Optimization of Fermentation Process of Pomegranate Peel and Schisandra Chinensis and the Biological Activities of Fermentation Broth: Antioxidant Activity and Protective Effect Against H2O2-induced Oxidative Damage in HaCaT Cells.

In this study, the lactobacillus fermentation process of pomegranate (Punica granatum L.) peel and Schisandra chinensis (Turcz.) Baill (PP&SC) was optimized by using the response surface method (RSM) coupled with a Box-Behnken design. The optimum fermentation condition with the maximal yield of ellagic acid (99.49 ± 0.47 mg/g) was as follows: 1:1 (w:w) ratio of pomegranate peel to Schisandra chinensis, 1% (v:v) of strains with a 1:1 (v:v) ratio of Lactobacillus Plantarum to Streptococcus Thermophilus, a 37 °C fermentation temperature, 33 h of fermentation time, 1:20 (g:mL) of a solid-liquid ratio and 3 g/100 mL of a glucose dosage. Under these conditions, the achieved fermentation broth (FB) showed stronger free radical scavenging abilities than the water extract (WE) against the ABTS+, DPPH, OH- and O2- radicals. The cytotoxicity and the protective effect of FB on the intracellular ROS level in HaCaT cells were further detected by the Cell Counting Kit-8 (CCK-8) assay. The results showed that FB had no significant cytotoxicity toward HaCaT cells when its content was no more than 8 mg/mL. The FB with a concentration of 8 mg/mL had a good protective effect against oxidative damage, which can effectively reduce the ROS level to 125.94% ± 13.46% (p < 0.001) compared with 294.49% ± 11.54% of the control group in H2O2-damaged HaCaT cells. The outstanding antioxidant ability and protective effect against H2O2-induced oxidative damage in HaCaT cells promote the potential for the FB of PP&SC as a functional raw material of cosmetics.

Review on Bee Products as Potential Protective and Therapeutic Agents in Male Reproductive Impairment.

Bee products are sources of functional food that have been used in complementary medicine to treat a variety of acute and chronic illnesses in many parts of the world. The products vary from location to location as well as country to country. Therefore, the aim of this review was to identify various bee products with potential preventive and therapeutic values used in the treatment of male reproductive impairment. We undertook a vigorous search for bee products with preventive and therapeutic values for the male reproductive system. These products included honey, royal jelly, bee pollen, bee brood, apilarnil, bee bread, bee wax, and bee venom. We also explained the mechanisms involved in testicular steroidogenesis, reactive oxygen species, oxidative stress, inflammation, and apoptosis, which may cumulatively lead to male reproductive impairment. The effects of bee pollen, bee venom, honey, propolis, royal jelly, and bee bread on male reproductive parameters were examined. Conclusively, these bee products showed positive effects on the steroidogenic, spermatogenic, oxidative stress, inflammatory, and apoptotic parameters, thereby making them a promising possible preventive and therapeutic treatment of male sub/infertility.

Green-lipped (greenshell™) mussel (Perna canaliculus) extract supplementation in treatment of osteoarthritis: a systematic review.

OBJECTIVES: Intervention studies using New Zealand green-lipped or greenshell™ mussel (GSM) (Perna canaliculus) extract in osteoarthritis (OA) patients have shown effective pain relief. This systematic review summarises the efficacy of GSM extracts in the treatment of OA. METHODS: A literature search of the three databases EMBASE, MEDLINE, and Scopus was performed to identify relevant articles published up to March 2020. Inclusion criteria were clinical trials published in English measuring the effect of supplementation of whole or a lipid extract from GSM on pain and mobility outcomes in OA patients. RESULTS: A total of nine clinical trials were included in systematic review, from which five studies were considered appropriate for inclusion in a forest plot. Pooled results showed that GSM extracts (lipid extract or whole powder) provide moderate and clinically significant treatment effects on a visual analogue scale (VAS) pain score (effect size: - 0.46; 95% CI - 0.82 to - 0.10; p = 0.01). The whole GSM extract improved gastrointestinal symptoms in OA patients taking anti-inflammatory medications. The GSM extract was considered to be generally well tolerated in most of the studies. CONCLUSION: The overall analysis showed that GSM provided moderate and clinically meaningful treatment effects on OA pain. However, the current evidence is limited by the number and quality of studies, and further larger and high-quality studies are needed to confirm the effectiveness and to identify the optimal GSM format. Nevertheless, it is worth considering using GSM extracts especially for patients seeking alternative pain relief treatments with fewer side effects compared to conventional treatment.

