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

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.

Keywords: Acute toxicity; Melodinus henryi; Monoterpenoid indole alkaloids; Subacute toxicity.

Fig. 1

a Effects of CE, MHTA and MHNA on the viability of RAW264.7 cells; b effects of CE, MHTA and MHNA on nitric oxide production of RAW264.7 cells; The effects of CE, MHTA and MHNA on inflammatory cytokines of RAW264.7 cells, c IL-6; D: TNF-α. Data represent mean ± SD, n = 3. ^#p < 0.05, means significant difference from the control group.*p < 0.05, means significant difference from the LPS group

Fig. 2

Inhibitory effects of CE, MHTA and MHNA on Con A-stimulated T lymphocyte proliferation (a) and LPS-stimulated B lymphocyte proliferation (b) in vitro. DXM was used as a positive control. The values are presented as mean ± SD of triplicates. *p < 0.05, means significant difference from the control group (0 μg/mL)

Fig. 3

Histopathological results of seven organs in mice after oral administration for 28 days. Liver: A1 (Control); A2 (125 mg/kg of MHTA); A3 (1000 mg/kg of MHTA). Kidney: B1 (Control); B2 (125 mg/kg of MHTA); B3 (1000 mg/kg of MHTA). Spleen: C1 (Control); C2 (125 mg/kg of MHTA); C3 (1000 mg/kg of MHTA). Heart: D1 (Control); D2 (125 mg/kg of MHTA); D3 (1000 mg/kg of MHTA). Lung: E1 (Control); E2 (125 mg/kg of MHTA); E3 (1000 mg/kg of MHTA). Testis: F1 (Control); F2 (125 mg/kg of MHTA); F3 (1000 mg/kg of MHTA). Ovary: G1 (Control); G2 (125 mg/kg of MHTA); G3 (1000 mg/kg of MHTA). All tissues were stained with H&E (200 ×)

Fig. 4

Chemical structures of compounds 1–15