Tongyangxiao Lotion for Postoperative Wound Healing After Anal Fistula Surgery

Tongyangxiao Lotion Accelerates Postoperative Wound Healing in Anal Fistula Surgery by Activating the PI3K-Akt-mTOR Pathway

This study tests whether a traditional Chinese herbal bath called Tongyangxiao (TYX) lotion helps surgical wounds heal faster in patients who have had anal fistula surgery. Anal fistulas are abnormal tunnels near the anus that often require surgery, but the wound is usually left open and heals slowly. The study compares TYX lotion with a standard antiseptic bath (potassium permanganate). Patients use one of the two baths once daily for 14 days after surgery. The main goal is to see how long it takes for the wound to close completely. The study also measures pain, wound size, inflammation, and proteins involved in healing. A total of 115 patients took part, and laboratory experiments with human skin cells were also performed to understand how TYX works.

Study Overview

• Status: Completed
• Conditions: Postoperative Wound Healing in Anal Fistula Surgery
• Intervention / Treatment: Other: Tongyangxiao (TYX) group; Other: Potassium permanganate (PP) group

Detailed Description

This prospective, single-blind, randomized controlled trial was conducted at two hospitals in China (The First Affiliated Hospital of Hebei University of Chinese Medicine and The First Affiliated Hospital of Henan University of Chinese Medicine) from June 2023 to June 2024. The study enrolled 115 patients aged 18-65 years with low simple anal fistula who underwent low anal fistulectomy. Patients were randomly assigned to either the Tongyangxiao (TYX) group (n=58) or the potassium permanganate (PP) group (n=57). Starting on postoperative day 2, the TYX group received a 15-minute sitz bath once daily with 1500 mL of TYX decoction (40°C) for 14 days. The TYX decoction contains ten herbs: Huangbai, Kushen, Danggui, Cangzhu, Qinjiao, Xixin, Fangfeng, Chuanjiao, Mingfan, and Mangxiao. The PP group received a 15-minute sitz bath with 1:5000 potassium permanganate solution (40°C) for the same duration.

The primary outcome was wound healing time (days from surgery to complete epithelialization). Secondary outcomes included wound area (measured by ImageJ at days 5,7,14), exudate score, pain by visual analog scale (VAS, days 5,10,14), serum and tissue levels of inflammatory cytokines (TNF-α, IL-6, IL-1β) by ELISA and immunohistochemistry, expression of PI3K-Akt-mTOR pathway proteins (p-PI3K, p-Akt, p-mTOR) by Western blot and immunohistochemistry, and collagen I/III expression by Western blot, qPCR, and immunohistochemistry. Safety was monitored by recording adverse events.

In parallel, network pharmacology predicted PI3K-Akt as a core pathway. An in vitro experiment using human fibroblast HFF-1 cells treated with TNF-α (50 ng/mL) was performed to model inflammation. Cells were treated with TYX lyophilized powder (0.1 or 0.5 mg/mL), the PI3K activator 740Y-P, or their combination. Cell migration was assessed by Transwell assay; pathway protein expression and collagen were measured by Western blot and immunofluorescence.

The study was approved by the Ethics Committee of Hebei University of Chinese Medicine (YXLL2021010) and the sub-center (2021HL-248-01). All patients gave written informed consent. No U.S. government funding or IND/IDE was involved.

Results demonstrate that TYX significantly shortened wound healing time, reduced pain and exudate, decreased inflammatory cytokines, and upregulated PI3K-Akt-mTOR phosphorylation and collagen deposition. In vitro, TYX reversed TNF-α-induced suppression of fibroblast migration and pathway activity. These findings support the clinical use of TYX lotion to accelerate postoperative wound healing in anal fistula surgery by activating the PI3K-Akt-mTOR signaling pathway.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000,
      • the First Affiliated Hospital of Henan University of Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age 18 to 65 years

Diagnosis of low simple anal fistula according to the Chinese expert consensus on diagnosis and treatment of anal fistula (2020 edition)

Traditional Chinese medicine pattern of damp-heat downward infusion

Underwent low anal fistulectomy

No surgical contraindications

Exclusion Criteria:

Complex or high anal fistula

Inflammatory bowel disease, diabetes mellitus, or severe cardiac / liver / renal dysfunction

