Combining Dendrobium Nobile Lindl To Ginsenoside-Mc1 Restores Cardioprotection In Hypercholesteremic Rats Via Modulating Tlr4/Myd88/Nf-Kappa B Signaling Pathway

Combination therapy may promisingly overcome the loss of cardioprotection during comorbidities. This study investigated the combination effects of Dendrobium nobile Lindl (DNL) and Ginsenoside-Mc1 (GMc1) in myocardial ischemia/reperfusion (l/R) injury and explore the possible involvement of TLR4/myD88/NF-kappa B pathway in hypercholesterolemic rats. Male Sprague-Dawley rats were fed a high-fat diet for 6-weeks to develop hypercholesterolemia. GMc1 (10 mg/kg, intraperitoneally) was administered for 4 weeks and DNL (80 mg/kg, orally) for 14 days before induction of in vivo I/R injury. Infarct sizes were analyzed through triphenyl-tetrazolium-chloride staining. Creatine-kinase, TNF-alpha and glutathione contents were quantified using ELISA. Protein expressions of TLR4/MyD88/NF-kappa B were detected through immunoblotting. All treatments significantly reduced infarct sizes as compared to untreated-hypercholesterolemic I/R group (p < 0.05) but the combination effect of DNL plus GMc1 was greater than those of individual effects (p < 0.01). The individual effects of treatments on reduction of proteins expression of inflammatory pathway were not consistent, however, their combination significantly downregulated all parameters of this pathway and increased glutathione contents as compared to untreated I/R rats (p < 0.01). Combining DNL to GMc1 treatment amplified their power to protect I/R hearts in hypercholesterolemic rats. Downregulation of TLR4/NF-kappa B/TNF-alpha inflammatory pathway and subsequent modulation of antioxidant capacity may have an important contribution in this cardioprotection.