Chronic periodontitis is a prevalent inflammatory disease characterized by polymicrobial infection and progressive destruction of periodontal supporting tissues. Its incidence has increased steadily in recent years (Gao et al., 2021). Dental plaque microorganisms are the main etiologic agents, contributing to the breakdown of gingiva, periodontal ligament, cementum, and alveolar bone (Lasica et al., 2024). Conventional management focuses on removing plaque and calculus, often supplemented with locally delivered antimicrobials such as tetracycline, metronidazole, minocycline, doxycycline, or chlorhexidine to control infection and inflammation (Gandhi et al., 2025). Therefore, local adjunctive drug therapy has emerged as an important management strategy aimed at directly acting on the periodontal microenvironment to enhance infection control and modulate inflammatory responses (Martinez-Garcia and Hernandez-Lemus, 2025).

The fundamental rationale for local drug delivery in the treatment of chronic periodontitis lies in its ability to directly deliver high concentrations of drugs to the affected site (periodontal pockets), thereby achieving effective killing or inhibition of pathogenic microorganisms while minimizing systemic absorption and its associated potential side effects (Vivek et al., 2025). Local drug administration is typically used as an adjunct to basic periodontal treatment (such as supragingival and subgingival scaling) for moderate to severe chronic periodontitis (Vivek et al., 2025). Its clinical benefits are primarily manifested in enhanced clearance of key periodontal pathogens and significant improvements in clinical indicators, such as reduced periodontal probing depth (PD), decreased bleeding on probing rates, and promotion of clinical attachment level (AL) gain (de Sousa et al., 2021; Gandhi et al., 2025; Vivek et al., 2025).

Minocycline hydrochloride is one of the representative local drugs in this category. As a broad-spectrum tetracycline derivative, minocycline hydrochloride exerts both antibacterial and anti-inflammatory actions in periodontitis (Yang et al., 2022). It modulates cytokine activity, alleviates inflammation and pain (Chugh et al., 2022) and effectively suppresses key periodontal pathogens such as Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Actinomyces species (Zeng et al., 2024). However, as a broad-spectrum antibiotic, it may disrupt the microbial balance in the oral environment, leading to dysbiosis (Chen et al., 2020). Xipayi Gingival Solution (Xipayi Guyin Ye, also referred to as Xipaiyigu Gingival Rinse in previous studies), a tea polyphenol–based preparation derived from Uyghur medicine, exhibits strong antibacterial, antiviral, and antioxidant effects and is widely used for gingival diseases and oral ulcers (Mai et al., 2021). Its core compound, tannin (a complex polyphenolic compound), possesses traditional effects such as tissue astringency, enhancement of local resistance, and hemostasis (Chen et al., 2020; Chen et al., 2024). Modern research indicates that the clinical efficacy of the solution primarily stems from its significant anti-inflammatory effects, sustained antibacterial activity, and ability to regulate oral microecological balance (Chen et al., 2020).

Based on this, Xipayi Gingival Solution theoretically complements the limitations of pure antibacterial therapy by more comprehensively regulating the imbalanced periodontal microenvironment through its antioxidant and anti-inflammatory properties. The combined use of Xipayi Gingival Solution and minocycline hydrochloride has a clear scientific basis: the former, through the antioxidant, anti-inflammatory, and broad-spectrum antibacterial effects of polyphenolic compounds (Chen et al., 2020; Mai et al., 2021; Chen et al., 2024), disrupts biofilm structure and alleviates oxidative damage; the latter, through its specific antibiotic action and enzyme inhibitory effects, targets and kills pathogenic bacteria while inhibiting tissue degradation (Chen et al., 2020; Chugh et al., 2022; Yang et al., 2022; Zeng et al., 2024). The combination of the two may produce a synergistic effect, more effectively controlling infection, breaking the inflammatory cycle, reducing tissue destruction, and potentially promoting periodontal tissue repair and functional recovery through different pathways. However, rigorous clinical studies are currently lacking to systematically evaluate the impact of this combined therapy on key pathophysiological indicators and important functional outcomes (such as chewing ability) in patients with chronic periodontitis.

Therefore, this study was conducted to systematically evaluate the efficacy of Xipayi Gingival Solution (Xipayi Guyin Ye) combined with minocycline hydrochloride in patients with chronic periodontitis, focusing on its effects on inflammatory cytokines, oxidative stress markers, and masticatory function. The findings aim to provide new evidence supporting an integrated local treatment strategy.

All patients in both groups first received standardized basic periodontal treatment performed by the same experienced attending dentist over a four-week period. The treatment procedures included: ① Oral hygiene instruction: Patients were thoroughly educated on the Bass brushing technique and advised to use dental floss or interdental brushes for daily plaque control; ② Supragingival scaling: Using an ultrasonic scaler (manufacturer: Satelec, France; model: P5 NEWT), plaque, calculus, and surface stains were completely removed from tooth crowns; ③ Subgingival curettage and root planning: Under local anesthesia, a Gracey curette (manufacturer: Hu-Friedy, USA) was employed to thoroughly remove subgingival plaque and calculus from periodontal pockets and to smooth the root surfaces.

On this basis, the control group received topical minocycline hydrochloride ointment (Manufacturer: Sunstar Inc., Japan; Approval No.: HJ20150106; Specification: 0.5 g per tube). Medication was applied once weekly by the physician for four consecutive weeks. Procedure: The periodontal pocket of the target tooth was isolated and dried, then the syringe tip of the ointment was carefully inserted to the base of the pocket, and the gel was injected slowly until the pocket was filled and a small overflow was visible. Patients were instructed to refrain from rinsing, drinking, or eating for one hour after application.

