New Monoterpenoid Glycosides from the Fruits of Hypericum patulum Thunb.

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1-2, named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3-5, named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum, paving the way for further exploration of monoterpenoid glycosides.

Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

Three New Ionone Glycosides from Rhododendron capitatum Maxim.

Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

Chemical Constituents with Anti-Proliferative Activity on Pulmonary Arterial Smooth Muscle Cells from the Roots of Anthriscus sylvestris (L.) Hoffm.

A chemical investigation of Anthriscus sylvestris roots led to the isolation and characterization of two new nitrogen-containing phenylpropanoids (1-2) and two new phenol glycosides (8-9), along with fifteen known analogues. Structure elucidation was based on HRESIMS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD). In addition, compounds 3, 6, 9-10, 12, and 17 exhibited inhibitory effects against the abnormal proliferation of pulmonary arterial smooth muscle cells with IC50 values ranging from 10.7 ± 0.6 to 57.1 ± 1.1 µM.

Health-Promoting Properties of Natural Flavonol Glycosides Isolated from Staphylea pinnata L.

Staphylea, also called bladdernuts, is a genus of plants belonging to the family Staphyleaceae, widespread in tropical or temperate climates of America, Europe, and the Far East. Staphylea spp. produce bioactive metabolites with antioxidant properties, including polyphenols which have not been completely investigated for their phytotherapeutic potential, even though they have a long history of use for food. Here, we report the isolation of six flavonol glycosides from the hydroalcoholic extract of aerial parts of Staphylea pinnata L., collected in Italy, using a solid-phase extraction technique. They were identified using spectroscopic, spectrometric, and optical methods as three quercetin and three isorhamnetin glycosides. Among the flavonol glycosides isolated, isoquercetin and quercetin malonyl glucoside showed powerful antioxidant, antimicrobial, and wound healing promoting activity and thus are valuable as antiaging ingredients for cosmeceutical applications and for therapeutic applications in skin wound repair.

Megastigmane glycosides from the traditional Uighur medicine Cydonia oblonga Mill.

Phytochemical investigation on the fruits of Cydonia oblonga Mill., a traditional Uighur medicine, led to the isolation of seven undescribed and nine known megastigmane glycosides. Their structures including absolute configurations were characterized by an extensive analysis of spectroscopic data including HRESIMS and NMR, combined with ECD calculations. Additionally, compounds 1, 2, 4, and 6-16 exhibited anti-inflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharides (LPS) with inhibitory rates of 10.79%-44.58% at 20 µM.

α-Glucosidase inhibitory flavonol glycosides from Cyclocarya paliurus (Batalin) Iljinskaja and their kinetics characteristics.

Seven previously undescribed flavonol glycosides including four rare flavonol glycoside cyclodimers, dicyclopaliosides A-C (1-3) with truxinate type and dicyclopalioside D (4) with truxillate type, as well as three kaempferol glycoside derivatives cyclopaliosides A-C (5-7), were obtained from the leaves of Cyclocarya paliurus. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. All compounds were evaluated for their inhibitory α-glucosidase activities. Among them, compounds 1-4 display strong inhibitory activities with IC50 values of 82.76 ± 1.41, 62.70 ± 4.00, 443.35 ± 16.48, and 6.31 ± 0.88 nM, respectively, while compounds 5-7 showed moderate activities with IC50 values of 4.91 ± 0.75, 3.64 ± 0.68, and 5.32 ± 0.53 µΜ, respectively. The structure-activity relationship analysis assumed that the cyclobutane cores likely contribute to the enhancement of α-glucosidase inhibitory activities of dimers. Also, the interaction mechanism between flavonol glycoside dimers and α-glucosidase were explored by the enzyme kinetic assay, indicating that compounds 1-3 exhibited mixed-type inhibition, while 4 showed uncompetitive inhibition. Additionally, the active compounds have also undergone molecular docking evaluation.

Ferroptosis pathways: Unveiling the neuroprotective power of cistache deserticola phenylethanoid glycosides.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease. AIM OF THE STUDY: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS. MATERIALS AND METHODS: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia. RESULTS: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe2+ efflux and regulating mitochondrial Fe2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer). CONCLUSIONS: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.

In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Association of enzymatic and optimized ultrasound-assisted aqueous extraction of flavonoid glycosides from dried Hippophae rhamnoides L. (Sea Buckthorn) berries.

