Frontiers in pharmacology · 2026
Diallyl trisulfide attenuates metabolic syndrome via integrated modulation of PCSK-9/LDL-R axis, redox homeostasis, and inflammatory cytokine networks in high-carbohydrate high-fat (HCHF) diet-fed rats.
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Ahmad Parvej, Shah Arunim, Alvi Sahir Sultan, Chaturvedi Chandra Prakash, Ahmad Saheem, Bin Sheeha Bodor, Puri Paridhi, Alothamali Omar W, Khan M Salman
Аннотация
BACKGROUND: Metabolic syndrome (MetS), a cluster of biochemical and physiological alterations leading to the development of cardiovascular disease and type 2 diabetes (T2DM), is a major health concern worldwide. Recently, elevated level of proprotein subtilisin/kexin type-9 (PCSK-9) along with dyslipidemia, high blood pressure, blood sugar, and triglycerides have been linked to the establishment and advancement of Mets.
AIM OF THIS STUDY: In this study, we explored the protective effects of diallyl trisulfide (DATS), a natural organosulfur compound derived from garlic, in a high-carbohydrate high-fat (HCHF) diet-induced rat model of MetS.
RESULTS: Herein, we report that DATS improves MetS parameters via significantly downregulating the mRNA expression of PCSK-9 (1.59-fold when compared with HCHF control) and its transcriptional activator, HNF-1α. Similarly, the mRNA expression (-3.19-fold) and the ex-vivo enzymatic activity of 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase (HMG-R) were attenuated in DATS-treated rats. In contrast, DATS significantly increased the low-density lipoprotein-receptor (LDL-R) mRNA expression by 1.98-fold. This unique regulation of PCSK-9/LDL-R axis, HNF1α, and HMG-R was well corroborated by the reduced plasma level of PCSK-9, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs). Furthermore, the mRNA expression and circulatory level of inflammatory cytokines i.e., interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α) and chemokines i.e., Chemokine (C-X-C motif) ligand (CXCL)-1, CXCL-2, and monocyte chemoattractant protein-1 (MCP-1) were also ameliorated after DATS intervention. The expression of peroxisome proliferator-activated receptors (PPAR)-α, β, and γ was also upregulated after treatment with DATS, when compared to untreated HCHF group.
CONCLUSION: This comprehensive investigation demonstrates that DATS mitigates HCHF diet-induced MetS by targeting molecular regulators of cholesterol homeostasis, oxidative stress, glycemic indices, and inflammation. These findings suggest that DATS may serve as a promising therapeutic agent in preventing and managing MetS and associated cardiometabolic risks.
AIM OF THIS STUDY: In this study, we explored the protective effects of diallyl trisulfide (DATS), a natural organosulfur compound derived from garlic, in a high-carbohydrate high-fat (HCHF) diet-induced rat model of MetS.
RESULTS: Herein, we report that DATS improves MetS parameters via significantly downregulating the mRNA expression of PCSK-9 (1.59-fold when compared with HCHF control) and its transcriptional activator, HNF-1α. Similarly, the mRNA expression (-3.19-fold) and the ex-vivo enzymatic activity of 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase (HMG-R) were attenuated in DATS-treated rats. In contrast, DATS significantly increased the low-density lipoprotein-receptor (LDL-R) mRNA expression by 1.98-fold. This unique regulation of PCSK-9/LDL-R axis, HNF1α, and HMG-R was well corroborated by the reduced plasma level of PCSK-9, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs). Furthermore, the mRNA expression and circulatory level of inflammatory cytokines i.e., interleukin (IL)-1, IL-6, tumor necrosis factor-α (TNF-α) and chemokines i.e., Chemokine (C-X-C motif) ligand (CXCL)-1, CXCL-2, and monocyte chemoattractant protein-1 (MCP-1) were also ameliorated after DATS intervention. The expression of peroxisome proliferator-activated receptors (PPAR)-α, β, and γ was also upregulated after treatment with DATS, when compared to untreated HCHF group.
CONCLUSION: This comprehensive investigation demonstrates that DATS mitigates HCHF diet-induced MetS by targeting molecular regulators of cholesterol homeostasis, oxidative stress, glycemic indices, and inflammation. These findings suggest that DATS may serve as a promising therapeutic agent in preventing and managing MetS and associated cardiometabolic risks.