Application status of risk assessment models for periodontal disease / 口腔疾病防治

@#Risk assessment models for periodontal disease provide dentists with a precise and consolidated evaluation of the prognosis of periodontitis, enabling the formulation of personalized treatment plans. Periodontal risk assessment systems have been widely applied in clinical practice and research. The application fields of periodontal risk assessment systems vary based on the distinctions between clinical periodontal parameters and risk factors. The assessment models listed below are commonly used in clinical practice, including the periodontal risk calculator (PRC), which is an individual-based periodontal risk assessment tool that collects both periodontal and systemic information for prediction; the periodontal assessment tool (PAT), which allows for quantitative differentiation of stages of periodontal disease; the periodontal risk assessment (PRA) and modified periodontal risk assessment (mPRA), which are easy to use; and the classification and regression trees (CART), which assess the periodontal prognosis based on a single affected tooth. Additionally, there are orthodontic-periodontal combined risk assessment systems and implant periapical risk assessment systems tailored for patients needing multidisciplinary treatment. This review focuses on the current application status of periodontal risk assessment systems.

Integrating Network Pharmacology and Component Analysis to Study the Potential Mechanisms of Qi-Fu-Yin Decoction in Treating Alzheimer's Disease.

Purpose: To elucidate the potential mechanisms of QFY for the treatment of Alzheimer's Disease (AD), and explore the effective substances of QFY. Materials and Methods: UPLC-LTQ-Orbitrap-MS was used to identify the chemical constituents of the serum samples and the cerebrospinal fluid samples of rats after QFY administration. Network pharmacology was used to predict potential targets and pathways of QFY against AD. The AD mice model was established by subcutaneous injection of D-gal for 8 consecutive weeks. New object recognition (NOR) and Morris water maze test (MWM) were used to evaluate the learning and memory abilities of mice. Moreover, the levels of TNF-α, IL-1ß, and IL-18 in the brain hippocampus of mice were determined by ELISA. The expression of Bax, Bcl-2, Caspase-1, PSD95, SYP, ICAM-1 and MCP-1 proteins in the hippocampus was detected by Western blotting. Furthermore, qRT-PCR was used to detect the gene expressions of PSD95, SYP, M1 and M2 polarization markers of microglia, including iNOS, CD16, ARG-1, and IL-10 in the hippocampus. Results: A total of 51 prototype compounds were detected in rat serum and 15 prototype components were identified in rat cerebrospinal fluid. Behavioral experiments revealed that QFY significantly increased the recognition index, decreased the escape latency, increased the platform crossing times and increased the residence time in the target quadrant. QFY also could alleviate the ultrastructural pathological changes in the hippocampus of AD mice. Meanwhile, QFY treatment suppressed the expression of inflammatory factors, such as TNF-α, IL-1ß, and IL-18. QFY improved the synaptic plasticity of the hippocampus in D-gal model mice by significantly increasing the expression of proteins and mRNAs of PSD95 and SYP. Conclusion: QFY could effectively improve the learning and memory impairment of D-gal-induced AD mice by inhibiting the excessive activation of microglia, enhancing the expression of M2 microglia, inhibiting the increase of inflammatory factors, cell adhesion factors and chemokines, anti-apoptosis, and improving synaptic plasticity.

Naringin Protects against Tau Hyperphosphorylation in Aß 25-35-Injured PC12 Cells through Modulation of ER, PI3K/AKT, and GSK-3ß Signaling Pathways.

Alzheimer's disease (AD) is the most common form of dementia and a significant social and economic burden. Estrogens can exert neuroprotective effects and may contribute to the prevention, attenuation, or even delay in the onset of AD; however, long-term estrogen therapy is associated with harmful side effects. Thus, estrogen alternatives are of interest for countering AD. Naringin, a phytoestrogen, is a key active ingredient in the traditional Chinese medicine Drynaria. Naringin is known to protect against nerve injury induced by amyloid beta-protein (Aß) 25-35, but the underlying mechanisms of this protection are unclear. To investigate the mechanisms of naringin neuroprotection, we observed the protective effect on Aß 25-35-injured C57BL/6J mice's learning and memory ability and hippocampal neurons. Then, an Aß 25-35 injury model was established with adrenal phaeochromocytoma (PC12) cells. We examined the effect of naringin treatment on Aß 25-35-injured PC12 cells and its relationship with estrogen receptor (ER), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and glycogen synthase kinase (GSK)-3ß signaling pathways. Estradiol (E2) was used as a positive control for neuroprotection. Naringin treatment resulted in improved learning and memory ability, the morphology of hippocampal neurons, increased cell viability, and reduced apoptosis. We next examined the expression of ERß, p-AKT (Ser473, Thr308), AKT, p-GSK-3ß (Ser9), GSK-3ß, p-Tau (Thr231, Ser396), and Tau in PC12 cells treated with Aß 25-35 and either naringin or E2, with and without inhibitors of the ER, PI3K/AKT, and GSK-3ß pathways. Our results demonstrated that naringin inhibits Aß 25-35-induced Tau hyperphosphorylation by modulating the ER, PI3K/AKT, and GSK-3ß signaling pathways. Furthermore, the neuroprotective effects of naringin were comparable to those of E2 in all treatment groups. Thus, our results have furthered our understanding of naringin's neuroprotective mechanisms and indicate that naringin may comprise a viable alternative to estrogen therapy.

