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Abstract 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-GSK3β/GSK3β 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.

This study systematically explores a green extraction process of T. crispa stems to selectively isolate therapeutic compounds, borapetoside C (BPC) and magnoflorine (MGF), recognized for their anti-diabetic properties. In agreement with Hansen solubility parameters prediction, H2O and EtOH were found to be suitable solvents for extraction of BPC and MGF, respectively, resulting in 33 % and 45 % extractabilities after 60 min. Further investigations demonstrated considerable increase in BPC extractability using 20 % EtOH:H2O mixture at 40 °C, with complete extraction achieved after 60 min. While for MGF, pure-EtOH at 40 °C, was the most suitable solvent, showing the highest selectivity and complete extraction after 100 min. The BPC-rich extract from 20 % EtOH:H2O exhibited higher anti-diabatic activity (IC50 = 0.63 ± 0.03 and 0.72 ± 0.04 mg/mL, respectively, for α-glucosidase and α-amylase enzymes inhibition activity), and considerably lower cytotoxicity to L6 and HepG2 cells, with IC50 = 0.26 ± 0.16 and 0.24 ± 0.02 mg/mL, respectively, compared with the MGF-rich extract obtained with pure-EtOH. Based on these results, a sequential extraction scheme was proposed involving initial pure-EtOH extraction to selectively and completely remove MGF, followed by extraction with a 20 % EtOH:H2O mixture to recover the remaining BPC, which was approximately 80 % of the BPC originally present. The obtained MGF-free BPC-rich extract showed significantly lower cytotoxicity (IC50 = 0.31 ± 0.06 mg/mL against L6 cell) and higher enzyme inhibition activities (IC50 = 0.53 ± 0.32 and 0.52 ± 0.02 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), comparable to acarbose (IC50 = 0.43 ± 0.02 and 0.83 ± 0.03 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), the result that potentially leads to the development of a promising industrial process to harness T. crispa for diabetes prevention and treatment.

Abstract 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.

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.

Abstract 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.

Abstract 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.

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

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.

Abstract 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.

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.

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.

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.

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-β-CD (RMβCD) 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/RMβCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMβCD 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/RMβCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.

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.

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.

A combination of ethanolic extract of Phyllanthus emblica fruits and ethanolic extract of Alpinia galanga rhizomes at a ratio of 7:3 (PE–AE (7:3)) exhibited synergistic antioxidant activities against DPPH·, ABTS·+, and superoxide anion (O2·−) radicals with Combination Indices (CIs) of 0.692 ± 0.048, 0.802 ± 0.033, and 0.840 ± 0.023, respectively. At concentrations of 20 and 50 µg/mL, the PE–AE (7:3) showed a significant decrease in intracellular reactive oxygen species against H2O2-induced oxidative stress in an endothelial cell line (ECV304) in dose-dependent manner, as well as an increase in cell survival. In addition, The PE–AE (7:3) at 50 µg/mL was as potent as quercetin at 10 µg/mL in the inhibition of H2O2-induced lipid peroxidation. The combinations of ellagic acid and hydroxycinnamic derivatives which attributed to synergistic antiradicals enhanced cytoprotective activity. This first report on synergistic combination of PE and AE has the potential to develop as new nutritional antioxidants.

ABSTRACT Peel extracts of litchi and rambutan, and that of tamarind seed coat were investigated in relation to their utility in skin-aging treatments. Standardized extracts of tamarind were significantly (p < 0.05) more efficient at O2 •- scavenging (IC50 = 27.44 ± 0.09) than those of litchi and rambutan (IC50 = 29.57 ± 0.30 and 39.49 ± 0.52 μg/ml, respectively) and the quercetin standard (IC50 = 31.88 ± 0.15 μg/ml). Litchi extract proved significantly (p < 0.05) more effective for elastase and collagenase inhibition (88.29 ± 0.25% and 79.46 ± 0.92%, respectively) than tamarind (35.43 ± 0.68% and 57.69 ± 5.97%) or rambutan (31.08 ± 0.38% and 53.99 ± 6.18%). All extracts were safe to human skin fibroblasts and inhibit MMP-2, with litchi extract showing significantly (p < 0.01) enhanced inhibition over the standard, vitamin C (23.75 ± 2.74% and 10.42 ± 5.91% at 0.05 mg/ml, respectively). Extracts suppress melanin production in B16F10 melanoma cells through inhibition of tyrosinase and TRP-2, with litchi extract being the most potent, even more so than kojic acid (standard). These results highlight the potential for adding value to agro-industrial waste, as the basis for the sustainable production of innovative, safe, anti-aging cosmetic products.

The article discusses the results of a study which examines the safety and effectiveness of extract from Salak plum peel as an antioxidant for cosmetics. The authors revealed the presence of ethyl acetate fraction as the most potent component of the extract using ferric reducing ability of plasma assays. They explained that ethyl acetate fraction demonstrated cellular oxidative prevention and damage treatment in normal human fibroblast cells.