?-Amylase and ?-Glucosidase Inhibitory Activities of Chemical Constituents from Wedelia chinensis (Osbeck.) Merr. Leaves.
ABSTRACT: As part of an ongoing search for new natural products from medicinal plants to treat type 2 diabetes, two new compounds, a megastigmane sesquiterpenoid sulfonic acid (1) and a new cyclohexylethanoid derivative (2), and seven related known compounds (3-9) were isolated from the leaves of Wedelia chinensis (Osbeck.) Merr. The structures of the compounds were conducted via interpretation of their spectroscopic data (1D and 2D NMR, IR, and MS), and the absolute configurations of compound 1 were determined by the modified Mosher's method. The MeOH extract of W. chinensis was found to inhibit ?-amylase and ?-glucosidase inhibitory activities as well as by the compounds isolated from this extract. Furthermore, compound 7 showed the strongest effect with IC50 values of 112.8?±?15.1??g/mL (against ?-amylase) and 785.9?±?12.7??g/mL (against ?-glucosidase). Compounds 1, 8, and 9 showed moderate ?-amylase and ?-glucosidase inhibitory effects. Other compounds showed weak or did not show any effect on both enzymes. The results suggested that the antidiabetic properties from the leaves of W. chinensis are not simply a result of each isolated compound but are due to other components such as the accessibility of polyphenolic groups to ?-amylase and ?-glucosidase activities.
Project description:For the development of "medical foods" and/or botanical drugs as defined USA FDA, clear and systemic characterizations of the taxonomy, index phytochemical components, and the functional or medicinal bioactivities of the reputed or candidate medicinal plant are needed. In this study, we used an integrative approach, including macroscopic and microscopic examination, marker gene analysis, and chemical fingerprinting, to authenticate and validate various species/varieties of Wedelia, a reputed medicinal plant that grows naturally and commonly used in Asian countries. The anti-inflammatory bioactivities of Wedelia extracts were then evaluated in a DSS-induced murine colitis model. Different species/varieties of Wedelia exhibited distinguishable morphology and histological structures. Analysis of the ribosomal DNA internal transcribed spacer (ITS) region revealed significant differences among these plants. Chemical profiling of test Wedelia species demonstrated candidate index compounds and distinguishable secondary metabolites, such as caffeic acid derivatives, which may serve as phytochemical markers or index for quality control and identification of specific Wedelia species. In assessing their effect on treating DSS induced-murine colitis, we observed that only the phytoextract from W. chinensis species exhibited significant anti-inflammatory bioactivity on DSS-induced murine colitis among the various Wedelia species commonly found in Taiwan. Our results provide a translational research approach that may serve as a useful reference platform for biotechnological applications of traditional phytomedicines. Our findings indicate that specific Wedelia species warrant further investigation for potential treatment of human inflammatory bowel disease.
Project description:<i>Wedelia chinensis</i>, which belongs to the Asteraceae family, is a procumbent, perennial herb. It has medicinal anti-inflammatory properties and has been traditionally used as folk medicine in East and South Asia for treating fever, cough and phlegm. In Taiwan, <i>W. chinensis</i> is a common ingredient of herbal tea. Previous studies showed that the plant leaves contain four major bioactive compounds, wedelolactone, demethylwedelolactone, luteolin and apigenin, that have potent antihepatoxic activity, and are thus used as major ingredients in phytopharmaceutical formulations. In this study, we set up optimal conditions for induction of ploidy in <i>W.</i> <i>chinensis</i>. Ploidy can be an effective method of increasing plant biomass and improving medicinal and ornamental characteristics. By using flow cytometry and chicken erythrocyte nuclei as a reference, the DNA content (2C) or genome size of <i>W. chinensis</i> was determined to be 4.80 picograms (pg) in this study for the first time. Subsequently, we developed the successful induction of five triploid and three tetraploid plants by using shoot explants treated with different concentrations (0, 0.25, 0.5, 1, 1.5, 2 g/L) of colchicine. No apparent morphological changes were observed between these polyploid plants and the diploid wild-type (WT) plant, except that larger stomata in leaves were found in all polyploid plants as compared to diploid WT. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was used to quantify the four index compounds (wedelolactone, demethylwedelolactone, luteolin, apigenin) in these polyploid plants, and fluctuating patterns were detected. This is the first report regarding polyploidy in the herbal plant <i>W. chinensis</i>.
Project description:Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies.