Yin Huo Tang, a traditional Chinese herbal formula, relives ovariectomy and empty bottle stimulation-induced menopause-like symptoms in mice.

Background: Yin Huo Tang (YHT), a traditional Chinese herbal formula, is effectively used for the clinical treatment of menopause-like symptoms in China. This study aimed to investigate its efficacy on menopause-like symptoms in mice using behavioral tests and histopathological assessment, and to determine its possible mechanism of action based on network pharmacology. Methods: Liquid chromatography-mass spectrometry (LC-MS) technology was used to identify the potential active ingredients of YHT. In mice, menopause-like symptoms were induced by combination of bilateral ovariectomy and empty bottle stimulation. The mice were then treated with the YHT aqueous extract for three weeks. Behavior, sleep state, body weight, organ index, and histomorphology were analyzed separately. Additionally, network pharmacology and molecular docking were used to predict the mechanisms underlying the action of YHT. Finally, serum estradiol was quantified to preliminarily verify the results of network pharmacology. Results: YHT not only improved the behavior of mice (attack and explore behavior reduced; modify behavior increased) but also ameliorated the sleep state (sleep time increased and incubation time reduced). YHT reduced body weight, increased uterine weight, and improved the histomorphology of some organs. Network pharmacology and molecular docking analyses revealed that the estrogen signaling pathway might play a key role in attenuating menopause-like symptoms. Furthermore, YHT treatment reversed the reduction in serum estradiol levels. Conclusions: YHT alleviates menopause-like symptoms in a mouse model, providing a rationale for using it as a potential therapeutic strategy.

Sagacious confucius' pillow elixir ameliorates Dgalactose induced cognitive injury in mice via estrogenic effects and synaptic plasticity.

Alzheimer's disease (AD) is a growing concern in modern society, and there is currently a lack of effective therapeutic drugs. Sagacious Confucius' Pillow Elixir (SCPE) has been studied for the treatment of neurodegenerative diseases such as AD. This study aimed to reveal the key components and mechanisms of SCPE's anti-AD effect by combining Ultra-high Performance Liquid Chromatography-electrostatic field Orbitrap combined high-resolution Mass Spectrometry (UPLC-LTQ/Orbitrap-MS) with a network pharmacology approach. And the mechanism was verified by in vivo experiments. Based on UPLC-LTQ/Orbitrap-MS technique identified 9 blood components from rat serum containing SCPE, corresponding to 113 anti-AD targets, and 15 of the 113 targets had high connectivity. KEGG pathway enrichment analysis showed that estrogen signaling pathway and synaptic signaling pathway were the most significantly enriched pathways in SCPE anti-AD, which has been proved by in vivo experiments. SCPE can exert estrogenic effects in the brain by increasing the amount of estrogen in the brain and the expression of ERα receptors. SCPE can enhance the synaptic structure plasticity by promoting the release of brain-derived neurotrophic factor (BDNF) secretion and improving actin polymerization and coordinates cofilin activity. In addition, SCPE also enhances synaptic functional plasticity by increasing the density of postsynaptic densified 95 (PSD95) proteins and the expression of functional receptor AMPA. SCPE is effective for treatment of AD and the mechanism is related to increasing estrogenic effects and improving synaptic plasticity. Our study revealed the synergistic effect of SCPE at the system level and showed that SCPE exhibits anti-AD effects in a multi-component, multi-target and multi-pathway manner. All these provide experimental support for the clinical application and drug development of SCPE in the prevention and treatment of AD.

TGF-ß signaling in the tumor metabolic microenvironment and targeted therapies.

