Researchers at Chongqing University have published a significant study demonstrating how salidroside, a natural compound derived from Rhodiola plants, can suppress hyperglycemia-induced M1 macrophage polarization to accelerate diabetic wound healing by restraining the mTOR pathway. The work, appearing in the September 2026 issue of International Immunopharmacology, provides fresh mechanistic insights into managing one of diabetes's most debilitating complications.

Diabetes affects hundreds of millions worldwide, with chronic wounds representing a major clinical challenge that often leads to infection, hospitalization, and amputation. The new findings highlight a potential therapeutic avenue rooted in modulating immune cell behavior under high-glucose conditions.

Understanding Diabetic Wound Healing Challenges

Normal wound repair proceeds through overlapping phases of hemostasis, inflammation, proliferation, and remodeling. In diabetes, persistent hyperglycemia disrupts this sequence, prolonging the inflammatory phase and impairing subsequent tissue regeneration. Elevated blood glucose promotes excessive production of pro-inflammatory cytokines and oxidative stress, which together hinder collagen deposition and angiogenesis.

Macrophages serve as central regulators during the inflammatory phase. These innate immune cells exhibit remarkable plasticity, shifting between pro-inflammatory M1 and anti-inflammatory, pro-repair M2 phenotypes. In diabetic wounds, the balance tilts heavily toward sustained M1 dominance, fueling chronic inflammation that stalls healing.

Macrophage Polarization and Its Role in Diabetes

M1 macrophages, classically activated by signals such as interferon-gamma and lipopolysaccharide, secrete tumor necrosis factor-alpha, interleukin-6, and other mediators that amplify inflammation and clear debris. While essential early in repair, prolonged M1 activity becomes detrimental. M2 macrophages, in contrast, support resolution by producing growth factors and promoting tissue remodeling.

Hyperglycemia skews polarization toward M1 through metabolic reprogramming. Increased glycolytic flux and activation of nutrient-sensing pathways sustain the inflammatory state. Restoring equilibrium between M1 and M2 phenotypes has therefore emerged as a promising strategy for diabetic wound management.

The mTOR Pathway as a Key Regulator

The mechanistic target of rapamycin (mTOR) pathway integrates signals from nutrients, energy status, and growth factors to control cell metabolism, proliferation, and survival. In macrophages, mTOR activation under hyperglycemic conditions drives glycolysis and favors M1 polarization. Inhibiting this pathway can reduce inflammatory output and facilitate a shift toward reparative phenotypes.

Previous studies have linked mTOR dysregulation to various diabetic complications. The Chongqing University team focused on whether salidroside could intervene at this node to restore macrophage homeostasis.

Study Design and Experimental Approach

The investigation combined transcriptomic analysis with targeted in vitro and in vivo experiments. Researchers used the RAW264.7 murine macrophage cell line cultured under high-glucose conditions to model hyperglycemia. Diabetic mouse models received subcutaneous salidroside injections at two dose levels to assess wound closure rates and tissue histology.

RNA sequencing identified differentially expressed genes, revealing enrichment in pathways related to inflammation and metabolism. Subsequent validation confirmed changes in polarization markers, cytokine profiles, and metabolic intermediates.

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Key Findings on Salidroside Effects

Salidroside treatment significantly accelerated wound closure in diabetic mice in a dose-dependent manner. Histological examination showed improved epidermal regeneration and reduced inflammatory infiltration. In vitro, the compound suppressed markers of M1 polarization while restraining glycolytic activity in macrophages exposed to high glucose.

Mechanistically, salidroside blocked hyperglycemia-induced activation of the mTOR signaling cascade. This inhibition lowered glycolytic flux, decreased production of pro-inflammatory mediators, and limited the M1 phenotype. The net result was enhanced transition toward resolution of inflammation and improved healing outcomes.

Institutional Context at Chongqing University

The study originates from the College of Bioengineering at Chongqing University, where corresponding authors Vivi Kasim and Shourong Wu lead active research programs in tumor biology, cell metabolism, and therapeutic angiogenesis. The institution's Key Laboratory for Biorheological Science and Technology of the Ministry of Education provided critical infrastructure for the work.

Funding support came from the Natural Science Foundation of Chongqing, underscoring regional commitment to biomedical innovation. Such university-led projects exemplify how Chinese higher education institutions contribute to global health solutions while training the next generation of researchers.

Broader Implications for Biomedical Research and Careers

These results add to a growing body of evidence positioning natural compounds as modulators of immune metabolism. For academics and PhD candidates, the work illustrates the value of integrating transcriptomics, cell biology, and animal models to dissect complex disease mechanisms.

Opportunities abound in related fields, including postdoctoral positions focused on immunometabolism, faculty roles in pharmacology and bioengineering departments, and industry collaborations developing wound-care therapeutics. Universities worldwide increasingly seek scholars capable of bridging basic mechanisms with translational applications.

Future Directions and Therapeutic Potential

While promising, salidroside's clinical translation will require further pharmacokinetic studies, safety profiling, and human trials. Combination approaches pairing the compound with existing wound-care technologies or stem-cell therapies may enhance efficacy.

The mTOR-glycolysis axis identified here offers additional druggable targets. Researchers are likely to explore related natural products and synthetic analogs that fine-tune macrophage behavior without broad immunosuppression.

Relevance to Global Diabetes Burden

With diabetes prevalence continuing to rise, effective adjunctive therapies for complications remain urgent. The International Diabetes Federation projects sustained growth in affected populations, particularly in Asia. University research programs like the one at Chongqing University play a vital role in addressing these regional and global needs.

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Perspectives from Stakeholders in Higher Education

University administrators note that high-impact publications strengthen institutional rankings and attract international talent. For early-career researchers, involvement in such projects builds competitive CVs for tenure-track positions and grants.

PhD-track job seekers benefit from exposure to interdisciplinary training that spans molecular biology, immunology, and animal modeling. Programs emphasizing translational outcomes prepare graduates for diverse career paths in academia, biotechnology, and clinical research.