Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents

Meilian Yang,Yaping Liu,Jianxin Cao,Qingwang Xue,Yudan Wang,Guy Sedar Singor Njateng,Zhifeng Fan,Guiguang Cheng,Tianrui Zhao

doi:10.1007/s13659-020-00252-2

Abstract

Melodinus henryi is a good source of terpenoid indole alkaloids, and traditionally used as a folk medicine in the treatment of meningitis and fracture. In order to further exploit their potential uses, its anti-inflammatory and immunosuppressive activities, safety evaluations and chemical profiles have been illustrated. Compared to the crude methanol extract from M. henryi and its non-alkaloidal fraction, the total alkaloidal fraction (MHTA) had the strongest anti-inflammatory and immunosuppressive activities. In the acute oral toxicity assay, the half lethal dose (LD50) of MHTA was more than 2000 mg/kg. The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe, and might damage spleen, liver, kidney, and heart when the dose is higher than 1000 mg/kg. In addition, a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids. Thus, in regard with the potent side effects of MHTA, it should be used with caution in the development of phytomedicine.Graphic

Highlights

Medicinal plants have a long history in the prevention and treatment of human various diseases due to their health promoting potentials [1]
Phytochemical studies have revealed that the stems, bark, leaves, and fruits of M. henryi present a series of structurally novel terpenoid indole alkaloids (TIAs) in the meric and dimeric forms, such as melodinines A-G [10] and V [11], melodinines X1‒X4 [12] and W1-W4 [13], melohenines A and B [14], melodinhenines afford six fractions (A-F), henrycinols A and B [15, 16]
The crude extract (CE), MHTA and MHNA were evaluated their cytotoxic effects on the RAW264.7 cells

Summary

Introduction

Medicinal plants have a long history in the prevention and treatment of human various diseases due to their health promoting potentials [1]. The natural products from medicinal plants are an important productive drug source for providing molecular scaffolds in the modern drug discovery research [2, 3]. Alkaloid is one of the most important classes of plant natural products with a large range of therapeutic properties, including anti-depressant, immunosuppressive, antimicrobial, anti-inflammatory, anti-tumor, etc. Plants of the genus Melodinus (Apocynaceae) are rich in terpenoid indole alkaloids (TIAs) and widely distributed in the tropical and sub-tropical regions [8]. M. henryi is a perennial vine mainly distributed in China, Thailand, and Burma [9] and has been used as a folk medicine for the treatment of infantile meningitis and fractures [9]. Some of them were characterized with complex polycyclic skeletons and some alkaloids have significant biological potentials, especially the cytotoxic activity [10, 11, 17]

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