Diverse effects of a Cyperus rotundus extract on glucose uptake in myotubes and adipocytes and its suppression on adipocyte maturation.

Cyperus rotundus rhizomes have been used in longevity remedies in Thailand for nourishing good health, which led us to investigate the effect on energy homeostasis, especially glucose utilization in myotubes and adipocytes, and on inhibition of lipogenesis in adipocytes. The results showed that an ethyl acetate extract of C. rotundus rhizomes (ECR) containing 1.61%w/w piceatannol, with a half-maximal concentration of 17.76 ± 0.03 µg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, caused upregulation and cell-membrane translocation of glucose transporters GLUT4 and 1 in L6 myotubes but downregulation and cytoplasmic localization of GLUT4 expression in 3T3-L1 adipocytes and was related to the p-Akt/Akt ratio in both cells, especially at 100 µg/mL. Moreover, ECR (25-100 µg/mL) significantly inhibited lipid accumulation via Adenosine Monophosphate-Activated Protein Kinase (AMPK), Acetyl CoA Carboxylase (ACC), and Glycogen Synthase Kinase (GSK) pathways. Its immunoblot showed increased expression of p-AMPKα/AMPKα and p-ACC/ACC but decreased expression of p-Akt/Akt and p-GSK3ß/GSK3ß in 3T3-L1 adipocytes. Moreover, the decreased expression of the adipogenic effectors, perilipin1 and lipoprotein lipase, in ECR-incubated adipocytes (50 and 100 µg/mL) indicated reduced de novo lipogenesis. Our study elucidated mechanisms of C. rotundus that help attenuate glucose tolerance in skeletal muscle and inhibit lipid droplet accumulation in adipose tissue.

Correction: Nukulkit et al. Eight Indole Alkaloids from the Roots of Maerua siamensis and Their Nitric Oxide Inhibitory Effects. Molecules 2022, 27, 7558.

After a proofreading check, some experimental data were inconsistent with the supplementary information in the original publication [...].

Relationship of phytochemicals and antioxidant activities in Gymnema inodorum leaf extracts.

Gynmena inodorum (GI) is a green leafy vegetable used in the Northern Thai cuisine which has antioxidant activities and may be applicable for preventing oxidative stress and aging-related disease. However, understanding the relationship between GI phytonutrients and their antioxidant properties has been unclear. The aims of this study were to identify the GI leaf phytochemicals and to study their antioxidant activities. A chromatogram of LC-ESI-MS/QTOF-MS showed that the GI leaves were potentially composed of phenolics, quinic acids, flavonoids, and triterpenoid saponins. This study was able to authenticate quercetin, kaempferol, and triterpenoid GIA1 in the samples. The GI materials with high contents of phenolics, flavonoids, quercetin, and kaempferol showed significant relation to antioxidation and protection in endothelial cell death suppressed by reactive nitrogen species. Meanwhile, triterpenoids had a low antioxidant impact. Ultimately, GI leaves with high phenolic compounds are a promising raw material to develop as an antioxidant functional food.

Semisynthesis of 5-O-ester derivatives of renieramycin T and their cytotoxicity against non-small-cell lung cancer cell lines.

The semisynthesis of 5-O-ester derivatives of renieramycin T was accomplished through the photoredox reaction of renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. This process led to the conversion of compound 1 to renieramycin T (2), which was subsequently subjected to Steglich esterification with appropriate acylating agents containing linear alkyl, N-tert-butoxycarbonyl-L-amino, and heterocyclic aromatic substituent. Notably, the one-pot transformation, combining the photoredox reaction and esterification led to the formation of 7-O-ester derivatives of renieramycin S due to hydrolysis. Subsequently, the in vitro cytotoxicity of the 17 semisynthesized derivatives against human non-small-cell lung cancer (NSCLC) cells in parallel with normal cell lines was evaluated. Among the tested compounds, 5-O-(3-propanoyl) ester of renieramycin T (3b) exhibited potent cytotoxic activity with half-maximal inhibitory concentration (IC50) values at 33.44 and 33.88 nM against H292 and H460 cell lines, respectively. These values were within the same range as compound 1 (IC50 = 34.43 and 35.63 nM) and displayed twofold higher cytotoxicity compared to compound 2 (IC50 = 72.85 and 83.95 nM). The steric characteristics and aromatic orientation of the 5-O-ester substituents played significant roles in their cytotoxicity. Notably, derivative 3b induced apoptosis with minimal necrosis, in contrast to the parental compound 1. Hence, the relationship between the structure and cytotoxicity of renieramycin-ecteinascidin hybrid alkaloids was investigated. This study emphasizes the potential of the series of 5-O-ester derivatives of renieramycin T as promising leads for the further development of potential anti-NSCLC agents.

