Aporphine alkaloids with in vitro antiplasmodial activity from the leaves of Phoebe tavoyana.

One new aporphine named tavoyanine A (1), along with four known aporphines laetanine (2), roemerine (3), laurolitsine (4), and boldine (5), and one morphinandienone type sebiferine (6) were isolated from the leaves of Phoebe tavoyana (Meissn.) Hook f. (Lauraceae). The isolation was achieved by chromatographic techniques, and the structural elucidation was performed via spectral methods. This paper also reports the antiplasmodial activity of roemerine (3), laurolitsine (4), boldine (5), and sebiferine (6). The results showed that 3-6 have a potent inhibitory activity against the growth of Plasmodium falciparum 3D7 clone, with IC50 values of 0.89, 1.49, 1.65, and 2.76 µg/ml, respectively.

Reflexin A, a new indole alkaloid from Rauvolfia reflexa induces apoptosis against colon cancer cells.

One new indole alkaloid, reflexin A (1), and two known indoles, macusine B (2) and vinorine (3), were isolated from the bark of Rauvolfia reflexa. Their structures were elucidated by 1D and 2D NMR, UV, IR, and MS spectroscopic analyses. Compound 1 displayed anticancer activity against HCT-116 colon cancer cells with an IC50 value of 30.24 ± 0.75 µM. The results implied that the newly isolated 1 induced apoptosis in HCT-116 cells, suggesting its possible role as an anticancer agent. In vivo acute toxicity study was performed on compound 1 to evaluate its safety profile.

Bioassay-Guided Isolation and in Silico Study of Antibacterial Compounds From Petroleum Ether Extract of Peperomia blanda (Jacq.) Kunth.

Bioassay-guided isolation protocol was performed on petroleum ether extract of Peperomia blanda (Jacq.) Kunth using column chromatographic techniques. Five compounds were isolated and their structures were elucidated via one-dimensional (1D) and two-dimensional (2D) NMR, gas chromatography mass sectroscopy (GCMS), liquid chromatography mass spectroscopy (LCMS), and ultraviolet (UV) and infrared (IR) analyses. Dindygulerione E (a new compound), and two compounds isolated from P. blanda for the first time-namely, dindygulerione A and flavokawain A-are reported herein. Antimicrobial activity was screened against selected pathogenic microbes, and minimum inhibitory concentrations (MIC) were recorded within the range of 62-250 µg/mL. Assessment of the pharmacotherapeutic potential has also been done for the isolated compounds, using the Prediction of Activity spectra for Substances (PASS) software, and different activities of compounds were predicted. Molecular docking, molecular dynamics simulation and molecular mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations have proposed the binding affinity of these compounds toward methylthioadenosine phosphorylase enzyme, which may explain their inhibitory actions.

Anti-malarial Activity of Isoquinoline Alkaloids from the Stem Bark of Actinodaphne macrophylla.

Seven isoquinoline alkaloids isolated from the bark of Actinodaphne macrophylla in this study demonstrated in vitro antiplasmodial activities against Plasmodium falciparum 3D7 with IC50 values of 0.08 µM, 0.05 µM, 1.18 µM, 3.11 µM, 0.65 µM, 0.26 µM, and 1.38 µM for cycleanine, 10-demethylxylopinine, reticuline, laurotetanine, bicuculine, α-hydrastine and anolobine, respectively, which are comparable with the reference standard, chloroquine. 10-Demethylxylopinine was found to be the most active of these compounds.

Extract of Woodfordia fruticosa flowers ameliorates hyperglycemia, oxidative stress and improves ß-cell function in streptozotocin-nicotinamide induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The art of Ayurveda and the traditional healing system in India have reflected the ethnomedicinal importance of the plant Woodfordia fruticosa Kurtz, which demonstrates its vast usage in the Ayurvedic preparations as well as in the management of diabetes by the traditional healers. AIMS OF STUDY: The study aimed to ascertain the antidiabetic potential of W. fruticosa flower methanolic extract (WF) on Streptozotocin (STZ)-nicotinamide-induced diabetic rat model. MATERIALS AND METHODS: Diabetes was induced in Sprague Dawley (SD) rats by STZ-nicotinamide and thereafter diabetic rats were treated with three different doses of WF (100, 200 and 400mg/kg body weight) respectively and glibenclamide as a positive control. Biochemical parameters such as blood glucose, serum insulin and C-peptide levels were measured with oxidative stress markers. Furthermore, histology of liver and pancreas was carried out to evaluate glycogen content and ß-cell structures. Moreover, immunohistochemistry and western blot analysis were performed on kidney and pancreas tissues to determine renal Bcl-2, pancreatic insulin and glucose transporter (GLUT-2, 4) protein expression in all the experimental groups. RESULTS: The acute toxicity study showed non-toxic nature of all the three doses of WF. Further, studies on diabetic rats exhibited anti-hyperglycemic effects by upregulating serum insulin and C-peptide levels. Similarly, WF shown to ameliorate oxidative stress by downregulating LPO levels and augmenting the antioxidant enzyme (ABTS). Furthermore, histopathological analysis demonstrate recovery in the structural degeneration of ß-cells mass of pancreas tissue with increase in the liver glycogen content of the diabetic rats. Interestingly, protective nature of the extract was further revealed by the immunohistochemical study result which displayed upregulation in the insulin and renal Bcl-2 expression, the anti apoptosis protein. Moreover, western blot result have shown slight alteration in the GLUT-2 and GLUT-4 protein expression with the highest dose of WFc treatment, that might have stimulated glucose uptake in the pancreas and played an important role in attenuating the blood glucose levels. CONCLUSION: The overall study result have demonstrated the potential of WF in the management of diabetes and its related complications, thus warrants further investigation on its major compounds with in depth mechanistic studies at molecular level.

