A new coumarin and a new flavonoid from Ochrocarpus longifolius.

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

[Study on chemical components of Hypericum himalaicum and mechanism of anti-inflammatory based on network pharmacology and molecular docking technology].

The chemical constituents of ethyl acetate from Hypericum himalaicum were isolated by silica gel column chromatography, gel column chromatography, and high-performance liquid chromatography. The structure of the isolated compounds was identified by modern spectral techniques(NMR, MS, IR, and UV), and the potential anti-inflammatory targets and action pathways were analyzed and predicted by network pharmacology and molecular docking methods.Ten compounds were isolated from H. himalaicum and identified as 5,9,11-trihydroxy-3,3-dimethyl-3H,8H-benzo[6,7][1,4]dioxepino[2,3-f]chromen-8-one(1), betulinic acid(2), demethyltorosaflavone C(3), kaempferol(4), quercetin(5), hyperwightin B(6), toxyloxanthone B(7), 1,7-dihydroxy-xanthone(8), emodin(9), and 1,7-dihydroxy-4-methoxy-xanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from H. himalaicum for the first time. Network pharmacology screened 60 key anti-inflammatory targets. By acting on TNF, AKT1, CASP3, and other key targets, involving PI3K-AKT signaling pathway, IL-17 signaling pathway, VEGF signaling pathway, MAPK signaling pathway, and other signaling pathways, and phosphorylation, cell migration and movement, protein tyrosine kinase, and other biological processes were regulated to achieve anti-inflammatory effects. The results of molecular docking show that the above components have good binding properties with the core targets.

Phytochemical investigation of Asarum sieboldii var. seoulense and the phenotypic profiles of its constituents against a Parkinson's Disease olfactory cell line.

Asarum sieboldii var. seoulense is a plant species under the family Aristolochiaceae and has been used for centuries as an ingredient in a well-known Traditional Chinese medicine (TCM), "Xixin", to treat symptoms of the neurodegenerative condition Parkinson's Disease (PD). Although there have been studies on the neuroprotective effect of this TCM, the phenotypic profiles of its chemical constituents against PD-implicated cellular organelles have not been reported. This research investigated the chemistry of A. sieboldii var. seoulense extract to identify the active small molecules that exhibited perturbation to the cellular compartments related to PD, potentially supporting its traditional application in treating this condition. 1H NMR-guided chemical investigation of this plant yielded twenty secondary metabolites which belong to isobutylamides, lignans and phenolics. The compounds were evaluated against an olfactory cell line derived from a PD patient using phenotypic assay. Several isolates, 2, 3, 7, 11, 13-16 and 18-20, were found to induce moderate perturbation to the staining of mitochondria, autophagosome and α-tubulin of the cells. Considering that PD pathogenesis is closely related to these cellular compartments, the results provided a rationale for the traditional application of Xixin in the treatment of PD.

Acute and 13 weeks subchronic toxicological evaluation of the flavonoid-rich extract of Sophora flavescens.

The roots of Sophora flavescens have a long history of use in Chinese medicine for the treatment of various medical conditions. Flavonoids from the ethyl acetate extract of S. flavescens have shown anti-inflammatory, anticancer, and antidiabetic properties. The objective of this study was to evaluate the toxicological profile of a flavonoid-rich extract of S. flavescens (SFEA). We conducted acute and sub-chronic oral toxicity studies of SFEA in Kunming (KM) mice and Sprague-Dawley (SD) rats. Acute oral administration of 9.0 g/kg SFEA did not result in mortality, clinical signs of toxicity, or abnormal changes in the body weight or food consumption patterns. No significant changes in hematological, blood biochemical, or histopathological parameters were observed. A 13-week sub-chronic toxicity study was conducted in SD rats; the rats were orally administrated with various doses of SFEA (in mg/kg): 0 (control), 40, 80, 400, 800, and 1200. Mortality, clinical signs, or treatment-related changes in body weight, food consumption, hematological parameters, blood biochemical parameters, organ weights, or histopathological parameters were not observed. We found that SFEA is practically nontoxic to KM mice at a dose of 9.0 g/kg and that the no-observed-adverse-effect-level (NOAEL) of SFEA in SD rats is greater than 1200 mg/kg.