A promising synthetic citric crosslinked ß-cyclodextrin derivative for antifungal drugs: Solubilization, cytotoxicity, and antifungal activity.

Effective antifungal therapy for the treatment of fungal keratitis requires a high drug concentration at the corneal surface. However, the use of natural ß-cyclodextrin (ßCD) in the preparation of aqueous eye drop formulations for treating fungal keratitis is limited by its low aqueous solubility. Here, we synthesized water-soluble anionic ßCD derivatives capable of forming water-soluble complexes and evaluated the solubility, cytotoxicity, and antifungal efficacy of drug prepared using the ßCD derivative. To achieve this, a citric acid crosslinked ßCD (polyCTR-ßCD) was successfully synthesized, and the aqueous solubilities of selected antifungal drugs, including voriconazole, miconazole (MCZ), itraconazole, and amphotericin B, in polyCTR-ßCD and analogous ßCD solutions were evaluated. Among the drugs tested, complexation of MCZ with polyCTR-ßCD (MCZ/polyCTR-ßCD) increased MCZ aqueous solubility by 95-fold compared with that of MCZ/ßCD. The inclusion complex formation of MCZ/ßCD and MCZ/polyCTR-ßCD was confirmed by spectroscopic techniques. Additionally, the nanoaggregates of saturated MCZ/polyCTR-ßCD and MCZ/ßCD solutions were observed using dynamic light scattering and transmission electron microscopy. Moreover, MCZ/polyCTR-ßCD solution exhibited good mucoadhesion, sustained drug release, and high drug permeation of porcine cornea ex vivo. Hen's Egg test-chorioallantoic membrane assay and cell viability study using Statens Seruminstitut Rabbit Cornea cell line showed that both MCZ/polyCTR-ßCD and MCZ/ßCD exhibited no sign of irritation and non-toxic to cell line. Additionally, antifungal activity evaluation demonstrated that all isolated fungi, including Candida albicans, Aspergillus flavus, and Fusarium solani, were susceptible to MCZ/polyCTR-ßCD. Overall, the results showed that polyCTR-ßCD could be a promising nanocarrier for the ocular delivery of MCZ.

Light-Mediated Transformation of Renieramycins and Semisynthesis of 4'-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.

The semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4'-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished through a light-induced intramolecular photoredox reaction using blue light (4 W) and Steglich esterification, respectively. Renieramycin M (4), a bis-tetrahydroisoquinolinequinone compound isolated from the Thai blue sponge (Xestospongia sp.), served as the starting material. The cytotoxicity of the 10 natural and semisynthesized renieramycins against non-small-cell lung cancer (NSCLC) cell lines was evaluated. The 5-O-(4'-pyridinecarbonyl) renieramycin T (11) compound exhibited high cytotoxicity with half-maximal inhibitory concentration (IC50) values of 35.27 ± 1.09 and 34.77 ± 2.19 nM against H290 and H460 cells, respectively. Notably, the potency of compound 11 was 2-fold more than that of renieramycin T (7) and equal to those of 4 and doxorubicin. Interestingly, the renieramycin-type derivatives with a hydroxyl group at C-5 and C-22 exhibited weak cytotoxicity. In silico molecular docking and dynamics studies confirmed that the mitogen-activated proteins, kinase 1 and 3 (MAPK1 and MAPK3), are suitable targets for 11. Thus, the structure-cytotoxicity study of renieramycins was extended to facilitate the development of potential anticancer agents for NSCLC cells.

Topical combined Phyllanthus emblica Linn. and simvastatin improves wound healing in diabetic mice by enhancing angiogenesis and reducing neutrophil infiltration.

