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J Ethnopharmacol. 2016 Feb 3;178:238-50. doi: 10.1016/j.jep.2015.12.015. Epub 2015 Dec 15.

The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6J mice.

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Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea.
AngioLab, Inc., Daejeon 305-509, Republic of Korea.
Department of Formula Sciences, College of Korean Medicine, Dongeui University, Busan 614-052, Republic of Korea.
Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea. Electronic address:



Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.


ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.


ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.


These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.


Adipogenesis; Angiogenesis; Anti-angiogenic plant; MMP; Melissa officinalis; Obesity

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