[Research progress on active ingredients of Coicis Semen].

As a common medicinal and edible resource in China, Coicis Semen has a long history of cultivation and medicinal use. Traditional Chinese medicine(TCM) clinically believes that Coicis Semen has the effect of strengthening the spleen and tonifying the lungs, clearing heat and dampness, removing pus and paralysis, and stopping diarrhea. Therefore, it is used to treat edema, foot odor, spleen deficiency, diarrhea, and other symptoms. The above effects are closely related to the active ingredients of Coicis Semen, such as esters, fatty acids, polysaccharides, proteins, as well as phenolic acids, sterols, flavonoids, lactams, triterpenes, alkaloids, and adenosine. Modern research has found that Coicis Semen also has anti-cancer, anti-inflammatory, antioxidant, hypoglycemic, and hypotensive effects and other pharmacological activities, and it can improve immunity and regulate lipid metabolism. Coicis Semen is widely distributed in China, mainly produced in Guizhou, Yunnan, Fujian, Sichuan, and other places, and the quality of Coicis Semen from different origins varies. From ancient times to the present, Coicis Semen processing methods have experienced the process from simple to complex, and the types of auxiliary materials are more extensive, such as soil, bran, and river sand. These processing methods have been inherited from generation to generation. Nowadays, the commonly used methods are bran-fried, stir-fried, sand-fried, etc. In this paper, by reviewing the relevant literature in China and abroad in recent years, the main active ingredients and related pharmacological effects of Coicis Semen are sorted out, and the effects of different origins and processing methods on the chemical composition of Coicis Semen are summarized, with a view to providing references for the comprehensive development and utilization of Coicis Semen and the further study of its mechanism of action.

Sequentially Released Liposomes Enhance Anti-Liver Cancer Efficacy of Tetrandrine and Celastrol-Loaded Coix Seed Oil.

Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.

Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Research on Coix seed as a food and medicinal resource, it's chemical components and their pharmacological activities: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix lacryma-jobi var. ma-yuen (Romanet du Caillaud) Stapf is a plant of the genus Coix in the Gramineae family. Coix seed is cultivated in various regions throughout China. In recent years, with the research on the medicinal value of Coix seed, it has received more and more widespread attention from people. Numerous pharmacological effects of Coix seed have been demonstrated through modern pharmacological studies, such as hypoglycemia, improving liver function, anti-tumor, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. AIMS OF THE STUDY: This article is a literature review. In recent years, despite the extensive research on Coix seed, there has yet to be a comprehensive review of its traditional usage, medicinal resources, chemical components, and pharmacological effects is still lacking. To fill this gap, the paper provides an overview of the latest research progress on Coix seed, aiming to offer guidance and references for its further development and comprehensive utilization. MATERIAL AND METHODS: To gather information on the traditional usage, phytochemical ingredients, and pharmacological properties of Coix seed, we conducted a literature search using both Chinese and English languages in five databases: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Springer. RESULTS: This article is a literature review. The chemical constituents of Coix seed include various fatty acids, esters, polysaccharides, sterols, alkaloids, triterpenes, tocopherols, lactams, lignans, phenols, flavonoids and other constituents. Modern pharmacological research has indeed shown that Coix seed has many pharmacological effects and is a natural anti-tumor drug. In addition to its anti-tumor effect, it also has pharmacological effects such as hypoglycemia, improving liver function, regulating intestinal microbiota, improving spleen function, and anti-inflammatory effects. CONCLUSIONS: This article provides a brief overview of the traditional uses, biotechnological applications, chemical components, and pharmacological effects of Coix seed. It highlights the importance of establishing quality standards, discovering new active ingredients, and exploring pharmacological mechanisms in Coix seed research. The article also emphasizes the significance of clinical trials, toxicology studies, pharmacokinetics data, and multidisciplinary collaboration for further advancements in this field. Overall, it aims to enhance understanding of Coix seed and its potential in pharmaceutical development and wellness products.

