# Periplaneta americana extract ameliorates recurrent oral ulcers in rats by enhancing the intestinal epithelial barrier and regulating gut microbiota

**Authors:** Kailing Li, Liping Yuan, Jingyu Zhang, Weijun Li, Guanhua Zhao, Zhongze Chen, Yongshou Yang, Zhengchun He, Peiyun Xiao, Mukul Godbole, Mukul Godbole, Mukul Godbole

PMC · DOI: 10.1371/journal.pone.0340453 · PLOS One · 2026-01-23

## TL;DR

This study shows that an extract from Periplaneta americana can treat recurring mouth ulcers in rats by improving gut health and reducing inflammation.

## Contribution

The novel finding is that PAD ameliorates ROUs by modulating gut microbiota and enhancing intestinal barrier function.

## Key findings

- PAD reduced inflammatory cell infiltration and downregulated IL-6 and TNF-α while upregulating IL-2, IL-10, and VEGF.
- PAD altered gut microbiota diversity and increased fecal short-chain fatty acid levels.
- PAD improved colon pathology, enhanced intestinal barrier function, and reduced colon cell apoptosis.

## Abstract

Recurrent oral ulcers (ROUs) of oral mucosa disease are difficult to cure and relapse easily. Periplaneta americana extract (PAD), a raw material used in Kangfuxin Liquid and Yunnan Baiyao toothpaste, contains a variety of growth factors such as polypeptides and sticky sugar amino acids that promote tissue repair; this can encourage the growth of granulation tissue and reduce inflammation on wound surfaces.

In this study, we used a rat model of ROU induced by an antigen emulsifier to assess the ameliorative effects of PAD on rat ROUs and to explore its mechanism of action.

The effect of PAD in rats was evaluated by an enzyme-linked immunosorbent assay (ELISA) kit, hematoxylin-eosin staining, immunohistochemistry, reverse transcription quantitative PCR (RT-qPCR), and Western Blot (WB). 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) were used to detect the changes in intestinal flora and its metabolite short-chain fatty acids (SCFAs) in the feces of rats, respectively.

PAD significantly reduced the infiltration of local inflammatory cells and significantly downregulated interleukin (IL)-6 and tumor necrosis factor (TNF-α), while upregulating IL-2, IL-10, and vascular endothelial growth factor (VEGF). In addition, PAD altered the diversity and abundance of the gut microbiota and increased fecal short-chain fatty acid levels. Notably, PAD can improve the pathological injury of the colon, enhance the intestinal barrier of the colon, and reduce the apoptosis of colon cells.

The oral administration of PAD may effectively treat ROUs via regulating metabolites and altering the composition of the intestinal microbiota, thereby improving the intestinal barrier function.

## Linked entities

- **Proteins:** IL6 (interleukin 6), TNF (tumor necrosis factor), IL2 (interleukin 2), IL10 (interleukin 10), VEGFA (vascular endothelial growth factor A)
- **Chemicals:** tumor necrosis factor-alpha (PubChem CID 44356648)
- **Species:** Periplaneta americana (taxon 6978), Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 24383] {aka BARS-38, Gapd}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, Cd4 (Cd4 molecule) [NCBI Gene 24932] {aka W3/25, p55}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Tjp1 (tight junction protein 1) [NCBI Gene 292994] {aka ZO-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Ocln (occludin) [NCBI Gene 83497], Cldn1 (claudin 1) [NCBI Gene 65129], Il2 (interleukin 2) [NCBI Gene 116562], Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, tumor necrosis factor [NCBI Gene 103694380], Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}
- **Diseases:** ROU (MESH:D019226), oral pain (MESH:D010146), oral mucosa disease (MESH:D009059), nasopharyngeal cancer (MESH:D009303), Inflammatory (MESH:D007249), Behcet's Disease (MESH:D001528), chronic (MESH:D002908), gastrointestinal adverse reactions (MESH:D005767), dizziness (MESH:D004244), neurological reactions (MESH:D009461), IMB (MESH:D007410), deaths (MESH:D003643), edema (MESH:D004487), mucosal immune disorder (MESH:D007154), fibrosis (MESH:D005355), ORCID iD (MESH:C535742), tumor (MESH:D009369), ulcerative colitis (MESH:D003093), ulcer (MESH:D014456), toxicity (MESH:D064420), oral mucositis (MESH:D013280), colonic pathological damage (MESH:D003108), squamous cell carcinoma of the head and neck (MESH:D000077195), GM (MESH:C536735), mucosal damage (MESH:D052016), aphthous stomatitis (MESH:D013281)
- **Chemicals:** hematoxylin (MESH:D006416), LM (MESH:D007978), PBS (MESH:D007854), Paraffin (MESH:D010232), water (MESH:D014867), lipopolysaccharide (MESH:D008070), colchicine (MESH:D003078), alkaloids (MESH:D000470), alcohol (MESH:D000438), sodium phenobarbital (MESH:D010634), sulfuric acid (MESH:C033158), pentanoic acid (MESH:D010421), inosine (MESH:D007288), paraformaldehyde (MESH:C003043), polyols (MESH:C024617), carbon (MESH:D002244), valeric acid (MESH:C038780), Acetic (MESH:D019342), PVDF (MESH:C024865), H&amp;E (MESH:D006371), eosin (MESH:D004801), nucleoside (MESH:D009705), butyric acid (MESH:D020148), Butyric (-), SCFA (MESH:D005232), 3,3'-diaminobenzidine (MESH:D015100), peptides (MESH:D010455), sulfur (MESH:D013455), triamcinolone acetonide (MESH:D014222), sodium dodecyl sulfate (MESH:D012967), imidazole (MESH:C029899), lipid (MESH:D008055), TRIzol (MESH:C411644), fatty acids (MESH:D005227), uracil (MESH:D014498), agarose (MESH:D012685), amino acid (MESH:D000596), methanol (MESH:D000432), thalidomide (MESH:D013792), adenosine (MESH:D000241), propionic acid (MESH:C029658), sugars (MESH:D000073893)
- **Species:** Homo sapiens (human, species) [taxon 9606], Ruminococcus (genus) [taxon 1263], Bacteroides (genus) [taxon 816], Mycoplasmatota (phylum) [taxon 544448], Lactobacillaceae (family) [taxon 33958], Clostridia (class) [taxon 186801], Bacillota (clostridial firmicutes, phylum) [taxon 1239], gut metagenome (species) [taxon 749906], Bacilli (class) [taxon 91061], Lactobacillus (genus) [taxon 1578], Lactobacillales (order) [taxon 186826], Rattus norvegicus (brown rat, species) [taxon 10116], Staphylococcus (genus) [taxon 1279], Enterococcus (genus) [taxon 1350], Mus musculus (house mouse, species) [taxon 10090], Periplaneta americana (American cockroach, species) [taxon 6978], Bifidobacterium (genus) [taxon 1678]

## Full text

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## Figures

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## References

86 references — full list in the complete paper: https://tomesphere.com/paper/PMC12829797/full.md

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Source: https://tomesphere.com/paper/PMC12829797