The combination group received the same minocycline hydrochloride regimen as the control group, together with Xipayi Gingival Solution (Xipayi Guyin Ye; Manufacturer: Xinqikang Pharmaceutical Co., Ltd.; Approval No.: Z65020012; Specification: 30 mL per bottle). The rinse was used three times daily—after breakfast, lunch, and dinner—for four weeks. Each time, approximately 3–5 mL of the undiluted solution was held in the mouth and swished for 2–3 minutes before swallowing (no significant or persistent staining will occur). During treatment, patients were advised to avoid smoking, alcohol consumption, and spicy foods.

This study provides novel evidence that combining Xipayi Gingival Solution (Xipayi Guyin Ye) with minocycline hydrochloride enhances clinical outcomes in patients with chronic periodontitis. Compared with minocycline monotherapy, the combined therapy improves periodontal clinical indicators, inflammation levels, oxidative stress status, as well as chewing function and pain perception in patients with chronic periodontitis, without increasing adverse reactions. These findings demonstrate that integrating a traditional Uyghur medicine preparation with a modern antibiotic produces synergistic antibacterial, anti-inflammatory, and antioxidant effects, representing an innovative adjunctive strategy for periodontal treatment.

The present study showed that following treatment, the combination group outperformed the control group in core periodontal indicators such as PD, AL, PLI, and SBI, indicating that the combination of Xipayi Gingival Solution and minocycline hydrochloride in the treatment of chronic periodontitis can improve patients’ periodontal health status. Minocycline hydrochloride itself has been proven effective in reducing key periodontal pathogens and improving clinical indicators (Arnett et al., 2023). The core polyphenolic component of Xipayi Gingival Solution, tannin (tannic acid), has been confirmed to possess anti-inflammatory, antibacterial, and antioxidant properties that can serve as an effective adjunct to basic periodontal treatment (Malcangi et al., 2025). The combination of the two may produce a synergistic effect through the targeted antibacterial action of minocycline and the broad-spectrum biofilm inhibition and local inflammation reduction by the polyphenolic substances in Xipayi Gingival Solution. The findings of this study are consistent with the principle of local antibiotic potentiation. A 2024 review pointed out that for periodontitis patients with diabetes, adding local adjunctive drugs (such as statins, metformin, antibiotics) to non-surgical treatment can more significantly reduce periodontal pocket depth and increase clinical attachment level in the short and medium term compared to basic treatment alone (Lin et al., 2024).

Further exploration revealed that the combination group outperformed the control group in reducing inflammatory factors such as hs-CRP, TNF-α, IL-1β, and IL-6, as well as improving oxidative stress indicators (decreased MDA, increased SOD, and GSH-Px). Xipayi Gingival Solution may inhibit inflammatory signaling pathways through its polyphenolic components (Malcangi et al., 2025), reducing the release of pro-inflammatory factors while scavenging free radicals and enhancing the activity of endogenous antioxidant enzymes (Chen et al., 2020; Yang et al., 2022; Lopez-Valverde et al., 2023), thereby complementing the anti-inflammatory effects of minocycline (Arnett et al., 2023; Zhang et al., 2024) and more comprehensively improving the periodontal microenvironment, breaking the vicious cycle of inflammation-oxidative stress (Dai et al., 2022; Chang et al., 2024). Chen et al. demonstrated that the combination of Xipayi mouth rinse and minocycline in the treatment of localized aggressive periodontitis significantly improved periodontal gingival status and reduced inflammatory factor levels (Chen et al., 2020). Notably, the core identified components of Xipayi Gingival Solution include polyphenolic compounds such as gallic acid (Chen et al., 2024). Polyphenols are widely recognized as potent free radical scavengers (Arunachalam et al., 2022; Tossetta et al., 2024). One study on similar plant polyphenols suggests that these components may upregulate the activity of endogenous antioxidant enzymes such as SOD and GSH-Px by activating the NRF2 pathway, which aligns with the observed changes in antioxidant enzyme levels in this study (Tossetta et al., 2024).

This study also found that the combination group outperformed the control group in improving chewing function scores and reducing pain scores, indicating that the combined therapy can more effectively improve patients’ chewing function and alleviate pain symptoms. Clinical evidence supports that Xipayi-based adjunctive therapy can promote gingival healing and enhance chewing efficiency (Mai et al., 2021), while minocycline-containing regimens effectively alleviate periodontal pain and discomfort (Chang et al., 2024). These findings collectively support the observed improvements in functional recovery and patient comfort in the combination group.

Regarding clinical outcomes, the overall effective rate in the combination group was 97.87%, significantly higher than 84.44% in the minocycline-only group, reflecting the advantage of combined therapy. The combination of Xipayi Gingival Solution and minocycline hydrochloride theoretically constitutes a complementary “antibacterial” and “anti-inflammatory/antioxidant” dual mechanism, while clinically achieving a synergistic effect of “efficacy enhancement” and “functional recovery.”

In conclusion, Xipayi Gingival Solution combined with minocycline improves periodontal health, reduces inflammatory and oxidative stress markers, restores masticatory function, and achieves superior clinical outcomes compared to minocycline alone, without increasing adverse reactions, offering a safe and effective strategy for chronic periodontitis management. However, as a single-center study with a limited sample size and short follow-up period, the generalizability of the results of this study is limited, and it fails to elucidate the mechanism of action of the combined therapy at the oral microbiome and molecular pathway levels. Future research should conduct multi-center, large-sample, long-term studies and utilize omics technologies to further validate its long-term efficacy and precisely dissect its molecular mechanisms for improving the periodontal microenvironment by regulating host immune-inflammatory pathways and antioxidant defense systems, thereby providing more solid evidence for the optimization and promotion of treatment regimens for chronic periodontitis.