Anti-diabetic compounds from Uvaria dulcis Dunal.

Medicinal plants have long been a source of lead compounds for drug discovery. Among these, the Annonaceae family has gained recognition for its potential to yield novel compounds, particularly those that can be used in the development of drugs targeting chronic diseases like diabetes mellitus (DM). We employed various chromatographic methods to isolate bioactive compounds from the roots, leaves, and twigs of Uvaria dulcis Dunal. We used spectroscopic methods to determine the chemical structures of these compounds. We successfully identified twelve known compounds from various parts of U. dulcis: patchoulenon, polygochalcone, 2'3'-dihydroxy-4',6'-dimethoxydihydrochalcone, 2',3'-dihydroxy-4',6'-dimethoxychalcone, chrysin, techochrysin, 8-hydroxy-5,7-dimethoxyflavanone, pinocembrin, 3-farnesylindole, onysilin, cinchonain la, and cinchonain lb. Interestingly, cinchonain la and cinchonain lb exhibited more potent anti-α-glucosidase activity than acarbose (standard drug), with IC50 values of 11.88 ± 1.41 µg/mL and 15.18 ± 1.19 µg/mL, respectively. Cinchonain la inhibited the DPP-IV enzyme, with IC50 value lower than the standard compound (diprotin A) at 81.78 ± 1.42 µg/mL. While 2',3'-dihydroxy-4',6'-dimethoxychalcone show more potent inhibitory effect than standard drug with IC50 value of 8.62 ± 1.19 µg/mL. Additionally, at a concentration of 10 µg/mL, cinchonain lb and 2',3'-dihydroxy-4',6'-dimethoxychalcone promoted glucose uptake in L6 myotubes cells to the same extent as 100 nM insulin. These findings suggest that cinchonain la, cinchonain lb, and 2',3'-dihydroxy-4',6'-dimethoxychalcone are the U. dulcis-derived bioactive compounds that hold promise as potential structures to use in the development of anti-diabetic drugs.

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum.

Two new cassane diterpenoids, 14ß-hydroxycassa-11(12),13(15)-dien-12,16-olide (1) and 6'-acetoxypterolobirin B (3), together with a known analogue, identified as 12α,14ß-dihydroxycassa-13(15)-en-12,16-olide (2), were isolated from the fruits of Pterolobium macropterum. Compound 1 is a cassane diterpenoid with a Δ11(12) double bond conjugated with an α,ß-butenolide-type, whereas compound 3 is a dimeric caged cassane diterpenoid with unique 6/6/6/6/6/5/6/6/6 nonacyclic ring system. The structures of 1 and 3 were characterized by extensive spectroscopic analysis combined with computational ECD analyses. The α-glucosidase inhibitory activity of isolated compounds was evaluated, and compounds 1 and 3 showed significant α-glucosidase inhibitory activity with IC50 values of 66 and 44 µM.

Alkaloids and Styryl lactones from Goniothalamus ridleyi King and Their α-Glucosidase Inhibitory Activity.

Gonioridleylactam (1), a new compound, is a unique dimeric aristolactam isolated from the EtOAc extract of the twigs of Goniothalamus ridleyi King. The structure of gonioridleylactam (1) consists of two different aristolactams linked together with two methylenedioxy bridges at C-3/C-3' and C-4/C-4', generating a ten-membered ring of [1,3,6,8]tetraoxecine. A new natural product, gonioridleyindole (3-hydroxymethyl-1-methyl-1H-benz[f]indole-4,9-dione, 2), together with eight known compounds (3-10) were also isolated from this plant. Their structures were extensively characterized by spectroscopic methods and comparisons were made with the literature. Compounds 1-4, 7, and 9 were evaluated for their α-glucosidase inhibitory activity. Of these, 3,5-demethoxypiperolide (7) displayed the highest α-glucosidase inhibitory activity, with an IC50 value of 1.25 µM.

Xanthones from the latex and twig extracts of Garcinia nigrolineata Planch. ex T. Anderson (Clusiaceae) and their antidiabetic and cytotoxic activities.

A new geranylated xanthone, nigrolineaxanthone AA (1) together with 18 known compounds (2-19) were isolated from latex and twig extracts of Garcinia nigrolineata Planch. ex T. Anderson. Some of the isolated compounds were assessed for their antidiabetic activities and cytotoxicity against three cancer cell lines. Of these, compounds 12 (IC50 value of 25.8 ± 0.2 µM), 16 (IC50 value of 124.8 ± 0.7 µM), and 17 (IC50 value of 44.4 ± 1.1 µM) exhibited the highest α-glucosidase inhibitory, α-amylase inhibitory, and glycation inhibition activities, respectively. Compound 11 showed glucose consumption and glucose uptake with IC50 values of 14.2 ± 0.8 µM and 3.1-fold. Compound 10 displayed cytotoxic activity against colon cancer (SW480) with an IC50 value of 4.3 ± 0.1 µM), while compound 2 showed cytotoxicity against leukemic cancer (K562) with IC50 value of 4.4 ± 0.3 µM.