Novel antioxidant peptides identified from coix seed by molecular docking, quantum chemical calculations and invitro study in HepG2 cells.

The aim of the study was to identify potent antioxidant peptides sourced from coix seed, analyze the structure-activity relationship through molecular docking and quantum chemical calculation. Molecular docking results showed that among thirteen peptides selected in silico, eight had favourable binding interaction with the Keap1-Kelch domain (2FLU). Promising peptides with significant binding scores were further evaluated using quantum calculation. It was shown that peptide FFDR exhibited exceptional stability, with a high energy gap of 5.24 eV and low Highest Occupied Molecular Orbitals (HOMO) and Lowest Unoccupied Molecular Orbitals (LUMO) values. Furthermore, FFDR displayed the capacity to enhance the expression of Nrf2-Keap1 antioxidant genes (CAT, SOD, GSH-Px) and improved cellular redox balance by increasing reduced glutathione (GSH) while reducing oxidized glutathione (GSSG) and malonaldehyde (MDA) levels. These findings highlight the potential of coix seed peptides in developing novel, effective and stable antioxidant-based functional foods.

A Probiotic Bacillus amyloliquefaciens D-1 Strain Is Responsible for Zearalenone Detoxifying in Coix Semen.

Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp., which commonly and severely contaminate food/feed. ZEN severely affects food/feed safety and reduces economic losses owing to its carcinogenicity, genotoxicity, reproductive toxicity, endocrine effects, and immunotoxicity. To explore efficient methods to detoxify ZEN, we identified and characterized an efficient ZEN-detoxifying microbiota from the culturable microbiome of Pseudostellaria heterophylla rhizosphere soil, designated Bacillus amyloliquefaciens D-1. Its highest ZEN degradation rate reached 96.13% under the optimal condition. And, D-1 can almost completely remove ZEN (90 µg·g-1) from coix semen in 24 h. Then, the D-1 strain can detoxify ZEN to ZEM, which is a new structural metabolite, through hydrolyzation and decarboxylation at the ester group in the lactone ring and amino acid esterification at C2 and C4 hydroxy. Notably, ZEM has reduced the impact on viability, and the damage of cell membrane and nucleus DNA and can significantly decrease the cell apoptosis in the HepG2 cell and TM4 cell. In addition, it was found that the D-1 strain has no adverse effect on the HepG2 and TM4 cells. Our findings can provide an efficient microbial resource and a reliable reference strategy for the biological detoxification of ZEN.

Network pharmacological analysis on the mechanism of Coix seed decoction for osteoarthritis of the knee.

Based on network pharmacology methods, we explored the mechanism of the classic Chinese medicine formula Coix seed decoction (CSD) in treating knee osteoarthritis (KOA). We searched each single drug in the CSD in the traditional Chinese medicine systematic pharmacology database in turn to obtain information on the active ingredients and target proteins of the CSD, and obtain the name of the genes corresponding to the target proteins through the UniProt database. We collected KOA-related genes from DisGeNET, GeneCards, comparative toxicogenomics database, and MalaCards database. The Venny online tool identified potential therapeutic targets by intersecting CSD and KOA target genes, while gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed using the Oebiotech Cloud Platform. A protein-protein interaction network was established using the String database; a "CSD-active ingredient-target gene-KOA" network plot was constructed using Cytoscape 3.9.1 software and screened for key targets and hub targets. Finally, molecular docking was performed for hub genes with high Degree values. A total of 227 effective target genes for CSD and 8816 KOA-related target genes were obtained, as well as 191 cross-target genes for CSD and KOA. We screened 37 key gene targets and identified the top 10 hub target genes in descending order of Degree value using protein-protein interaction and Cytoscape 3.9.1 software (TNF, IL-6, MMP-9, IL-1ß, AKT-1, VEGFα, STAT-3, PTGS-2, IL-4, TP53). Gene ontology analysis showed that the biological process of CSD treatment of KOA mainly involves cytokine-mediated signaling pathway, negative regulation of apoptotic process, cellular response to hypoxia, cellular response to cadmium ion, response to estradiol, and extrinsic apoptotic signaling pathway in absence of ligand. Kyoto encyclopedia of genes and genomes analysis revealed major signaling pathways including Cellular senescence, TNF signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results show that the core components bind well to the core targets. In conclusion, CSD may exert therapeutic effects on KOA by inhibiting pathological processes such as inflammatory response, apoptosis, cellular senescence, and oxidative stress.

