Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.

Two new cucurbitane-type triterpenoid saponins from the fruit of Citrullus colocynthis.

Two new cucurbitane-type triterpenoid saponins, 2,20ß,22ß-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-ß-D-glucopyranoside (1), 2,20ß,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-ß-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 µM against paracetamol-induced HepG2 cell damage.

Six new iridoid glycosides from the whole plants of Hedyotis diffusa.

Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (1), Z-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (2), E-6-O-caffeoyl scandoside methyl ester (3), E-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (4), Z-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (5), and E-6-O-p-coumaroyl-4'-O-acetyl scandoside methyl ester (6). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.

Three new flavonoids from the roots of Sophora tonkinensis.

Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Development and validation of a nomogram-assisted tool to predict potentially reversible cognitive frailty in Chinese community-living older adults.

BACKGROUND: Cognitive frailty (CF) is a complex and heterogeneous clinical syndrome that indicates the onset of neurodegenerative processes and poor prognosis. In order to prevent the occurrence and development of CF in real world, we intended to develop and validate a simple and timely diagnostic instrument based on comprehensive geriatric assessment that will identify patients with potentially reversible CF (PRCF). METHODS: 750 community-dwelling individuals aged over 60 years were randomly allocated to either a training or validation set at a 4:1 ratio. We used the operator regression model offering the least absolute data dimension shrinkage and feature selection among candidate predictors. PRCF was defined as the presence of physical pre-frailty, frailty, and mild cognitive impairment (MCI) occurring simultaneously. Multivariate logistic regression was conducted to build a diagnostic tool to present data as a nomogram. The performance of the tool was assessed with respect to its calibration, discrimination, and clinical usefulness. RESULTS: PRCF was observed in 326 patients (43%). Predictors in the tool were educational background, coronary heart disease, handgrip strength, gait speed, instrumental activity of daily living (IADL) disability, subjective cognitive decline (SCD) and five-times-sit-to-stand test. The diagnostic nomogram-assisted tool exhibited good calibration and discrimination with a C-index of 0.805 and a higher C-index of 0.845 in internal validation. The calibration plots demonstrated strong agreement in both the training and validation sets, while decision curve analysis confirmed the nomogram's efficacy in clinical practice. CONCLUSIONS: This tool can effectively identify older adults at high risk for PRCF, enabling physicians to make informed clinical decisions and implement proper patient-centered individual interventions.

Eight new arnebinol B-based meroterpenoids with planar chirality in the constrained 6/10/5 tricyclic skeleton from Arnebia euchroma and their cytotoxicities.

Eight new arnebinol B-based meroterpenoids ((-)-1, 2, 3, (-)-5, and 7-10) with a constrained 6/10/5 tricyclic backbone were isolated from the roots of Arnebia euchroma. The planar and steric structures of these new compounds were unambiguously elucidated by extensive spectroscopic analyses, X-ray diffraction crystallography, and ECD calculations. The predominant relative orientation between H-7 and the Z double bond with a methyl substituent in the rigid 10-membered carbocycle, along with the planar chirality of the Z double bond was analyzed and discussed for the first time. The illustration of the planar chirality derived from the Z double bond should be paid great importance during the structure elucidation on these homologous meroterpenoids. All the isolated meroterpenoids were screened for their cytotoxicities against the HCT-8, PANC-1, HGC-27, HepG2, and PC9 cell lines, and compounds (+)-5 and (-)-5 exhibited the most potent cytotoxicity.

Two dimers generated by lithospermic decarboxylation coupling from Danshen.

To further reveal the active ingredients of Danshen, we systematically studied its chemical components and obtained two new lithospermic acid derivatives (compounds 1 and 2) together with five known phenylpropionic acids (compounds 3-7) from the dried rhizomes of Salvia miltiorrhiza. The structures of the two new compounds were determined by multiple spectral analyses (UV, IR, HR-ESI-MS, NMR, and ECD). In addition, the absolute configurations were established by chiral analysis and calculated and experimental circular dichroism spectra. Biological research indicated that compound 1 could significantly inhibit the proliferation of isoproterenol (ISO)-treated cardiac fibroblasts (AC16 cells), and MMP9 was found to be the most likely target of compound 1. The protein expression and mRNA levels of MMP9 were increased in ISO-induced AC16 cells, which could be reversed by treatment with compound 1. Furthermore, this treatment could alleviate the migration and activation of ISO-induced cardiac fibroblasts.

Photoinduced Irreversible Intramolecular Proton Transfer of Arnebinones B, D, and E: The Case of Photoenolization at the p-Benzoquinone-CH2/CH-π System.