Transforming growth factor-ß (TGF-ß) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-ß signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an "engine" of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-ß signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-ß ligands act as an "endocrine" cytokine and influence host metabolism. Therefore, having insight into the role of TGF-ß signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-ß to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-ß-dependent mechanism reprogramming, paving the way for TGF-ß-related antitumor therapy from the perspective of metabolism.

A Famous Chinese Medicine Formula: Yinhuo Decoction Antagonizes the Damage of Corticosterone to PC12 Cells and Improves Depression by Regulating the SIRT1/PGC-1α Pathway.

The study aimed to explore the antidepressant effect of Yinhuo Decoction and further to explore its underlying molecular mechanism acting on depressant. Here, high-performance liquid chromatography (HPLC) analysis was used to the composition analysis. Postmenopausal depression (PMD) model and corticosterone (CORT)-induced cell model were constructed. Adrenal coefficient and hematoxylin and eosin staining were applied to assess changes in the adrenal glands. MTT staining, Hoechst 33342 staining, and JC-1 fluorescence staining were used to detect the PC12 activity and apoptosis. CORT and oxidative stress indicators were measured using commercial kits. Western blot and immunohistochemical were used to detect the protein expression of GCR. In addition, genes related to SIRT1/PGC-1α pathway were also tested. In PMD model mice, Yinhuo Decoction evidently increased adrenal coefficient and relieved adrenal lesions. Meanwhile, we observed that Yinhuo Decoction reduced the CORT and GCR levels. In CORT-treated PC12 cells, Yinhuo Decoction remarkably reduced cytotoxicity and apoptosis. Besides, Yinhuo Decoction attenuated the oxidative stress response. Mechanically, we confirmed that Yinhuo Decoction reduced CORT-induced PC12 damage by regulating SIRT1/PGC-1α pathway. Thus, we concluded that Yinhuo Decoction antagonized CORT-induced injury in PC12 cells and improved depression in PMD mice. This provided a new direction for the treatment of depression.

LncRNA: A Potential Target for Host-Directed Therapy of Candida Infection.

Despite various drugs work against Candida, candidiasis represents clinical management challenges worldwide due to the rising incidence and recurrence rate, as well as epidemics, of new drug-resistant pathogens. Recent insights into interactions between Candida and hosts contribute to exploring novel therapeutic strategies, termed host-directed therapies (HDTs). HDTs are viable adjuncts with good efficacy for the existing standard antifungal regimens. However, HDTs induce other response unintendedly, thus requiring molecular targets with highly specificity. Long noncoding RNAs (lncRNAs) with highly specific expression patterns could affect biological processes, including the immune response. Herein, this review will summarize recent advances of HDTs based on the Candida-host interaction. Especially, the findings and application strategies of lncRNAs related to the host response are emphasized. We propose it is feasible to target lncRNAs to modulate the host defense during Candida infection, which provides a new perspective in identifying options of HDTs for candidiasis.

Tissue Distribution of Total Flavonoids Extracts of Drynariae Rhizoma in Young and Old Rats by UPLC-MS/MS Determination.

Drynariae Rhizoma (Kunze ex Mett.) J. Sm. has been extensively used in China, Japan, and Korea to treat osteoporosis and tonify kidneys. A rapid and validated UPLC-MS/MS method for simultaneous determination of the seven analytes including neoeriocitrin, luteolin-7-O-ß-D-glucoside, astragalin, naringin, eriodictyol, naringenin, and kaempferol in rats' various tissues (heart, liver, spleen, lung, kidney, stomach, brain, uterus, ovary, and small intestine) using quercetin as the internal standard (IS) was developed after oral administration of TFDR to rats. Tissues samples were retreated by protein precipitation with methanol. The chromatographic separation was performed using an ACQUITY UPLC™ BEH C18 column (2.1 × 50 mm; 1.7 µm) at 35°C. The mobile phase consisted of 1% acetic acid in water as the aqueous phase (A) and 100% acetonitrile as the organic phase (B). All analytes and IS were quantified through electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. MS transitions were m/z 597.5 ⟶ 289.2 for neoeriocitrin, m/z 449.1 ⟶ 287.1 for luteolin-7-O-ß-D-glucoside, m/z 449.1 ⟶ 287.1 for astragalin, m/z 581.5 ⟶ 273.2 for naringin, m/z 289.2 ⟶ 153.1 for eriodictyol, m/z 273.2 ⟶ 153.1 for naringenin, m/z 287.1 ⟶ 153.1 for kaempferol, and m/z 303.2 ⟶ 153.1 for quercetin (IS). The mean extraction recovery of the seven analytes and IS in tissue samples at three levels of quality control (QC) samples ranged from 82.72% to 118.57%, and the RSD was ≤14.98%. The intraday and interday precision (RSD) were all less than 14.98%, and the accuracy (RE) ranged from -13.96% to 14.96%, which indicated that the present method was not an issue. Tissues distribution showed neoeriocitrin, luteolin-7-O-ß-D-glucoside, astragalin, naringin, and naringenin could transfer across the blood-brain barrier, which may form the basis of TFDR entering the brain to play an anti-AD role. Compared with the 8-month-old rats, a higher concentration of naringin was found in the ovaries of the 18-month-old rats; this result indicated that it may regulate the autonomic nervous dysfunction of the cerebrospinal system through the hypothalamus-pituitary-ovary axis, thus playing an anti-AD role, but further research is needed. Naringenin, eriodictyol, and kaempferol have a higher concentration in the liver and kidney; this phenomenon may be related to the traditional Chinese medicine theory that there is a definite relationship between the liver and kidney meridian. These results provide reliable data support for further study of the pharmacological mechanism of TFDR, formulation of drug delivery schemes, and development of new Chinese medicines in the treatment of AD.