Flexible processing technology of coix seed prolamins by combined heat-ultrasound: Effects on their enzymatic hydrolysis characteristics and the hypoglycemic activities of derived peptides.

The self-assembled structures of coix seeds affected the enzymatic efficiency and doesn't facilitate the release of more active peptides. The influence of heating combined with ultrasound pretreatment (HT + US) on the structure, enzymatic properties and hydrolysates (CHPs) of coix seed prolamin was investigated. Results showed that the structural of coix seed prolamins has changed after HT + US, including increased surface hydrophobicity, reduced α-helix and random coil content, and a decrease in particle size. So that, leads to changes in thermodynamic parameters such as an increase in the reaction rate constant and a decrease in activation energy, enthalpy and enthalpy. The fractions of <1000 Da, degree of hydrolysis and α-glucosidase inhibitory were increased in the HT + US group compared to single pretreatment by 0.68%-17.34%, 12.69%-34.43% and 30.00%-53.46%. The peptide content and α-glucosidase inhibitory activity of CHPs could be maintained at 72.21 % and 57.97 % of the initial raw materials after in vitro digestion. Thus, the findings indicate that HT + US provides a feasible and efficient approach to can effectively enhance the enzymatic hydrolysis efficiency and hypoglycaemic efficacy of CHPs.

Antioxidant and Antiaging Activity of Fermented Coix Seed Polysaccharides on Caenorhabditis elegans.

Aging is closely related to many diseases and is a long-term challenge that humans face. The oxidative damage caused by the imbalance of free radicals is an important factor in aging. In this study, we investigate the antioxidant and antiaging activities of fermented coix seed polysaccharides (FCSPs) via in vitro and in vivo experiments. The FCSPs were extracted by fermenting coix seed with Saccharomyces cerevisiae for 48 h and utilizing water-extracted coix seed polysaccharides (WCSPs) as a control. Their antiaging activity and mechanism were evaluated based on the antiaging model organism Caenorhabditis elegans (C. elegans). The results showed that the molecular weight of the FCSPs extracted by fermentation was smaller than that of the WCSPs, making them more easily absorbed and utilized. At a concentration of 5 g/L, the FCSPs' capacity to scavenge the DPPH·, ABTS+·, OH·, and O2-· radicals was greater than the WCSPs' capacity by 10.09%, 14.40%, 49.93%, and 12.86%, respectively. Moreover, C. elegans treated with FCSPs exhibited higher antioxidant enzyme activities and a lower accumulation of malonaldehyde. By inhibiting the expression of the pro-aging genes daf-2 and age-1, and upregulating the expression of the antiaging genes daf-16, sod-3, skn-1, and gcs-1 in the insulin/insulin-like growth factor-1 (IIS) signaling pathway, the FCSPs could effectively enhance stress tolerance and delay C. elegans aging. The lifespan of C. elegans in the FCSPs group was 5.91% higher than that of the WCSPs group. In conclusion, FCSPs exert better antioxidant and antiaging effects than WCSPs, which can act as a potential functional ingredient or supplement in food.

Bioavailability of Coix Seed Polyphenols in a MKN28/Caco-2 Continuous Transport Model and Their Lipid-Lowering Effects via Modulating Adipocyte Differentiation of 3T3-L1 Cells.

