Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells

<i>Platycladus orientalis</i>, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation a...

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Main Authors: Chan Hee Cho, Si Hyeon Chae, Ngoc Han Le Thi, Sung Hee Um, Seulah Lee, Jae Sik Yu, Ki Sung Kang, Ki Hyun Kim
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Plants
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Online Access:https://www.mdpi.com/2223-7747/14/9/1357
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author Chan Hee Cho
Si Hyeon Chae
Ngoc Han Le Thi
Sung Hee Um
Seulah Lee
Jae Sik Yu
Ki Sung Kang
Ki Hyun Kim
author_facet Chan Hee Cho
Si Hyeon Chae
Ngoc Han Le Thi
Sung Hee Um
Seulah Lee
Jae Sik Yu
Ki Sung Kang
Ki Hyun Kim
author_sort Chan Hee Cho
collection DOAJ
description <i>Platycladus orientalis</i>, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation aimed at discovering bioactive natural products and elucidating their mechanisms of action from various natural sources, we investigated a methanol (MeOH) extract of <i>P. orientalis</i> leaves. This investigation led to the isolation and identification of a labdane-type diterpene, lambertianic acid (LA), via column chromatography and HPLC purification. The structure of LA was elucidated using LC/MS and NMR spectroscopic analyses, including HR-ESIMS, while its absolute configuration was confirmed through electronic circular dichroism (ECD) calculations. Recent studies have reported that labdane-type diterpenes exhibit diverse pharmacological activities, such as anticancer, anti-inflammatory, anti-obesity, and hypolipidemic effects. Notably, LA has been shown to modulate adipocyte metabolism via AMPK signaling; however, its role in skeletal muscle atrophy remains unexplored. Therefore, in this study, we investigated the effects of LA on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Treatment with LA at concentrations of 25 µM and 50 µM significantly rescued myotube diameter and reduced the expression of atrophy-related proteins, including MuRF-1 and atrogin-1/MAFbx, without compromising cell viability at these moderate concentrations. These findings suggest that LA derived from <i>P. orientalis</i> exerts protective effects against skeletal muscle atrophy, highlighting its potential as a promising natural therapeutic candidate for muscle-wasting disorders.
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spelling doaj-art-254df2c4f3b84369a334cfae2eb4371c2025-08-20T03:52:56ZengMDPI AGPlants2223-77472025-04-01149135710.3390/plants14091357Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy CellsChan Hee Cho0Si Hyeon Chae1Ngoc Han Le Thi2Sung Hee Um3Seulah Lee4Jae Sik Yu5Ki Sung Kang6Ki Hyun Kim7School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, Republic of KoreaDepartment of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Oriental Medicine Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin 17104, Republic of KoreaDepartment of Integrative Biological Sciences and Industry, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 05006, Republic of KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea<i>Platycladus orientalis</i>, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation aimed at discovering bioactive natural products and elucidating their mechanisms of action from various natural sources, we investigated a methanol (MeOH) extract of <i>P. orientalis</i> leaves. This investigation led to the isolation and identification of a labdane-type diterpene, lambertianic acid (LA), via column chromatography and HPLC purification. The structure of LA was elucidated using LC/MS and NMR spectroscopic analyses, including HR-ESIMS, while its absolute configuration was confirmed through electronic circular dichroism (ECD) calculations. Recent studies have reported that labdane-type diterpenes exhibit diverse pharmacological activities, such as anticancer, anti-inflammatory, anti-obesity, and hypolipidemic effects. Notably, LA has been shown to modulate adipocyte metabolism via AMPK signaling; however, its role in skeletal muscle atrophy remains unexplored. Therefore, in this study, we investigated the effects of LA on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Treatment with LA at concentrations of 25 µM and 50 µM significantly rescued myotube diameter and reduced the expression of atrophy-related proteins, including MuRF-1 and atrogin-1/MAFbx, without compromising cell viability at these moderate concentrations. These findings suggest that LA derived from <i>P. orientalis</i> exerts protective effects against skeletal muscle atrophy, highlighting its potential as a promising natural therapeutic candidate for muscle-wasting disorders.https://www.mdpi.com/2223-7747/14/9/1357<i>Platycladus orientalis</i>lambertianic acidelectronic circular dichroism (ECD) calculationsC2C12muscle atrophydexamethasone
spellingShingle Chan Hee Cho
Si Hyeon Chae
Ngoc Han Le Thi
Sung Hee Um
Seulah Lee
Jae Sik Yu
Ki Sung Kang
Ki Hyun Kim
Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells
Plants
<i>Platycladus orientalis</i>
lambertianic acid
electronic circular dichroism (ECD) calculations
C2C12
muscle atrophy
dexamethasone
title Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells
title_full Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells
title_fullStr Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells
title_full_unstemmed Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells
title_short Lambertianic Acid from <i>Platycladus orientalis</i> Inhibits Muscle Atrophy in Dexamethasone-Induced C2C12 Muscle Atrophy Cells
title_sort lambertianic acid from i platycladus orientalis i inhibits muscle atrophy in dexamethasone induced c2c12 muscle atrophy cells
topic <i>Platycladus orientalis</i>
lambertianic acid
electronic circular dichroism (ECD) calculations
C2C12
muscle atrophy
dexamethasone
url https://www.mdpi.com/2223-7747/14/9/1357
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