Danggui Buxue Decoction Alleviates Cyclophosphamide-induced Myelosuppression by Regulating β-hydroxybutyric Acid Metabolism and Suppressing Oxidative Stress

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2023 Apr 25

PMID 37096658

Authors

Yiqiao Gao

Yixin Zhang

Wei Liu

Nan Zhang

Qinghe Gao

Jingfang Shangguan

Na Li

Ying Zhao

Yanlong Jia

Affiliations

Soon will be listed here.

Abstract

Context: Danggui Buxue Decoction (DBD) is an effective complementary medicine in alleviating myelosuppression after chemotherapy (MAC). However, its mechanism of action is elusive.

Objective: To illustrate that regulating β-hydroxybutyric acid (β-OHB) metabolism and suppressing oxidative stress could be a potential mechanism of action for DBD in alleviating MAC.

Materials And Methods: After HPLC quantification and dose testing (3, 6 and 10 g/kg, gavage) of DBD, Sprague-Dawley rats were divided into control, cyclophosphamide (CTX) (30 mg/kg CTX for 5 days, intraperitoneal administration) and CTX + DBD groups (6 g/kg DBD for 14 days, gavage). Blood cell counts, thigh bone histological examination, β-OHB levels, oxidative stress indices and HDAC1 activity were tested. The biological function of β-OHB was verified (hBMSC cells were incubated in culture mediums that contained 40 μM CTX and β-OHB in 0, 1, 2.5, 5, 10 mM) and (MAC rat model, 3 g/kg β-OHB for 14 days, gavage).

Results: Rats in the CTX + DBD group showed upregulated blood cell counts (118-243%), β-OHB levels (495 nmol/mL in blood, 122 nmol/mg in marrow supernatant) and downregulated HDAC1 activity (59%), and oxidative stress indices (60-85%). , 5 mM β-OHB improved hBMSC cell migration (123%) and proliferation (131%). , rats treated with 3 g/kg β-OHB showed upregulated blood cell counts (121-182%) and downregulated HDAC1 activity (64%) and oxidative stress indices (65-83%).

Discussion And Conclusions: DBD, a traditional Chinese medicine, alleviates MAC by intervening in β-OHB metabolism and oxidative stress.

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