At present, most of the research on coix seed polyphenols (CSPs) focuses on the separation, purification, structure analysis, and biological functions of specific components, and few studies have considered the overall bioavailability and the metabolites that play a role after digestion and absorption and their biological functional activities. In this study, we constructed a MKN28 and Caco-2 cell monolayer continuous transport model (MCTM) to study the bioavailability of CSPs in the digestion and absorption stages of the stomach and small intestine. Using this model, we innovatively divided CSPs into easy-to-digest and hard-to-digest polyphenols and studied their intracellular lipid-lowering function and their influence on human intestinal flora. Transwell experiments showed that ferulic acid, rutin, naringin, arbutin, and syringetin had high transmembrane transport efficiency, especially syringetin. The methylation reaction in the monolayer membrane of Caco-2 cells may be the reason for the higher transport rate of syringetin. Further experiments showed that CPL reduced TG accumulation by more than 50% during 3T3-L1 differentiation and promoted the transformation of adipocytes into brown cells (p < 0.05). Finally, in vitro fermentation experiments showed that CSP_AP can increase the abundance of Lactobacillus and Bifidobacterium of human gut microbiota at the genus level (p < 0.05).

Self-emulsifying System Co-loaded with Paclitaxel and Coix Seed Oil Deeply Penetrated to Enhance Efficacy in Cervical Cancer.

BACKGROUND: Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility. OBJECTIVE: CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel. METHODS: Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model. RESULTS: The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site. CONCLUSION: With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.

An icaritin-loaded microemulsion based on coix oil for improved pharmacokinetics and enhanced antitumor efficacy.

Combinational icaritin (IC) and coix seed oil (CSO) holds promising potential in the treatment of hepatocellular carcinoma. However, traditional cocktail therapy is facing difficulties to optimize the synergistic antitumor efficacy due to the asynchronous pharmacokinetics. Therefore, we developed an icaritin-loaded microemulsion based on coix seed oil (IC-MEs) for improved pharmacokinetics and enhanced antitumor efficacy. The preparation technology of IC-MEs was optimized by the Box-Behnken design and the pharmaceutical properties were characterized in detail. IC-MEs show synergistic antiproliferation against HepG2 cells compared with monotherapy. The mechanism is associated with stronger apoptosis induction via enhancing caspases-3 activity. IC-MEs significantly improve the bioavailability of IC due to the encapsulation of coix oil-based microemulsion and also obtain the desired liver accumulation and elimination. More importantly, IC-MEs exhibit the overwhelming antitumor ability among all of the treatments on the HepG2 xenograft-bearing mice. This study verifies the feasibility of using coix oil-based microemulsion to improve the antitumor effect of water-insoluble components.

Antiglycation Effects of Adlay Seed and Its Active Polyphenol Compounds: An In Vitro Study.

This study aimed to evaluate the antiglycation effects of adlay on protein glycation using in vitro glycation assays. Adlay seed was divided into the following four parts: the hull (AH), testa (AT), bran (AB), and polished adlay (PA). A solvent extraction technique and column chromatography were utilized to investigate the active fractions and components of adlay. Based on a BSA-glucose assay, the ethanolic extracts of AT (ATE) and AB (ABE) revealed a greater capacity to inhibit protein glycation. ATE was further consecutively partitioned into four solvent fractions with n-hexane, ethyl acetate (ATE-Ea), 1-butanol (ATE-BuOH), and water. ATE-BuOH and -Ea show marked inhibition of glucose-mediated glycation. Medium-high polarity subfractions eluted from ATE-BuOH below 50% methanol with Diaion HP-20, ATE-BuOH-c to -f, exhibited superior antiglycation activity, with a maximum inhibitory percentage of 88%. Two phenolic compounds, chlorogenic acid and ferulic acid, identified in ATE-BuOH with HPLC, exhibited potent inhibition of the individual stage of protein glycation and its subsequent crosslinking, as evaluated by the BSA-glucose assay, BS-methylglyoxal (MGO) assay, and G.K. peptide-ribose assay. In conclusion, this study demonstrated the antiglycation properties of ATE in vitro that suggest a beneficial effect in targeting hyperglycemia-mediated protein modification.