(6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester, Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial-Mediated Apoptosis in Human Breast Adenocarcinoma Cells.

Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.

Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum (King) Heusden against ethanol-induced acute gastric lesion in animal models.

A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation.

Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Upregulation of insulin secretion and downregulation of pro-inflammatory cytokines, oxidative stress and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats by Pseuduvaria monticola bark extract.

The current study aimed to ascertain the antidiabetic potential of Pseuduvaria monticola bark methanolic extract (PMm) using in vitro mechanistic study models. In particular, the study determined the effect of PMm on cellular viability, 2-NBDG glucose uptake, insulin secretion, and NF-κB translocation in mouse pancreatic insulinoma cells (NIT-1). Furthermore, in vivo acute toxicity and antidiabetic studies were performed using streptozotocin (STZ)-induced type 1 and STZ-nicotinamide-induced type 2 diabetic rat models to evaluate various biochemical parameters and markers of oxidative stress and pro-inflammatory cytokines. Five isoquinoline alkaloids and three phenolic compounds were tentatively identified in the PMm by LC/MS Triple TOF. The study results showed that PMm is non-toxic to NIT-1 cells and significantly increased the glucose uptake and insulin secretion without affecting the translocation of NF-κB. Moreover, the non-toxic effects of PMm were confirmed through an in vivo acute toxicity study, which revealed that the serum insulin and C-peptide levels were significantly upregulated in type 2 diabetic rats and that no significant changes were observed in type 1 diabetic rats. Similarly, PMm was found to downregulate the levels of oxidative stress and pro-inflammatory cytokines in type 2 diabetic rats by alleviating hyperglycemia. Therefore, we conclude that PMm may be developed as an antidiabetic agent for the treatment of type 2 diabetes-associated conditions.

The methanolic fraction of Centratherum anthelminticum seed downregulates pro-inflammatory cytokines, oxidative stress, and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats.

This study aimed to ascertain the potential of Centratherum anthelminticum seeds methanolic fraction (CAMFs) for the management of type 2 diabetes and its associated complications. CAMFs was initially tested on ß-TC6 cells for H(2)O(2)-induced nuclear factor-κB (NF-κB) translocation effects. The result displayed that CAMFs significantly inhibited NF-κB translocation from cytoplasm into the nucleus, dose-dependently. Furthermore, a 12-week sub-chronic CAMFs study was carried out on streptozotocin (STZ)-nicotinamide-induced type 2 diabetic rat model to evaluate glycemia, essential biochemical parameters, lipid levels, oxidative stress markers, and pro-inflammatory cytokines level. Our study result showed that CAMFs reduced hyperglycemia by increasing serum insulin, C-peptide, total protein, and albumin levels, significantly. Whereas, elevated blood glucose, glycated hemoglobin, lipids and enzyme activities were restored to near normal. CAMFs confirmed antioxidant potential by elevating glutathione (GSH) and reducing malondialdehyde (MDA) levels in diabetic rats. Interestingly, CAMFs down-regulated elevated tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 in the tissues and serum of the diabetic rats. We conclude that CAMFs exerted apparent antidiabetic effects and demonstrated as a valuable candidate nutraceutical for insulin-resistant type 2 diabetes and its associated complications such as dyslipidemia, oxidative stress, and inflammation.

Pseuduvarines A and B, two new cytotoxic dioxoaporphine alkaloids from Pseuduvaria rugosa.

Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino moiety, were isolated from the stem bark of Pseuduvaria rugosa and their structures were elucidated by combination of 2D-NMR spectroscopic analysis. Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60 (1: IC50, 0.9, 21.7, and >50.0 µM, respectively, 2: IC50 >50.0, 15.7, and 12.4 µM, respectively).