Project description:<h4>Scope</h4>Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored.<h4>Methods and results</h4>C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF) orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-?, IL-4, IFN-?, IL-17, TGF-?, IL-12) revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight) was not toxic to mice.<h4>Conclusion</h4>Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease.
Project description:<h4>Background</h4>Wedelia chinensis has been reported as a folk medicine for the treatment of different diseases including neurodegenerative disease. Although the plant has been studied well for diverse biological activities, the effect of this plant in neurological disorder is largely unknown. The present study was undertaken to evaluate the cholinesterase inhibitory and antioxidant potential of W. chinensis.<h4>Methods</h4>The extract and fractions of the plant were evaluated for acetylcholinesterase and butyrylcholinesterase inhibitory activity by modified Ellman method. The antioxidant activity was assessed in several in vitro models/assays such as reducing power, total antioxidant capacity, total phenolic and flavonoid content, scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical and hydroxyl radical, and inhibition of brain lipid peroxidation. Chromatographic and spectroscopic methods were used to isolate and identify the active compound from the extract.<h4>Results</h4>Among the fractions, aqueous fraction (AQF) and ethylacetate fraction (EAF) exhibited high inhibition against acetylcholinesterase (IC<sub>50</sub>: 40.02 ± 0.16 μg/ml and 57.76 ± 0.37 μg/ml) and butyrylcholinesterase (IC<sub>50</sub>: 31.79 ± 0.18 μg/ml and 48.41 ± 0.05 μg/ml). Similarly, the EAF and AQF had high content of phenolics and flavonoids and possess strong antioxidant activity in several antioxidant assays including DPPH and hydroxyl radical scavenging, reducing power and total antioxidant activity. They effectively inhibited the peroxidation of brain lipid in vitro with IC<sub>50</sub> values of 45.20 ± 0.10 μg/ml and 25.53 ± 0.04 μg/ml, respectively. A significant correlation was observed between total flavonoids and antioxidant and cholinesterase inhibitory activity. Activity guided chromatographic separation led to the isolation of a major active compound from the EAF and its structure was elucidated as apigenin by spectral analysis.<h4>Conclusions</h4>The potential ability of W. chinensis to inhibit the cholinesterase activity and peroxidation of lipids suggest that the plant might be useful for the management of AD.
Project description:Context: Paederia foetida L. (Rubiaceae) is an edible plant distributed in Asian countries including Malaysia. Fresh leaves have been traditionally used as a remedy for indigestion and diarrhea. Several phytochemical studies of the leaves have been documented, but there are few reports on twigs. Objective: This study investigates the enzyme inhibition of P. foetida twig extracts and compound isolated from them. In addition, in silico molecular docking of scopoletin was investigated. Materials and methods: Plants were obtained from two locations in Malaysia, Johor (PFJ) and Pahang (PFP). Hexane, chloroform and methanol extracts along with isolated compound (scopoletin) were evaluated for their enzyme inhibition activities (10,000-0.000016?µg/mL). The separation and identification of bio-active compounds were carried out using column chromatography and spectroscopic techniques, respectively. In silico molecular docking of scopoletin with receptors (?-amylase and ?-glucosidase) was carried out using AutoDock 4.2. Results: The IC50 values of ?-amylase and ?-glucosidase inhibition activity of PFJ chloroform extract were 9.60 and 245.6?µg/mL, respectively. PFP chloroform extract exhibited ?-amylase and ?-glucosidase inhibition activity (IC50?=?14.83 and 257.2?µg/mL, respectively). The ?-amylase and ?-glucosidase inhibitory activity of scopoletin from both locations had IC50 values of 0.052 and 0.057?µM, respectively. Discussion and conclusions: Separation of PFJ chloroform extract afforded scopoletin (1), stigmasterol (2) and ?-sitosterol (3) and the PFP chloroform extract yielded (1), (2), (3) and ergost-5-en-3-ol (4). Scopoletin was isolated from this species for the first time. In silico calculations gave a binding energy between scopoletin and ?-amylase of -6.03?kcal/mol.
