Angelica dahurica (Fish. ex Hoffm.) Benth. et Hook. f. 白芷 (Baizhi, Chinese Angelica)

Background: Herbal medicine Angelica dahurica is widely employed for the treatment of rheumatism and pain relief in China. Oxypeucedanin is a major component of the herb. Objectives : The objectives of this study are aimed at the investigation of mechanism-based inactivation of CYP2B6 and CYP2D6 by oxypeucedanin, characterization of the reactive metabolites associated with the enzyme inactivation, and identification of the P450s participating in the bioactivation of oxypeucedanin. Methods : Oxypeucedanin was incubated with liver microsomes or recombinant CYPs2B6 and 2D6 under designed conditions, and the enzyme activities were measured by monitoring the generation of the corresponding products. The resulting reactive intermediates were trapped with GSH and analyzed by LC-MS/MS. Results : Microsomal incubation with oxypeucedanin induced a time-, concentration-, and NADPH-dependent inhibition of CYPs2B6 and 2D6 with kinetic values of KI/kinact 1.82 µM/0.07 min-1 (CYP2B6) and 8.47 µM/0.044 min-1 (CYP2D6), respectively. Ticlopidine and quinidine attenuated the observed time-dependent enzyme inhibitions. An epoxide and/or γ-ketoenal intermediate(s) derived from oxypeucedanin was/were trapped in microsomal incubations. CYP3A4 was the primary enzyme involved in the bioactivation of oxypeucedanin. Conclusion : Oxypeucedanin was a mechanism-based inactivator of CYP2B6 and CYP2D6. An epoxide and/or γ-ketoenal intermediate(s) may be responsible for the inactivation of the two enzymes.

Download Full-text

Angelica dahurica and Rheum officinale Facilitated Diabetic Wound Healing by Elevating Vascular Endothelial Growth Factor

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500713 ◽

2021 ◽

pp. 1-19

Author(s):

Yuh-Huey Chao ◽

Wan-Ting Yang ◽

Ming-Chang Li ◽

Fwu-Lin Yang ◽

Ru-Ping Lee

Keyword(s):

Vascular Endothelial Growth Factor ◽

Wound Healing ◽

Growth Factor ◽

Smooth Muscle Actin ◽

Intraperitoneal Administration ◽

Angelica Dahurica ◽

Vascular Endothelial ◽

Sprague Dawley ◽

Diabetic Wounds ◽

Endothelial Growth Factor

Traditional Chinese medicine (TCM) provides alternative treatment choices for diabetic wounds. The aim of this study was to evaluate the effects of Angelica dahurica and Rheum officinale (ARE) on diabetic wounds and its underlying action mechanism. A total of 36 healthy male Sprague–Dawley rats were randomly divided into three groups: diabetes mellitus (DM) rats treated with ARE (DM-ARE), DM rats treated with 0.9% saline (DM-NS), and non-DM rats treated with 0.9% saline (NDM-NS). DM was induced by intraperitoneal administration of 40 mg/kg of streptozotocin after a 2-week high-fat diet feeding. After excisional skin wounds and treatments, the remaining wound area (RWA) in each group was measured. The RWA in the DM-NS group (69.60% ± 2.35%) was greater than that in the DM-ARE (55.70% ± 1.85%) and NDM-NS groups (52.50% ± 2.77%) on day 6. Besides, the DM-ARE group showed higher vascular endothelial growth factor (VEGF), higher inducible nitric oxide synthase (iNOs), higher [Formula: see text]-smooth muscle actin ([Formula: see text]-SMA), and lower nuclear factor kappa-light-chain-enhancer of activated B cell (NF-[Formula: see text]B) expression in the wound skin tissue. These results showed that treatment with ARE shifted the recovery pattern of diabetic rats to the pattern of nondiabetic rats, indicating that ARE may improve wound healing in diabetic conditions.

Download Full-text