Medicinal Mushrooms against Influenza Viruses.

This review provides results obtained by scientists from different countries on the antiviral activity of medicinal mushrooms against influenza viruses that can cause pandemics. Currently, the search for antiviral compounds is relevant in connection with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Medicinal mushrooms contain biologically active compounds (polysaccharides, proteins, terpenes, melanins, etc.) that exhibit an antiviral effect. The authors present the work carried out at the State Research Center of Virology and Biotechnology Vector in Russia, whose mission is to protect the population from biological threats. The research center possesses a collection of numerous pathogenic viruses, which allowed screening of water extracts, polysaccharides, and melanins from fruit bodies and fungal cultures. The results of investigations on different subtypes of influenza virus are presented, and special attention is paid to Inonotus obliquus (chaga mushroom). Compounds produced from this mushroom are characterized by the widest range of antiviral activity. Comparative data are presented on the antiviral activity of melanin from natural I. obliquus and submerged biomass of an effective strain isolated in culture against the pandemic strain of influenza virus A/California/07/09 (H1N1 pdm09).

Antrodia camphorata extract (ACE)-induced apoptosis is associated with BMP4 expression and p53-dependent ROS generation in human colon cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia camphorata (AC) is a rare functional fungus in Taiwan and is known as traditional Chinese medicine. It has been reported to inhibit proliferation and promote apoptosis in human cancer cells. AIM OF THE STUDY: To investigate the potential mechanism of apoptosis induced in colon cancer cells by Antrodia camphorata extract (ACE). MATERIALS AND METHODS: The MTT assay and crystal violet staining were used to determine relative cell viability in vitro at 24 and 48 h. The effects of ACE on apoptosis were determined by Hoechst 33342 staining and flow cytometric analysis following Annexin V-FITC/PI staining. The gene expression profile of HCT116 cells was assessed by the RNA sequencing system. In combination with RNA-seq data and qRT-PCR, Western blot analysis was used to evaluate expression of proteins. The intracellular ROS of HCT116 cells were determined using a DCFH-DA fluorescence probe. RESULTS: ACE significantly reduces cell viability in a dose-dependent manner and triggers apoptosis. To explore the underlying mechanism, we performed transcriptome analysis of ACE-treated colon cancer HCT116 cells. Bioinformatics analyses showed that ACE treatment is associated with pathways in cancer. We further used Cytoscape to analyze hub genes in this network. Among them, BMP4, which is associated with cancer cell death through regulation of the tumor suppressor p53, was significantly decreased at both mRNA and protein levels in ACE treatment groups. We found that cell death is reversible via inactivation or knockdown of p53 gene and reduction of reactive oxygen species (ROS) generation in response to ACE exposure, indicating that p53 plays an important role in ROS generation induced by ACE. Meanwhile, ROS scavenger NAC was used to verify that cell death is reversible via reduction of ROS. CONCLUSION: Our findings demonstrate that ACE has potential as an anticancer agent that induces apoptosis through BMP4 and p53-dependent response to ROS in human colon cancer.

Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence. AIM OF THE STUDY: Erectile dysfunction (ED) has become a major health problem for the global ageing population. The aim of this study is therefore to evaluate the effect of peptide-rich preparations from C. gigas oysters on ED and related conditions as increasing evidence suggests that peptides are important bioactive components of marine remedies and seafood. MATERIALS AND METHODS: Crassostrea oyster peptide (COP) preparations COP1, COP2 and COP3 were obtained from C. gigas oysters by trypsin, papain or sequential trypsin-papain digestion, respectively. The contents of testosterone, cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in mice and/or cells were measured by enzyme-linked immunosorbent assays. Real-time PCR was used to assess the expression of genes associated with sex hormone secretion pathways. The model animal Caenorhabditis elegans was also used to analyze the gene expression of a conserved steroidogenic enzyme. In silico analysis of constituent peptides was performed using bioinformatic tools based on public databases. RESULTS: The peptide-rich preparation COP3, in which >95% peptides were <3000 Da, was found to increase the contents of male mouse serum testosterone and cAMP, both of which are known to play important roles in erectile function, and to increase the activity of mouse penile NOS, which is closely associated with ED. Further investigation using mouse Leydig-derived TM3 cells demonstrates that COP3 was able to stimulate the production of testosterone as well as NO, a pivotal mediator of penile erection. Real-time PCR analysis reveals that COP3 up-regulated the expression of Areg and Acvr2b, the genes known to promote sex hormone secretion, but not Fst, a gene involved in suppressing follicle-stimulating hormone release. Furthermore, COP3 was also shown to up-regulate the expression of let-767, a well-conserved C. elegans gene encoding a protein homologous to human 17-ß-hydroxysteroid dehydrogenases. Preliminary bioinformatic analysis using the peptide sequences in COP3 cryptome identified 19 prospective motifs, each of which occurred in more than 10 peptides. CONCLUSIONS: In this paper, Crassostrea oyster peptides were prepared by enzymatic hydrolysis and were found for the first time to increase ED-associated biochemical as well as molecular biology parameters. These results may help to explain the ethnopharmacological use of oysters and provide an important insight into the potentials of oyster peptides in overcoming ED-related health issues.

Active ingredients and mechanisms of Phellinus linteus (grown on Rosa multiflora) for alleviation of Type 2 diabetes mellitus through network pharmacology.

Phellinus linteus (mushroom) grown on Rosa multiflora (PL@RM), exposed beneficial effect and safety on Type 2 diabetes mellitus (T2DM) from Korean folk remedies. However, its active chemical constituents and mechanism(s) against T2DM have not been confirmed. Hence, we deciphered the active compounds and mechanism(s) of PL@RM against T2DM through network pharmacology. GC-MS of PL@RM manifested 54 compounds and drug-likeness properties of these compounds were confirmed by Lipinski's rule. The compound (40) related genes were composed of Similarity Ensemble Approach (SEA) and SwissTargetPrediction (STP). The overlapping genes (61) between the two databases were identified. Besides, the T2DM related genes (4,736) were extracted from DisGeNet and OMIM database. In parallel, a Venn diagram was constructed between the overlapping genes (61) and T2DM related genes (4,736), and finally, 48 genes were picked. The interactive networks between compounds and overlapping genes were plotted and visualized by RStudio. In addition, KEGG Pathway enrichment analysis was evaluated by String. String analysis showed that the mechanisms of PL@RM against T2DM were related to 16 pathways, where inhibition of gluconeogenesis by inactivating metabolic pathways was noted as the hub pathway of PL@RM against T2DM. Besides, bubble chart indicated that activation of the AMPK signaling pathway might enhance the insulin receptor (IR) phosphorylation, which is regarded the key signaling pathway of PL@RM against T2DM. Furthermore, the autodock vina revealed the promising binding affinity energy of the epicholesterol (the most drug-likeness compound) on HMGCR (hub gene). Overall, this work hints at the therapeutic evidence of PL@RM on T2DM, and this data expound the main chemical compounds and mechanisms of PL@RM against T2DM.

Synthetic Pyrethroid, Natural Product, and Entomopathogenic Fungal Acaricide Product Formulations for Sustained Early Season Suppression of Host-Seeking Ixodes scapularis (Acari: Ixodidae) and Amblyomma americanum Nymphs.

