Limonoids From the Genus Melia (Meliaceae): Phytochemistry, Synthesis, Bioactivities, Pharmacokinetics, and Toxicology.

Wenxiang Fan,Zhengtao Wang,Li Yang,Linhong Fan

doi:10.3389/fphar.2021.795565

Abstract

Limonoids, as the vital bioactive chemical compounds in genus Melia plants, have attracted significant attention owing to their exclusive structural characteristics and remarkable biological activity. These compounds can be usually classified into two categories, including the ring-intact group and the ring-C-seco group. Benefiting from the development of separation and analysis technology, more than 200 limonoids have been isolated and identified from this genus. There is growing evidence that limonoids from genus Melia possess diverse pharmacological activities, especially anti-cancer effects, insecticidal activities, and anti-botulism effects. Toosendanin, one of the paramount limonoids, was considered as the pivotal bioactive marker in two medicinal herbs, including Melia toosendan Sieb. et Zucc and Melia azedarach L. In particular, limonoids are found to exhibit non-negligible toxic effects, a finding which needs further research. Besides this, the lack of clinical research data seriously hinders its further development and utilization, and necessary clinical trials should be taken into consideration. In this review, we systematically summarized the phytochemical compounds and their synthesis methods, pharmacological activities, and the structure–activity relationship, pharmacokinetics, and toxicology of genus Melia-derived limonoids. We believe that this up-to-date review could provide scientific evidence for the application of limonoids as agents beneficial to health in future clinical practice.

Highlights

Genus Melia, a model genus of Meliaceae, has about 20 species in the world and is widely distributed in tropical and subtropical regions of the Eastern Hemisphere
The limonoids isolated from genus Melia possess certain similar skeleton structures and can be classified into diverse types, including trichilin class, vilasinin class, havanensin class, azadirone class, nimbolinin class, nimbolidin class, salannin class, ohchinolal class, meliacarpinin class, meliacarpin class, and others
Enormous attempts have been devoted to synthesize, semisynthesize, and biosynthesize the momentous TSN and other limonoids, no ideal tactic was established for the complicated synthesis process yet

Summary

INTRODUCTION

Genus Melia, a model genus of Meliaceae, has about 20 species in the world and is widely distributed in tropical and subtropical regions of the Eastern Hemisphere. Juss., a plant of the genus Azadirachta, is often wrongly recognized as M. azedarach L. for their similar morphological characteristics and botanical name (Saleem et al, 2018) Owing to their multiple bioactivities, the Melia plants have been used as folk herbs in treating leprosy, eczema, asthma, malaria, fever, and pain (Xie. Limonoids, Bioactive Natural Compounds et al, 2008). Various types of chemical compounds have been isolated and identified from different parts of genus Melia plants, including limonoids (triterpenoids), steroids, alkaloids, flavonoids, anthraquinones, etc. The distribution of these compounds varied in different parts of the plants, of which the fruit, bark, and root bark possessed higher content Those parts mentioned above are consistent with the medicinal parts of M. toosendan and M. azedarach.

Azedarachin B 6 Sendanin

34 Meliarachin C

53 Meliarachin I

90 Mesendanin J

Findings

CONCLUSION