The present study aimed to investigate the effects of combined Phyllanthus emblica Linn. (PE) and simvastatin (SIM) on diabetic wounds in male BALB/C mice. Bilateral full thickness wound excisions were performed in the control and diabetic groups (45 mg/kg streptozotocin, intraperitoneally injected daily for 5 days). The diabetic mice received daily treatment with four different types of cream: Vehicle [diabetes mellitus (DM) + Vehicle group], 100% PE (DM + PE group), 5% SIM (DM + SIM group) and combined 100% PE + 5% SIM (DM + Combination group) for 4, 7 and 14 days. The tissue malondialdehyde (MDA) and IL-6 protein levels, the number of infiltrated neutrophils, and the percentages of wound closure (%WC), capillary vascularity (%CV) and re-epithelialization (%RE) were subsequently measured. The results indicated that in the DM + Combination group, %CV and %WC were significantly increased when compared with the DM + Vehicle group on days 7 and 14. The tissue MDA content on day 14, and the number of infiltrated neutrophils on days 4 and 7 were significantly reduced in the DM + Combination group compared with those in the DM + Vehicle group. Furthermore, a strong positive correlation was revealed between %CV and %WC in the five groups on day 7 (r=0.736; P=0.0003). These findings indicated that topical application of combined PE and SIM could enhance wound healing by upregulating angiogenesis and reducing neutrophil infiltration in mice with diabetic wounds.

Potential role of a novel biphenanthrene derivative isolated from Aerides falcata in central nervous system diseases.

Central nervous system (CNS) diseases are a significant health burden globally, with the development of novel drugs lagging behind clinical needs. Orchidaceae plants have been traditionally used to treat CNS diseases, leading to the identification of therapeutic leads against CNS diseases from the Aerides falcata orchid plant in the present study. The study isolated and characterized ten compounds, including a previously undescribed biphenanthrene derivative, Aerifalcatin (1), for the first time from the A. falcata extract. The novel compound 1 and known compounds, such as 2,7-dihydroxy-3,4,6-trimethoxyphenanthrene (5), agrostonin (7), and syringaresinol (9), showed potential activity in CNS-associated disease models. Notably, compounds 1, 5, 7, and 9 demonstrated the ability to alleviate LPS-induced NO release in BV-2 microglial cells, with IC50 values of 0.9, 2.5, 2.6, and 1.4 µM, respectively. These compounds also significantly inhibited the release of pro-inflammatory cytokines, IL-6 and TNF-α, reflecting their potential anti-neuroinflammatory effects. Additionally, compounds 1, 7, and 9 were found to reduce cell growth and migration of glioblastoma and neuroblastoma cells, indicating their potential use as anticancer agents in the CNS. In summary, the bioactive agents isolated from the A. falcata extract offer plausible therapeutic options for CNS diseases.

In vitro and in silico studies of 7'',8''-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors.

Excessive macrophage activation induces the release of high levels of inflammatory mediators which not only amplify chronic inflammation and degenerative diseases but also exacerbate fever and retard wound healing. To identify anti-inflammatory molecules, we examined Carallia brachiata-a medicinal terrestrial plant from Rhizophoraceae. Furofuran lignans [(-)-(7''R,8''S)-buddlenol D (1) and (-)-(7''S,8''S)-buddlenol D (2)] isolated from the stem and bark inhibited nitric oxide (half maximal inhibitory concentration (IC50): 9.25 ± 2.69 and 8.43 ± 1.20 micromolar for 1 and 2, respectively) and prostaglandin E2 (IC50: 6.15 ± 0.39 and 5.70 ± 0.97 micromolar for 1 and 2, respectively) productions in lipopolysaccharide-induced RAW264.7 cells. From western blotting, 1 and 2 suppressed LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner (0.3-30 micromolar). Moreover, analysis of the mitogen-activated protein kinase (MAPK) signaling pathway showed decreased p38 phosphorylation levels in 1- and 2-treated cells, while phosphorylated ERK1/2 and JNK levels were unaffected. This discovery agreed with in silico studies which suggested 1 and 2 bound to the ATP-binding site in p38-alpha MAPK based on predicted binding affinity and intermolecular interaction docking. In summary, 7'',8''-buddlenol D epimers demonstrated anti-inflammatory activities via p38 MAPK inhibition and may be used as viable anti-inflammatory therapies.

Caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide as a non-steroidal inhibitor for steroid 5α-reductase type 1 using a human keratinocyte cell-based assay and molecular dynamics.

Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of caffeic acid (1) and its amide derivatives (2 - 4) against the steroid 5α-reductase type 1 (SRD5A1) produced by human keratinocyte cells coupled with the non-radioactive high-performance thin-layer chromatography detection revealed that caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide (4) was a promising non-steroidal suppressor, with a half-maximal inhibitory concentration (IC50) of 1.44 ± 0.13 µM and relatively low cytotoxicity with an IC50 of 29.99 ± 8.69 µM. The regulatory role of compound 4 against SRD5A1 involved both suppression of SRD5A1 expression and mixed mode SRD5A1 inhibition. The Ki value of compound 4 was 2.382 µM based on the whole-cell kinetic studies under specific conditions. Molecular docking and molecular dynamics simulations with AlphaFold generated the human SRD5A1 structure and confirmed the stability of compound 4 at the SRD5A1 catalytic site with greater interactions, including hydrogen bonding of the key M119 amino-acid residue than those of finasteride and dutasteride. Thus, compound 4 shows the potential for further development as an SRD5A1 suppressor for androgenic alopecia treatment.

Phytochemicals from Vanda bensonii and Their Bioactivities to Inhibit Growth and Metastasis of Non-Small Cell Lung Cancer Cells

The most prevalent lung cancer is non-small cell lung cancer (NSCLC). This lung cancer type often develops other organ-specific metastases that are critical burdens in the treatment process. Orchid species in the genus Vanda have shown their potential in folkloric medication of diverse diseases but not all its species have been investigated, and little is known about their anticancer activities against NSCLC. Here, we firstly profiled the specialized metabolites of Vanda bensonii and examined their capability to inhibit growth and metastasis of NSCLC using NCI-H460 cells as a study model. Four phytochemicals, including phloretic acid methyl ester (1), cymbinodin-A (2), ephemeranthoquinone B (3), and protocatechuic acid (4), were isolated from the whole plant methanolic extract of V. bensonii. The most distinguished cytotoxic effect on NCI-H460 cells was observed in the treatments with crude methanolic extract and compound 2 with the half maximal inhibitory concentrations of 40.39 µg mL−1 and 50.82 µM, respectively. At non-cytotoxic doses (10 µg mL−1 or 10 µM), only compound 1 could significantly limit NCI-H460 cell proliferation when treated for 48 h, while others excluding compound 4 showed significant reduction in cell proliferation after treating for 72 h. Compound 1 also significantly decreased the migration rate of NCI-H460 cells examined through a wound-healing assay. Additionally, the crude extract and compound 1 strongly affected survival and growth of NCI-H460 cells under anchorage-independent conditions. Our findings proved that natural products from V. bensonii could be promising candidates for the future pharmacotherapy of NSCLC.

Eight Indole Alkaloids from the Roots of Maerua siamensis and Their Nitric Oxide Inhibitory Effects.

Maerua siamensis (Capparaceae) roots are used for treating pain and inflammation in traditional Thai medicine. Eight new indole alkaloids, named maeruanitriles A and B, maeroximes A-C, and maeruabisindoles A-C, were isolated from them. Spectroscopic methods and computational analysis were applied to determine the structure of the isolated compounds. Maeroximes A-C possesses an unusual O-methyloxime moiety. The bisindole alkaloid maeruabisindoles A and B possess a rare azete ring, whereas maeruabisindole C is the first indolo[3,2-b]carbazole derivative found in this plant family. Five compounds [maeruanitriles A and B, maeroxime C, maeruabisindoles B, and C] displayed anti-inflammatory activity by inhibiting nitric oxide (NO) production in the lipopolysaccharide-induced RAW 264.7 cells. Maeruabisindole B was the most active inhibitor of NO production, with an IC50 of 31.1 ± 1.8 µM compared to indomethacin (IC50 = 150.0 ± 16.0 µM) as the positive control.

Development of Fenofibrate/Randomly Methylated ß-Cyclodextrin-Loaded Eudragit® RL 100 Nanoparticles for Ocular Delivery.

Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-ß-CD (RMßCD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RMßCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMßCD complex. FE-loaded Eudragit® nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen's egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RMßCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.

5-O-(N-Boc-l-Alanine)-Renieramycin T Induces Cancer Stem Cell Apoptosis via Targeting Akt Signaling.

