[Mechanism of herbal cake-separated moxibustion combined with atorvastatin in treating ApoE-/- atherosclerotic mice based on the integrin/YAP/JNK signaling pathway].
Li H, Luo H, et al. • Zhen ci yan jiu = Acupuncture research • 2026
Herbal cake-separated moxibustion combined with atorvastatin exerts synergistic effects, ameliorates serum lipid profiles, mitigates endothelial dysfunction of aorta, and attenuates inflammatory responses in AS mice, potentially via modulation of the integrin/YAP/JNK signaling pathway in the aorta.
Key Findings
Results
ApoE-/- atherosclerotic model mice showed significant increases in body weight, aortic lipid plaque area, and multiple serum biomarkers compared to blank controls.
Model group exhibited increased body weight (P<0.01) and significantly increased arterial lipid plaque area (P<0.01) compared to blank group.
Serum TC, TG, LDL-C, IL-6, IL-8, TNF-α, ET-1, and VEGF levels were all elevated (P<0.01) in the model group.
HDL-C and NO levels decreased in the model group compared to blank group (P<0.01).
Aortic pathological changes included thickened intima, foam cells and lipid deposition, hypertrophic edema of smooth muscle cells, thinning of elastic fibers, widened endothelial cell gaps, and rupture of elastic membranes.
Results
Model group mice showed upregulation of integrin αVβ3, YAP, p-JNK1/2, ICAM-1, and VCAM-1 proteins in the aorta, with downregulation of p-YAP.
Compared to the blank group, protein expression of integrin αVβ3, YAP, p-JNK1/2, ICAM-1, and VCAM-1 were all increased (P<0.01) in the model group aorta.
p-YAP protein expression was reduced (P<0.01) in the model group compared to blank group.
Protein levels were measured by Western blot.
These changes indicate activation of the integrin/YAP/JNK signaling pathway in atherosclerosis.
Results
All three treatment groups (medicine, moxibustion, and combined) significantly reduced body weight and improved aortic pathological morphology compared to the model group.
Medicine group, herbal cake-separated moxibustion group, and combined treatment group all showed reduced body weight (P<0.01) compared to model group.
Weight change difference was significantly lower than that of the model group (P<0.01) in all treatment groups.
Aortic lumen structure became more regular with thinner intima, reduced foam cells and lipid deposition, and alleviated smooth muscle cell edema, hypertrophy, and inflammatory infiltration.
All other measured indicators showed significant improvement compared to the model group (P<0.01, P<0.05).
Treatment duration was 8 weeks for all groups.
Results
Compared to the moxibustion-only group, both the atorvastatin-only group and the combined treatment group showed superior reductions in plaque area, LDL-C, ET-1, VEGF, and aortic adhesion molecule expression.
Medicine group and combined treatment group exhibited reduced plaque area compared to moxibustion group (P<0.05, P<0.01).
Serum NO level increased in medicine and combined groups compared to moxibustion group (P<0.01).
LDL-C, ET-1, and VEGF levels decreased in medicine and combined groups vs. moxibustion group (P<0.01).
Protein expressions of p-JNK1/2, ICAM-1, and VCAM-1 in the aorta were reduced in medicine and combined groups vs. moxibustion group (P<0.05, P<0.01).
Atorvastatin (medicine) group additionally showed decreased serum TC, TG, IL-6, IL-8, TNF-α (P<0.01) and increased HDL-C (P<0.01), as well as reduced aortic integrin αVβ3 and YAP protein expressions and increased p-YAP expression (P<0.05), compared to moxibustion group.
Results
The combined treatment group showed superior reductions in body weight, serum lipids (TC, TG), inflammatory cytokines (IL-6, IL-8, TNF-α), and integrin/YAP pathway proteins compared to either monotherapy group.
Combined treatment group showed greater reduction in body weight than both medicine group and moxibustion group (P<0.05, P<0.01).
Serum TC, TG, IL-6, IL-8, and TNF-α levels were more reduced in combined group vs. both monotherapy groups (P<0.01, P<0.05).
Aortic integrin αVβ3 and YAP protein expressions were more reduced in the combined group (P<0.01, P<0.05) compared to both other treatment groups.
Serum HDL-C level was more elevated in combined group (P<0.01) vs. both other groups.
p-YAP protein expression was more increased in combined group (P<0.01) vs. both other groups, indicating greater YAP phosphorylation/inactivation.
Methods
The study used ApoE-/- mice on a high-fat diet to model atherosclerosis, with herbal cake-separated moxibustion applied at acupoints CV17 (Danzhong) and CV8 (Shenque).
Male ApoE-/- mice were randomly divided into model, medicine, moxibustion, and combined treatment groups with 9 mice per group; male C57BL/6J mice served as blank controls.
Moxibustion was applied every other day, 3 times per week for 8 weeks.
Atorvastatin calcium was administered by gavage at 3 mg·kg-1·d-1, once daily for 8 weeks.
Outcome measures included body weight, HE staining, Oil Red O staining, serum biochemical analysis, ELISA for cytokines and vascular markers, colorimetric assay for NO, and Western blot for signaling proteins.
What This Means
This research suggests that combining a traditional Chinese medicine technique called herbal cake-separated moxibustion (a form of heat therapy applied through medicated herb cakes over specific body points) with the cholesterol-lowering drug atorvastatin produces better results in treating atherosclerosis (hardening and narrowing of arteries) than either treatment alone. The study used mice genetically engineered to develop atherosclerosis when fed a high-fat diet and tested four groups: untreated diseased mice, mice receiving atorvastatin only, mice receiving moxibustion only, and mice receiving both treatments together. After 8 weeks, the combination group showed greater reductions in body weight, blood cholesterol and fat levels, and inflammatory markers (substances that signal ongoing inflammation) compared to either treatment alone.
This research suggests that the combination therapy works at least partly through a biological pathway involving proteins called integrin αVβ3, YAP, and JNK in the walls of arteries. In diseased mice, these proteins were abnormally active and contributed to arterial damage. All treatments reduced this abnormal activity, but the combined therapy was most effective at normalizing the integrin/YAP/JNK signaling pathway, reducing artery wall inflammation, and improving the physical appearance of the artery under the microscope. The moxibustion-only treatment was less effective than atorvastatin alone for some measures like cholesterol levels, but contributed meaningfully to reducing inflammation and improving outcomes when added to drug therapy.
This research suggests that integrating traditional moxibustion with standard statin drug treatment may offer a synergistic benefit for atherosclerosis management. However, this was an animal study using genetically modified mice, and the specific herbal cake formulation and moxibustion technique used may not be standardized across different practitioners. Further research in humans would be needed to determine whether these findings translate to clinical settings and to establish safety and optimal protocols for combined therapy.
Li H, Luo H, Zhu M, Xue K, Lu X, Cui J. (2026). [Mechanism of herbal cake-separated moxibustion combined with atorvastatin in treating ApoE-/- atherosclerotic mice based on the integrin/YAP/JNK signaling pathway].. Zhen ci yan jiu = Acupuncture research. https://doi.org/10.13702/j.1000-0607.20250861