Arnebinones B, E, and D (1-3) have been found to be sensitive to light, generating complex and diverse proton transfer products when triggered by light. A unique two-step irreversible intramolecular proton transfer of 1 produced five scalemic mixtures, of which four possessed intriguing dual planar chirality. The unprecedented orientation epimerization equilibrium of the intra-annular double bond was first observed and researched in the homologous meroterpenoids by HPLC monitoring and DFT calculations. A "p-benzoquinone-CH2/CH-π" moiety in the structure was the common key feature for the occurrence of this type of photoenolization reaction. The product transformation processes and universality of this photoinduced irreversible proton transfer reaction were analyzed together with the cytotoxic activities of arnebinones B, D, and E, and their photoreaction products.

New dimeric phloroglucinol derivatives from Agrimonia pilosa and their hepatoprotective activities.

Five new dimeric phloroglucinol derivatives, agrimones A - E (1-5), were isolated from the whole plant of Agrimonia pilosa. Their structures including absolute configurations were determined by a series of spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR), complemented with the comparison of the experimental and calculated ECD spectra, and gauge-independent atomic orbital (GIAO) NMR calculations. Notably, compounds 1 and 2 represent a highly oxidized 6/6/6 tricyclic ring skeleton based on the cis-fused paraquinone and chroman. Compounds 1a, 4, and 5 exhibited moderate hepatoprotective activities against APAP-induced HepG2 cell injury at 10 µM.

Neuroprotective and anti-inflammatory phenylethanoidglycosides from the fruits of Forsythia suspensa.

Neuroinflammation is emerging as a crucial reason of major neurodegenerative diseases in recent years. Increasingly evidences have supported that bioactive natural products from traditional Chinese medicines have efficiency for neuroinflammation. Forsythia suspensa, a typical medicinal herb, showed potential neuroprotective and anti-inflammatory properties in previous pharmacological studies. In our research to obtain neuroprotective and anti-inflammatory natural products, three unprecedented C6-C7'/C6-C16' linked phenylethanoidglycoside dimers (1-3), three new phenylethanoidglycosides (4-6), and six known compounds (7-12) were isolated from the fruits of Forsythia suspensa. Their structures were determined by comprehensive spectroscopic data and comparison to the literature data. All isolated compounds were evaluated their neuroprotective and anti-inflammatory activities. Compounds 1 and 10 exhibited significant neuroprotective activities with the cell viability values of 75.24 ± 8.05% and 93.65 ± 10.17%, respectively, for the serum-deprivation and rotenone induced pheochromocytoma (PC12) cell injury. Meanwhile, compound 1 exhibited excellent anti-inflammatory activity against tumor necrosis factor (TNF)-α expression in LPS induced RAW264.7 cells with the IC50 value of 1.30 µM. This study revealed that the bioactive phenylethanoidglycosides may attenuate neuroinflammation through their neuroprotective and anti-inflammatory activities.

Seven new prenylated flavanones from the roots of Sophora flavescens and their anti-proliferative activities.

Aiming to discover potent anti-proliferative agents from the roots of Sophora flavescens, seven new prenylated flavanones were isolated, along with 16 known compounds. Their structures were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, UV, IR, CD, and HRESIMS) and comparison to literature data. In the in vitro assay, 21 showed anti-proliferative activity against human hepatoma cells (HepG2). Studies of its mechanism revealed that 21 could significantly activate autophagic flux and trigger ROS release in HepG2 cells. Western blot experiments demonstrated that 21 could activate the key signaling protein of autophagy and ROS, while it does not affect the main protein of the apoptosis signaling pathway. These results suggested that 21 mediates its anti-proliferative effects through autophagic cell death, which is apoptosis-independent.

Bioactive amides from Polygonum cuspidatum.

One pair of new amides enantiomers (1a and 1b) and two known amides were isolated from the rhizomes of Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. Notably, compound 1 possesses unique C-C connection between feruloyltyramine and resveratrol. Their absolute configurations were determined by the ECD method. All compounds were evaluated for their α-glucosidase inhibitory activity and compounds 2 and 3 showed significant inhibitory activity with IC50 values of 2.82 and 13.06 µmol/L, respectively (positive control acarbose, IC50 385 µmol/L).

Three new monocyclic monoterpenoid O-glycosides from the roots of Glycyrrhiza uralensis.

Three new monocyclic monoterpenoid containing ß-D-apiofuranosyl-(1→2)-O-ß-D-glucopyranosyl moieties, together with three other known monocyclic monoterpenoid O-glycosides, were obtained from the roots of Glycyrrhiza uralensis for the first time. Their structures were determined by UV, IR, HRESIMS, and 1D and 2D NMR data.[Formula: see text].

