Protective Effect of Electroacupuncture on Chemotherapy-Induced Salivary Gland Hypofunction in a Mouse Model.

Radiotherapy and chemotherapy can impair salivary gland (SG) function, which causes xerostomia and exacerbate other side effects of chemotherapy and oral infection, reducing patients' quality of life. This animal study aimed to assess the efficacy of electroacupuncture (EA) as a means of preventing xerostomia induced by 5-fluorouracil (5-FU). A xerostomia mouse model was induced via four tail vein injections of 5-FU (80 mg/kg/dose). EA was performed at LI4 and LI11 for 7 days. The pilocarpine-stimulated salivary flow rate (SFR) and salivary glands weight (SGW) were recorded. Salivary immunoglobulin A (SIgA) and lysozyme were determined via enzyme-linked immunosorbent assay (ELISA). SG was collected for hematoxylin and eosin staining to measure acini number and acinar cell size. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and aquaporin 5 (AQP5) mRNA expressions in SG were quantified via RT-qPCR. 5-FU caused significant decreases in SFR, SGW, SIgA, lysozyme, AQP5 expression, and acini number, while TNF-α and IL-1ß expressions and acinar cell size were significantly increased. EA treatment can prevent 5-FU damage to the salivary gland, while pilocarpine treatment can only elevate SFR and AQP5 expression. These findings provide significant evidence to support the use of EA as an alternative treatment for chemotherapy-induced salivary gland hypofunction and xerostomia.

Effect of Vitamin D Supplementation on Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this study, we aimed to assess the effects of vitamin D (vit. D) supplementation in relieving the symptoms of primary dysmenorrhea. A comprehensive systematic database search of randomized controlled trials (RCTs) was performed. Oral forms of vit. D supplementation were included and compared with a placebo or standard care. The degree of dysmenorrhea pain was measured with a visual analogue scale or numerical rating scale. Outcomes were compared using the standardized mean difference (SMD) and 95% confidence intervals (CIs) in a meta-analysis. RCTs were assessed using the Cochrane risk-of-bias v2 (RoB 2) tool. The meta-analysis included 8 randomized controlled trials involving 695 participants. The results of the quantitative analysis showed a significantly lower degree of pain in the vit. D versus placebo in those with dysmenorrhea (SMD: -1.404, 95% CI: -2.078 to -0.731). The results of subgroup analysis revealed that pain lessened when the average weekly dose of vit. D was over 50,000 IU, in which dysmenorrhea was relieved regardless of whether vit. D was administered for more or less than 70 days and in any dose interval. The results revealed that vit. D treatment substantially reduced the pain level in the primary dysmenorrhea population. We concluded that vit. D supplementation is an alternative treatment for relieving the pain symptoms of dysmenorrhea.

Adlay Seed (Coix lacryma-jobi L. var. Ma-yuen Stapf.) Ethanolic Extract Fractions and Subfractions Induce Cell Cycle Arrest and Apoptosis in Human Breast and Cervical Cancer Cell Lines.

The antitumor effects of Coix lacryma-jobi L. var. ma-yuen Stapf. (adlay seed) ethanolic extract have been increasingly shown. This study aimed to investigate the beneficial effects of both the fractions and subfractions of adlay seed ethanolic extract on the human breast (MCF-7) and cervical (HeLa) cancer cell lines, as well as exploring their possible mechanisms of action. The ethanolic extracts were obtained from different parts of adlay seed, including AHE (adlay hull extract), ATE (adlay testa extract), ABE (adlay bran extract) and PAE (polished adlay extract). The results of a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl- tetrazolium bromide (MTT) assay showed that AHE-Ea and ATE-Ea showed significant growth inhibitory effects in a dose-dependent manner. The results also showed that the AHE-Ea-K, AHE-Ea-L, ATE-Ea-E and ATE-Ea-F subfractions inhibited cell proliferation, induced cell cycle arrest in the G0/G1 phase and decreased CDK4/Cyclin D1 protein expression. Finally, the extract activated caspase-3 activity and PARP protein expression, which induced MCF-7 and HeLa cell apoptosis. We then used liquid chromatography-mass spectrometry (LC/MS) to identify the potential active components., Quercetin showed an anticancer capacity. In conclusion, the AHE-Ea-K, AHE-Ea-L, ATE-Ea-E and ATE-Ea-F subfractions showed antitumor effects through the inhibition of MCF-7 and HeLa cell line viability, as well as inducing apoptosis and cell cycle arrest.

Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment.

Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of life of afflicted patients. Therefore, developing approaches to manage chemotherapy- and radiotherapy-induced adverse reactions gained greater attention in recent years. Glycyrrhiza glabra (licorice), a perennial plant that is one of the most frequently used herbs in traditional Chinese medicine, has been heavily investigated in relation to cancer therapy. Licorice/licorice-related regimes, used in combination with chemotherapy, may improve the adverse effects of chemotherapy. However, there is little awareness of licorice-containing herbs alleviating reactions to radiotherapy and chemotherapy, or to other induced adverse reactions in cancer treatment. We aimed to provide a descriptive review, and to emphasize the possibility that licorice-related medicines could be used as an adjuvant regimen with chemotherapy to improve quality of life (QoL) and to reduce side effects, thus, improving compliance with chemotherapy. The experimental method involved searching different databases, including PubMed, the Cochrane Library, and Wang Fang database, as of May 2022, to identify any relevant studies. Despite a lack of high-quality and large-scale randomized controlled trials, we still discovered the potential benefits of licorice-containing herbs from published clinical studies. These studies find that licorice-containing herbs, and their active ingredients, reduce the adverse reactions caused by chemotherapy and radiotherapy, and improve the QoL of patients. This comprehensive review will serve as a cornerstone to encourage more scientists to evaluate and develop effective Traditional Chinese medicine prescriptions to improve the side effects of chemotherapy and radiation therapy.

In Vitro Antimicrobial Potential of CAPE and Caffeamide Derivatives against Oral Microbes.

Caffeic acid phenethyl ester (CAPE) is a natural component isolated from propolis and used in traditional medicine. We aimed to investigate the antimicrobial properties and action mechanism of CAPE and caffeamide derivatives (26G and 36M) against oral disease microbes. We resolved the minimum inhibitory and bactericidal concentrations of 26G and 36M and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation and antibiotic resistance gene expression in methicillin-resistant Staphylococcus aureus (MRSA). Our results revealed that 26G and 36M showed the best anticancer and antimicrobial activities, respectively, compared with the other four caffeamide derivatives. Both 26G and 36M showed heat-dependent decreases in antimicrobial activity. The 36M derivative was stable irrespective of pH, whereas 26G was not stable under high pH conditions. Biofilm formation and antibiotic resistance-related gene expression were consistent with their respective phenotypes. This study provides evidence for the potential application of CAPE and caffeamide derivatives in dental medicine to cure or prevent oral diseases.

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models.

Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.

Adlay Testa (Coix lachryma-jobi L. var. Ma-yuen Stapf.) Ethanolic Extract and Its Active Components Exert Anti-Proliferative Effects on Endometrial Cancer Cells via Cell Cycle Arrest.

Endometrial cancer is the most common malignant tumors of gynecologic neoplasms in Western society. In recent years, the incidence of endometrial cancer has increased, and it has become the third most common female gynecological cancer (after ovarian and cervical cancer) in Taiwan. Adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been demonstrated to have bioactive polyphenols, flavonoids, phytosterols, and essential nutrients for health benefits, including anticancer effects in humans. However, little is known about the effect of adlay seeds on endometrial cancer. Our study aimed to investigate the potential growth inhibitory effects of several adlay seed fractions, including ethyl acetate (ATE-EA) and its bioactive constituents, separately on endometrial cancer cells-HEC-1A (phosphatase and tensin homolog-positive) and RL95-2 (phosphatase and tensin homolog-negative)-and identify related active ingredients. In addition, the potential active fractions and the phytochemical compounds were elucidated. The results demonstrate superior activity of ATE-EA with significant in vitro cell proliferation inhibitory capacity, particularly its C.D.E.F-subfraction. Moreover, HPLC- and GC/FID-based quantification of ATE-EA subfractions showed that phenolic compounds (caffeic acid, protocatechuic acid, and p-hydroxybenzaldehyde), flavonoids, steroids, and fatty acid compounds exert anti-proliferative effects in the cell model. Finally, it was shown that cell growth and cell cycle arrest most significantly occurred in the in G1 or G2/M phase under ATE-EA treatment. Collectively, our results demonstrate an antiproliferative effect of ATE-EA on endometrial cancer cells that suggest a positive health outcome for women from consumption of these compounds.