Chemistry, Bioactivity, and Prediction of the Quality Marker (Q-Marker) of Ferula Plants in China: A Review.

The genus of Ferula belongs to the family Apiaceae, and many Ferula plants are used as traditional Chinese medicines. Ferula plants were initially identified as early as the "Newly Revised Materia Medica" written in the Tang Dynasty (AD 659), and several of them are also recognized as the traditional medicines of the Uygur, Kazakh, and Mongolian. Ferula plants are distributed in China, Russia, India, Africa, Central Asia, and other places. Currently, the chemical components derived from Ferula plants are mainly coumarins, sesquiterpenes, and volatile oils. Ferula plants can exhibit diverse pharmacological activities such as anti-allergy, analgesia, relieving cough, anticoagulation, and anti-tumor. Therefore, this article summarized the domestic research conducted on the genus Ferula, appropriately combines the research status of the foreign genus Ferula, and describes the chemical composition, biological activity, toxicity issues, and Q-marker prediction. In addition, all the related studies about the genus Ferula are summarized by analyzing the various databases such as CNKI, Wanfang data, PubChem and SciFinder.

UPLC-MS Analysis, Quantification of Compounds, and Comparison of Bioactivity of Methanol Extract and Its Fractions from Qiai (Artemisia argyi Lévl. et Van.).

The Artemisia argyi Lévl. et Van. growing in the surrounding areas of Qichun County in China are called Qiai (QA). Qiai is a crop that can be used both as food and in traditional folk medicine. However, detailed qualitative and quantitative analyses of its compounds remain scarce. The process of identifying chemical structures in complex natural products can be streamlined by combining UPLC-Q-TOF/MS data with the UNIFI information management platform and its embedded Traditional Medicine Library. For the first time, 68 compounds in QA were reported by the method in this study. The method of simultaneous quantification of 14 active components in QA using UPLC-TQ-MS/MS was reported for the first time. Following a screening of the activity of QA 70% methanol total extract and its three fractions (petroleum ether, ethyl acetate, and water), it was discovered that the ethyl acetate fraction enriched with flavonoids such as eupatilin and jaceosidin had the strongest anti-inflammatory activity, while the water fraction enriched with chlorogenic acid derivatives such as 3,5-di-O-caffeoylquinic acid had the strongest antioxidant and antibacterial activity. The results provided the theoretical basis for the use of QA in the food and pharmaceutical industries.

Phlegmacaritones A and B, a Pair of Serratane-Related Triterpenoid Epimers with an Unprecedented Carbon Skeleton from Phlegmariurus carinatus.

A pair of novel serratane-related triterpenoid epimers, phlegmacaritones A (1) and B (2), possessing an unprecedented 15,30-lactone-14,15-seco skeleton, six new serratane-type triterpenoids, phlegmanols G-L (3-5 and 14-16), and 16 known compounds were isolated from the whole plant of Phlegmariurus carinatus. The structures of the new metabolites were established on the basis of comprehensive spectroscopic data analysis and electronic circular dichroism calculations. A possible biosynthetic pathway for phlegmacaritones A (1) and B (2) was proposed. All compounds were submitted to cytological profiling on a cell line derived from a patient with Parkinson's disease. Phlegmacaritone B (2) induced a distinct phenotypic profile with alterations in α-tubulin, mitochondria, and autophagosomal and early endosomal features.

Discovery of bicyclic polyprenylated acylphloroglucinols from Hypericum himalaicum with glucose transporter 4 translocation activity.

