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Page 6 Li et al. J Transl Genet Genom 2021;5:163-72 https://dx.doi.org/10.20517/jtgg.2021.22

Figure 2. Dietary feeding of the KRE reduces tumorigenesis in TRAMP mice. (A) Upper panel, schematic presentation of intervention
protocol by the KRE in the TRAMP model. Lower panel, average GU weights in different treatment groups. **P < 0.01. (B) Percentages
of mice with large tumor formation. *P < 0.05 and **P < 0.01. (C) 0.6% KRE food results in a reduction of food consumption over time.
(D) Dietary feeding of 0.3% and 0.6% KRE food reduces mean body weight gain of TRAMP mice over time. KRE: Kava root extract;
TRAMP: transgenic adenocarcinoma of the mouse prostate; GU: genitourinary.

Figure 3. Kavalactones inhibits MAO-A enzyme activity. (A, B) Kawain and methysticin were docked with MAO-A protein by
Autodocktools program, and the superimposed binding of kawain and methysticin to MAO-A, respectively, was observed in Pymol
program. 2D molecular structures of kawain and methysticin are shown to interact with key amino acids on the predicted binding site.
(C) MAO-A enzyme activities were analyz ed in prostate cancer C4-2B and LNCaP cell lysates after treatment with 0.1% DMSO
(control), KRE and kavalactones for 24 h. MAO-A: Monoamine oxidase A; KRE: kava root extract. *P < 0.05.

In vitro LSD1 inhibitory activity assay shows that kawain and methysticin have the most significant
inhibition against LSD1 enzyme activity among the tested kavalactones [Figure 4C]. In addition, protein
expression levels of dimethylated H3K9 were observed to be significantly increased in KRE, methysticin,