Kaempferia parviflora Rhizome Extract as Potential Anti-Acne Ingredient.

Kaempferia parviflora (Black ginger) is used widely in medical fields as an anti-microorganism and anti-inflammation. In this study, the aim was to evaluate the in vitro and in vivo anti-acne efficacy of black ginger extract. The results indicate that the methanol and ethanol extracts showed the highest total phenolic contents, without a significant difference, whereas the n-hexane extract showed the highest total flavonoid content. Nine flavones were detected using UPLC-QTOF-MS, and the ethyl acetate extract showed the highest amount of 5,7-dimethoxyflavone (DMF) according to HPLC. Antibacterial activity against Staphylococcus aureus, S. epidermidis, and Cutibacterium acnes was observed. All the extracts showed antimicrobial activity against C. acnes, revealing MICs in the range of 0.015 to 0.030 mg/mL, whereas the ethyl acetate extract inhibited the growth of S. epidermidis with a MIC of 3.84 mg/mL. In addition, the ethyl acetate extract showed the highest activity regarding nitric oxide inhibition (IC50 = 12.59 ± 0.35 µg/mL). The ethyl acetate extract was shown to be safe regarding cell viability at 0.1 mg/mL. The anti-acne efficacy was evaluated on volunteers. The volunteers were treated in two groups: one administered a 0.02% ethyl acetate extract gel-cream (n = 9) and one administered a placebo (n = 9) for 6 weeks. The group treated with the gel-cream containing the extract showed 36.52 and 52.20% decreases in acne severity index (ASI) after 4 and 6 weeks, respectively, and 18.19 and 18.54% decreases in erythema, respectively. The results suggest that K. parviflora could be a potent active ingredient in anti-inflammatory and anti-acne products.

Cytotoxic and antibacterial xanthones from the roots of Maclura cochinchinensis.

Three new furanoxanthones, macochinxanthones A-C (1-3) and sixteen known xanthones (4-19) were isolated from the roots of Maclura cochinchinensis. Their structures were elucidated by spectroscopic analysis including NMR, UV and IR, as well as mass spectrometry. Chiral-phase HPLC analysis of 1-3 revealed that they were scalemic mixtures with an enantiomeric excess (ee) of 0.05%, 36.8% and 8%, respectively. Most of the isolated xanthones exhibited potent cytotoxicity against four cancer cell lines (KB, HelaS3, A549 and HepG2) with IC50 values in the range of 1.29-90.15 µM. In addition, many of them displayed antibacterial activity against Gram-positive bacteria and Methicillin resistant Stephylococus aureus (MRSA) with MIC values in the range of 4-128 µg/mL.

Derrisrobustones A-D, isoflavones from the twig extract of Derris robusta (DC.) Benth. and their α-glucosidase inhibitory activity.

Three previously undescribed isoflavones, derrisrobustones A-C, and a previously undescribed natural isoflavone, derrisrobustone D, along with eight known isoflavones, were isolated from the twig extract of Derris robusta (DC.) Benth. All structures were identified by extensive spectroscopic analysis. Derrisrobustones A-C were obtained as scalemic mixtures and were resolved by chiral HPLC. The (1″R, 2″R) absolute configuration of (+)-derrisrobustone B was established by single-crystal X-ray crystallography using Cu Kα radiation. The absolute configurations of derrisrobustones A and C were determined by analysis of experimental and calculated ECD data. All compounds were evaluated for their α-glucosidase inhibitory activity. Of these, derrubone displayed the best α-glucosidase inhibitory activity with an IC50 value of 64.2 µM.

α-Glucosidase inhibitory and α-amylase inhibitory activities of compounds isolated from Uvaria rufa Blume.

A new C-benzylated flavone, uvariaruflavone (1), along with 13 known compounds (2-14) were isolated from the twig and leaf extracts of Uvaria rufa Blume. Their structures were established by extensive spectroscopic methods. Flavones (5-8) and cyclohexene (10) were isolated from U. rufa for the first time. Most of the isolated compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Of these, uvariaruflavone (1) showed the highest α-glucosidase inhibitory activity with an IC50 value of 44.3 µM, while ferrudiol (12) displayed the highest α-amylase inhibitory activity with an IC50 value of 73.5 µM.

Macluracochinones A-E, antimicrobial flavonoids from Maclura cochinchinensis (Lour.) Corner.

