Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

Abstract

Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook.f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-gamma). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

Fig. 1

Structure of triptolide (1).

Fig. 2

The outline of terpenoid biosynthesis via MVA pathway in the cytoplasm.

Fig. 3

The outline of terpenoid biosynthesis via DOXP pathway in the plastid.

Fig. 4

Proposed action of triptolide (1) on the genes involved in the inflammation and immunosuppressive cascade in T cells. The glucocorticoid receptor-1 complex cannot activate glucocorticoid-responsive genes (1), while potentially suppressing the levels of NF-κB and AP-1 (2, not documented) producing a combination of antiinflammatory and steroid sparing effects. Triptolide (1) also inhibits the transcription of TNF-α (3) and blocks the activation of NF-κB (4), resulting in the inhibition of transcription of the inflammation-related genes.

Fig. 5

Bioactive dihydroagarofurans in Tripterygium. Ac = acetate, Cin = cinnamoyl, Bz = benzoyl, Fur = furanoyl, Nic = nicotinoyl.

Fig. 6

Wilforine-type active sesquiterpene alkaloids in Tripterygium. Ac = acetate, Bz = benzoyl, Fur = furanoyl, Nic = nicotinoyl.

Fig. 7

Euonymine-type active sesquiterpene alkaloids in Tripterygium.

Fig. 8

Structure of wilforonide (29).

Fig. 9

Bioactive triptolide derivatives in Tripterygium.

Fig. 10

Diterpene diepoxides in Tripterygium with biological activity.

Fig. 11

Structure of triptophenolide (37).

Fig. 12

Bioactive benzenoid abietanes from Tripterygium.

Fig. 13

Structure of quinone 21 (46).

Fig. 14

Bioactive diterpene quinoids from Tripterygium.

Fig. 15

Bioactive five-ring kauranes from Tripterygium.

Fig. 16

Bioactive four-ring kauranes from Tripterygium.

Fig. 17

Structure of labd-13(E)-ene-8α, 15-diol (62).

Fig. 18

Structure of 13-epi-manoyl oxide-18-oic acid (63).

Fig. 19

Bioactive quinone methides from Tripterygium.

Fig. 20

Bioactive five-ring friedelanes/friedooleananes with saturated rings from Tripterygium.

Fig. 21

Bioactive six-ring friedelanes/friedooleananes with saturated rings from Tripterygium.

Fig. 22

Bioactive friedooleananes with a benzenoid ring from Tripterygium.

Fig. 23

Bioactive five-ring oleananes from Tripterygium.

Fig. 24

Bioactive six-ring oleananes from Tripterygium.

Fig. 25

Bioactive ursanes from Tripterygium.

Fig. 26

Bioactive steroids from Tripterygium.

Fig. 27

Structure of zeorin (107).