Centipeda minima (L.) A. Braun & Asch is a well-studied plant in Chinese medicine that is used for the treatment of several diseases. A recent study has revealed the effects of extract of Cetipeda minima (CMX) standardized by brevilin A in inducing hair growth. However, the mechanism of action of CMX in human hair follicle dermal papilla cells (HFDPCs) has not yet been identified. We aimed to investigate the molecular basis underlying the effect of CMX on hair growth in HFDPCs. CMX induced the proliferation of HFDPCs, and the transcript-level expression of Wnt family member 5a (Wnt5a), frizzled receptor (FZDR), and vascular endothelial growth factor (VEGF) was upregulated. These results correlated with an increase in the expression of growth-related factors, such as VEGF and IGF-1. Immunoblotting and immunocytochemistry further revealed that the phosphorylation of ERK and JNK was enhanced by CMX in HFDPCs, and β-catenin accumulated significantly in a dose-dependent manner. Therefore, CMX substantially induced the expression of Wnt signaling-related proteins, such as GSK phosphorylation and β-catenin. This study supports the hypothesis that CMX promotes hair growth and secretion of growth factors via the Wnt/β-catenin, ERK, and JNK signaling pathways. In addition, computational predictions of drug-likeness, together with ADME property predictions, revealed the satisfactory bioavailability score of CMX compounds, exhibiting high gastrointestinal absorption. We suggest that CMX could be used as a promising treatment for hair regeneration and minimization of hair loss.

Janus kinase 3 (JAK3) inhibitors have been used effectively in the treatment of several cases of alopecia universalis and its variants. Our study aims to evaluate whether the emulsion extract of brevilin A from Centipeda minima (CMX) stimulates hair regrowth in a clinical trial, as a JAK3 inhibitor, combined with network pharmacology-based analysis. CMX showed potent inhibition of JAK3 in a concentration-dependent manner. Significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects. The gene set enrichment analysis showed that the targets of CMX are mainly associated with the JAK-STAT signaling pathway, cytokine–cytokine receptor interactions, and the MAPK signaling pathway. This study suggests that the medicinal herbal extract CMX is useful in the treatment of mild to moderate vertex balding that contribute to the visible improvements in hair growth observed in treated patients.

Brevilin A, which has anticancer activities against a range of cancers, is an abundant constituent of the medicinal herb Centipeda minima (L.) A. Braun & Asch, which has also been reported to have anticancer activity against breast cancer cells. However, the anticancer activities of C. minima and brevilin A against human gastric cancer have yet to be reported. In this study, we aimed to evaluate the cytotoxicity and molecular basis underlying the anticancer activities of extracts of C. minima (CMX) and brevilin A against human gastric cancer (AGS) cells. We deduced the potential targets and mechanisms underlying the anticancer activity of brevilin A based on a network pharmacology approach. CCND1, CDK4, and BCL2L1 were identified as the key anticancer genes targeted by brevilin A. Cytotoxicity analyses revealed that CMX and brevilin A reduced the viability of AGS cells to levels below 50% (9.73 ± 1.29 µg/mL and 54.69 ± 1.38 μM, respectively). Furthermore, Hoechst 33342, annexin V, and propidium iodide staining and western blot analyses revealed that CMX and brevilin A promoted a significant induction of apoptotic cell death by upregulating the expression of cleaved caspase-8 and cleaved caspase-3 and reducing the ratio of Bax to Bcl-2, which is partially consistent with the findings of our network pharmacology analysis. Collectively, our observations indicate that CMX and brevilin A are novel sources of herbal medicine with potential utility as effective agents for the treatment of gastric cancer.

Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein β. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.