Phenylethanoid glycoside-enriched fraction of Clerodendrum glandulosum ameliorates oxidative stress and mitochondrial dysfunction via PGC1α/TFAM upregulation.

Abstract

Clerodendrum glandulosum is utilized as a soup or vegetable in Northeast India and has been reported to exhibit a range of medicinal and pharmacological properties. Its use in traditional cuisine and medicine highlights its potential importance in both dietary and therapeutic applications. This study focuses on the bioactive potential of the ethyl acetate fraction (EAF) derived from the hydro-alcoholic extract of C. glandulosum leaves against palmitate-induced oxidative stress and mitochondrial dysfunction. The EAF exhibited significant radical scavenging activities, with IC₅₀ values of 29.56 µg/mL (ABTS inhibition) and 36.61 µg/mL (DPPH inhibition). Additionally, EAF demonstrated strong anti-glycation properties, effectively reducing fructosamine levels and protein carbonylation while increasing total thiol content. Phytochemical analysis revealed the presence of several bioactive compounds--namely verbascoside, isoverbascoside, and ferulic acid--associated with potential biological activities. Chromatographic analysis showed that verbascoside is the primary compound, with a concentration of 240.41 ± 8.62 µg/mg. Furthermore, EAF pretreatment significantly lowered the levels of reactive oxygen species, DNA damage, and lactate dehydrogenase release in palmitate-induced cells. During extracellular flux analysis for mitochondrial and glycolysis stress tests, EAF treatment demonstrated effective recovery of mitochondrial respiration and ATP production in palmitate-induced cells. EAF also upregulated essential mitochondrial markers, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM), which enhanced mitochondrial biogenesis and function. Overall, our study underscores the potential of the EAF from Clerodendrum glandulosum as a therapeutic agent to mitigate oxidative stress and mitochondrial dysfunction. This study suggests the efficacy of the active compounds for further development of phytopharmaceutical interventions for metabolic syndrome and related disorders.