The phytochemical investigation of the fruit and leaf extracts of Maclura cochinchinensis (Lour.) Corner (Moraceae) resulted in the isolation and identification of four undescribed isoflavones (macluracochinones A-D) and one undescribed flavone (macluracochinone E), together with 24 known compounds. The structures of the undescribed compounds were elucidated using nuclear magnetic resonance (NMR) and high-resolution electrospray ionization time-of-flight mass spectrometry (HRESITOFMS) experiments. Gancaonin M, lupiwighteone, lupalbigenin, warangalone, auriculatin, and millexatin F displayed good antibacterial activities against Gram-positive bacteria with MIC values in the range of 1-8 µg/mL. Lupalbigenin showed strong activities against methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus with the same MIC value of 1 µg/mL.

Spirosteroids and α-glucosidase inhibitory norlignans from Asparagus racemosus Willd. roots.

Three undescribed spirosteroids, asparacemosones A-C, an undescribed spiro-21-norsteroid, asparacemosone D, along with seven known compounds were isolated from Thai herbal plant Asparagus racemosus Willd. roots. Their structures were elucidated by spectroscopic analysis including NMR, UV, IR and mass spectrometry. The absolute configurations of asparacemosones A, B, and D were determined by single crystal X-ray diffraction using CuKα radiation. Among the isolated compounds, the norlignan nyasol and three acetylenic norlignans demonstrated potent α-glucosidase inhibition, with IC50 values ranging from 0.003 to 0.004 µM which is 5 × 104 fold more potent than the standard acarbose.

In Vitro Anti-Inflammatory, Anti-Oxidant, and Cytotoxic Activities of Four Curcuma Species and the Isolation of Compounds from Curcuma aromatica Rhizome.

The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as the isolation of compounds from the most active crude extract (C. aromatica) were investigated. The crude extract of C. aromatica showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 value of 102.3 µg/mL. The cytotoxicity effect of C. aeruginosa, C. comosa, C. aromatica, and C. longa extracts assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 200 µg/mL were 12.1 2.9, 14.4 4.1, 28.6 4.1, and 46.9 8.6, respectively. C. aeruginosa and C. comosa presented apoptosis cells (57.7 3.1% and 32.6 2.2%, respectively) using the CytoTox-ONE™ assay. Different crude extracts or phytochemicals purified from C. aromatica were evaluated for their anti-inflammatory properties. The crude extract of C. aromatica showed the highest potential to inhibit NF-κB activity, followed by C. aeruginosa, C. comosa, and C. longa, respectively. Among the various purified phytochemicals curcumin, germacrone, curdione, zederone, and curcumenol significantly inhibited NF-κB activation in tumor necrosis factor (TNF) stimulated HaCaT keratinocytes. Of all compounds, curcumin was the most potent anti-inflammatory.

α-Glucosidase inhibitory and nitric oxide production inhibitory activities of alkaloids isolated from a twig extract of Polyalthia cinnamomea.

The first phytochemical investigation of Polyalthia cinnamomea led to the isolation and identification of two new oxoprotoberberine alkaloids, (-)-(13aS)-polyalthiacinnamines A and B, together with eleven known compounds. The structures of the new compounds were elucidated by extensive spectroscopic methods. The absolute configuration of miliusacunine E and consanguine B was established by X-ray diffraction analysis using Cu Kα radiation and ECD spectra, whereas the absolute configurations of polyalthiacinnamines A and B were established by comparison of their ECD spectra and specific rotations with those of miliusacunine E and consanguine B. Compounds 1-4, 6, and 8 exhibited α-glucosidase inhibitory activities (IC50 values ranging from 11.3 to 57.9 µM) better than a positive control (acarbose, IC50 83.5 µM). Compound 2 also exhibited NO production inhibitory activity with an IC50 value of 24.4 µM (indomethacin, a positive control, IC50 = 32.2 µM).

Styryllactones from Goniothalamus tamirensis.

The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods. Goniotamirenone A was synthesized via a [2 + 2] cycloaddition reaction of 6-styrrylpyran-2-one in quantitative yield. The absolute configurations of goniotamirenones B and C were identified from experimental and calculated ECD data, while the absolute configurations of (-)-5-acetoxygoniothalamin, (-)-isoaltholactone, parvistone E, and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one were identified by single-crystal X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with relevant compounds reported in the literature. (-)-5-Acetoxygoniothalamin exhibited potent cytotoxicity against the colon cancer cell line (HCT116) with an IC50 value of 8.6 µM which was better than the standard control (doxorubicin, IC50 = 9.7 µM), while (Z)-6-styryl-5,6-dihydro-2-pyranone was less active with an IC50 value of 22.1 µM.

