A Chalcone from Ashitaba (Angelica keiskei) Stimulates Myoblast Differentiation and Inhibits Dexamethasone-Induced Muscle Atrophy

Abstract

Ashitaba, Angelica keiskei Koidzumi (AK), as a traditional medicine in Korea, Japan, and China, has been known as an elixir of life having therapeutic potential. However, there is no scientific evidence to support that Ashitaba can enhance or maintain muscle strength. To find a new therapeutic agent from the medicinal plant, we evaluated the anti-myopathy effect of chalcones from ethanol extract of AK (EAK) in cellular and animal models of muscle atrophy. To examine anti-myopathy activity, EAK was treated into dexamethasone injected rats and muscle thickness and histopathological images were analyzed. Oral administration of EAK (250 or 500 mg/kg) alleviated muscle atrophic damages and down-regulated the mRNA levels of muscle-specific ubiquitin-E3 ligases. Among ten compounds isolated from EAK, 4-hydroxyderricin was the most effective principle in stimulating myogenesis of C2C12 myoblasts via activation of p38 mitogen-activated protein kinase (MAPK). In three cellular muscle atrophy models with C2C12 myoblasts damaged by dexamethasone or cancer cell-conditioned medium, 4-hydroxyderricin protected the myosin heavy chain (MHC) degradation through suppressing expressions of MAFbx, MuRF-1 and myostatin. These results suggest that the ethanol extract and its active principle, 4-hydroxyderricin from AK, can overcome the muscle atrophy through double mechanisms of decreasing muscle protein degradation and activating myoblast differentiation.

Flavonoids: nutraceutical potential for counteracting muscle atrophy

“…Isobavachalcone is a prenylated chalcone compound found in ashitaba (A. keiskei) and babchi (P. corylifolia) (Han et al, 2020;Kweon et al, 2019). Isobavachalcone isolated from A. keiskei extract elevated both the transcriptional activity of MyoD and the protein expression of MHC in C2C12 myotubes (Kweon et al, 2019). This increase in the transcriptional activity of MyoD in response to isobavachalcone was consistent with the findings of another study in which isobavachalcone was derived from P. corylifolia (Han et al, 2020).…”

“…In terms of the stimulatory effect of these compounds on MyoD transcriptional activity, 4-hydroxyderricin was more effective than isobavachalcone, indicating that the methoxy group in 4-hydroxyderricin is critical for stimulating myogenesis. 4-Hydroxyderricin also stimulated both myogenesis and myogenesis-related genes, including MHC, myogenin, and MyoD, by activating p38 protein (Kweon et al, 2019). Moreover, 4-hydroderricin treatment upregulated MHC expression and downregulated MuRF1, atrogin-1, and myostatin in three in vitro models of muscle wasting.…”

“…Recently, ashitaba (Angelica keiskei) extract has been reported to improve running performance and elevate the gastrocnemius muscle mass in dexamethasone-treated rats by decreasing MuRF1 and atrogin-1 expression and increasing MyoD and myogenin expression (Kweon et al, 2019). A. keiskei also stimulated myogenesis in C2C12 myotubes, as shown by an increase in MHC expression.…”

“…Isobavachalcone is a prenylated chalcone compound found in ashitaba (A. keiskei) and babchi (P. corylifolia) (Han et al, 2020;Kweon et al, 2019). Isobavachalcone isolated from A. keiskei extract elevated both the transcriptional activity of MyoD and the protein expression of MHC in C2C12 myotubes (Kweon et al, 2019).…”

Plants-Derived Biomolecules as Potent Antiviral Phytomedicines: New Insights on Ethnobotanical Evidences against Coronaviruses

“…Its bioactive components include chalcones, flavanones and coumarins, coumarins phenolic, acetylenes, sesquiterpene, diterpene, and triterpenes [ 144 , 146 ]. A. keiskei is known and considered to be antiviral, anticancer, anti-inflammatory, anti-obesity, anti-oxidative, anti-coagulant, anti-tumor, anti-mutagenic, anti-diabetic, antibacterial and hepato-protective [ 144 , 145 , 146 ]. Park et al, 2016 extracted bioactive components (9 alkylated chalcones and 4 coumarins) from A. keiskei plant [ 146 ], and revealed that the extracted chalcones were able to significantly block the entry of coronavirus (SARS-CoV-1) by inhibiting the chymotrypsin-like protease (75% inhibition using 30 µg/mL dose) and a papain-like protease (88% inhibition using 30 µg/mL dose) [ 146 ].…”