A comprehensive meta-analysis examining the effects of Danhong injection (DHI) on inflammatory factors and vascular endothelial function in patients with unstable angina pectoris (UAP) has revealed significant therapeutic benefits, though researchers emphasize the need for higher-quality studies to strengthen the evidence base.
The systematic review, published in Frontiers in Pharmacology, analyzed 46 randomized controlled trials involving 4,601 participants with UAP. The study represents the first comprehensive evaluation specifically focused on DHI's impact on inflammatory markers and endothelial function in this patient population.
Significant Reduction in Inflammatory Markers
The meta-analysis demonstrated that DHI treatment significantly reduced multiple inflammatory biomarkers associated with cardiovascular disease progression. High-sensitivity C-reactive protein (hs-CRP) levels showed a substantial decrease (SMD = -1.34, 95% CI [-1.77, -0.90], P < 0.00001), along with significant reductions in tumor necrosis factor-alpha (TNF-α) (SMD = -0.84, 95% CI [-1.54, -0.15], P = 0.02) and interleukin-6 (IL-6) (SMD = -1.05, 95% CI [-1.86, -0.25], P = 0.01).
According to the researchers, these inflammatory factors play crucial roles in atherosclerosis development. "hs-CRP is a vascular inflammation marker and a predictor of myocardial infarction," the study authors noted. "TNF-α and IL-6 are important pro-inflammatory factors that promote the accumulation of immune complexes in endothelial cells, which increase the risk of thrombosis and participate in the vascular inflammatory response and coronary atherosclerosis."
Improved Vascular Endothelial Function
The analysis also revealed significant improvements in vascular endothelial function markers. DHI treatment increased nitric oxide (NO) levels (SMD = 1.51, 95% CI [1.04, 1.97], P < 0.00001) while reducing endothelin/endothelin-1 (ET/ET-1) levels (SMD = -2.01, 95% CI [-2.57, -1.46], P < 0.00001) and homocysteine (Hcy) levels (SMD = -0.55, 95% CI [-0.71, -0.39], P < 0.00001).
The researchers explained the clinical significance of these findings: "NO is a key vasodilator secreted by endothelial cells and a central regulator of vascular endothelial function. ET-1 is released by endothelial cells during acute and chronic vascular injury and is the most potent vasoconstrictor. NO and ET-1 maintain a dynamic equilibrium in healthy vessels and work together to regulate vascular tone."
Treatment Protocol and Safety Profile
All included studies administered DHI intravenously at doses ranging from 20-40 mL/day for 7-30 days, combined with conventional Western medicine. The treatment protocol showed a favorable safety profile, with adverse event rates comparable between DHI and control groups (RR = 1.12, 95% CI [0.73, 1.72], P = 0.61).
The most commonly reported adverse events were gastrointestinal reactions, including nausea, vomiting, abdominal pain, and flatulence. Of the 21 trials that reported adverse events, 11 reported no adverse events in either group, while the remaining 10 reported a total of 70 adverse events.
Study Limitations and Quality Concerns
Despite the promising results, the researchers identified significant limitations in the evidence quality. Using the GRADE assessment system, the quality of evidence ranged from "very low" to "low," primarily due to high risk of bias, imprecision, and inconsistency across studies.
"The quality of the 46 included trials was 'very low' to 'low,' and there was a lack of high-quality trials rigorously designed under the CONSORT protocol," the authors noted. "A significant number of trials lacked explicit methodological information, such as randomization protocols, concealment of allocation, and blinding techniques."
Clinical Implications and Future Directions
The study's findings suggest that DHI may offer therapeutic benefits for UAP patients by addressing both inflammatory processes and endothelial dysfunction, two key mechanisms underlying coronary artery disease progression. The researchers noted that DHI's active components include salvianolic acids, danshensu, protocatechuic aldehyde, rosmarinic acid, caffeic acid, and hydroxysafflor yellow A, which have demonstrated cardiovascular protective effects.
However, the authors emphasized caution in clinical application: "Considering the overall low quality of the original studies, further large-scale, high-quality RCTs are imperative to provide robust evidence for clinical practice."
The meta-analysis represents an important step in evaluating traditional Chinese medicine interventions for cardiovascular disease, providing systematic evidence for DHI's potential therapeutic role while highlighting the critical need for more rigorous clinical research to establish definitive treatment guidelines.
