Investigating Khat (Catha edulis Forsk) Bioactive compounds for HMG-CoA Reductase Inhibition and Hyperlipidemia Management

The prevalence of metabolic diseases such hyperlipidemia and cardiovascular diseases (CVDs) has risen as a result of the global increase in the consumption of high-fat diets (Siddiqi, 2022). One of the known therapies that prevents hyperlipidemia is to decrease the level of blood cholesterol and LDL-C. Statins remain the gold standard therapy by inhibiting HMG-CoA Reductase, the rate-limiting enzyme in cholesterol biosynthesis. However, their adverse effects, including myopathy, hepatotoxicity, and drug intolerance, highlight the need for alternative or complementary lipid-lowering agents (Khatiwada & Hong, 2024). Plant-based compounds with bioactive phytochemicals have emerged as promising therapeutic candidates (Muscoli et al., 2022). Catha edulis is traditionally consumed in East Africa and Yemen for its stimulant effects, but its phytochemical richness suggests additional pharmacological properties (Kiros, 2020; Getasetegn, 2016). Lyophilization preserves labile compounds such as cathinone, maintaining extract integrity for bioactivity studies. By integrating GC-MS phytochemical profiling, in vivo evaluation in high-fat diet–induced hyperlipidemic rats, and molecular docking analyses, this study provides a dual experimental–computational approach to elucidate the lipid-modulatory potential of khat and identify candidate natural inhibitors of HMG-CoA Reductase.