Publications by authors named "Sasithorn Sirilun"

18 Publications

  • Page 1 of 1

Modified Riceberry rice extract suppresses melanogenesis-associated cell differentiation through tyrosinase-mediated MITF downregulation on B16 cells and zebrafish embryos.

Res Pharm Sci 2020 Oct 19;15(5):491-502. Epub 2020 Oct 19.

Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Background And Purpose: Excessive melanin production caused by overactive tyrosinase (TYR) enzyme results in several dermatological problems. The TYR inhibitor, derived from metabolite changes during fermentation, has been well recognized for pigmentation control.

Experimental Approach: This study is interested in alternative anti-melanogenic agents from bio-modified Riceberry rice through fermentation. Modified Riceberry rice extract (MRB) was evaluated for its cytotoxicity, melanin content, melanin excretion, and TYR activity in B16 cells. TYR and their melanogenesis-related molecules such as TYR-related proteins-1 and -2, and microphthalmia-associated transcription factor (MITF) were determined. The anti-melanogenic activity and toxicity were also tested using the embryonic zebrafish model. Furthermore, comprehensive genotoxicity testing was verified by cytokinesis-block micronucleus cytome assay.

Findings/results: The study found that non-cytotoxic concentrations of MRB at 20 and 40 mg/mL inhibited melanogenesis and melanin excretion by interfering B16 cell morphology. Cellular TYR enzymatic activity was also suppressed in the treated cells. The mRNA transcription and protein expression levels of TYR and MITF decreased by dose-dependent and time-dependent manners with MRB treatment. In the animal model, MRB was found to be safe and potent for melanogenesis-related TYR inhibition in embryonic zebrafish at 20 and 30 mg/mL. The toxicity of effective doses of MRB showed no genotoxicity and mutagenicity.

Conclusion And Implications: This study suggests that MRB has anti-melanogenesis potential through TYR and its-related protein inhibitions. MRB is also safe for applications and maybe a promising anti-melanogenic agent for hyperpigmentation control.
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http://dx.doi.org/10.4103/1735-5362.297852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879784PMC
October 2020

Physicochemical and prebiotic properties of resistant starch from Linn., ABB group, cv. Kluai Namwa Luang.

Heliyon 2020 Dec 21;6(12):e05789. Epub 2020 Dec 21.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.

Resistant starch (RS), a current health trend, can be obtained from various natural sources. Linn., ABB group, cv. Kluai Namwa Luang is a good source of RS. This is the first study to investigate the physicochemical properties, RS contents, and prebiotic properties of unpeeled raw banana powder (URB), peeled raw banana powder (PRB), and banana starch (BS) from Kluai Namwa Luang. Their physicochemical properties were characterized by scanning electron microscope, differential scanning calorimeter, and X-ray diffractometer. The RS contents were determined using the Megazyme Resistant Starch Assay Kit. The prebiotic properties are reported as a prebiotic index (PI). The particle morphology of URB, PRB, and BS granules showed a smooth surface with irregular size and shape. Their gelatinization temperatures were 74-78 °C. All samples exhibited typical B-type diffraction patterns. URB contained the highest dietary fiber (9.7 ± 0.2 g per 100 g of dried sample), whereas BS contained the highest RS content (74.1 ± 0.1 g per 100 g of dried sample). Both URB and BS possessed excellent probiotic growth promotion, prebiotic properties with PI values comparable to the commercial inulin, and were highly resistant to digestive enzymes. Therefore, BS from Kluai Namwa Luang is suggested as functional nutrient in health promotion products.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758519PMC
December 2020

Anti- and anti-biofilm activities of dextranase and its encapsulation in alginate beads for application in toothpaste.

PeerJ 2020 17;8:e10165. Epub 2020 Nov 17.

Innovation Center for Holistic Health, Nutraceuticals and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Mueang Chiang Mai, Chiang Mai, Thailand.

Background: The accumulation of plaque causes oral diseases. Dental plaque is formed on teeth surfaces by oral bacterial pathogens, particularly , in the oral cavity. Dextranase is one of the enzymes involved in antiplaque accumulation as it can prevent dental caries by the degradation of dextran, which is a component of plaque biofilm. This led to the idea of creating toothpaste containing dextranase for preventing oral diseases. However, the dextranase enzyme must be stable in the product; therefore, encapsulation is an attractive way to increase the stability of this enzyme.

Methods: The activity of food-grade fungal dextranase was measured on the basis of increasing ratio of reducing sugar concentration, determined by the reaction with 3, 5-dinitrosalicylic acid reagent. The efficiency of the dextranase enzyme was investigated based on its minimal inhibitory concentration (MIC) against biofilm formation by ATCC 25175. Box-Behnken design (BBD) was used to study the three factors affecting encapsulation: pH, calcium chloride concentration, and sodium alginate concentration. Encapsulation efficiency (% EE) and the activity of dextranase enzyme trapped in alginate beads were determined. Then, the encapsulated dextranase in alginate beads was added to toothpaste base, and the stability of the enzyme was examined. Finally, sensory test and safety evaluation of toothpaste containing encapsulated dextranase were done.

Results: The highest activity of the dextranase enzyme was 4401.71 unit/g at a pH of 6 and 37 °C. The dextranase at its MIC (4.5 unit/g) showed strong inhibition against the growth of . This enzyme at 1/2 MIC also showed a remarkable decrease in biofilm formation by . The most effective condition of dextranase encapsulation was at a pH of 7, 20% w/v calcium chloride and 0.85% w/v sodium alginate. Toothpaste containing encapsulated dextranase alginate beads produced under suitable condition was stable after 3 months of storage, while the sensory test of the product was accepted at level 3 (like slightly), and it was safe.

