This study employed the α-glucosidase inhibitory activity model as an anti-diabetic assay and implemented a bioactivity-guided isolation strategy to identify novel natural compounds with potential therapeutic properties. Hypericum sampsoniiwas investigated, leading to the isolation of two highly modified seco-polycyclic polyprenylated acylphloroglucinols (PPAPs) (1 and 2), eight phenolic derivatives (3-10), and four terpene derivatives (11-14). The structures of compounds 1 and 2, featuring an unprecedented octahydro-2H-chromen-2-one ring system, were fully characterized using extensive spectroscopic data and quantum chemistry calculations. Six compounds (1, 5-7, 9, and 14) exhibited potential inhibitory effects against α-glucosidase, with IC₅₀ values ranging from 0.050 ± 0.0016 to 366.70 ± 11.08 μg·mL^-1. Notably, compound 5 (0.050 ± 0.0016 μg·mL^-1) was identified as the most potential α-glucosidase inhibitor, with an inhibitory effect about 6900 times stronger than the positive control, acarbose (IC₅₀ = 346.63 ± 15.65 μg·mL^-1). A docking study was conducted to predict molecular interactions between two compounds (1 and 5) and α-glucosidase, and the hypothetical biosynthetic pathways of the two unprecedented seco-PPAPs were proposed.
Molecular Structure ; Hypericum/chemistry* ; alpha-Glucosidases ; Magnetic Resonance Spectroscopy ; Glycoside Hydrolase Inhibitors/pharmacology*

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.
Phloroglucinol ; Hypericum/chemistry* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Drugs, Chinese Herbal/chemistry*

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.
Hypericum/chemistry* ; Xanthones ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy ; Glucose

Hyperforin is a representative polycyclic polyprenylated acylphloroglucinols (PPAPs) that exerts a variety of pharmacological activities. The complete biosynthesis pathway of hyperforin has not been elucidated due to its complex structure and unclear genetic background of its source plants. This mini-review focuses on the bioactivity and biosynthesis of hyperforin. These analyses can provide useful insights into the biosynthesis investigations of hyperforin and other PPAPs with complex structures.
Phloroglucinol/chemistry* ; Terpenes/chemistry* ; Hypericum/chemistry* ; Molecular Structure

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 μmol·L^-1.
Animals ; Anti-Inflammatory Agents/pharmacology* ; Hypericum/chemistry* ; Molecular Structure ; PC12 Cells ; Phloroglucinol/pharmacology* ; Rats

The stems and branches of Hypericum petiolulatum were extracted by alcohol and liquid-liquid extraction. Seven furofuran lignans were isolated from the ethyl acetate fraction of ethanol extract of H. petiolulatum by using silica gelchromatography, Sephadex LH-20 chromatography, medium-pressure liquid chromatography and preparative HPLC. Their structures were identified by the spectroscopic methods as pinoresinol (1), medioresinol (2), 8-acetoxypinoresinol (3), epipinoresinol (4), (+)-syringaresinol (5), (+)-1-hydroxysyringaresinol (6) and erythro-buddlenolE (7). All the isolates were firstly found in H. petiolulatum. In the bioassay, compound 7 showed remarkable antioxidative activity inhibiting Fe(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rate 38% at a concentration of 1 x 10(-6) mol · L(-1) (positive control Vit E with the inhibitory rate of 35% at the same concentration).
Animals ; Antioxidants ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Hypericum ; chemistry ; Lipid Peroxidation ; drug effects ; Microsomes, Liver ; drug effects ; metabolism ; Molecular Structure ; Oxidative Stress ; drug effects ; Plant Stems ; chemistry ; Rats

Animals ; Antioxidants ; metabolism ; Fatigue ; blood ; Female ; Hypericum ; chemistry ; Male ; Mice ; Mice, Inbred ICR ; Physical Conditioning, Animal ; Plant Extracts ; pharmacology