Hyperhimatins A-P (1-16), sixteen new bicyclic polyprenylated acylphloroglucinols (BPAPs), were isolated and identified from Hypericum himalaicum. The planner structures of hyperhimatins A-P were confirmed via extensive NMR and careful HRESIMS data analysis. The absolute configurations of the new compounds were mainly determined by electronic circular dichroism (ECD) calculation, NMR calculation, and the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. All compounds were assessed for the glucose transporter 4 (GLUT-4) translocation and expression enhancing effects in L6 myotubes. Compounds 1-16 could promote the GLUT-4 expression by the range of 1.95-6.04 folds, and accelerate the GLUT-4 fusion with the plasma membrane ranged from 53.56% to 76.97% at a consistence of 30 µg/mL, among compound 10 displayed the strongest GLUT-4 translocation effect.

Correction: Liu et al. Identification of C21 Steroidal Glycosides from Gymnema sylvestre (Retz.) and Evaluation of Their Glucose Uptake Activities. Molecules 2021, 26, 6549.

After careful examination, we found that the structures [...].

[A new xanthone from Hypericum lagarocladum].

Repeated silica gel column chromatography, reversed-phase C_(18) column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and semi-preparative medium pressure liquid chromatography were performed to separate and purify the chemical constituents of Hypericum lagarocladum. Spectroscopic methods such as mass spectrometry(MS) and nuclear magnetic resonance(NMR) combined with physicochemical properties were adopted in identifying the structure of the isolated compounds. Ten compounds were isolated from the ethyl acetate fraction of H. lagarocladum and identified as lagarxanthone A(1), 1,7-dihydroxyxanthone(2), 3,4,5-trihydroxyxanthone(3), 2,7-dihydroxy-1-methoxyxanthone(4), 1,3-dihydroxy-7-methoxyxanthone(5), 1,5-dihydroxy-8-methoxyxanthone(6), 3,4-dihydroxy-2-methoxyxanthone(7), 3,4-dihydroxy-5-methoxyxanthone(8), 2,3-dimethoxyxanthone(9), and 2,3,4-trimethoxyxanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from this plant for the first time. These ten compounds were tested for glucose uptake in L6 cells, and the results showed that all the compounds had no significant effect on glucose uptake.

Penpolonin A-E, cytotoxic α-pyrone derivatives from Penicillium polonicum.

Five new α-pyrone derivatives, named penpolonin A-E (1-5), together with two known compounds (6-7) were acquired from the endophytic fungus Penicillium polonicum isolated from the roots of Camptotheca acuminata Decne. Their structures were established by combination of NMR and HRESIMS data and the absolute configurations of 1-5 were determined by NMR calculations and comparison of experimental and calculated ECD data. Compounds 3 and 7 exhibited moderate cytotoxicity against Hep-2, TU212 human laryngeal cancer cells with IC50 values ranging from 31.6 to 45.1 µg/ml, compound 4 showed weak cytotoxicity against the Hep-2 and TU212 cell lines with IC50 values of 69.2 and 68.7 µg/ml.

New flavonoids from the roots of Sophora davidii (Franch.) Skeels and their glucose transporter 4 translocation activities.

Five new flavanones, davidones A-E (1-5), one new isoflavonoid, cyclolicoisoflavones A3 (8), together with seven known compounds were isolated from the petroleum ether and the ethyl acetate fractions of the roots of Sophora davidii (Franch.) Skeels. The structures of new compounds were established by 1D and 2D NMR and MS data. The absolute configuration of 1-5 was assigned by NMR calculations and comparing its experimental and calculated ECD spectra. Flavanones were the main active principles responsible for the glucose transporter 4 (GLUT-4) translocation activities of SD-PE and SD-EtOAc. Compounds 1-7 and acacetin (12) promoted GLUT-4 translocation by the range of 1.35-3.00 folds, respectively.

Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans.

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

Identification of C21 Steroidal Glycosides from Gymnema sylvestre (Retz.) and Evaluation of Their Glucose Uptake Activities.