Allergy to any component of Tongyangxiao lotion or potassium permanganate

Pregnancy or lactation

Participation in another clinical trial within 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tongyangxiao (TYX) group; Patients receive a 15-minute sitz bath once daily with 1500 mL of Tongyangxiao decoction (40°C) from postoperative day 2 for 14 consecutive days. The decoction contains ten herbs: Huangbai (Phellodendron chinense), Kushen (Sophora flavescens), Danggui (Angelica sinensis), Cangzhu (Atractylodes lancea), Qinjiao (Gentiana macrophylla), Xixin (Asarum sieboldii), Fangfeng (Saposhnikovia divaricata), Chuanjiao (Zanthoxylum bungeanum), Mingfan (Alumen), and Mangxiao (Natrii Sulfas).	Other: Tongyangxiao (TYX) group; Patients receive a 15-minute sitz bath once daily with 1500 mL of Tongyangxiao decoction (40°C) from postoperative day 2 for 14 consecutive days. The decoction contains ten herbs: Huangbai (Phellodendron chinense), Kushen (Sophora flavescens), Danggui (Angelica sinensis), Cangzhu (Atractylodes lancea), Qinjiao (Gentiana macrophylla), Xixin (Asarum sieboldii), Fangfeng (Saposhnikovia divaricata), Chuanjiao (Zanthoxylum bungeanum), Mingfan (Alumen), and Mangxiao (Natrii Sulfas).; Other: Potassium permanganate (PP) group; atients receive a 15-minute sitz bath once daily with 1500 mL of 1:5000 potassium permanganate solution (40°C) from postoperative day 2 for 14 consecutive days.; Other Names: Active Comparator
Active Comparator: Potassium permanganate (PP) group; Patients receive a 15-minute sitz bath once daily with 1500 mL of 1:5000 potassium permanganate solution (40°C) from postoperative day 2 for 14 consecutive days.	Other: Tongyangxiao (TYX) group; Patients receive a 15-minute sitz bath once daily with 1500 mL of Tongyangxiao decoction (40°C) from postoperative day 2 for 14 consecutive days. The decoction contains ten herbs: Huangbai (Phellodendron chinense), Kushen (Sophora flavescens), Danggui (Angelica sinensis), Cangzhu (Atractylodes lancea), Qinjiao (Gentiana macrophylla), Xixin (Asarum sieboldii), Fangfeng (Saposhnikovia divaricata), Chuanjiao (Zanthoxylum bungeanum), Mingfan (Alumen), and Mangxiao (Natrii Sulfas).; Other: Potassium permanganate (PP) group; atients receive a 15-minute sitz bath once daily with 1500 mL of 1:5000 potassium permanganate solution (40°C) from postoperative day 2 for 14 consecutive days.; Other Names: Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound healing time	Number of days from surgery to complete wound closure (complete epithelialization without need for dressing).Time Frame	From date of surgery until complete epithelialization, assessed daily up to 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound area	Description: Wound area (cm²) measured by tracing the wound margin on transparent film and calculated using ImageJ software.	Postoperative days 5, 7, and 14
Exudate score	Graded as 0=none, 1=mild (only on dressing), 2=moderate (soaking < half of dressing), 3=severe (soaking ≥ half of dressing).	Postoperative days 5, 7, and 14
Pain score (VAS)	Visual analog scale from 0 (no pain) to 10 (worst pain).	Postoperative days 5, 10, and 14
Inflammatory cytokines (TNF-α, IL-6, IL-1β)	Measured in serum by ELISA and in wound tissue by immunohistochemistry.	Postoperative days 7 and 14
PI3K-Akt-mTOR pathway proteins (p-PI3K, p-Akt, p-mTOR)	Expression levels and phosphorylation ratios measured by Western blot and immunohistochemistry in wound tissue.	Postoperative days 7 and 14
Collagen I and Collagen III	Protein and mRNA expression measured by Western blot, immunohistochemistry, and RT-qPCR in wound tissue	Postoperative days 7 and 14

Collaborators and Investigators

• Sponsor: Yongkang An

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Tongyangxiao Lotion; Anal fistula; Wound Healing; PI3K-Akt-mTOR signaling pathway; Traditional Chinese medicine
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Rectal Diseases; Digestive System Fistula; Fistula; Intestinal Fistula; Pathological Conditions, Signs and Symptoms; Rectal Fistula; Inorganic Chemicals; Population Characteristics; Demography; Potassium Compounds; Manganese Compounds; Population Groups; Potassium Permanganate
• Other Study ID Numbers: YXLL2021010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No