We compared the ability of product formulations representing a synthetic pyrethroid acaricide (Talstar P Professional Insecticide), a natural product-based acaricide (Essentria IC3), and an entomopathogenic fungal acaricide (Met52 EC Bioinsecticide) to suppress Ixodes scapularis Say and Amblyomma americanum (L.) nymphs when applied following USEPA approved manufacturers' label recommendations for tick control using hand-pumped knapsack sprayers before the beginning of their seasonal activity period in the spring. We applied Met52 EC Bioinsecticide (11% Metarhizium anisopliae Strain F52) to five 100 m2 plots (10.6 ml AI/plot) in mid-April 2020. Two weeks later at the end of April 2020, we treated an additional five 100 m2 plots each with either Talstar P Professional Insecticide (7.9% bifenthrin @ 2.5 ml AI/plot) or Essentria IC3 (10% rosemary oil, 5% geraniol, and 2% peppermint oil @ 86.6 ml AI/plot). Weekly sampling of all plots through the end of June 2020 showed that both Met52 EC Bioinsecticide and Essentria IC3 failed to maintain a 90% suppression threshold for I. scapularis, compared to control plots, and required two additional applications over the course of the trial. In contrast, Talstar P Professional Insecticide suppressed 100% of I. scapularis nymphs and ≥96 and 100% of A. americanum nymphs and adults, respectively. Such pre-season applications of synthetic pyrethroids significantly reduce the early season acarological risk for exposure to host-seeking ticks as well as the frequency of acaricide applications.

SARS-CoV-2 and the safety margins of cell-based biological medicinal products.

With the pandemic emergence of SARS-CoV-2, the exposure of cell substrates used for manufacturing of medicines has become a possibility. Cell lines used in biomanufacturing were thus evaluated for their SARS-CoV-2 susceptibility, and the detection of SARS-CoV-2 in culture supernatants by routine adventitious virus testing of fermenter harvest tested.

Status of a real-life cohort of patients with moderate-to-severe plaque psoriasis treated with secukinumab and considerations on the use of biological agents in the Covid-19 era.

INTRODUCTION: In light of the current Covid-19 pandemic and the ongoing, extensive debate about the use of biological agents in psoriatic patients, we felt compelled to relate our experience in the use of secukinumab in the same cohort before and during the lockdown in Italy. Areas covered: Secukinumab was not discontinued, and there were no cases of confirmed infection with SARS-CoV-2 in this cohort. Expert opinion: In our practice, there is no evidence favoring the discontinuation of secukinumab in these patients. We also present a brief commentary on the use of biological agents in patients with moderate-to-severe plaque psoriasis.

Anti-convulsant effects of cultures bear bile powder in febrile seizure via regulation of neurotransmission and inhibition of neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural bear bile powder (NBBP) has been used to treat seizures for thousands of years, but its application is greatly restricted due to ethical reasons. Cultured bear bile powder (CBBP), which is produced by biotransformation, may be an appropriate substitute for NBBP. However, the anti-convulsant effects of CBBP and its mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate the anti-convulsant effects and possible mechanisms of CBBP in a febrile seizure (FS) rat model. MATERIALS AND METHODS: FS was induced by placing the rats in a warm water bath (45.5 °C). The incidence rate and latency of FS, and hematoxylin-eosin staining (HE) were conducted for neurological damage. The levels of 4 bile acids and 8 main neurotransmitters in vivo were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The expression of bile acid related transports, neurotransmitter receptors, inflammatory factors, neurotrophic factors and glial fibrillary acidic protein (GFAP) in hippocampal tissues were detected by real-time PCR, western blotting, and immunohistochemistry. RESULTS: Pre-treatments with CBBP and similarly, NBBP, significantly reduced the incidence rate and prolonged the latency of FS. Additionally, CBBP alleviated the histological injury induced by FS in the rat hippocampus tissue. LC-MS/MS analyses revealed that CBBP markedly increased the levels of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA) in FS rats. Furthermore, the content of gamma-aminobutyric acid (GABA) was up-regulated in rats pre-treated with CBBP whereas GFAP was down-regulated. CBBP also significantly suppressed the expression of interleukin -1ß (IL-1ß), tumor necrosis factor α (TNF-α), nuclear factor kappa B (NF-κB), and brain-derived neurotrophic factor (BDNF) and its TrkB receptors, and improved the expression of GABA type A receptors (GABAAR) and farnesoid X receptors (FXR). CONCLUSIONS: The present study demonstrated that CBBP had anti-convulsant effects in a FS rat model. CBBP may protect rats against FS, probably by up-regulating FXR, which was activated by increasing brain bile acids, up-regulating GABAergic transmission by inhibiting BDNF-TrkB signaling, and suppressing neuroinflammation by inhibiting the NF-κB pathway.

