Zunjar Vishwanath, Dash Ranjeet Prasad, Jivrajani Mehul, Trivedi Bhavna, Nivsarkar Manish
Department of Chemistry, Faculty of Science, Maharaja Sayajirao University of Baroda, Vadodara, Gujarat 390002, India.
Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad, Gujarat 380054, India.
J Ethnopharmacol. 2016 Apr 2;181:20-5. doi: 10.1016/j.jep.2016.01.035. Epub 2016 Jan 23.
The decoction of Carica papaya Linn. leaves is used in folklore medicine in certain parts of Malaysia and Indonesia for the treatment of different types of thrombocytopenia associated with diseases and drugs. There are several scientific studies carried out on humans and animal models to confirm the efficacy of decoction of papaya leave for the treatment of disease induced and drug induced thrombocytopenia, however very little is known about the bio-active compounds responsible for the observed activity. The aim of present study was to identify the active phytochemical component of Carica papaya Linn. leaves decoction responsible for anti-thrombocytopenic activity in busulfan-induced thrombocytopenic rats.
Antithrombocytopenic activity was assessed on busulfan induced thrombocytopenic Wistar rats. The antithrombocytopenic activity of different bio-guided fractions was evaluated by monitoring blood platelet count. Bioactive compound carpaine was isolated and purified by chromatographic methods and confirmed by spectroscopic methods (LC-MS and 1D/2D-1H/13C NMR) and the structure was confirmed by single crystal X-ray diffraction. Quantification of carpaine was carried out by LC-MS/MS equipped with XTerra(®) MS C18 column and ESI-MS detector using 90:10 CH3CN:CH3COONH4 (6mM) under isocratic conditions and detected with multiple reaction monitoring (MRM) in positive ion mode.
Two different phytochemical groups were isolated from decoction of Carica papaya leaves: phenolics, and alkaloids. Out of these, only alkaloid fraction showed good biological activity. Carpaine was isolated from the alkaloid fraction and exhibited potent activity in sustaining platelet counts upto 555.50±85.17×10(9)/L with no acute toxicity.
This study scientifically validates the popular usage of decoction of Carica papaya leaves and it also proves that alkaloids particularly carpaine present in the leaves to be responsible for the antithrombocytopenic activity.
番木瓜叶煎剂在马来西亚和印度尼西亚的某些地区被用于民间医学,以治疗与疾病和药物相关的不同类型血小板减少症。已经对人类和动物模型进行了多项科学研究,以证实木瓜叶煎剂治疗疾病诱导和药物诱导血小板减少症的疗效,然而,对于导致观察到的活性的生物活性化合物知之甚少。本研究的目的是鉴定番木瓜叶煎剂中负责在白消安诱导的血小板减少症大鼠中产生抗血小板减少活性的活性植物化学成分。
对白消安诱导的血小板减少症Wistar大鼠评估抗血小板减少活性。通过监测血小板计数评估不同生物导向组分的抗血小板减少活性。通过色谱方法分离和纯化生物活性化合物番木瓜碱,并通过光谱方法(LC-MS和1D/2D-1H/13C NMR)进行确认,其结构通过单晶X射线衍射得以证实。使用配备XTerra(®) MS C18柱和ESI-MS检测器的LC-MS/MS,在等度条件下使用90:10 CH3CN:CH3COONH4(6mM),并在正离子模式下通过多反应监测(MRM)对番木瓜碱进行定量。
从番木瓜叶煎剂中分离出两种不同的植物化学组:酚类和生物碱。其中,只有生物碱组分显示出良好的生物活性。从生物碱组分中分离出番木瓜碱,其在维持血小板计数高达555.50±85.17×10(9)/L时表现出强效活性,且无急性毒性。
本研究科学地验证了番木瓜叶煎剂的普遍用途,并且还证明叶片中存在的生物碱尤其是番木瓜碱是抗血小板减少活性的原因。