Potent α-glucosidase inhibitory activity of compounds isolated from the leaf extracts of Uvaria hamiltonii.

The phytochemical investigation of the leaf extracts of Uvaria hamiltonii (Annonaceae) led to the isolation and identification of ten compounds including a new seco-cyclohexene (1) together with nine known compounds (2-10). Their structures were elucidated by intensive analysis by spectroscopic methods and comparisons of their spectroscopic data with those of compounds reported in the literature. Compounds 2, 8, and 9 showed potent α-glucosidase inhibitory activity with the IC50 values ranging from 2.6-7.1 µM.

Dasymaschalolactams A-E, Aristolactams from a Twig Extract of Dasymaschalon dasymaschalum.

Five new aristolactam alkaloids (1-5), dasymaschalolactams A-E, and the first isolation of dasymaschalolactone (17) as a natural product, together with 19 known compounds (6-16 and 18-25) were isolated from the twig extract of Dasymaschalon dasymaschalum. Their structures were elucidated by spectroscopic methods as well as comparisons made from the literature. Compounds 20 and 21 showed α-glucosidase inhibitory activities with IC50 values of 4.5 and 24.7 µM, respectively.

Uvarialuridols A-C, three new polyoxygenated cyclohexenes from the twig and leaf extracts of Uvaria lurida.

The first phytochemical investigation of Uvaria lurida resulted in the isolation and identification of three new polyoxygenated cyclohexenes, (+)-(1R,2S,3R,6S)-uvarialuridols A-C (1-3), together with 10 known compounds (4-13). All new structures were elucidated by spectroscopic methods and HRESIMS. The absolute configurations of compounds 1 and 5 were confirmed by X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of compounds 2-4 were identified from comparisons of their specific rotations and ECD spectra with those of known compounds. Compound 11 showed α-glucosidase inhibitory activity with an IC50 value of 30 µM which was better than the standard control, acarbose (74 µM) whereas, compound 10 exhibited nitric oxide (NO) production inhibitory activity with an IC50 value of 37 µM.

A tocotrienol quinone dimer and xanthones from the leaf extract of Garcinia nigrolineata.

Four new compounds (1-4) together with six known compounds (5-10) were isolated from the leaf extract of Garcinia nigrolineata. Compound 4 is a rare tocotrienol quinone dimer. The structures were elucidated based on NMR and MS data. All isolated compounds were evaluated for their antibacterial activities.

α-Glucosidase Inhibitory Flavonoids and Oxepinones from the Leaf and Twig Extracts of Desmos cochinchinensis.

Four new flavonoids (1-4), a new benzyl benzoate derivative (5), five new oxepinones (6-10), and 14 known compounds (11-24) were isolated from the leaf and twig extracts of Desmos cochinchinensis. Their structures were established by spectroscopic methods. The structure of 1 was also confirmed by X-ray diffraction data. The absolute configurations of 3, 4, and 6-10 were determined from comparisons of their ECD spectra with those of relevant reported compounds. Compounds 1, 2, 6, 8, 10, 12-15, and 17 showed α-glucosidase inhibitory activities with IC50 values ranging from 0.2 to 4.9 µM.

Amides and Flavonoids from the Fruit and Leaf Extracts of Melodorum siamensis.

Four new chalcones (1, 10, 13, and 14), a new flavanone, (9), a new amide (8), and 19 known compounds were acquired from Melodorum siamensis. The structures were established by NMR and MS data analyses. Compounds 1 (er 1.4:1) and 2 (er 1.1:1) were scalemic and were resolved to yield (-)-1 and (+)-1 and (-)-2 and (+)-2, respectively. The absolute configurations of these compounds were determined from experimental and calculated ECD data. The structures and configurations of (-)-2 and (+)-8 were identified by single-crystal X-ray diffraction analysis. Compound 11 showed nuclear factor-κB inhibitory effects (IC50 = 9 µM) in a pancreatic ß cell line (MIN-6 cells).

Polyoxygenated Cyclohexenes and Their Chlorinated Derivatives from the Leaves of Uvaria cherrevensis.

The chemical study of leaf extracts from Uvaria cherrevensis resulted in the identification of 11 new polyoxygenated cyclohexenes, cherrevenols A-K (1-11), and a new seco-cyclohexene derivative, cherrevenol L (12). Nine known compounds (13-21) were also isolated. Three of the isolated compounds are chlorinated polyoxygenated cyclohexenes. The structures of these compounds were determined using spectroscopic methods and, in some cases (compounds 2, 6, 8, and 10), single-crystal X-ray crystallographic structural analysis or chemical correlation (compounds 6 and 7). Compounds 6 and 7 were both isolated as scalemic mixtures (ee 23-24%).