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Plant-derived Exosome-like Nanovesicles: Novel Therapeutics from Nature

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Hyo In Kim, Hye-Lin Kim, Leo E. Otterbein, Jinbong Park*

1 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, MA 02215, United States
2 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul
02447, Republic of Korea
* E-mail: thejinbong@khu.ac.kr

Abstract
Plant-derived exosome-like nanovesicles have emerged as a promising class of natural

therapeutics due to their low immunogenicity, high absorption efficiency, and capacity to carry
diverse bioactive cargos such as RNAs, proteins, lipids, and metabolites. This presentation will
highlight the therapeutic potential of these plant-derived nanovesicles, with a particular focus
on their application in metabolic diseases. Here, we investigate exosome-like nanovesicles

derived from the medicinal plant Platycodon grandiflorus (P-ELNs) as a potential anti-obesity
therapy. P-ELNs, when administered in vitro to 3T3-L1 adipocytes, activated AMP-activated
protein kinase (AMPK), leading to suppressed adipogenesis, enhanced lipolysis, and improved
glucose homeostasis. This correlated in vivo in a murine model of high-fat diet (HFD)-fed mice

where P-ELN treatment reduced body weight gain and white adipose tissue (WAT) mass as
compared to control. Moreover, P-ELN treatment promoted glycolytic beige fat formation and
induced non-shivering thermogenesis. P-ELNs showed a favorable safety profile with no
systemic, hepatic, or renal toxicity observed. Collectively, these findings support P-ELNs as a

safe and effective therapeutic strategy to reduce body weight in part by promoting AMPK-
dependent remodeling of inguinal WAT into glycolytic beige fat. The novelty and impact of our
findings lie in both the identification of P-ELNs as a safe, plant-based nanotherapeutic, and in
the conceptual advance that glycolytic beige fat can be pharmacologically regulated. We view

this as a paradigm shift in obesity treatment strategies, positioning glycolytic beige fat as a
viable therapeutic target by P-ELNs.

Keywords: Platycodon grandiflorus; Plant-derived exosome-like nanovesicles; Obesity;
AMP-activated protein kinase; Glycolytic beige fat

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