The main purpose of the present study was to determine the effect of associating an optimized ultrasound-assisted extraction (UAE) protocol with enzyme-assisted extraction (EAE) in aqueous media, using the dried berries of Hippophae rhamnoides L. (sea buckthorn) as plant material. A specialized software was used for the determination of potential optimal extraction parameters, leading to the development of four optimized extracts with different characteristics (UAE ± EAE). For these extracts, buffered or non-buffered solutions have been used, with the aim to determine the influence of adjustable pH on extractability. As enzymatic solution, a pectinase, cellulase, and hemicellulase mix (2:1:1) has been applied, acting as pre-treatment for the optimized protocol. The highest extractive yields have been identified for non-buffered extracts, and the E-UAE combination obtained extracts with the highest overall in vitro antioxidant activity. The HPLC-MSn analysis demonstrated a rich composition in different types of isorhamnetin-O-glycosides, as well as some quercetin-O-glycosides, showing a high recovery of specific flavonol-type polyphenolic species. Moreover, we have tentatively identified two flavanols (i.e., catechin and epigallocatechin) and one flavone derivative (i.e., luteolin).

Properties, extraction and purification technologies of Stevia rebaudiana steviol glycosides: A review.

For health and safety reasons, the search for green, healthy, and low-calorie sweeteners with good taste has become the demand of many consumers. Furthermore, the need for sugar substitutes of natural origin has increased dramatically. In this review, we briefly discussed the safety and health benefits of stevia sweeteners and enumerated some examples of physiological functions of steviol glycosides (SGs), such as anti-inflammatory, anti-obesity, antihypertensive, anti-diabetes, and anticaries, citing various evidence related to their application in the food industry. The latest advances in emerging technologies for extracting and purifying SGs and the process variables and operational strategies were discussed. The impact of the extraction methods and their comparison against the conventional techniques have also been demonstrated. These technologies use minimal energy solvents and simplify subsequent purification stages, making viable alternatives suitable for a possible industrial application. Furthermore, we also elucidated the potential for advancing and applying the natural sweeteners SGs.

Rapid purification and scale-up of tilianin using counter-current chromatography with rectangular horizontal tubing.

In counter-current chromatography (CCC), linear scale-up is an ideal amplification strategy. However, when transferring from analytical to predictable preparative processes with high throughput, linear scale-up would be challenging due to limitations imposed by differences in instrument parameters, such as gravitational forces, tubing cross-section area, tubing length, column volume and flow rate. Some effective scale-up strategies have been studied for different instrument parameters, but so far, these scale-up works have only been tested on standard circular (SC) tubing. The previous research of our group found that rectangular horizontal (RH) tubing can double the separation efficiency compared with conventional SC tubing, and has industrial production potential. This paper used the separation of tilianin from Dracocephalum moldavica L. as an example to demonstrate how to scale up the optimized process from analytical SC tubing to preparative RH tubing. After systematic optimization of solvent systems, sample concentration and flow rate on the analytical CCC, the optimized parameters obtained were successfully transferred to the preparative CCC. The results showed that a crude sample of 2.07 g was successfully separated using a solvent system of n-hexane - ethyl acetate - ethanol - water (1:4:1:5, v/v/v/v) in reversed phase mode, and the three consecutive separations produced a total of 380 mg tilianin in 75 min with high purities of 98.3%, as analyzed by HPLC. The total throughput achieved from the analytical to semi-preparative scale was improved by 138 times (from 12 mg/h to 1.66 g/h), while the column volume was increased by only 46.5 times (from 15.5 mL to 720 mL). This is the successful application of CCC for the separation and purification of tilianin. Given that SC tubing is the traditional configuration for CCC columns, this study is a necessary step to prove the applicability of RH tubing columns for routine use and potential large-scale industrial applications.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction of Ipomoea alba seeds.