[Total flavonoids of Drynariae Rhizoma regulates ER-p38 MAPK signaling pathway to improve scopolamine-induced learning and memory impairments in model mice].

This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERß expression was detected by immunohistochemistry, and the expression levels of ERß and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERß, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERß and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.

Protective mechanism of kaempferol against Aß25-35-mediated apoptosis of pheochromocytoma (PC-12) cells through the ER/ERK/MAPK signalling pathway.

INTRODUCTION: Progressive accumulation of amyloid-ß (Aß) is a pathological trait of Alzheimer's disease (AD). Amyloid-ß increases free radical production in neuronal cells, leading to neuronal cell death. Hormone replacement therapy can reduce the incidence of AD, and oestrogen significantly improves the clinical signs in patients with AD. However, the long-term use of oestrogen causes a variety of diseases. Phytoestrogens have been reported to bind and activate oestrogen receptors in mammals and humans to produce oestrogen-like or anti-oestrogen-like effects. Kaempferol is a flavonoid phytoestrogen that can produce a certain protective effect in neurons. However, the molecular mechanism of kaempferol in AD is unclear. MATERIAL AND METHODS: This study used pheochromocytoma (PC-12) cells that were damaged by Aß25-35 as an in vitro model of AD, and oestradiol was a positive control. The cells were incubated with kaempferol alone or in combination with fulvestrant (an antagonist of ER) and U0126 (an inhibitor of ERK) in Aß25-35 culture. Cell activity was measured by the MTT method. Cell apoptosis was evaluated by flow cytometry. Gene and protein expression levels were tested by qRT-PCR and Western blotting. RESULTS: This study demonstrated that kaempferol protected PC-12 cells from Aß25-35-induced cell death and apoptosis in a dose-dependent manner. Treatment with fulvestrant (an antagonist of ER) and U0126 (an inhibitor of ERK) significantly increased the apoptosis of PC-12 cells. Moreover, kaempferol promoted the expression of anti-apoptotic molecules and inhibited the expression of pro-apoptotic molecules, which were blocked by fulvestrant and U0126. CONCLUSIONS: Kaempferol protected PC-12 cells against Aß25-35-induced cell apoptosis through the ER/ERK/MAPK signalling pathway.

Analysis of methylation-driven genes for predicting the prognosis of patients with head and neck squamous cell carcinoma.

To help provide evidence for prognosis prediction and personalized targeted therapy for patients with head and neck squamous cell carcinoma (HNSCC), we investigated prognosis-specific methylation-driven genes in HNSCC. Survival time data, RNA sequencing data, and methylation data for HNSCC patients were downloaded from The Cancer Genome Atlas. The MethylMix R package based on the ß mixture model was utilized to screen genes with different methylation statuses in tumor tissues and adjacent normal tissues, and a total of 182 HNSCC-related methylation-driven genes were then identified. A survival prediction scoring model based on multivariate Cox analysis was developed to screen the genes related to the prognosis of HNSCC, and a linear risk model of the methylation status of six genes (INA, LINC01354, TSPYL4, MAGEB2, EPHX3, and ZNF134) was constructed. The prognostic values of the six genes were further independently explored by survival analysis combined with methylation and gene expression analyses. The 5-year survival rate in the high-risk group of patients in the test set was 30.4% (95% CI: 22.7%-40.8%) and that in the low-risk group of patients was 65.5% (95% CI: 56.1%-76.5%). The area under the receiver operating characteristic curve for the model was 0.723, which further verified the specificity and sensitivity of the model. In addition, subsequent combined survival analysis revealed that all six genes could be used as independent prognostic markers and thus might be potential drug targets. The innovative method provides new insight into the molecular mechanism and prognosis of HNSCC.