Adlay (Coix lacryma-jobi L.) Polyphenol Improves Hepatic Glucose and Lipid Homeostasis through Regulating Intestinal Flora via AMPK Pathway.

SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic syndrome characterized of abnormal lipid deposition in the liver. Adlay polyphenol (AP), an effective component extracted from Coix lacryma-jobi L., has been reported that it can be used as a dietary supplement to prevent NAFLD. In this study, the mechanism and action of AP on lipid metabolism and regulation of intestinal flora are investigated. METHODS AND RESULTS: AP significantly decreases the lipid accumulation in free fatty acid-treated HepG2 cells. Western blot results indicate that AP improves lipid metabolism via activating the p-AMPK/p-ACC pathway. In vivo experiments show AP treatment significantly decreases the body weight, liver weight, hepatic triglyceride, and total cholesterol contents, as well as the serum glucose levels in high fat diet-fed mice, which may affect lipid accumulation by activating AMPK pathway and changing intestinal bacterial communities and intestinal microbiome metabolism. CONCLUSION: AP can be used as a food supplement for improving lipid metabolic dysfunction and reducing the incidence of metabolic diseases.

Ethanol Extracts of Rice Bran and Whole Grain Adlay Seeds Mitigate Colonic Inflammation and Damage in Mice with Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with frequent relapsing inflammation in the colon. Whole grains have been promoted as healthy and sustainable foods; however, the use of whole gains in UC is inconclusive. The aim of this study was to investigate the effects of ethanol extracts of rice bran (RBE) and whole-grain adlay seeds (ADE) on inflammation, oxidative stress, and colonic damage in UC. Male C57BL/6JNarl mice were intra-rectal injected twice with 2,4-dinitrobenzene sulfonic acid to induce (day 0) and reactivate (day 21) UC. Control mice were fed AIN-93M diet (R group) and injected with a vehicle. UC mice were fed AIN-93M diet (UC group) supplemented with RBE (RBE group) or ADE (ADE group) for 21 days. The results showed that the UC group had an increased disease activity index, plasma interleukin (IL)-6 and glutathione levels, microscopic injury scores, and inflammatory cytokine and chemokine levels in the colon and decreased colonic claudin-4 compared to the R group. RBE and ADE supplementation significantly reduced UC-elevated plasma IL-6 and colonic glutathione and pro-inflammatory cytokines and a chemokine. In addition, RBE and ADE supplementation significantly decreased T-helper-cell-associated cytokines in the plasma and colon. Moreover, RBE supplementation increased colonic IL-10 and tight junction protein claudin-4 levels, and ADE supplementation alleviated diarrhea in UC mice. In conclusion, these results suggest that RBE and ADE may mitigate colonic inflammation, oxidative stress, and damage in UC relapse.

Actional Mechanisms of Active Ingredients in Functional Food Adlay for Human Health.

Medicinal and food homologous adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) plays an important role in natural products promoting human health. We demonstrated the systematic actional mechanism of functional ingredients in adlay to promote human health, based on the PubMed, CNKI, Google, and ISI Web of Science databases from 1988 to 2022. Adlay and its extracts are rich in 30 ingredients with more than 20 health effects based on human and animal or cell cultures: they are anti-cancer, anti-inflammation, anti-obesity, liver protective, anti-virus, gastroprotective, cardiovascular protective, anti-hypertension, heart disease preventive, melanogenesis inhibiting, anti-allergy, endocrine regulating, anti-diabetes, anti-cachexia, osteoporosis preventive, analgesic, neuroprotecting, suitable for the treatment of gout arthritis, life extending, anti-fungi, and detoxifying effects. Function components with anti-oxidants are rich in adlay. These results support the notion that adlay seeds may be one of the best functional foods and further reveal the action mechanism of six major functional ingredients (oils, polysaccharides, phenols, phytosterols, coixol, and resistant starch) for combating diseases. This review paper not only reveals the action mechanisms of adding adlay to the diet to overcome 17 human diseases, but also provides a scientific basis for the development of functional foods and drugs for the treatment of human diseases.