Cancer stem cells (CSCs) drive aggressiveness and metastasis by utilizing stem cell-related signals. In this study, 5-O-(N-Boc-l-alanine)-renieramycin T (OBA-RT) was demonstrated to suppress CSC signals and induce apoptosis. OBA-RT exerted cytotoxic effects with a half-maximal inhibitory concentration of approximately 7 µM and mediated apoptosis as detected by annexin V/propidium iodide using flow cytometry and nuclear staining assays. Mechanistically, OBA-RT exerted dual roles, activating p53-dependent apoptosis and concomitantly suppressing CSC signals. A p53-dependent pathway was indicated by the induction of p53 and the depletion of anti-apoptotic Myeloid leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins. Cleaved poly (ADP-ribose) polymerase (Cleaved-PARP) was detected in OBA-RT-treated cells. Interestingly, OBA-RT exerted strong CSC-suppressing activity, reducing the ability to form tumor spheroids. In addition, OBA-RT could induce apoptosis in CSC-rich populations and tumor spheroid collapse. CSC markers, including prominin-1 (CD133), Octamer-binding transcription factor 4 (Oct4), and Nanog Homeobox (Nanog), were notably decreased after OBA-RT treatment. Upstream CSCs regulating active Akt and c-Myc were significantly decreased; indicating that Akt may be a potential target of action. Computational molecular modeling revealed a high-affinity interaction between OBA-RT and an Akt molecule. This study has revealed a novel CSC inhibitory effect of OBA-RT via Akt inhibition, which may improve cancer therapy.

Three New Dihydrophenanthrene Derivatives from Cymbidium ensifolium and Their Cytotoxicity against Cancer Cells.

From the aerial parts of Cymbidium ensifolium, three new dihydrophenanthrene derivatives, namely, cymensifins A, B, and C (1−3) were isolated, together with two known compounds, cypripedin (4) and gigantol (5). Their structures were elucidated by analysis of their spectroscopic data. The anticancer potential against various types of human cancer cells, including lung, breast, and colon cancers as well as toxicity to normal dermal papilla cells were assessed via cell viability and nuclear staining assays. Despite lower cytotoxicity in lung cancer H460 cells, the higher % apoptosis and lower % cell viability were presented in breast cancer MCF7 and colon cancer CaCo2 cells treated with 50 µM cymensifin A (1) for 24 h compared with the treatment of 50 µM cisplatin, an available chemotherapeutic drug. Intriguingly, the half-maximum inhibitory concentration (IC50) of cymensifin A in dermal papilla cells at >200 µM suggested its selective anticancer activity. The obtained information supports the further development of a dihydrophenanthrene derivative from C. ensifolium as an effective chemotherapy with a high safety profile for the treatment of various cancers.

Tandem mass spectrometry of aqueous extract from Ficus dubia sap and its cell-based assessments for use as a skin antioxidant.

Since 2006, Ficus dubia has been reported as a new Ficus species in Thailand. As per our recent report, the red-brown aqueous extract of F. dubia sap (FDS) has been determined to strongly exhibit in vitro anti-radicals. However, the phytochemicals in the FDS extract related to health-promoting antioxidation have not been explored. Thus, in this study, we aimed to investigate the chemical components of the F. dubia sap extract by liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-MS/QTOF-MS) and its potential use in cosmetics in terms of cellular antioxidation on keratinocytes (HaCaT), phototoxicity, and irritation on 3D skin cell models following standard tests suggested by the Organization for Economic Cooperation and Development (OECD). It was found that the sap extract was composed of quinic acid and caffeoyl derivatives (e.g., syringoylquinic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, and dimeric forms of caffeoylquinic acids). The extract has significantly exhibited antioxidant activity against H2O2-induced oxidative stress in HaCaT cells. The cellular antioxidative effect of the FDS extract was remarkably dependent on the presence of 3- and 4-O-caffeoylquinic acid in the extract. Furthermore, the FDS extract showed negative results on skin phototoxicity and irritation. Overall, the results reveal that the FDS extract could be developed as a new antioxidant candidate for a skin healthcare product.

S-deoxydihydroglyparvin from Glycosmis parva inhibits lipopolysaccharide induced murine macrophage activation through inactivating p38 mitogen activated protein kinase.

Macrophages play major roles to produce several pro-inflammatory and inflammatory mediators in chronic inflammatory diseases. All current anti-inflammatory drugs target these mediators to alleviate inflammation. Searching for new anti-inflammatory agents is always needed due to problems from the clinical use of current anti-inflammatory drugs. We intended to evaluate the anti-inflammatory potential of three main compounds, arborinine, methylatalaphylline, and S-deoxydihydroglyparvin (DDGP), from Glycosmis parva leaves and branches on macrophage stimulated by lipopolysaccharide (LPS). Only DDGP demonstrated a potent inhibitor of LPS-activated macrophages. Results indicated that the mRNA level of inducible nitric oxide synthase (iNOS) was inhibited by the treatment in accompany with the decreased nitric oxide (IC50 at 3.47 ± 0.1 µM). DDGP was shown to suppress tumor necrosis factor-α, interleukin (IL)-1, and IL-6 at the mRNA expression and at the released protein levels. In addition, DDGP inhibited the several chemokines, monocyte chemoattractant protein-1 and macrophage inflammatory proteins-1α, and enzymes for prostaglandin (PG) synthesis. It also inhibited PGE2 production. On LPS signaling pathways, DDGP profoundly decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the LPS-treated cells. It had little or no effect on the activation of JNK, ERK and nuclear factor kappa B. In conclusion, results suggested that DDGP from G. parva inhibited expression and production of inflammatory molecules in LPS-activated macrophages through suppressing p38 MAPK activation. DDGP should be a good candidate anti-inflammatory agent in the future.