In vitro antimicrobial and antipro-inflammation potential of honokiol and magnolol against oral pathogens and macrophages.

BACKGROUND/PURPOSE: Honokiol and magnolol are natural components isolated from Magnolia bark that is used in traditional Chinese and Japanese herbal medicine. These two isomers are used as a component of dietary supplements and cosmetic products. In this study, we investigated the antimicrobial effect of honokiol and magnolol on pathogens causing oral diseases, their mechanism of action in biofilm formation and drug resistance of oral pathogens, and inflammatory regulation in mammalian cells. METHODS: We determined the minimum inhibitory concentration and minimum bactericidal concentration of honokiol and magnolol, and their stability at different temperatures and pH. We also evaluated their effect on biofilm formation, antibiotic-resistance gene expression in MRSA, and pro-inflammatory gene expression in mammalian cells. RESULTS: Honokiol showed better antimicrobial activity than magnolol. Both honokiol and magnolol showed stable bacterial inhibitory activity over a wide range of temperature and pH, reduced biofilm formation, and antibiotic resistance in oral pathogens. The biofilm formation- and antibiotic resistance-related gene expression was consistent with the respective phenotypes. Furthermore, these two isomers repressed the expression of pro-inflammatory genes in RAW264.7 cells. CONCLUSION: Our study provides evidence of the potential application of honokiol and magnolol in dental medicine to cure or prevent oral diseases.

Application of the solvent extraction technique to investigation of the anti-inflammatory activity of adlay bran.

The current study utilised a bioassay-directed chemical analysis scheme to screen the anti-inflammatory activity of fractions and compounds from adlay bran (AB). Liquid-liquid extraction couple with liquid chromatography-mass spectrometry (LC-MS) was applied to the isolation, analysis and identification of active components in AB samples. Ethanol extracts of AB (ABE) and ethyl acetate extracts AB (ABEa) were obtained and further partitioned with different solvents. The results showed that among all 16 kinds of fractions from ABE and ABEa, ABEa-Ea-B (80% Ea/n-hexane sub-fraction from ABE-Ea) had the most potent inhibitory effects on NO production, iNOS and COX-2 expressions, and proinflammatory IL-6 and TNF-α secretion in lipopolysaccharide-activated RAW264.7 cells system. Mechanistic data from luciferase reporter-gene assay revealed that the anti-inflammatory action of ABEa-Ea-B may be associated with inhibition of NF-kB transcriptional activity. Notably, tangeretin, nobiletin, and p-hydroxybenzoic acid were found to be the main active compounds for the anti-inflammatory properties in ABEa-Ea-B.

Association of expression aberrances and genetic polymorphisms of lysyl oxidase with areca-associated oral tumorigenesis.

PURPOSE: Areca nut use is the major cause of oral squamous cell carcinoma (OSCC) in Southern Asians. Areca nut contains a high level of free copper ions. Lysyl oxidase (LOX) is a copper-activated enzyme critical for extracellular matrix organization. Contradictory evidence has been put forward to suggest that LOX may be either an oncogenic or a suppressive element. This study investigated the oncogenic significance of LOX in areca-associated OSCC. EXPERIMENTAL DESIGN: The expression assays and polymorphism analysis were done to know the clinicopathologic implications of LOX status in OSCC. Knockdown and overexpression experiments were conducted to know the phenotypic effects of LOX on OSCC cells. RESULTS: Up-regulation of LOX mRNA and LOX protein expression in OSCCs relative to adjacent oral mucosa was found. Precancerous lesions had the highest LOX mRNA expression. Areca nut extract up-regulated LOX expression in oral epithelial cells. Knockdown of LOX induced cellular migration and invasion, but it reduced the anchorage-independent growth and xenographic tumorigenesis of OSCC cells. The reduction of migration and invasion by LOX overexpression was partially rescued by blockage of LOX activity. The Arg158Gln polymorphism was associated with earlier clinical stage of OSCC. Wild-type LOX overexpression induced anchorage-independent growth in OSCC cells, but this was not for LOXArg158Gln overexpression. CONCLUSION: LOX exerts oncogenic roles in areca-associated OSCC. This potential could be affected by the existence of LOX propeptide domain or genetic polymorphism.