Resin glycosides act as laxatives in crude drugs derived from plants of the Convolvulaceae family. These compounds have exhibited antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug resistance-modulating properties, as well as cytotoxicity against cancer cells. This study investigated the organic acid, hydroxyl fatty acid, monosaccharide, and glycosidic acid components of the crude resin glycoside fraction obtained from the methanol extract of Ipomoea alba L. (Convolvulaceae) seeds, which was subjected to alkaline and acidic hydrolysis. The alkaline hydrolysis yielded acetic, isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids as organic acid components, along with a glycosidic acid fraction. The acidic hydrolysis of the glycosidic acid fraction resulted in the isolation of 11S-hydroxytetradecanoic and 11S-hydroxyhexadecanoic acids as hydroxyl fatty acid components, as well as d-glucose, d-quinovose, d-fucose, d-xylose, and l-rhamnose as monosaccharide components. In addition, 10 new glycosidic acid methyl esters were isolated from the glycosidic acid fraction treated with trimethylsilyldiazomethane-hexane, along with one known glycosidic acid methyl ester. Of these, eight compounds contained new glycans. Four of these compounds were unusual natural glycosides with four glycosidic linkages to one monosaccharide. Their structures were determined using MS and NMR spectral analyses, which provided valuable insights into the unique glycosidic composition of I. alba seeds.

Oleanane-Type Triterpene Glycosides from Camellia phanii and Their α-Glucosidase Inhibitory Activity.

Three new oleanane-type triterpene saponins, named camphanosides A-C (1-3), along with five known compounds, chikusetsusaponin IVa (4), spinasaponin A 28-O-glucoside (5), (-)-epicatechin (6), (-)-epicatechin 3-O-gallate (7), and (-)-epigallocatechin 3-O-gallate (8) were isolated from the leaves Camellia phanii Hakoda & Ninh. Their structures were established by 1D and 2D-NMR and mass spectral analysis and chemical methods. Moreover, compounds 1-5 were also evaluated for α-glucosidase inhibitory activity. Compounds 1-3 exhibited moderate α-glucosidase inhibitory activity with IC50 values of 230.7±18.0, 251.4±22.7, and 421.4±25.6 µM, respectively.

New Diterpenes and Diterpene Glycosides with Antibacterial Activity from Soft Coral Lemnalia bournei.

Five new biflorane-type diterpenoids, biofloranates E-I (1-5), and two new bicyclic diterpene glycosides, lemnaboursides H-I (6-7), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei. Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 µM.

Aurantoside L, a New Tetramic Acid Glycoside with Anti-Leishmanial Activity Isolated from the Marine Sponge Siliquariaspongia japonica.

A new tetramic acid glycoside, aurantoside L (1), was isolated from the sponge Siliquariaspongia japonica collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L (1) composed of a tetramic acid bearing a chlorinated polyene system and a trisaccharide part was elucidated using spectral analysis. Aurantoside L (1) showed anti-parasitic activity against L. amazonensis with an IC50 value of 0.74 µM.

Highly oxidized rearranged derivatives of quinochalcone C-glycosides from Carthamus tinctorius.

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 µM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.

Cryptobuchanosides A-G: seven previously undescribed triterpene glycosides from Cryptolepis buchananii R.Br. ex Roem. and Schult. with nitric oxide production inhibition activity.

In this study, nine triterpene glycosides including seven previously undescribed compounds (1-7), were isolated from leaves of Cryptolepis buchananii R.Br. ex Roem. and Schult. using various chromatographic methods. The chemical structures of the compounds were elucidated to be 3-O-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (1), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (2), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosyluncargenin C 28-O-ß-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (3), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosylhederagenin 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (4), 3-O-ß-D-glucopyranosylarjunolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (5), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß- D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (6), 3-O-ß-D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (7), asiatic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (8), and 3-O-ß-D-glucopyranosylasiatic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (9), through infrared, high-resolution electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance spectral analyses. The isolates inhibited nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 18.8-58.5 µM, compared to the positive control compound, dexamethasone, which exhibited an IC50 of 14.1 µM.

Alkylphthalides with intracellular triglyceride metabolism-promoting activity from the rhizomes of Cnidium officinale Makino.

Methanol extract of the Cnidium officinale Makino rhizome, which is used as a crude drug Cnidium Rhizome (Cnidii Rhizoma; "Senkyu" in Japanese) and is listed in the Japanese Pharmacopoeia XVIII, showed intracellular triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells. Thirty-five constituents, including two new alkylphthalide glycosides, senkyunosides A (1) and B (2), and a neolignan with a new stereoisomeric structure (3), were isolated in the extract. Their stereostructures were elucidated based on chemical and spectroscopic evidence. Among the isolates, several alkylphthalides, (Z)-3-butylidene-7-methoxyphthalide (9) and senkyunolides G (10), H (14), and I (15), and a polyacetylene falcarindiol (26), were found to show significant activity without any cytotoxicity at 10 µM.