Ethnopharmacological relevance: Aqarqarha (Anacyclus pyrethrum) DC root has long been used as a traditional an-tiepileptic remedy in Unani system of medicine over centuries. Aim of the Study: To rationalize the ethnom...Ethnopharmacological relevance: Aqarqarha (Anacyclus pyrethrum) DC root has long been used as a traditional an-tiepileptic remedy in Unani system of medicine over centuries. Aim of the Study: To rationalize the ethnomedical claim and screen for anxiolytic and neurotoxicity profile of ethanolic extract of Aqarqarha (Anacyclus pyrethrum) root (APE). Materials and Methods: The anticonvulsant and anxiolytic potential of APE (100-800 mg/kg) was evaluated against Pentylenetetrazole (PTZ), Bicuculline (BCL), Increasing current electroshock (ICES) and Elevated plus maze(EPM) models. Rotarod test was employed as neurotoxicity model including an additional higher dose (1600 mg/kg). Results: The APE showed significant anticonvulsant activity (p i.p.) in a dose-dependent manner but against BCL (30 mg/kg, i.p.) at the dose 800 mg/kg only (p 0.05). The extract also showed anxiolytic behaviour in EPM (p Conclusions: The results suggested significant anticonvulsant activity of APE against PTZ and BCL but failure against ICES. Moreover, APE also exhibited anxiolytic potential without any evidence of neurotoxicity at the effective dose level. We concluded that anticonvulsant effect of APE is probably mediated by enhancing GABAergic neurotransmission.展开更多
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 enantiome...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[16.8.2.11,23.04,28.05,17.09,16.011,15.021,27]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 Cav2.1 with IC50 values of 1.10±0.26,4.20±0.07,2.20±0.24,and 10.40±0.69μmol/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±0.13μmol/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.展开更多
文摘Ethnopharmacological relevance: Aqarqarha (Anacyclus pyrethrum) DC root has long been used as a traditional an-tiepileptic remedy in Unani system of medicine over centuries. Aim of the Study: To rationalize the ethnomedical claim and screen for anxiolytic and neurotoxicity profile of ethanolic extract of Aqarqarha (Anacyclus pyrethrum) root (APE). Materials and Methods: The anticonvulsant and anxiolytic potential of APE (100-800 mg/kg) was evaluated against Pentylenetetrazole (PTZ), Bicuculline (BCL), Increasing current electroshock (ICES) and Elevated plus maze(EPM) models. Rotarod test was employed as neurotoxicity model including an additional higher dose (1600 mg/kg). Results: The APE showed significant anticonvulsant activity (p i.p.) in a dose-dependent manner but against BCL (30 mg/kg, i.p.) at the dose 800 mg/kg only (p 0.05). The extract also showed anxiolytic behaviour in EPM (p Conclusions: The results suggested significant anticonvulsant activity of APE against PTZ and BCL but failure against ICES. Moreover, APE also exhibited anxiolytic potential without any evidence of neurotoxicity at the effective dose level. We concluded that anticonvulsant effect of APE is probably mediated by enhancing GABAergic neurotransmission.
基金supported by the National Key R&D Program of China(2020YFE0205600)the Biological Resources Program,Chinese Academy of Sciences(KFJ-BRP-007-011,China)+2 种基金National Natural Science Foundation of China(22477034 and 22277034)Interdisciplinary Research Program of HUST(2023JCYJ037,China)International Cooperation Project of Hubei provincial key R&D plan(2023EHA040,China).
文摘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[16.8.2.11,23.04,28.05,17.09,16.011,15.021,27]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 Cav2.1 with IC50 values of 1.10±0.26,4.20±0.07,2.20±0.24,and 10.40±0.69μmol/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±0.13μmol/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.
