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Int J Mol Sci. 2017 Apr 17;18(4). pii: E846. doi: 10.3390/ijms18040846.

The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function.

Author information

1
Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea. sdsd2586@naver.com.
2
Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea. lhr6515@naver.com.
3
Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea. tbvjwhdtlsdl@naver.com.
4
Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea. kelberoth30@naver.com.
5
Department of Formula Sciences, College of Korean Medicine, Dongeui University, Busan 47340, Korea. ssshin@deu.ac.kr.
6
Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea. yoon60@mokwon.ac.kr.

Abstract

Similar to neoplastic tissues, growth and development of adipose tissue are thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is associated with development and progression of nonalcoholic fatty liver disease (NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity-induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube formation in vitro. HFD increased VAT angiogenesis and induced weight gains including body weight, VAT mass and visceral adipocyte size compared with LFD. However, HFD-ALS led to weight reductions without affecting calorie intake compared with HFD. HFD-ALS also reduced serum ALT and AST levels and improved lipid metabolism. HFD-ALS suppressed steatosis, infiltration of inflammatory cells, and accumulation of collagen in livers. HFD-ALS modulated hepatic expression of genes involved in lipid metabolism, inflammation, fibrosis, antioxidation, and apoptosis. Concomitantly, analysis of VAT function revealed that HFD-ALS led to fewer CD68-positive macrophage numbers and lower expression of inflammatory cytokines compared with HFD. Our findings show that the anti-angiogenic herbal extract ALS-L1023 attenuates NAFLD by targeting VAT during obesity, suggesting that angiogenesis inhibitors could aid in the treatment and prevention of obesity-induced human NAFLD.

KEYWORDS:

Melissa officinalis; herbal medicine; visceral adipose inflammation; visceral obesity

PMID:
28420164
PMCID:
PMC5412430
DOI:
10.3390/ijms18040846
[Indexed for MEDLINE]
Free PMC Article
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