Long-term estrogen deprivation changes the response to antianxiety drugs in mice in the elevated plus maze test.

Estrogen deficiency increases the incidence of female anxiety disorders; however, whether estrogen deficiency alters responses to anxiolytic drugs is unknown. We studied whether long-term estrogen deprivation (ovariectomy, OVX) changes the behavior of mice to anxiolytic drugs (buspirone, diazepam, and venlafaxine), using the elevated plus maze (EPM) test. The percentages of EPM open-arm time and EPM open-arm entries of the OVX mice decreased significantly compared to control, and sham mice 2 months after OVX. The response to buspirone increased in the OVX mice at 1 week, while OVX decreased the response to diazepam at 2 months. Moreover, we found the efficacy of diazepam was significantly decreased, compared to buspirone and venlafaxine, at 2 months. These results suggest that OVX may change responses to different anxiolytic drugs. Not all anti-anxiety drugs appear to be suitable for anxiety caused by estrogen deficiency.

Discovery of potential therapeutic targets for non-small cell lung cancer using high-throughput metabolomics analysis based on liquid chromatography coupled with tandem mass spectrometry.

Lung cancer is a severe health problem and threatens a patient's quality of life. The metabolites present in biological systems are expected to be key mediators and the changes in these metabolites play an important role in promoting health. Metabolomics can unravel the global metabolic changes and identify significant biological pathways involved in disease development. However, the role of metabolites in lung cancer is still largely unknown. In the present study, we developed a liquid chromatography coupled with tandem mass spectrometry method for biomarker discovery and identification of non-small cell lung cancer (NSCLC) from metabolomics data sets and aimed to investigate the metabolic profiles of NSCLC samples to identify potential disease biomarkers and to reveal the pathological mechanism. After cell metabolite extraction, the metabolic changes in NSCLC cells were characterized and targeted metabolite analysis was adopted to offer a novel opportunity to probe into the relationship between differentially regulated cell metabolites and NSCLC. Quantitative analysis of key enzymes in the disturbed pathways by proteomics was employed to verify metabolomic pathway changes. A total of 13 specific biomarkers were identified in NSCLC cells related with metabolic disturbance of NSCLC morbidity, which were involved in 4 vital pathways, namely glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis, tyrosine metabolism and sphingolipid metabolism. The proteomics analysis illustrated the obvious fluctuation of the expression of the key enzymes in these pathways, including the downregulation of 3-phosphoglycerate dehydrogenase, phosphoserine phosphatase, tyrosinase and argininosuccinic acid catenase. NSCLC occurrence is mainly related to amino acid and fatty acid metabolic alteration. These findings highlight that the metabolome can provide information on the molecular profiles of cells, which can aid in investigating the metabolite changes to reveal the pathological mechanism.

Effects of bavachin and its regulation of melanin synthesis in A375 cells.

The aim of the present study was to investigate the effect of bavachin treatment on A375 cells and the regulation of melanin synthesis. The cultured A375 cells in vitro were treated with bavachin; and the effect of bavachin on cell activity, tyrosinase (TYR) activity and melanin synthesis were respectively tested by the MTT assay, L-dopa oxidation assay and the NaOH lysis assay. The expression levels of TYR and c-Jun N-terminal kinases (JNK) proteins were tested by western blot analysis. The expression levels of TYR, tyrosinase-related protein-1 (TRP-1), TRP-2, extracellular signal-regulated kinase 1 (ERK1), ERK2 and JNK2 mRNA were tested by the reverse transcription-polymerase chain reaction assay. Simultaneously, the effect of estrogen receptor inhibitor (ICI182780) and ERK pathway inhibitor (U0126) was also tested on A375 cells following bavachin. The safe dose of bavachin significantly inhibited melanin synthesis and TYR activity. Bavachin (10 µmol/l) inhibited the expression of TYR and JNK proteins, and the expression of TYR, TRP-1, TRP-2, ERK1, ERK2 and JNK2 mRNA in A375 cells. ICI182780 and U0126 could significantly reverse the bavachin treatment on the protein expression levels and the mRNA expression of TYR, TRP-1, TRP-2, ERK1, ERK2 and JNK2. In conclusion, bavachin inhibited the synthesis of melanin on A375 cells by inhibiting the protein and mRNA expression of TYR, TRP-1, TRP-2, ERK1, ERK2 and JNK2.