Methyl vanillate

The dimerization of methyl vanillate improves its effect against breast cancer cells via pro-oxidant effect

Phenolic phytochemicals are a group of organic compounds with potent antioxidant features but can also act as powerful pro-oxidants. These characteristics are effective in reducing metastatic potential in cancer cells, and this effect has been associated with reactive oxygen species (ROS). Methyl vanillate (MV) and its dimer, methyl divanillate (DMV), are potent antioxidants. In the present study, we investigated the effects of MV and DMV on breast cancer cell lines MCF-7 and MDA-MB-231 and compared the results using the non-tumor cell line HB4a. Our results indicated that the compounds performed a pro-oxidant action, increasing the generation of ROS. DMV decreased the viability cell, showing a higher apoptotic effect and inhibition of proliferation than MV on both cell lines, with significant differences between groups (p < 0.05). Some modulation of NOX4, NOX5, and DUOX were observed, but the results did not correlate with the intracellular production of ROS. The dimer showed more effectivity and pro-oxidant effect than MV, impacting cell line MCF-7 in higher extension than MDA-MB-231. In conclusion, and corroborating with reported works, the dimerization of natural phenolic compounds was associated with improved beneficial biological effects as a potential cytotoxic agent to tumor cells.

Synergistic Osteogenesis of Biocompatible Reduced Graphene Oxide with Methyl Vanillate in BMSCs

Methyl vanillate (MV), a recently characterized small molecule, can promote the Wnt/β-catenin signaling pathway and induce osteoblast differentiation both in vitro and in vivo. On the other hand, graphene-based materials have been introduced into the field of biomedical sciences in the past decade, and graphene oxide (GO), which serves as an efficient nanocarrier for drug delivery, has attracted great attention for its biomedical applications in tissue engineering. This study aimed to develop a biocompatible gelatin-reduced graphene oxide (GOG) for MV delivery so as to realize the effective osteogenesis for bone repair. First, GOG was prepared, and its morphology as well as properties were then characterized using scanning electron microscope (SEM), transmission electron microscopy (TEM), atomic force microscope (AFM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA), respectively. In addition, the endocytosis of GOG in bone marrow stromal cells (BMSCs) was also investigated with the treatment of Rhodamine 6G (R6G)-labeled GOG. Our results found that GOG could be easily absorbed by cells and was distributed in both nucleus and cytoplasm, thus suggesting the favorable biocompatibility of GOG. Moreover, the effect of MV on osteogenesis was also tested, the results of which indicated that MV could promote BMSC osteogenesis in a concentration-dependent manner, and significant enhancement could be achieved at the concentration of 1 μg/mL. In addition, the complex containing different concentrations of GOG and an optimal concentration of MV was used to investigate the synergistic effect between GOG and MV on pro-osteogenesis. The results revealed that the weight ratio of MV/GOG of 1:1000 could attain remarkably enhanced osteoinduction in BMSCs, as evaluated by alkaline phosphatase (ALP) assay, alizarin red S (ARS) staining, immunofluorescence staining, and gene expression of related osteogenic markers. Taken together, these data had provided strong evidence that the complex of MV and GOG could induce osteogenesis, which was promising for bone tissue engineering.

Hovenia dulcis Thunb extract and its ingredient methyl vanillate activate Wnt/β-catenin pathway and increase bone mass in growing or ovariectomized mice

The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV), one of the ingredients in HDT, also activated the Wnt/β-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.

Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-α/IFN-γ-induced chemokines production in HaCaT cells

Objectives: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells.
Methods: HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically.
Key findings: In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells.
Conclusion: These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.

Topical application of the Wnt/β-catenin activator methyl vanillate increases hair count and hair mass index in women with androgenetic alopecia

Background: Activation of the WNT/β-catenin pathway has emerged as a potential therapeutic target in androgenetic alopecia (AGA). Methyl vanillate (MV) - a safe plant-derived ingredient - has been recently shown to activate the WNT/β-catenin signaling. Objectives Two distinct substudies were conducted. First, we designed a 6-month, uncontrolled, open-label clinical study to investigate whether topically applied MV may increase hair count and hair mass index (HMI) in female AGA. Second, we conducted a molecular study on the effect of MV on WNT10B mRNA expression in scalp biopsies of women with AGA.
Methods: A total of 20 Caucasian women (age range: 25-57 years) with AGA (Sinclair grade 1-2) were included. The research product was an alcohol-free formulation supplied in the form of a spray containing 0.2% MV as the active ingredient.
Results: In the clinical study, hair count and HMI were found to increase at 6 months by 6% (P < 0.01) and 12% (P < 0.001), respectively, compared with baseline. No participant discontinued treatment due to adverse effects, and the overall patient satisfaction was good. At the molecular level, the topical application of the research product resulted in a 32% increase in WNT10B mRNA expression levels in the temporal scalp area (P < 0.001).
Conclusion: Our pilot data suggest that topical MV can increase hair count and HMI by inducing WNT10B expression in the scalp, potentially serving as a novel treatment strategy for female AGA.