Neophathalides A and B, two pairs of unusual phthalide analog enantiomers from Ligusticum chuanxiong.

Two pairs of unusual phthalide analog enantiomers, (+)- and (-)-neophathalides A and B [(+)- and (-)-1 and 2], were isolated from the rhizome of Ligusticum chuanxiong Hort. Notably, neophathalide A presented a novel spiro-[4.5]dec-6-ene skeleton that originated from an aldol condensation process from sedanonic acid. Neophathalide B is an unprecedented 3-substituted phthalide analog that possesses a four-membered lactone ring system. The structures of the compounds were established using UV, IR, HRESIMS, NMR and ECD methods. All of the compounds were evaluated for their hepatoprotective activity against N-acetyl-p-aminophenol-induced HepG2 cell injury. Compounds 1a, 1b, and 2a exhibited moderate hepatoprotective activity compared with the positive control drug bicyclol at a concentration of 10 µM (p < 0.01).

Archromones A-F, unusual polycyclic dearomatic geranylquinol derivatives from the roots of Arnebia euchroma.

Eight new geranylquinol derivatives (1-8) were purified from the roots of Arnebia euchroma. Compounds 1-6 possess an unprecedented dearomatic benzocogeijerene skeleton with a rare trans-fused hydronaphthalene moiety. Their structures and absolute configurations were elucidated by HRESIMS, NMR, ECD, and X-ray diffraction. A convenient strategy for rapid determination of the relative configuration of H-1/H-7/Me-16 and the absolute configuration at C-1 for 1-6 was summarized. Compound 2 exhibited cytotoxicity against all the tested cell lines, namely PC9, BGC823, HCT116, HepG2, HeLa, and U87-MG, with IC50 values ranging from 13.7 to 29.3 µM.

Chemical constituents of Ligusticum chuanxiong and their anti-inflammation and hepatoprotective activities.

Ligusticum chuanxiong Hort is a famous health promoting plant cultivated in China, and widely consumed due to its various curative effects. To study the potential bioactive constituents from the rhizome of L. chuanxiong, a chemical investigation was thus performed. In present study, we report the isolation and identification of ten new compounds, including two coumarins (1-2), four lignans (3-6), and four phenols (7-10), along with five known compounds (11-15) from the rhizome of L. chuanxiong. The structures of these compounds were unambiguously established by HR-ESI-MS, UV, IR, CD, NMR spectral data and comparison to reported data. Meanwhile, the anti-inflammation and hepatoprotective activities of all these compounds were evaluated. The results show that compounds 5, 6 and 7 showed excellent inhibition of NO production in LPS-induced RAW 264.7 cells stronger than curcumin, and compounds 5, 7 and 9 exhibited greater hepatoprotective effect than that of bicyclol.

Seven new 1-oxygenated cholestane glycosides from Ornithogalum saundersiae.

As the continuous scientific research, seven new 1-oxygenated cholestane glycosides named osaundersiosides 1 A - 1 G were isolated from an EtOH extract of the bulbs of Ornithogalum saundersiae. Their structures were deduced by means of spectroscopic data, chemical evidence and the results of hydrolytic cleavage. The cytotoxicity and anti-inflammatory effects of osaundersiosides 1 A - 1 G were evaluated, but none of them displayed significant activities. [Formula: see text].

Three new compounds from the rhizome of Ligusticum chuanxiong and their anti-inflammation activities.

Phytochemical investigation of the rhizome of Ligusticum chuanxiong Hort led to the isolation and identification of three new compounds, chuanxiongoside A, (2E,4E)-8-(6-O-inositolyl)-8-oxo-2,7-dimethyl-octadienoic acid (2), chuanxiongoside C (3). The structures of these compounds were unambiguously established by HR-ESI-MS, UV, IR, CD, NMR spectral data and comparison to reported data. All the isolated compounds (1-3) were investigated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells. All compounds showed excellent inhibition of NO production stronger than curcumin. [Formula: see text].

New phenolic glycosides from Polygonum cuspidatum.

Two new isobenzofuranone derivatives, polyphthaliside A (1) and polyphthaliside B (2), and a new isocoumarin derivative, polyisocoumarin (3), were isolated from Polygonum cuspidatum. Their structures were elucidated by detailed spectroscopic analysis and chemical methods. The cytotoxicity activity and PTP1B inhibitory activity of compounds 1-3 were estimated and none of them exhibited activities at a concentration of 10 µM.