Gymnema sylvestre (Retz.) Schult is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of G. sylvestre, a chemical investigation was thus performed. In this research, four new C21 steroidal glycosides sylvepregosides A-D (1-4) were isolated along with four known compounds, gymnepregoside H (5), deacetylkidjoladinin (6), gymnepregoside G (7) and gymnepregoside I (8), from the ethyl acetate fraction of G. sylvestre. The structures of the new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. Compounds 1-6 promoted glucose uptake by the range of 1.10- to 2.37-fold, respectively. Compound 1 showed the most potent glucose uptake, with 1.37-fold enhancement. Further study showed that compounds 1 and 5 could promote GLUT-4 fusion with the plasma membrane in L6 cells. The result attained in this study indicated that the separation and characterization of these compounds play an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.

Chemical Constituents from Roots of Sophora davidii (Franch.) Skeels and Their Glucose Transporter 4 Translocation Activities.

Sophora davidii (Franch.) Skeels is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of S. davidii, a chemical investigation was thus performed. In this research, two new stilbene oligomers, Davidiol E-F (1-2), one new 4-aryl-substituted isoflavan Davidinin A (3), and one new 2-arylbenzofuran dimer, Shandougenine C (4), as well as six known compounds (5-10) were obtained from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. The structures of new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. The absolute configuration of 1-3 was assigned by comparing its experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-10 promoted glucose transporter 4 (GLUT-4) translocations by the range of 1.28-2.60 folds, respectively. Compound 9 showed the most potent glucose transporter 4 translocations with 1.60 fold enhancement. The result attained in this study indicated that the separation and characterization of these compounds plays an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.

Davidones F and G, Two Novel Flavonoids from Sophora davidii (Franch.) Skeels.

An unprecedented novel flavanone davidone F (1) with a seven-membered ring side chain, and a novel flavanonol davidone G (2), along with 11 known flavonoids, were isolated from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. Their planar structures were established by UV, IR, HRESIMS, 1D and 2D NMR data. The relative configurations of 1 and 2 were determined by calculation of NMR chemical shift values, the absolute configuration of 1 and 2 were assigned by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Moreover, compounds 1-13 were screened for the translocation activity of glucose transporter 4 (GLUT-4), and the fluorescence intensity was increased to the range of 1.56 and 2.79 folds. Compounds 1 and 2 showed moderate GLUT-4 translocation activity with 1.64 and 1.79 folds enhancement, respectively, at a concentration of 20 µg/mL.

Davidone C Induces the Death of Hepatocellular Carcinoma Cells by Promoting Apoptosis and Autophagy.

Davidone C is a newly discovered flavonoid compound purified from the ethyl acetate-soluble fraction of Sophora davidii (Franch.) Skeels. This study explored the anti-tumor activity of davidone C on hepatocellular carcinoma HepG2 and Bel-7402 cells and its mechanism through MTT method, morphological observation, flow cytometry and Western blotting. The results showed that davidone C significantly inhibited the proliferation of HepG2 and Bel-7402 cells in a time- and dose-dependent manner. The morphological changes of apoptotic cells can be observed under an inverted microscope, such as cell floating, chromosome condensation, apoptotic bodies, and other phenomena. The expressions of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, davidone C administration can down-regulate the expression of Grp78, and simultaneously up-regulate the expression of caspase-7 and caspase-12, indicating that the apoptotic mechanism might be related to the ERS pathway. In addition, davidone C can down-regulate the expression of p62, and simultaneously up-regulate the expression of LC3-I and LC3-II with a quantitative dependence, suggesting that the mechanism of apoptosis may be related to the autophagy signal pathway. All these results showed davidone C has potential effects on hepatocellular carcinoma.

[Polycyclic polyprenylated acylphloroglucinols from Hypericum species and their biological activities].

