Abstract

Introduction: Asari Radix et Rhizoma (ARR) and dried ginger (Zingiber officinalis) (DG) are often used together in drug preparations in traditional Chinese medicine (TCM) to treat respiratory diseases, including cold, bronchitis and pneumonia. Previous studies suggested that ARR and/or DG may influence the pharmacokinetics of other herbal components. In the current study, we examined pharmacokinetic interactions between ARR and DG in rats after oral administration.

Methods: We developed a method based on ultra-high-performance liquid chromatographytandem mass spectrometry to simultaneously measure serum concentrations of two active components each in ARR (L-asarinin and sesamin) and DG (6-gingerol and 6-shogaol). Adult Sprague- Dawley rats were starved overnight, then given ARR extract, DO extract, or a co-decoction of ARR and DG by gastric gavage (6 g raw material per kg body weight; n = 6 per group). Blood samples were collected prior to drug administration and at the following times (h) afterward: 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0. Pharmacokinetic parameters were compared using Student’s t test for independent samples.

Results: A simple, rapid, sensitive analytical method has been developed to detect four bioactive components simultaneously in the ARR-DG herbal pair. Pharmacokinetic parameters including C_max, T_max, T_1/2 and AUC_(0~t) were calculated using the non-compartmental model with the DAS 2.0 pharmacokinetic software. For L-asarinin, T_max was 2.00 ± 0.00 h in ARR animals and 1.67±0.26 h in ARR-DG animals (P<0.05), T1/2 was 8.58 ± 1.75 h in ARR and 11.93 ± 2.13 h in ARR-DG (P<0.05). For 6-gingerol, C_max was 350.48 ± 23.85 ng/mL in DG animals and 300.21 ± 20.02 ng/mL in ARR-DG (P<0.01), T_max was 2.83 ± 0.41 h in DG and 2.17 ± 0.41 h in ARR-DG (P<0.05) and AUC_(0~t) was 1.93 ± 0.15 mg/mL.h in ARR and 1.70 ± 0.15 mg/mL.h in ARR-DG (P<0.05). For 6-shogaol, C_max was 390.28 ± 26.02 ng/mL in DG animals and 455.63 ± 31.01 ng/mL in ARR-DG (P<0.01), T_max was 2.93 ± 0.10 h in DG and 1.92 ± 0.10 h in ARR-DG (P<0.01), T_1/2 was 3.74 ± 0.29 h in DG and 3.28 ± 0.22 h in ARR-DG (P<0.01), and AUC_(0~t) was 2.15 ± 0.18 mg/mL.h in DG and 2.73 ± 0.15 mg/mL.h in ARR-DG (P<0.01).

Conclusion: Pharmacokinetic interactions between ARR and DG decreased T_max, increased T_1/2 but did not affect the overall bioavailability of L-asarinin in ARR. The interactions in ARR-DG decreased C_max and T_max but increased T1/2 and AUC_(0~t) of 6-gingerol in DG. The interactions increased Cmax and AUC_(0~t) but decreased Tmax and T_1/2 of 6-shogaol in DG. Interactions in ARRDG did not affect the pharmacokinetics of sesamin.

Keywords: Asari Radix et Rhizoma, dried ginger (Zingiber officinalis), pharmacokinetics, drug interaction, UPLCTQ/ MS, TCM.

Graphical Abstract