S. zalacca fruit extracts. Methods: The fresh fruit was collected, cleaned, peeled, and dried using freeze dryer. The flesh powder was extracted using solvent with different concentration of ethanol and water (100, 80, 60, 40, 20, 0%). All extracts were tested for α-glucosidase inhibitory activity and phytochemical constituents were evaluated using different chemical methods. The extract showing highest α-glucosidase inhibitory activity was tested for acute toxicity studies according to the up and down method. A dose (0.15, 0.48, 1.54, 4.91 and 5.00 g/ kg body weight) of the extract was used in 15 healthy male rats. The rats were observed for 4 h first day, then daily for 14 days. Result(s): The highest yield was determined for the extract of 80% concentration, whereas the highest α-glucosidase inhibitory activity (IC50 13.43±2.43 µg/mL), total phenolic content (TPC) (14.12+1.19 µg AAE/g) resulted for the extract of 60% concentration. The phytochemical screening showed the presence of saponins, carbohydrates and cardiac glycoside while alkaloids and flavonoids were not detected in all the extract. The five doses caused neither visible signs of toxicity nor mortality. The LD50 is above 5000 mg/kg. Conclusion(s): The ethanol and water extract possessed some active principles having -glucosidase inhibitory activity and is safe following single oral administration dose but not via the intraperitoneal route. Purpose: To evaluate the phytochemical constituent screening, α-glucosidase inhibitory activity and in vivo preliminary toxicity study of ethanol and water S. zalacca fruit extracts. Methods: The fresh fruit was collected, cleaned, peeled, and dried using freeze dryer. The flesh powder was extracted using solvent with different concentration of ethanol and water (100, 80, 60, 40, 20, 0%). All extracts were tested for α-glucosidase inhibitory activity and phytochemical constituents were evaluated using different chemical methods. The extract showing highest α-glucosidase inhibitory activity was tested for acute toxicity studies according to the up and down method. A dose (0.15, 0.48, 1.54, 4.91 and 5.00 g/ kg body weight) of the extract was used in 15 healthy male rats. The rats were observed for 4 h first day, then daily for 14 days. Result(s): The highest yield was determined for the extract of 80% concentration, whereas the highest α-glucosidase inhibitory activity (IC50 13.43±2.43 µg/mL), total phenolic content (TPC) (14.12+1.19 µg AAE/g) resulted for the extract of 60% concentration. The phytochemical screening showed the presence of saponins, carbohydrates and cardiac glycoside while alkaloids and flavonoids were not detected in all the extract. The five doses caused neither visible signs of toxicity nor mortality. The LD50 is above 5000 mg/kg. Conclusion(s): The ethanol and water extract possessed some active principles having -glucosidase inhibitory activity and is safe following single oral administration dose but not via the intraperitoneal route

FT-IR- based metabolomics approach to characterize the α-glucosidase inhibitory activity of Salak fruit

Salak fruit (Salacca zalacca (Gaertn.) Voss), locally known as snake fruit is used domestically as food and other medicinal applications in south Asia. The quality control is important for medicinal. Thus, this study was conducted to evaluate α-glucosidase inhibitory activity of Salak fruit extracts and Fourier Transform Infrared spectroscopy (FT-IR)-based fingerprinting with combination of orthogonal partial least-squares (OPLS) was applied to develop a rapid method for quality control of this fruit. Extraction with different solvent ratios of ethanol-water (100, 80, 60, 40 ,20, 0%) was used to get 36 extracts and α-glucosidase inhibitory activity of the samples were determined. The FTIR-ATR spectra of hydro-ethanolic extracts were measured in the region 600 and 4000 cm-1 at a resolution of 4 cm-1. Multivariate analysis with combination of orthogonal partial least-squares (OPLS) algorithm was used to correlate the α-glucosidase inhibitory activity of the samples with the infrared spectral data. The OPLS biplot model identified several functional groups (C=O, O-H C-O, C-N, C-H and C=C) strongly induced α-glucosidase inhibitory activity. A successful the model was validated by comparing the model intercept values with original values