GABA_A Receptor Modulators from the Chinese Herbal Drug Junci Medulla – The Pith of Juncus effusus

Abstract

The gamma-amino butyric acid (GABA) type A (GABA_A) receptor represents a crucial target for clinical agents in the treatment of anxiety and insomnia. Using the two-microelectrode voltage clamp technique on recombinant α ₁ β ₂ γ _2S GABA_A receptors, effusol (1) and dehydroeffusol (2) were isolated in a bioactivity-guided approach from the pith of Juncus effusus L. Both compounds concentration-dependently enhanced GABA induced chloride currents (I_GABA) by a maximum 188 ± 20 (1) and 239 ± 18 % (2), independent of the benzodiazepine (BZ) binding site. This activity on the GABA_A receptor may explain the traditional use of J. effusus as a sedative and anxiolytic agent in Chinese medicine.

Juncus effusus L. (Juncaceae) - GABA(A) receptor - voltage clamp - positive allosteric modulation - dehydroeffusol - effusol

References

• 1 Somers J M, Goldner E M, Waraich P, Hsu L. Prevalence and incidence studies of anxiety disorders: a systematic review of the literature.  Can J Psychiatry. 2006;  51 100-113
• 2 Roth T. Sleep and society.  Sleep Med. 2009;  10 S1-S2
• 3 Stevens J C, Pollack M H. Benzodiazepines in clinical practice: consideration of their long-term use and alternative agents.  J Clin Psychiatry. 2005;  66 21-27
• 4 Lader M, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care.  CNS Drugs. 2009;  23 19-34
• 5 Sullivan S S. Insomnia pharmacology.  Med Clin North Am. 2010;  94 563-580
• 6 Roy-Byrne P P, Bystritsky A, Russo J, Craske M G, Sherbourne C D, Stein M B. Use of herbal medicine in primary care patients with mood and anxiety disorders.  Psychosomatics. 2005;  46 117-122
• 7 Kinrys G, Coleman E, Rothstein E. Natural remedies for anxiety disorders: potential use and clinical applications.  Depress Anxiety. 2009;  26 259-265
• 8 Salter S, Brownie S. Treating primary insomnia – the efficacy of valerian and hops.  Aust Fam Physician. 2010;  39 433-437
• 9 Bensky D, Clavey S, Stoeger E. Chinese herbal medicine: Materia Medica. 3rd edition. Seattle: Eastland Press; 2006: 1311
• 10 Della Greca M, Fiorentino A, Monaco P, Previtera L. Cycloartane triterpenes from Juncus effusus.  Phytochemistry. 1994;  35 1017-1022
• 11 Kovacs A, Vasas A, Hohmann J. Natural phenanthrenes and their biological activity.  Phytochemistry. 2008;  69 1084-1110
• 12 Liao Y J, Zhai H F, Zhang B, Duan T X, Huang J M. Anxiolytic and sedative effects of dehydroeffusol from Juncus effusus in mice.  Planta Med. 2011;  77 416-420
• 13 Olsen R W, Sieghart W. GABA(A) receptors: subtypes provide diversity of function and pharmacology.  Neuropharmacology. 2009;  56 141-148
• 14 Johnston G A, Hanrahan J R, Chebib M, Duke R K, Mewett K N. Modulation of ionotropic GABA receptors by natural products of plant origin.  Adv Pharmacol. 2006;  54 285-316
• 15 Bhattacharyya J. Structure of effusol: A new phenolic constituent from Juncus effusus.  Experientia. 1980;  36 27-28
• 16 Shima K, Toyota M, Asakawa Y. Phenanthrene derivatives from the medullae of Juncus effusus.  Phytochemistry. 1991;  30 3149-3151
• 17 Khom S, Baburin I, Timin E N, Hohaus A, Sieghart W, Hering S. Pharmacological properties of GABA(A) receptors containing gamma1 subunits.  Mol Pharmacol. 2006;  69 640-649
• 18 Baburin I, Beyl S, Hering S. Automated fast perfusion of Xenopus oocytes for drug screening.  Pflugers Arch. 2006;  453 117-123