Emerging systemic drugs in the treatment of plaque psoriasis.

INTRODUCTION: Psoriasis is a common, chronic inflammatory skin condition that affects 2-3% of the US population and represents a large psychosocial burden for patients. Over the last decade, highly effective targeted therapies for psoriasis have been developed - namely, those targeting interleukin (IL)-17 and IL-23. The success of biologic agents targeting IL-17 and IL-23 underscores the importance of the IL-23/T helper (Th)17 cell axis in psoriasis pathogenesis. Oral small molecule drugs - such as Janus kinase (JAK) inhibitors, tyrosine kinase 2 (TYK2) inhibitors, and fumaric acid esters (FAEs) - are also being investigated for the treatment of psoriasis. AREAS COVERED: This article reviews systemic biologic and oral small molecule drugs currently undergoing clinical trials for the treatment of plaque psoriasis. EXPERT OPINION: Many patients with psoriasis have mild disease, and many with mild disease do not seek medical care for their condition. Many patients with mild disease could be adequately treated with topical treatments and phototherapy; however, adherence and feasibility have often been an issue with these treatment types. There seems to be limited room for development of novel biologics, as the existing ones are extraordinarily safe, effective, and convenient with few injections. Patients would prefer a safe, effective oral treatment; however, JAK inhibitors seem unlikely to fill this role completely.

Modulation of Hematological Indices of Normal and Alloxan-Induced Diabetic Rabbits by Aqueous Extract of Pleurotus tuberregium Sclerotia.

OBJECTIVE: The ability of an aqueous extract of the sclerotia of Pleurotus tuberregium to modulate hematological parameters was investigated in normal and alloxan treated rabbits. METHODS: The extract was subjected to atomic absorption spectrophotometric and flame ionization detector-coupled-gas chromatographic (GC-FID) analysis. Diabetes mellitus was induced by a 120 mg/kg body weight intravenous injection of alloxan. Metformin was orally administered at 50 mg/kg, while the extract was administered (both to normal and diabetic rabbits) at 100, 200 and 300 mg/kg. RESULTS: Analysis of the extract showed that it had high contents of calcium, magnesium, manganese and potassium. Eleven known glycosides were detected, comprising mainly of amygdalin (37.7%), digoxin (14.4%), dhurrin (14.0%), linamarin (13.6%), prunasin (10.8%) and digitoxin (8.4%). Also detected were twelve known saponins, consisting mainly of sapogenin (40.3%) and neochlorogenin (21.8%); and twelve known lignans, consisting mainly of matairesinol (59.7%), secoisolariciresinol (20.9%) and lariciresinol (14.9%). Compared to the Diabetic control, the hematocrit, hemoglobin concentration, mean cell hemoglobin, mean cell hemoglobin concentration, mean corpuscular volume, red cell distribution width; and red cell, total white cell, lymphocytes, granulocytes and platelet counts of the treated groups were significantly (p<0.05) higher. CONCLUSION: The above result showed that the extract had a positive effect on the hemopoietic system of the treated animals, at least at the doses at which it was administered in this study.

Fabrication of natural-origin antibacterial nanocellulose films using bio-extracts for potential use in biomedical industry.

This study explores the modification of bacterial nanocellulose (BNC), produced in fermented tea medium with bio-extracts from herbal plants, to produce entirely natural antibacterial nanocellulose films. The antibacterial property was imparted by impregnating the synthesized BNC into bio-extracts of Terminalia arjuna (arjuna), Azadirachta indica (neem), Withania somnifera (ashwagandha), Tinospora cordifolia (giloy), and Murraya koenigii (curry leaves). FE-SEM analysis of modified BNC films revealed the presence of cloudy layer of bio-extracts over the BNC nanofibrous network. The modified BNC production was confirmed by ATR-FTIR. The modified BNC showed tremendous antibacterial activity against Escherichia coli (E. coli) and Aerococcus viridians (A. viridans). T. arjuna modified BNC showed the highest antibacterial activity against E. coli and A. viridans with inhibition zone of 27.08 mm and 26.34 mm, respectively, while M. koeniggi modified BNC showed the lowest antibacterial activity for both E. coli and A. viridans with inhibition zone of 14 mm and 14.2 mm, respectively. The water retention, moisture content and porosity values reflect highly hydrophilic nature of BNC films and their well suitability for varied biomedical applications like antibacterial wound dressings, herbal biomasks, scaffoldings, etc. The modification of BNC films with the bio-extracts used in this study has not been reported previously.

