P-85
生命科学

Ashwagandha Extracts Protect Hepatocytes
from Palmitate Acid Induced Lipid Accumulation
and Oxidative Stress
SATテクノロジー・ショーケース 2022

■ Introduction
Ashwaganda (Withania Somnifera) is an ayurvedic herb
commonly used for a variety of health benefits in Indian
traditional home medicine system. It is enriched in steroidal
lactones that have been shown to be the bioactives. Amongthe active withanolides, Withaferin A (Wi-A) has beenshown to possess good anticancer activity and Withanone(Wi-N) has been shown to possess antistress and antiaging
potentials including improvement of memory and brain
function1-3. In this study, we aim to investigate the effect ofAshwagandha extracts and some purified withanolides onsteatosis, abnormal retention of fat within a cell or organ that
often affects liver as non-alcoholic fatty liver disease(NAFLD)4.

proliferator-activated receptor (PPAR)γ, a key factor
involved in hepatic lipogenesis, showed decrease in cells
treated with some of these extracts. PPARα, the transcription
factor that upregulating fatty acid oxidization was induced
by PA treatment related to a beneficial effect in preventing
lipotoxicity and decreased in specific extract-treated cells.
Ashwagandha extracts may provide a useful natural
resource with anti-steatosis and anti-oxidative stress activity,
maintaining liver health and NAFLD prevention.
■ Reference[1] AN Sari, et. al., Cancers (Basel). 12(5), 1160 (2020).
[2] S Garg, et. al., J Gerontol A Biol Sci Med Sci. 75(6), 1031 (2020).
[3] S Garg, et. al., Ann. Neurosci. 25(4),201 (2018).
[4] DH Ipsen, et. al., Cell Mol Life Sci. 75(18), 3313 (2018).

■ Material & methods
Cytotoxicity of these extracts on human hepatocytes(Huh-7) was evaluated by cell viability assays. Nontoxic
doses were used to treat the cells subjected to activated lipid
accumulation by palmitic acid (PA). The lipolygenesis wasevaluated by Oil Red O, triglyceride (TG) assays andReactive oxygen species (ROS) assays, and the expressionof molecules involved in this process.

Ss■ Results & discussion
Wi-A and Wi-N have been demonstrated as major
bioactive ingredients. Based on this, we engineered methods
to obtain extracts from Ashwagandha leaves and stems. The
four kinds of extracts; (i) high amount of total withanolides(a) high ratio of Wi-A and (b) high ratio of Wi-N and (ii) low
amount of total withanolides- (a) high ratio of Wi-A and (b)high ratio of Wi-N were selected. Cytotoxicity studies ofthese compounds showed higher cytotoxicity of (ia); theother three were mild.
Cells were treated with PA to induce lipid accumulation.
We found that in cells pre-treated with specificAshwahandha extracts, TG and ROS accumulation weredecreased. Of note, Sterol regulatory element-binding
protein-1c (SREBP-1c), and its downstream effector-Fatty
acid synthase (FASN), the key regulators of lipogenesis
showed downregulation in specific extract-treated cells.
Furthermore,theexpressionofPeroxisome

The protein level of fatty acid synthase (FASN) was decreasedby Ashwaganda extracts pretreatment.

代表発表者
所
属

李 冬陽（LI DONGYANG）
産業技術総合研究所 細胞分子工学研究部門
AIST-INDIA 機能性資源連携研究室

問合せ先〒305-8565 茨城県つくば市東 1-1-1 中央第 5-41
TEL：029-861-2900

FAX：029-861-2900

E-mail: li.dongyang@aist.go.jp‒ 87 ‒■キーワード： （1）Ashwagandha extracts（2）Lipid accumulation（3）Oxidative stress