Drug Discovery Insights from Medicinal Beetles in Traditional Chinese Medicine

Abstract

Traditional Chinese medicine (TCM) was the primary source of medical treatment for the people inhabiting East Asia for thousands of years. These ancient practices have incorporated a wide variety of materia medica including plants, animals and minerals. As modern sciences, including natural products chemistry, emerged, there became increasing efforts to explore the chemistry of this materia medica to find molecules responsible for their traditional use. Insects, including beetles have played an important role in TCM. In our survey of texts and review articles on TCM materia medica, we found 48 species of beetles from 34 genera in 14 different families that are used in TCM. This review covers the chemistry known from the beetles used in TCM, or in cases where a species used in these practices has not been chemically studied, we discuss the chemistry of closely related beetles. We also found several documented uses of beetles in Traditional Korean Medicine (TKM), and included them where appropriate. There are 129 chemical constituents of beetles discussed.

Keywords: Beetle; Chemical defense; Coleoptera; Secondary metabolites; Traditional Chinese Medicine; Traditional Korean Medicine.

Fig. 1

Pheromones identified from Bostrichid beetles. Compounds 1-3 were identified from Lyctus africanus. Compounds 4 and 5 are examples of pheromones identified from other genera of Bostrichids.

Fig. 2

Representative compounds described from jewel beetles (Coleoptera: Buprestidae). Compounds 6 and 7 are buprestins A and B. Compounds 8 and 9 are buprestins D and G.

Fig. 3

Chemical defenses identified from Carabid beetles. Compound 10 and 11 are 1,4-benzoquinone and 2-methyl-1,4-benzoquinone identified from members of the subfamily Brachininae. Compounds 12-14 are in substituted phenols identified from members of the subfamily Harpalinae. Compounds 15-18 are examples of some defensive compounds identified from the subfamily Carabinae.

Fig. 4

Pheromones identified from Anoplophora spp. Male sex pheromones, 4-(n-heptyloxy)-butanal (19), 4-(n-heptyloxy)-butan-1-ol (20), and (3E,6E)-α-farnesene (21). Compounds 22-24 are female sex pheromones gomadalatone A-C (left to right). Several long-chain alkanes, alkenes, and ketones were also identified as female specific sex and trail pheromones, but are not shown here (see text for citations).

Fig. 5

Compound 25 is juvenile hormone III, which is produced by Apriona germari males and transferred to females during copulation. Compounds 26-28 are fuscumol, fuscumol acetate, and geranylacetone, respectively, which are sex pheromones identified from Lamiinae longhorn beetles. Both enantiomers are made by Lamiinae, but they vary by species. (S)-Sulcatol (29) and sulcatone (30) are sex pheromones identified from Lamiinae longhorn beetles.

Fig. 6

Pheromones identified from weevils. Compounds 31-34 are pheromones isolated from Cyrtotrachelus buqueti. Compounds 35-38 are pheromones isolated from Rhynchophorus spp., which are also in the subfamily Dryophthorinae. Compounds 39-42 are pheromones from weevils in the subfamily Curculioninae.

Fig. 7

Chemical constituents of Cybister tripunctatus. Compounds 43-45 are benzoic acid, 4-hydroxybenzaldehyde, methyl 4-hydroxybenzoate. Compounds 46 and 47 are 11-deoxycorticosterone, and 20β-hydroxypregn-4-ene-3-one. Compounds 48 and 49 are cybisterol, and 21-hydroxypregna-4,6-diene-3,20-dione.

Fig. 8

Compounds identified from Elaterid beetles. Compounds 50 and 51 are hexanoic acid and pentanoic acid, identified from members of the subfamily Dendrometrinae. Compounds 52 and 53 are examples of pheromones identified from members of the subfamily Elaterinae (absolute configuration of 53 is unknown). Compounds 54-58 are examples of some defensive compounds identified from the subfamily Agrypinae.

Fig. 9

Chemical constituents of Gyrinus spp. Compounds 59 and 60 are gyrinidal, and isogyrinidal. Compounds 61 and 62 are gyrinidione, and gyrinidone (relative and absolute configuration not fully described in the literature). Compounds 63-66 are 3-methylbutanal, 3-methyl-1-butanol, 2-methyl-1-propanol, 6-methyl-5-hepten-2-one.

Fig. 10

Representative defensive compounds from fireflies (Coleoptera: Lampyridae). Compounds 67 and 68 are δ-terpinene, and γ-terpinene. Compounds 69 and 70 are lucibufagin C, and 2-methoxy-3-(1-methylpropyl) pyrazine (absolute configuration of 70 was not described in the literature).

Fig. 11

Compounds likely to be present in most Meloidae, including Epicauta, Lytta, Meloe, and Mylabris. Compound 71 is cantharidin, compounds 72 and 73 are R-(+)-palasonin, and S-(-)-palasonin.

Fig. 12

Compounds 74-79 are examples of cantharidin analogs identified from Mylabris phalerata.

Fig. 13

Compounds 80-82 are identified from adult Allomyrina dichotoma.

Fig. 14

Pheromones identified from Anomala spp. Compounds 83-85 are (R)-buibuilactone, (R)-japonilure, (S)-japonilure. Compounds 86-88 are (E)-2-nonen-1-ol, (E)-2-nonenal, (Z)-7-tetradecen-2-one. Compounds 89 and 90 are methyl (Z)-5-tetradecenoate and methyl benzoate.

Fig. 15

Compounds identified from Catharsius molossus. Compounds 91 and 92 are N-acetyldopamine dimers. Compounds 93-95 are N-acetyldopamine dimer derivatives.

Fig. 16

Compounds 96-99 are pheromones identified from dung beetles in the genus Kheper, subfamily Scarabaeinae.

Fig. 17

Compounds reported from Holotrichia spp. Compounds 100 and 101 are flavonoids catechin and tricin. Compounds 102-105 are pheromones identified from Holotrichia spp. Compounds 106-111 are phenolic compounds from H. diomphalia.

Fig. 18

Representative compounds reported from Protaetia brevitarsis. Compounds 112-115 are simple aromatic compounds. Compounds 116 and 117 are diketopiperazines. Compounds 118-121 are β-carbolines. Compounds 122 and 123 are N-acetyldopamine dimers.

Fig. 19

Compounds identified from Paederus fuscipes. Compounds 124-126 are pederin, pseudopederin, pederone.

Fig. 20

Compounds 11 and 127-129 are major compounds identified from the defensive secretions of Ulomoides dermestoides.