PPARγ: Potential Therapeutic Target for Ailments Beyond Diabetes and its Natural Agonism.

Intense research interests have been observed in establishing PPAR gamma as a therapeutic target for diabetes. However, PPARγ is also emerging as an important therapeutic target for varied disease states other than type 2 diabetes like neurodegenerative disorders, cancer, spinal cord injury, asthma, and cardiovascular problems. Furthermore, glitazones, the synthetic thiazolidinediones, also known as insulin sensitizers, are the largely studied PPARγ agonists and the only ones approved for the treatment of type 2 diabetes. However, they are loaded with side effects like fluid retention, obesity, hepatic failure, bone fractures, and cardiac failure; which restrict their clinical application. Medicinal plants used traditionally are the sources of bioactive compounds to be used for the development of successful drugs and many structurally diverse natural molecules are already established as PPARγ agonists. These natural partial agonists when compared to full agonist synthetic thiazolidinediones led to weaker PPARγ activation with lesser side effects but are not thoroughly investigated. Their thorough characterization and elucidation of mechanistic activity might prove beneficial for counteracting diseases by modulating PPARγ activity through dietary changes. We aim to review the therapeutic significance of PPARγ for ailments other than diabetes and highlight natural molecules with potential PPARγ agonistic activity.

Small molecules and extrinsic factors promoting differentiation of stem cells into insulin-producing cells.

In the modern world, type-2 diabetes mellitus has become a leading public healthcare problem, due to major risks of morbidity and mortality. Prevalence has increased significantly in recent decades. Treatment involves oral hypoglycemic agents or insulin replacement therapy. Development is ongoing for cell-based diabetes therapies using stem cells with the potential to differentiate into insulin-producing cells (IPCs): embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and stem cells from adult pancreas, liver, central nervous system, bone marrow and adipose tissue. Successful induction of iPSCs, however, depends on the quantity and quality of available stem cells and the development of adapted protocols determining the environment of extrinsic factors and involvement of small molecules. Validating such new cell therapies must be founded on this experimental rationale.

Anti-inflammatory and immune-modulating effects of rice callus suspension culture (RCSC) and bioactive fractions in an in vitro inflammatory bowel disease model.

BACKGROUND: Rice callus suspension culture (RCSC) has been shown to exhibit potent antiproliferative activity in multiple cancer cell lines. RCSC and its bioactive compounds can fill the need for drugs with no side effects. HYPOTHESIS/PURPOSE: The anti-inflammatory potential of RCSC and its bioactive fractions on normal colon epithelial cell lines, was investigated. STUDY DESIGN: Three cell lines, InEpC, NCM356 and CCD841-CoN were treated with proinflammatory cytokines followed by RCSC. Cytoplasmic and nuclear ROS were assayed with fluorescent microscopy and flow cytometer. Expression analysis of immune-related genes was performed in RCSC-treated cell lines. RCSC was fractionated using column chromatography and HPLC. Pooled fractions 10-18 was used to test for antiproliferative activity using colon adenocarcinoma cell line, SW620 and anti-inflammatory activity using CCD841-CoN. Mass spectrometric analysis was performed to identify candidate compounds in four fractions. RESULTS: RCSC treatment showed differential effects with higher cytoplasmic ROS levels in NCM356 and CCD841-CoN and lower ROS levels in InEpC. Nuclear generated ROS levels increased in all three treated cell lines. Flow cytometry analysis of propidium iodide stained cells indicated mitigation of cell death caused by inflammation in RCSC treated groups in both NCM356 and CCD841-CoN. Genes encoding transcription factors and cytokines were differentially regulated in NCM356 and CCD841-CoN cell lines treated with RCSC which provided insights into possible pathways. Analysis of pooled fractions 10-18 by HPLC identified 8 peaks. Cell viability assay with fractions 10-18 using SW620 showed that the number of viable cells were greatly reduced which was similar to 6X and 33X RCSC with very little effect on normal cells which similar to 1X RCSC. RCSC fractions increased nuclear and cytoplasmic ROS vs. both untreated and inflammatory control. Analysis of four fractions by mass spectrometry identified 4-deoxyphloridzin, 5'-methoxycurcumin, piceid and lupeol as candidate compounds which are likely to be responsible for the antiproliferative, anti-inflammatory and immune-regulating properties of RCSC. CONCLUSION: RCSC and its fractions showed anti-inflammatory activity on inflamed colon epithelial cells. Downstream target candidate genes which are likely to mediate RCSC effects were identified. Candidate compounds responsible for the antiproliferative and anti-inflammatory activity of RCSC and its fractions provide possible drug targets.