Molecular Action Mechanism of Coixol from Soft-Shelled Adlay on Tyrosinase: The Future of Cosmetics.

Coix lacryma-jobi var. ma-yuen L. Gramineae is widely cultivated in Taiwan. Literature regarding the molecular action mechanism of coixol on tyrosinase and the application of coicis seed extracts to the processing of facial masks is still lacking. Solvent extractability analysis revealed that most of the polyphenolics in coicis seeds were water soluble (3.17 ± 0.12 to 3.63 ± 0.07 µg/mLGAE). In contrast, the methanolic extract contained the most flavonoids (0.06 ± 0.00~0.26 ± 0.03 µg/mL QE) and coixol (11.43 ± 0.13~12.83 ± 0.14 µg/mL), showing potent antioxidant capability. Additionally, the contents of coixenolide (176.77 ± 5.91 to 238.60 ± 0.21 µg/g), phytosterol (52.45 ± 2.05 to 58.23 ± 1.14 mg/g), and polysaccharides (3.42 ± 0.10 to 4.41 ± 0.10 mg/g) were rather high. The aqueous extract (10 µg/mL) and the ethanolic extract (1 mg/mL) showed no cytotoxicity to B16F10 melanocytes. More attractively, the ethanolic extract at 1 mg/mL caused 48.4% inhibition of tyrosinase activity in B16F10 melanocytes, and 50.7% on human tyrosinase (hTyr) fragment 369-377. Conclusively, the coicis seed extracts containing abundant nutraceuticals with promising anti-hTyr activity and moisturizing capability can serve as good ingredients for facial mask processing.

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.

Coix seed oil regulates mitochondrial functional damage to induce apoptosis of human pancreatic cancer cells via the PTEN/PI3K/AKT signaling pathway.

BACKGROUND: Coix seed oil (CSO) has a wide range of anticancer effects. However, the mechanism of action against pancreatic cancer (PC) and regulation of mitochondria in vitro is still unclear. MATERIALS AND RESULTS: This research investigated the possible mechanism of CSO induction of PC cell apoptosis and regulating mitochondrial functional damage. Proliferation of PC cells, mitochondrial membrane potential (MMP), qualitative and quantitative analysis of PC cell apoptosis, openness of mitochondrial permeability transition pore, related protein expression, generation of reactive oxygen species (ROS), and gene expression were determined by cell counting kit-8, JC-1 staining, acridine orange and ethidium bromide staining, flow cytometry, calcein-AM/cobalt staining, western blotting, dichlorofluorescein diacetate probe, and quantitative real-time reverse transcription-polymerase chain reaction, respectively. We confirmed that PTEN protein was involved in CSO-induced PANC-1 cell apoptosis and mitochondrial functional damage. CSO induced depolarization of MMP, increased opening of the mitochondrial permeability transition pore, increased ROS production, and further increased mitochondrial damage. Additionally, CSO downregulated expression of p-AKT and p-PI3K proteins; upregulated protein expression of cleaved caspase-9, Bax, cleaved caspase-3 and cytochrome c; and downregulated expression of Bcl-2 by upregulating the PTEN gene. The corresponding protein expression was consistent with the gene expression level. Furthermore, the loss of function of PTEN protein reduces the ability of CSO to induce apoptosis of PANC-1 cells and damage to mitochondrial function. CONCLUSIONS: CSO induces apoptosis of PANC-1 PC cells by modulating mitochondrial functional impairment and related apoptotic molecules via PTEN, which may be closely related to the PI3K/AKT signaling pathway.

Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.