Identification and evaluation of agents isolated from traditionally used herbs against Ophiophagus hannah venom

The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydroandrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.

Editorial

Full text: Welcome to issue 1 of 2012 and a belated Happy New Year to all CLAE readers and BCLA members. The hardest job I had for this issue was to decide which papers to include and which papers to hang on to and save for issue 2 of 2012. At the end of December when I was choosing the content for this issue there were additional 5 papers that could have been included. The final choice came down to various factors; such as first come first served – i.e. which papers had been ready and waiting the longest; secondly which papers had been submitted the earliest; are there similar papers so that it may be beneficial to publish them alongside this paper; and also was the content something which needed to be out there quicker than other papers as it was a current hot topic? But it should be noted that once papers are proofed and deemed ready by authors they are published in the epub version and put online for others to see in their final version. An epub version is given a DOI number (digital object identifier) so that it can be cited by other authors. Apart from being on line the only other difference is that an epub version is essentially waiting to be assigned to a particular issue. So those papers that are being held off for issue 2 of this year are actually already available for you to read (and cite) on line. In this issue there is a paper related to the cost of different contact lens replacement schedules – this may be a topic that is debated more in the future since as a society we are thinking more ‘green’ and all trying to help by reducing our carbon footprint, whether that be by recycling or using less in the first place. A timely review paper on the management of allergic eye disease may help us to better manage those patients we see in the spring with pollen allergies. We have two papers looking at different aspects in keratoconus patients, another looking at a modified fluoret strip and its application in measuring tear break up time and a review paper on corneal erosions. Another interesting paper comes from Professor Harminder Dua and his team. Professor Dua is the UK Royal College of Ophthalmologists’ president and has been interested in corneal anatomy and physiology for much of his research career. Finally, an unusual case of an ocular injury related to a snake bite. Overall I would say there is enough to sink your ‘fangs’ into! Finally, it gives me great pleasure in announcing the newest person to join our Editorial Board, Dr Florence Malet. Dr Malet is an Ophthalmologist and since September 2000 she has been at the Bordeaux Hospital in France developing the Contact Lens Unit of in the Ophthalmology University Department. She is ex-president of the French Contact Lens Society and president of the European Contact Lens Society of Ophthalmologists.

In-vitro and in-vivo antivenin activity of 2-[2-(5,5,8a-trimethyl-2- methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde against Ophiophagus hannah venom

Objectives Curcuma zedoaroides A. Chaveerach & T. Tanee, locally known as Wan-Paya-Ngoo-Tua-Mia, is commonly used in the North-Eastern part of Thailand as a 'snakebite antidote'. The aim of this study was to isolate the active compound from the rhizome of C. zedoaroides, to determine its structure and to assess its antagonistic activity in vitro and in vivo against King cobra venom. Methods The active compound was obtained from C. zedoaroides by extraction with acetone followed by purification using column chromatography; its X-ray structure was determined. Its inhibition of venom lethality was studied in vitro in rat phrenic nerve-hemidiaphragms and in vivo in mice. Key findings The acetone extract of the Curcuma rhizomes contained a C20 dialdehyde, [2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene] -succinaldehyde, as the major component. The isolated curcuma dialdehyde was found active in vitro and in vivo for antivenin activity against the King cobra venom. Using isolated rat phrenic nerve-hemidiaphragm preparations, a significant antagonistic effect on the inhibition of neuromuscular transmission was observed in vitro. Inhibition on muscle contraction, produced by the 4 μg/ml venom, was reversed by 2-16 μg/ml of Curcuma dialdehyde in organ bath preparations over a period of 2 h. Mice intraperitoneally injected with 0.75 mg/kg venom and dialdehyde at 100 mg/kg had a significantly increased survival time. Injection of Curcuma dialdehyde (100 mg/kg) 30 min before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group. Conclusions The in vitro and in vivo evaluation confirmed the medicinal use of traditional snake plants against snakebites. The bioactivity is linked to an isolated molecule and not a result of synergistic effects of a mixture. The active compound was isolated and the structure fully elucidated, including its stereochemistry. This dialdehyde is a versatile chemical building block and can be easily obtained from this plant source. © 2010 Royal Pharmaceutical Society of Great Britain.