Nutritional Composition, Anti-Diabetic Properties and Identification of Active Compounds Using UHPLC-ESI-Orbitrap-MS/MS in Mangifera odorata L. Peel and Seed Kernel.

Mangifera odorata fruit, the hybrid forms between M. indica (mango) and M. foetida (bacang), has been shown to exhibit potential antioxidant activity, and the fruit waste could demonstrate functional and nutritional potential. In the present study, the nutritional composition (proximate, sugars, vitamins and minerals analyses), the anti-diabetic activities and phytochemical profile of M. odorata peel and seed kernel were investigated for the first time. The results indicated that seed kernel rich in fat, protein, carbohydrate, and ash while peel contained significantly greater amount of fiber, minerals, ß-Carotene and ascorbic acid compared to seed kernel. The samples were then extracted using different solvents (acetone, ethanol, methanol at 60%, v/v and pure deionized water) and their anti-diabetic activities (α-amylase and α-glucosidase inhibition assay) were determined. Seed kernel had the lowest IC50 values for α-amylase and α-glucosidase inhibition assay in 60% ethanol and 60% acetone, respectively. Due to the toxic effect and high volatility of acetone, the ethanolic extracts of samples were further analyses for their phytochemical profile using high performance liquid chromatography-mass spectrometry (LC-MS) and ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UHPLC-ESI-Orbitrap-MS/MS). The most abundant compounds identified were phenolic acid, ellagic acid, and flavonoid. These findings suggest that M. odorata fruit wastes, especially the seed kernel possesses promising ability to be used as functional ingredient in the food industry.

Chemical Profile, In Vitro Enzyme Inhibitory, and Antioxidant Properties of Stereum Species (Agaricomycetes) from Turkey.

Recently, mushroom species have been the focus of researchers' interest because of several bioactivities. The aim of this study was to investigate the chemical profile and biological activities of various extracts of two Stereum species (S. rugosum and S. sanguinolentum). Antioxidant activity was tested using ß-carotene-linoleic acid, DPPH scavenging, ABTS·+ scavenging, cupric-reducing antioxidant capacity (CUPRAC), and metal chelating assays. The extracts were also tested for their enzyme inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). HPLC-DAD was applied for the analysis of phenolic compounds, and fatty acid compositions were determined using GC and GC-MS. When fumaric acid and catechin hydrate were found as the most abundant phenolic compounds in both Stereum species, oleic acid and palmitic acid were identified as major fatty acids. Both of the studied Stereum methanol extracts were determined as the most active in ß-carotene-linoleic acid, DPPR, ABTS·+, and CUPRAC assays; the n-hexane extracts were found to be most active in metal chelating and AChE inhibitory activity assays. In addition, the methanol extract of S. sanguinolentum (IC50: 34.26 ± 0.31 µg/mL) showed higher ABTS·+ scavenging activity than α-tocopherol (IC50: 38.51 ± 0.54 µg/mL). The acetone extracts were found as potent inhibitors against BChE. These results suggest that Stereum species could be an antioxidant source and cholinesterase agent in pharmaceutic, food, and cosmetics industries.