Project description:Type 2 diabetes is a metabolic disorder, characterized by hyperglycemia and glucose intolerance. Natural products and its derived active compounds may be achievable alternatives for the treatment of type 2 diabetes. In present study we investigated the antidiabetic potential of Ficus microcarpa and isolated bioactive compounds i.e., Plectranthoic acid A (PA-A) and 3,4,5,7-Flavantetrol (FL). Anti-hyperglycemic potential was evaluated via ?-glucosidase, ?-amylase and dipeptidyl peptidase 4 (DPP-4) assays. 5'AMP-activated kinase (AMPK) activation potential was assessed by using primary hepatocytes. Distribution of PA-A in different parts of Ficus microcarpa was evaluated by using rapid high-performance liquid chromatography (HPLC). Ethyl acetate fraction (FME) exhibited significant inhibition of ?-glucosidase, ?-amylase, and DPP-4, therefore, was selected for isolation of bioactive compounds. Among isolated compounds PA-A was more potent and possessed pleotropic inhibitory activity with IC50 values of 39.5, 55.5, and 51.4 ?M against ?-glucosidase, ?-amylase, and DPP-4, respectively. Our results showed that PA-A is also a potent activator of AMPK which is a central hub of metabolic regulation. Molecular docking studies confirmed the activity of PA-A against ?-glucosidase, ?-amylase, and DPP-4. Rapid HPLC method revealed that maximum concentration of PA-A is present in the stem (2.25 ?g/mg dry weight) of Ficus microcarpa. Both in vitro and in silico studies proposed that Ficus microcarpa and its isolated compound PA-A could be an important natural source for alleviating the symptoms of type 2 diabetes mellitus and we suggest that PA-A should be explored further for its ultimate use for the treatment of type 2 diabetes.
Project description:<h4>Background</h4> Diabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus. <h4>Methods</h4> The crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B. <h4>Results</h4> Initially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC50 values of 67, 70, < 0.1, 89 and 16 μg/mL against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 respectively. Three compounds (Nt01, Nt02 and Nt03) were isolated from Nt.EtAc of N. thomsonianum. The isolated compounds Nt01, Nt02 and Nt03 exhibited IC50 values of 58.93, 114.93 and 19.54 μM against α-glucosidase, while 56.25, 96.54 and 24.39 μM against α-amylase respectively. Comparatively, the standard acarbose observed IC50 values were 10.60 and 12.71 μM against α-glucosidase, α-amylase respectively. In PTP1B assay, the compounds Nt01, Nt02 and Nt03 demonstrated IC50 values of 12.96, 36.22 and 3.57 μM in comparison to the standard ursolic acid (IC50 of 3.63 μM). The isolated compounds also gave overwhelming results in DPPH assay. Molecular docking based binding interactions for α-glucosidase, α-amylase and PTP1B were also encouraging. <h4>Conclusions</h4> In the light of current results, it is obvious that N. thomsonianum is potential medicinal plant for the treatment of hyperglycemia. Overall, Nt.EtAc was dominant fraction in all in-vitro activities. Three compounds Nt01, Nt02 and Nt03 were isolated from ethyl acetate fraction. The Nt03 specifically was most potent in all in-vitro assays. The molecular docking studies supported our in-vitro results. It is concluded that N. thomsonianum is a rich source of bioactive antidiabetic compounds which can be further extended to in-vivo based experiments. <h4>Supplementary Information</h4> The online version contains supplementary material available at 10.1186/s12906-021-03443-7.
Project description:Different oleanolic acid (OA) oxime ester derivatives (<b>3a</b>-<b>3t</b>) were designed and synthesised to develop inhibitors against <i>α</i>-glucosidase and <i>α</i>-amylase. All the synthesised OA derivatives were evaluated against <i>α</i>-glucosidase and <i>α</i>-amylase <i>in vitro.</i> Among them, compound <b>3a</b> showed the highest <i>α</i>-glucosidase inhibition with an IC<sub>50</sub> of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound <b>3f</b> exhibited the highest <i>α</i>-amylase inhibitory with an IC<sub>50</sub> of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds <b>3a</b> and <b>3f</b> were reversible and mixed types towards <i>α</i>-glucosidase and <i>α</i>-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds <b>3a</b> and <b>3f</b> against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (<b>3a-3t</b>) were synthesised and screened against α-glucosidase and α-amylase.Compound <b>3a</b> showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound <b>3f</b> presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and <i>in silico</i> studies analysed the binding between compounds and α-glucosidase or α-amylase.
Project description:Four new ent-kaurane diterpenoids, namely, 3?-tigloyloxypterokaurene L3 (1), ent-17-hydroxy-kaura-9(11),15-dien-19-oic acid (2), and wedelobatins A (3) and B (4), together with 11 known ent-kaurane diterpenoids (5-15), were isolated from the ethanol extract of Wedelia trilobata. All the structures of 1–15 were elucidated on the basis of spectroscopic studies. <h4>Electronic Supplementary Material</h4> Supplementary material is available for this article at 10.1007/s13659-013-0029-4 and is accessible for authorized users.