Inhibitory effects of Gymnema inodorum (Lour.) Decne leaf extracts and its triterpene saponin on carbohydrate digestion and intestinal glucose absorption.

ETHNOPHARMACOLOGICAL RELEVANCE: Chiang-Da, Gymnema inodorum (Lour.) Decne. (GI), is an ethnomedicinal plant that has been used for diabetic treatment since ancient times. One of the anti-diabetic mechanisms is possibly related to the actions of triterpene glycoside, (3ß, 16ß)-16,28-dihydroxyolean-12-en-3-yl-O-ß-D-glucopyranosyl-ß-D-glucopyranosiduronic acid (GIA1) in decreasing carbohydrate digestive enzymes and intestinal glucose absorption in the gut system. AIMS OF THE STUDY: To observe the amount of GIA1 in GI leaf extracts obtained from different ethanol concentrations and to investigate the anti-hyperglycemic mechanisms of the extracts and GIA1. MATERIALS AND METHODS: The crude extracts were prepared using 50%v/v to 95%v/v ethanol solutions and used for GIA1 isolation. The anti-hyperglycemic models included in our study examined the inhibitory activities of α-amylase/α-glucosidase and intestinal glucose absorption related to sodium glucose cotransporter type 1 (SGLT1) using Caco-2 cells. RESULTS: GIA1 was found about 8%w/w to 18%w/w in the GI extract depending on ethanol concentrations. The GI extracts and GIA1 showed less inhibitory activities on α-amylase. The extracts from 75%v/v and 95%v/v ethanol and GIA1 significantly delayed the glycemic absorption by lowering α-glucosidase activity and glucose transportation of SGLT1. However, the 50%v/v ethanolic extract markedly decreased the α-glucosidase activity than the SGLT1 function. CONCLUSION: Differences in the GIA1 contents and anti-glycemic properties of the GI leaf extract was dependent on ethanol concentrations. Furthermore, the inhibitory effects of the 75%v/v and 95%v/v ethanolic extracts on α-glucosidase and SGLT1 were relevant to GIA1 content.

A new dihydrophenanthrene from Cymbidium finlaysonianum and structure revision of cymbinodin-A.

1-(4-Hydroxybenzyl)-4,6-dimethoxy-9,10-dihydrophenanthrene-2,7-diol (13), a new dihydrophenanthrene, was isolated along with ferulic acid esters (1), eight phenanthrene derivatives (2, 3, 6-11) and three bibenzyls (4, 5, 12) from an epiphytic orchid, Cymbidium finlaysonianum. The molecular structure of cymbinodin-A (2) was revised based on spectroscopic data and comparison with the literature. Compounds 2, 3, and 6-13 were evaluated and shown to be cytotoxic against human small cell lung cancer (NCI-H187) cell line. Cymbinodin-A displayed the highest cytotoxicity with an IC50 value of 3.73 µM.

Anticancer activity of arborinine from Glycosmis parva leaf extract in human cervical cancer cells.

Glycosmis parva is a small shrub found in Thailand. Ethyl acetate (EtOAc) extract from its leaves has been shown to exert anticancer effects in vitro; however, the compound responsible for this activity has not been isolated and characterized. In this study, we demonstrate that arborinine, a major acridone alkaloid in the EtOAc fraction, decreased proliferation and was strongly cytotoxic to HeLa cervical cancer cells without significantly affecting normal cells. The compound also inhibited tumor spheroid growth much more potently than chemotherapeutic drugs bleomycin, gemcitabine, and cisplatin. In addition, unlike cisplatin, arborinine activated caspase-dependent apoptosis without inducing DNA damage response. We further show that arborinine strongly suppressed cancer cell migration by downregulating expression of key regulators of epithelial-mesenchymal transition. Taken together, our data provide important insights into the molecular mechanism of arborinine's anticancer activity, supporting its potential use for treating cervical cancer.