Hypromellose

To evaluate the effects of GW2580 (LC Laboratories, PKC Pharmaceuticals Inc.) following 6 weeks BCAS, mice were fed with a control diet (RM1) or a diet containing GW2580 [Modified LabDiet® PicoLab EURodent Diet 14%, 5L0W (5LF2) with 0.1% (1000 ppm) GW2580 (LC Laboratories); TestDiet] for 6 weeks, beginning 24 hours post‐surgery.
For the evaluation of microglial proliferation, mice were dosed orally with 5‐bromo‐2′‐deoxyuridine (BrdU; 50 mg/kg in 0.5% Hypromellose and 0.1% Tween80; Sigma Aldrich) for 3 consecutive days prior to sacrifice.

All reagents, standards, and solvents were used as analytical grade. Caffeic acid (≥98%, HPLC) was purchased from Sigma-Aldrich Chemie GmBh (Steinheim, Germany). d(+)-glucose monohydrate, starch, hypromellose, poloxamer 407 (Kolliphor P 407), β-cyclodextrin, and PROSOLV SMCCTM 50 were obtained from Sigma-Aldrich GmbH (Buchs, Switzerland) and (Penwest, UK), respectively, and all were used as excipients. Ethanol (96%) was purchased from AB “Vilniaus degtine” (Vilnius, Lithuania). Phosphate-buffered saline (PBS) (pH~7.4) was obtained from Gibco (Paisley, UK). Ultrapure water was produced using a water purification system Milli-Q^® (Millipore, Arlington, MA, USA). Chromatographic grade acetonitrile and trifluoracetic acid (TFA) were obtained from Sigma-Aldrich Chemie GmbH (Steinheim, Germany).

All solvents, reagents, and standards used were of analytical grade. Acetonitrile, acetic acid, D(+)-glucose monohydrate, hypromellose, Aerosil^TM 200, microcrystalline cellulose, silicon dioxide and starch were obtained from Sigma-Aldrich GmbH (Buchs, Switzerland), and ethanol was obtained from Stumbras AB (Kaunas, Lithuania). Hyperoside, rutin, quercitrin, phloridzin, procyanidin B1, procyanidin B2, and chlorogenic acid standards were purchased from Extrasynthese (Genay, France), reynoutrin, (+)-catechin and (−)-epicatechin were purchased from Sigma-Aldrich GmbH (Buchs, Switzerland), and avicularin, procyanidin C1, and isoquercitrin were purchased from Chromadex (Santa Ana, USA). In this study, we used deionized water produced by the Milli-Q^® (Millipore, Bedford, MA, USA) water purification system.

Six-weeks old NOD.Cg-Prkdc^scid Il2rg^tm1wjl/SzJ mice were obtained from Charles River (Charles River Laboratories Italia Srl). The animals were housed in pathogen-free conditions, and experiments were performed according to the National Regulation on Animal Research Resources and approved by the Institutional Review Board (Aut n°190/2021-PR (risp prot.22418.151)). UPMM3 cells (10⁷) were injected subcutaneously in 16 mice that were randomised in 4 groups of 4 mice each. Trametinib and cerivastatin were initially dissolved in DMSO and diluted into an aqueous pooled dose containing a final concentration of 0.5% hypromellose (Sigma-Aldrich) and 0.05% Tween-80 (Sigma), in saline. Control animals received the vehicle. Final maximal DMSO concentration was 8.8% v/v. Mice weight and tumours were measured weekly. Tumour volume was calculated as follows: V = ½ × L × W × H.