Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis. Using a molecular networking approach, five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of Anacyclus pyrethrum (A. pyrethrum). Their structures were elucidated by comprehensive spectroscopic data analysis, including LR-HSQMBC and ¹H-¹⁵N HMBC, quantum ¹³C NMR DP4+ and ECD calculations, and single-crystal X-ray diffraction analysis. Anacyphrethines A (1) and B (2) are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.1^1,23.0^4,28.0^5,17.0^9,16.0^11,15.0^21,27] nonacosane motif. Their biosynthetic pathways are proposed involving key aldol, hydroamination, and Schiff base reactions. All isolates showed potent analgesic effects in vivo. Even at a lower dose of 0.2 mg/kg, (±)-1 and (+)-1 still exhibited more potent analgesic activities than morphine. Interestingly, the racemic mixture (±)-1 showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg; while, (±)-1 showed significant analgesic activities comparable to (+)-1 at lower doses of 0.2 and 0.04 mg/kg. (+)-1 had stronger analgesic effect than (-)-1 at five tested does. Further tests on 44 analgesic-related targets demonstrated that (+)-1 showed significant inhibitory effects against many ion channels such as TRPM8, Kv1.2, Kv1.3, and Ca_v2.1 with IC₅₀ values of 1.10 ± 0.26, 4.20 ± 0.07, 2.20 ± 0.24, and 10.40 ± 0.69 μmol/L, respectively, while (-)-1 primarily inhibited TRPC6, Kv1.2, and Kv1.3 ion channels with IC₅₀ values of 0.81 ± 0.05, 0.91 ± 0.04, and 1.50 ± 0.13 μmol/L, respectively, without affecting the opioid receptors, suggesting their non-opioid analgesic potentials. The molecular dockings provided structural guidance to develop potent non-opioid analgesics.

Objective To stuy the clinical value of combined DWI and PWI in diagnosis of cerebral infarction (CI) at different stages.Methods One hundred and sixty-eight elderly CI patients were divided into hyperacute phase group (n =32),acute phase group (n =64),subacute phase group (n=45) and chronic phase group (n=27).Their DWI and PWI parameters and abnormal brain regions were compared.Results The ADC on DWI for injured lateral brain tissue was significantly lower than that on DWI for unjured lateral brain tissue in hyperacute phase group and acute phase group (0.39±0.08 vs 0.83±0.03;0.32±0.07 vs 0.91±0.05,P＜0.01).However,the ADC on DWI for the injured lateral brain tissue was significantly higher than that on DWI for the uninjured lateral brain tissue in subacute phase group and chronic phase group (1.54±0.34 vs 0.85±0.07,2.01±1.29 vs 0.90±0.05,P＜0.01).The PWI showed that the CBV was smaller and the CBF was slower while the MTT and TTP were longer in CI patients at different stages.DWI＜PWI,DWI＞PWI,and DWI=PWI in abnormal signal region were more frequently detected in hyperacute phase,acute phase subacute phase and chronic phase respectively.Conclusion PWI can show ischemic penumbra while DWI can highlight infarct foci in CI patients.Combined PWI and DWI can display the CBF in CI patients at different stages,and can thus provide reference for the clinical treatment of CI.

The present study examined the protective effect of the ethanol extract of Sarcopyramis nepalensis (EESN) on agents-induced hepatotoxicity in mice and the possible mechanism. Acute liver injury was induced by administration of either CCl(4) or D-GalN. The animals were divided into 5 groups in terms of different treatment: normal group, CCl(4) or D-GalN group, silymarin or bifendate group, low dose EESN group (10 mg/kg) and high dose EESN group (30 mg/kg). Liver function was evaluated by detecting the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The oxidize stress markers were measured, including malondialdehyde (MDA), glutathione peroxidase (GSH) and superoxide dismutase (SOD). Liver tissues were histopathologically examined by hematoxylin-eosin (H&E) staining. The acute toxicity study revealed that there was no toxicity of EESN at the dose of 5 g/kg in mice. The levels of ALT and AST in serum, and the MDA level in live tissues were significantly increased and the activities of SOD and GSH substantially decreased in mice after CCl(4) or D-GalN treatment. These biochemical and oxidize stress markers were profoundly improved after treatment with EESN at different doses, which was similar to the results of silymarin or bifendate treatment. The histophathological examination revealed the significant improvement in the pathological changes of the liver in EESN-treated mice as compared to those in CCl(4) or D-GalN group. It was concluded that EESN possesses potential antioxidant and hepatoprotective properties and has therapeutic potential for liver diseases.
Animals ; Ethanol ; chemistry ; Female ; Liver ; drug effects ; Male ; Mice ; Plant Extracts ; chemistry ; pharmacology

The present study examined the protective effect of the ethanol extract of Sarcopyramis nepalensis (EESN) on agents-induced hepatotoxicity in mice and the possible mechanism. Acute liver injury was induced by administration of either CCl(4) or D-GalN. The animals were divided into 5 groups in terms of different treatment: normal group, CCl(4) or D-GalN group, silymarin or bifendate group, low dose EESN group (10 mg/kg) and high dose EESN group (30 mg/kg). Liver function was evaluated by detecting the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The oxidize stress markers were measured, including malondialdehyde (MDA), glutathione peroxidase (GSH) and superoxide dismutase (SOD). Liver tissues were histopathologically examined by hematoxylin-eosin (H&E) staining. The acute toxicity study revealed that there was no toxicity of EESN at the dose of 5 g/kg in mice. The levels of ALT and AST in serum, and the MDA level in live tissues were significantly increased and the activities of SOD and GSH substantially decreased in mice after CCl(4) or D-GalN treatment. These biochemical and oxidize stress markers were profoundly improved after treatment with EESN at different doses, which was similar to the results of silymarin or bifendate treatment. The histophathological examination revealed the significant improvement in the pathological changes of the liver in EESN-treated mice as compared to those in CCl(4) or D-GalN group. It was concluded that EESN possesses potential antioxidant and hepatoprotective properties and has therapeutic potential for liver diseases.

The aim of the study is to investigate chemical constituents of the leaves of Pieris japonica. The isolation and purification of the constituents were performed by various chromatography and spectral analysis. Three new phenolic glucosides, erythro-syringoylglycerol 4-O-β-D-glucoside (1),1-(2-β-D-glucopyranoxyl-4-methoxyl-6-hydroxyphenyl)-3-hydroxyl-1-propanone (3),erythro-1-(4-hydroxyl-3-methoxyphenyl)-2-[4-(3-β-D-glucopyranoxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol (4), along with five known phenolic glucosides, syringoylglycerol 8-O-β-D-glucoside (2), magnolenin C (5), syringaresinol mono-β-D-glucoside (6), 3-(4-hydroxyl-3-methyphenyl)-1-propanol-1-O-β-D-glucoside (7) and 3,5-dimethoxyl-4-hydroxybenzyl alcohol 4-O-β-D-glucoside (8) were isolated and identified from the plant leaves. Compounds 1 and 2 inhibited significantly (P<0.01) the proliferation of murine T and B cells at concentration of 1×10-6 mol·L-1, in vitro.