Hypericum species are distributed widely in China, especially in the southwest. This genus is rich in species types in China, including 55 species and 8 subspecies. The main chemical constituents of Hypericum species are flavonoids, xanthones and polycyclic polyprenylated acylphloroglucinols(PPAPs). PPAPs are characterized by polycyclic and branched-chain substitutions in their structures, which make their structure types diverse. Moreover, they have been found to have antitumor, antiviral, antibacterial, anti-inflammatory and other biological activities. This research classified and summarized 344 polycyclic polyprenylated acylphloroglucinols from Hypericum plants in order to provide a scientific basis for further development and utilization of PPAPs from the genus.

A biflavonoid-rich extract from Selaginella moellendorffii Hieron. induces apoptosis via STAT3 and Akt/NF-κB signalling pathways in laryngeal carcinoma.

Selaginella moellendorffii Hieron. (SM), a perennial evergreen plant, has been used in the treatment of acute infectious hepatitis, thoracic and hypochondriac lumbar contusions, systemic oedema and thrombocytopaenia. However, the role of a biflavonoid-rich extract from SM (SM-BFRE) in anti-larynx cancer has rarely been reported. In this study, the in vitro and in vivo anti-laryngeal cancer activity and potential mechanisms of SM-BFRE were investigated. An off-line semipreparative liquid chromatography-nuclear magnetic resonance protocol was carried out to determine six biflavonoids from SM-BFRE. In vitro, MTT assay revealed that SM-BFRE inhibited the proliferation of laryngeal carcinoma cells. A wound healing assay indicated that SM-BFRE suppressed the migration of laryngeal cancer cells. Hoechst 33 258 and Annexin V-FITC/PI double staining assays were performed and verified that SM-BFRE induced apoptosis in laryngeal carcinoma cells. The Hep-2 bearing nude mouse model confirmed that SM-BFRE also exhibited anticancer effect in vivo. In addition, Western blot analysis demonstrated that SM-BFRE exerted its anti-laryngeal cancer effect by activating the mitochondrial apoptotic pathway and inhibiting STAT3 and Akt/NF-κB signalling pathways. All results suggested that SM-BFRE could be considered as a potential chemotherapeutic drug for laryngeal cancer.

Dehydrocostus lactone inhibits cell proliferation and induces apoptosis by PI3K/Akt/Bad and ERS signalling pathway in human laryngeal carcinoma.

The anti-cancer effect of dehydrocostus lactone (DHL) derived from Saussurea costus (Falc.) Lipech against laryngeal carcinoma was assessed. The cytotoxic activity of DHL against laryngeal carcinoma is still obscure. Therefore, our study investigated the role of DHL in the growth inhibition of laryngeal carcinoma in vitro and in vivo, and the molecular mechanism of DHL-induced apoptosis in cancer cells of the larynx. The results showed that DHL inhibits the viability, migration and proliferation of Hep-2 and TU212 cells with little toxic effects on human normal larynx epithelial HBE cell line. Flow cytometry analysis (FAC) analysis and staining assay (Hoechst 33258) indicated that DHL stimulated Hep-2 and TU212 cell apoptosis in a dose-dependent manner. Mechanistically, DHL is capable of inhibiting Hep-2 and TU212 cell viability via promoting p53 and P21 function, meanwhile DHL dose-dependently induces Hep-2 and TU212 cells apoptosis via activating mitochondrial apoptosis by inhibiting PI3K/Akt/Bad pathway and stimulating endoplasmic reticulum stress-mediated apoptosis pathway. In vivo, DHL inhibited the growth of the Hep-2 nude mouse xenograft model and observed no significant signs of toxicity in the organs of nude mice. In vivo experiments further confirmed the anti-cancer effect of DHL on laryngeal carcinoma cells in vitro, and DHL-treated nude mice can reduce the volume of tumours. Together, our study indicated that DHL has the potential to inhibit human laryngeal carcinoma via activating mitochondrial apoptosis pathway by inhibiting PI3K/Akt/Bad signalling pathway and stimulating endoplasmic reticulum stress-mediated apoptosis pathway, providing a strategy for the treatment of human laryngeal carcinoma.