Objective

2

To evaluate the safety and efficacy of

Sanhuang Zhenzhu

Ointment

in the external treatment of diabetic foot ulcer （DFU） and its effects on local microenvironment-related factors.

Methods

2

A total of 68 patients with DFU who were hospitalized in the Second Zone of the Department of Peripheral Vascular Medicine （Tongzhou Campus） at Dongzhimen Hospital， Beijing University of Chinese Medicine， from August 2022 to June 2024， were enrolled and randomly assigned to either the observation group or the control group using a random number table. A

fter admission， both groups received standardized glycemic control and basic treatments such as antihypertensive and lipid-lowering therapies. The observation group received external application of

Sanhuang Zhenzhu

Ointment

， with dressing changes once daily for 21 consecutive days. Ulcer area was recorded on days 0， 7， 14， and 21 of treatment， and wound healing rate and traditional Chinese medicine （TCM） syndrome scores were calculated. Clinical efficacy was compared between the two groups. On days 0 and 21， histopathological changes in wound tissues were observed. Serum levels of interleukin （IL）-1β， IL-6， vascular endothelial growth factor （VEGF）， and basic fibroblast growth factor （bFGF） were measured. Alpha diversity analysis of wound microbiota was conducted using metagenomic sequencing to assess microbial composition， richness， and diversity. Wound infection severity was evaluated using the infection grading system of the International Working Group on the Diabetic Foot （IWGDF）/Infectious Diseases Society of America （IDSA）， and peripheral neuropathy was assessed using the Toronto Clinical Scoring System （TCSS）.

Results

2

On day 21， the ulcer area in both groups was significantly reduced compared to that on day 0 （

P

<

0.05）. On days 14 and 21， the wound healing rates in both groups were significantly higher than those on day 7 （

P

<

0.05）， and the observation group showed significantly higher wound healing rates than the control group on days 7， 14， and 21 （

P

<

0.01）. On day 21， TCM syndrome scores were significantly lower than those on day 0 in both groups （

P

<

0.05）， with the total effective rate in the observation group significantly higher than in the control group （

χ

2

=8.332，

P

<

0.05）. After treatment， both groups showed reduced inflammatory cell infiltration， increased fibroblast proliferation， and neovascularization in wound

tissues. The observation group demonstrated more pronounced reductions in inflammatory infiltration， greater fibroblast proliferation， and more neovascular formation compared to the control group. On day 21， serum IL-6 and TNF-α levels were significantly decreased， while bFGF and VEGF levels were significantly increased in both groups compared to those on day 0 （

P

<

0.05）. Moreover， IL-6 and TNF-α levels were significantly lower， and bFGF and VEGF levels significantly higher in the observation group than the control group （

P

<

0.05）. Alpha diversity analysis revealed that microbial richness and diversity and colony diversity in the observation group were significantly reduced on day 21 compared to those on day 0 （

P

<

0.05）， and were also significantly lower than in the control group （

P

<

0.05）. On day 21， both groups showed improvements in IWGDF/IDSA infection grade， CRP levels， and TCSS scores compared to baseline （

P

<

0.05）， with the observation group performing significantly better than the control group across all indicators （

P

<

0.05）. No abnormalities were observed in liver and kidney function or routine blood tests before and after treatment in either group， and no adverse reactions occurred during the treatment period.

Conclusion

2

External application of

Sanhuang Zhenzhu

Ointment

is safe and effective for the treatment of DFU. It significantly improves local microenvironment-related factors.