Hypericin is one of the most important phenanthoperylene quinones extracted mainly from plants of the genus Hypericum belonging to the sections Euhypericum and Campylosporus of Keller's classification. Widespread attention to the antiviral and anti-tumor properties of hypericin has spurred investigations of the chemical synthesis and biosynthesis of this unique compound. However, the synthetic strategies are challenging for organic and biological chemists. In this review, specific significant advances in total synthesis, semi-synthesis, and biosynthesis in the past decades are summarized.
Antineoplastic Agents, Phytogenic ; Antiviral Agents ; Humans ; Hypericum ; chemistry ; metabolism ; Perylene ; analogs & derivatives ; chemical synthesis ; metabolism ; Plant Extracts ; biosynthesis ; chemical synthesis

OBJECTIVETo explore the synergistic antidepressant effect of quercetin and hyperforin (HF, extracted from Hypericum perforatum).

METHODSMale ICR mice were divided into nine groups:blank control, positive control (Paroxetine, 10 mg/kg), quercetin groups (A: 5 mg/kg, B: 10 mg/kg, C: 20 mg/kg), Hypericum perforatum extract (HF 10 mg/kg),combination groups (A: quercetin 2.5 mg/kg + HF 5 mg/kg,B:quercetin 5 mg/kg + HF 5 mg/kg,C: quercetin 10 mg/kg + HF 5 mg/kg). All drugs were administered intragastrically. Reserpine reversal tests were used to compare the reversal effects of drugs on body temperature decline, eyelid ptosis and akinesia. Tail suspension test was used to compare immobility time in each group.

RESULTSCombination group B showed no significant difference (P>0.05) compared with combination group C in reserpine reversal tests and tail suspension test. However, its body temperature reversal effect was significantly higher (P<0.01) than that of quercetin group B, and its effect in shortening immobility time was stronger than that of HF 10 mg/kg group (P<0.05) and quercetin group B (P<0.01).

CONCLUSIONThe combination of quercetin and Hypericum perforatum extract in certain ratio has significant synergistic antidepressant effect in ICR mice.

Animals ; Antidepressive Agents ; pharmacology ; Depression ; drug therapy ; Disease Models, Animal ; Hypericum ; chemistry ; Male ; Mice ; Mice, Inbred ICR ; Plant Extracts ; pharmacology ; Quercetin ; pharmacology

OBJECTIVETo study zedoary turmeric oil (ZTO) and the pharmacokinetics of its homemade compound antiviral preparation in New Zealand rabbits.

METHODRP-HPLC was used to determinate the content of germacrone in rabbit plasma after oral administration.

RESULTAfter oral administration of ZTO and its homemade compound antiviral preparation, the plasma concentration-time curve of germacrone is in conformity to two-compartment open model. The pharmacokinetic parameters of ZTO: t1/2alpha, t1/2beta, Vd, CL, AUC and Ka were (1.52 +/- 0.59), (1.97 +/- 0.27) h, (47.59 +/- 2.29) L x kg(-1), (176.77 +/- 7.65) L x h(-1) x kg(-1), (5.70 +/- 0.70) mg x h x L(-1) and (0.97 +/- 0.11) h(-1), respectively, while those of compound preparation were (0.41 +/- 0.03), (1.47 +/- 0.35) h, (75.21 +/- 5.21) L x kg(-1), (287.79 +/- 6.39) L x h(-1) x kg(-1), (3.91 +/- 0.53) mg x h x L(-1) and (5.14 +/- 1.26) h(-1), respectively. There was no significant difference between the above two groups of pharmacokinetic parameters, expect that Ka of compound preparation was significantly higher than that of ZTO (P < 0.05).

CONCLUSIONHypericum perforatum in compound preparation doesn't impact the distribution and elimination of active ingredients of ZTO in New Zealand rabbits, but it improves the absorption speed, and shortens the time of drug absorption, which contributes to rapid efficacy of ZTO in rabbits.

Animals ; Antiviral Agents ; pharmacokinetics ; Curcuma ; chemistry ; Drug Compounding ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Hypericum ; chemistry ; Male ; Plant Oils ; pharmacokinetics ; Rabbits ; Sesquiterpenes, Germacrane ; pharmacokinetics