Hovenia dulcis Thunb Extract and Its Ingredient Methyl Vanillate Activate Wnt/β-Catenin Pathway and Increase Bone Mass in Growing or Ovariectomized Mice

Abstract

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.

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

“…The results of our clinical and molecular studies indicate that topically applied MV − a safe plant‐derived ingredient – may increase both hair count and HMI by promoting WNT10B mRNA expression in the treated scalp of women with AGA. We also identified significant positive correlations between the increase of WNT10B expression in the scalp and the magnitude of increase in both hair density and HMI.…”

“…7 Methyl vanillate (MV) À a plant-derived ingredient that can be used in cosmetic preparationshas been previously shown to activate the WNT/b-catenin pathway in human cells in a dose-dependent manner. 18 In this report, we intended to prove the concept that stimulation of this pathway by topical MV could serve as a potential strategy for promoting hair growth in AGA. To this aim, two distinct substudies were conducted.…”

Hovenia Dulcis Extract Reduces Lipid Accumulation in Oleic Acid‐Induced Steatosis of Hep G2 Cells via Activation of AMPK and PPARα/CPT‐1 Pathway and in Acute Hyperlipidemia Mouse Model

“…Hovenia dulcis Thunb (HDT) has been traditionally applied to liver diseases in Asian countries (Hyun et al ., ). Furthermore, HDT has been scientifically proved to have anti‐fatigue (Na et al ., ), hematopoietic (Cha et al ., ), anti‐diabetes (Ji et al ., ), neuroprotective (Li et al ., ), antioxidant (Li et al ., ), hepatoprotective (Wang et al ., ), anti‐allergic (Yoshikawa et al ., ), and anti‐adipogenic (Kim et al ., ) activities to date. Nevertheless, the underlying anti‐fatty liver mechanism of HDT was not fully understood until now.…”

Spontaneous poisoning by Hovenia dulcis in dairy cattle in Southwest Parana, Brazil

“…In Asian herbal medicine, H. dulcis leaves and fruits are prescribed as diuretics and antidotes (Teschke and Eickhoff 2015) and as neuro and hepatic protectors (Cha et al 2014). They are also extensively used for minimizing the effects of acute alcoholic intoxication (hangovers), since they have antioxidants capable of reducing the oxidative stress associated to alcohol metabolism (Xiong et al 2012).…”

“…Therewithal, a recent study carried out by Cha et al (2014) showed that this plant synthesizes an effective anabolic agent for treating osteoporosis. However, consistent evidences indicate that the extended use of H. dulcis teas and infusions can lead to irreversible liver dysfunction, which only treatment is hepatic transplantation (Kim et al 2012).…”