Inhibitory Effect of Isopanduratin A on Adipogenesis: A Study of Possible Mechanisms

Abstract

The root of Boesenbergia rotunda, a culinary plant commonly known as fingerroot, has previously been reported to possess anti-obesity activity, with four flavonoids identified as active principles, including pinostrobin, panduratin A, cardamonin, and isopanduratin A. However, the molecular mechanisms underlying the antiadipogenic potential of isopanduratin A remain unknown. In this study, isopanduratin A at non-cytotoxic concentrations (1–10 μM) significantly suppressed lipid accumulation in murine (3T3-L1) and human (PCS-210-010) adipocytes in a dose-dependent manner. Downregulation of adipogenic effectors (FAS, PLIN1, LPL, and adiponectin) and adipogenic transcription factors (SREBP-1c, PPARγ, and C/EBPα) occurred in differentiated 3T3-L1 cells treated with varying concentrations of isopanduratin A. The compound deactivated the upstream regulatory signals of AKT/GSK3β and MAPKs (ERK, JNK, and p38) but stimulated the AMPK-ACC pathway. The inhibitory trend of isopanduratin A was also observed with the proliferation of 3T3-L1 cells. The compound also paused the passage of 3T3-L1 cells by inducing cell cycle arrest at the G0/G1 phase, supported by altered levels of cyclins D1 and D3 and CDK2. Impaired p-ERK/ERK signaling might be responsible for the delay in mitotic clonal expansion. These findings revealed that isopanduratin A is a strong adipogenic suppressor with multi-target mechanisms and contributes significantly to anti-obesogenic activity. These results suggest the potential of fingerroot as a functional food for weight control and obesity prevention.

Potential Lipolytic Effect of Panduratin A Loaded Microspicule Serum as a Transdermal Delivery Approach for Subcutaneous Fat Reduction

“…This indicated that low concentration of isopanduratin A could reduce cellular fat accumulation in human preadipocytes. 19) Therefore, treatment of 3T3-L1 adipocytes with BP-3 extract at the concentrations of 1 to 10 µg/mL during adipogenesis markedly decreased triglyceride accumulation without cytotoxicity, indicating that the anti-obesity potential of BP-3 extract can reduce adipogenesis and lipid accumulation.…”

“…2) Additionally, the mechanism of the lipolytic action of isopanduratin A have been reported as the suppressive effect on 3T3-L1 adipogenesis by downregulating adipogenic effectors (fatty acid synthase (FAS), perilipin 1 (PLIN1), lipoprotein lipase (LPL), and adiponectin) and adipogenic transcription factors (sterol regulatory element-binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), and CCA AT/enhancer binding protein α (C/EBPα)), which these lipid metabolism proteins are essential for maintaining cellular lipid homeostasis and associated with metabolic conditions such as hyperlipidemia, insulin resistance, atherosclerosis, and obesity. 19) BP-3 extract-loaded MS serum was successfully formulated with a good appearance and smooth texture upon application onto the skin. MS serum strongly increased the skin permeability of panduratin A, because microneedling can create transportation routes for many compounds through the skin.…”

Anti-Obesity Effect of Lactobacillus acidophilus DS0079 (YBS1) by Inhibition of Adipocyte Differentiation through Regulation of p38 MAPK/PPARγ Signaling

“…Isopanduratin A and other phytochemicals positively affect fat formation through activation of the AMP-activated protein kinase (AMPK)-acetyl-CoA carboxylase (ACC) pathway. Isopanduratin A causes dephosphorylation of p-ERK/ERK signaling, which slows adipogenesis in 3T3-L1 cells by inducing growth arrest [ 38 , 39 ]. However, the specific processes involved in the regulation of MCE during adipogenesis by LAB remain unclear.…”