Preclinical evidence of adenosine for early intervention in Bungarus multicinctus envenomation.

Abstract

INTRODUCTION: Snakebites, one of the world's deadliest neglected tropical diseases, predominantly affect impoverished rural communities in tropical and subtropical regions. The clinical management of snakebite envenomation currently relies heavily on antivenom serum, which is often inaccessible and expensive in these areas. Thus, effective and cost-efficient therapies for treating snakebite envenomation are urgently needed. Pimpinella diversifolia DC, a herb widely distributed across Asia, has long been used in traditional medicine for the treatment of snake venom poisoning. OBJECTIVES: To investigate the efficacy of P. diversifolia in counteracting venom-induced lethality caused by various neurotoxic venoms in mouse models and in vitro experiments. METHODS: The protective effects of P. diversifolia against various neurotoxic venoms were evaluated in C57BL/6 mice by intraperitoneal administration of the aqueous extract immediately after injection of snake venom. The primary components of P. diversifolia were identified using liquid chromatography-mass spectrometry, and the compounds were subsequently assessed for their ability to protect against neurotoxicity. Additionally, the neurotoxic effects of Bungarus multicinctus venom and efficacy of the drug against venom-induced neurotoxicity were examined in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. RESULTS: P. diversifolia partially prevented lethality in some of the mice injected with various snake venoms. Adenosine, one of the most abundant compounds in the extract, significantly prevented lethality in mice caused by B. multicinctus venom, with 100% survival observed within 48 h. Adenosine markedly attenuated the neurotoxic effects of B. multicinctus venom in BC and PND preparations, and prevented the inhibition of muscular contractions induced by exogenous acetylcholine and carbamylcholine. CONCLUSION: Adenosine may have a protective role against B. multicinctus venom-induced neurotoxicity in preclinical models, warranting further investigation into its mechanisms and clinical applicability.