Conclusion: This research achieved an alternative health product for oral care by formulating toothpaste with dextranase encapsulated in effective alginate beads to act against cariogenic bacteria, like , by preventing dental plaque.
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http://dx.doi.org/10.7717/peerj.10165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678491PMC
November 2020

Potential of Linn. for digestive function promotion by supporting sp.

Heliyon 2020 Oct 12;6(10):e05247. Epub 2020 Oct 12.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.

is a beneficial bacteria that could inhibit pathogenic potential of other microorganisms. This is the first study to develop a potential tablet from Linn. (locally known as Kluai Namwa) using the direct compression method to support sp. We compared the amount of resistant starch and prebiotic properties of the dry powder from unpeeled raw fruit, peeled raw fruit, and starch from . These dry powders were formulated into tablets using the direct compression method and evaluated for their prebiotic index compared to their native powder. Resistant starch, which possessed the highest prebiotic index, generated a tablet that possessed remarkable in vitro prebiotic properties. All tablets met the requirement of the United States Pharmacopeia. Therefore, resistant starch tablets from are suggested for use as a health promotion product.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567041PMC
October 2020

Optimization of Fungal Dextranase Production and Its Antibiofilm Activity, Encapsulation and Stability in Toothpaste.

Molecules 2020 Oct 18;25(20). Epub 2020 Oct 18.

Innovation Center for Holistic Health, Nutraceuticals and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.

Dextranase catalyzes the degradation of the substrate dextran, which is a component of plaque biofilm. This enzyme is involved in antiplaque accumulation, which can prevent dental caries. The activity of crude dextranase from TISTR 3511 was assessed, and the maximum value (7.61 unit/g) was obtained at 37 °C and pH 6. The Plackett-Burman design was used to obtain significant factors for enhancing fungal dextranase production, and three influencing factors were found: Dextran, yeast extract concentration and inoculum age. Subsequently, the significant factors were optimized with the Box-Behnken design, and the most suitable condition for dextranase activity at 30.24 unit/g was achieved with 80 g/L dextran, 30 g/L yeast extract and five day- old inoculum. The use of 0.85% alginate beads for encapsulation exhibited maximum dextranase activity at 25.18 unit/g beads, and this activity was stable in toothpaste for three months of testing. This study explored the potential production of fungal dextranase under optimal conditions and its encapsulation using alginate for the possibility of applying encapsulated dextranase as an additive in toothpaste products for preventing dental caries.
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http://dx.doi.org/10.3390/molecules25204784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587561PMC
October 2020

Putative Mechanisms Responsible for the Antihyperglycemic Action of HII01 in Experimental Type 2 Diabetic Rats.

Nutrients 2020 Oct 1;12(10). Epub 2020 Oct 1.

Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Despite the updated knowledge of the impact of gut dysbiosis on diabetes, investigations into the beneficial effects of individual bacteria are still required. This study evaluates the antihyperglycemic efficacy of HII01 and its possible mechanisms in diabetic rats. Diabetic rats were assigned to receive vehicle, HII01 (10 CFU/day), metformin 30 (mg/kg) or a combination of HII01 and metformin. Normal rats given vehicle and HII01 were included. Metabolic parameters, including in vitro hemi-diaphragm glucose uptake, skeletal insulin-signaling proteins, plasma lipopolysaccharide (LPS), gut permeability, composition of gut microbiota and its metabolites, as well as short-chain fatty acids (SCFAs), were assessed after 12 weeks of experiment. The results clearly demonstrated that HII01 improved glycemic parameters, glucose uptake, insulin-signaling proteins including pAkt, glucose transporter 4 (GLUT4) and phosphorylation of AMP-activated protein kinase (pAMPK), tumor necrosis factor (TNF-α) and nuclear factor-κB (NF-kB) in diabetic rats. Modulation of gut microbiota was found together with improvement in leaky gut, endotoxemia and SCFAs in diabetic rats administered HII01. In conclusion, HII01 alleviated hyperglycemia in diabetic rats primarily by modulating gut microbiota along with lessening leaky gut, leading to improvement in endotoxemia and inflammation-disturbed insulin signaling, which was mediated partly by PI3K/Akt signaling and AMPK activation.
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http://dx.doi.org/10.3390/nu12103015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601916PMC
October 2020

Organic acids and 2,4-Di--butylphenol: major compounds of WM36 cell-free supernatant against growth, survival and virulence of Typhi.

PeerJ 2020 20;8:e8410. Epub 2020 Jan 20.

Innovation Center for Holistic Health, Nutraceuticals and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.

Background: Typhi (. Typhi), the causative agent of typhoid fever, causes serious systemic disease in humans. Antibiotic treatment is required for the . Typhi infection, while the inappropriate use of antibiotics causes increased drug-resistant . Typhi. Hence, alternative therapies through non-antibiotic approaches are urgently needed. The use of beneficial lactic acid bacterium and/or its metabolites to control typhoid fever represent a promising approach, as it may exert protective actions through various mechanisms.

Method: In this study, the cell-free culture supernatant (CFCS) of WM36 was evaluated via the antibacterial activity, and its metabolites were identified. In addition, the effects of CFCS on virulence behaviors were also investigated.

Result: Based on strong inhibition the growth of . Typhi DMST 22842, organic acids (lactic acid and acetic acid) and 2,4-Di--butylphenol (2,4 DTBP), were the main antibacterial metabolites presented in CFCS of strain WM36. Minimum inhibitory concentration (MIC) at 40% WM36-CFCS dramatically reduced the . Typhi population to more than 99.99% at 4 h and completely inhibited biofilm formation, while sub-MIC at 20% (v/v) and MIC could reduce 100% of motility. Additionally, sub-MIC at only 10% (v/v) WM36-CFCS did down-regulate the expression of virulence genes which are responsible for the type-III secretion system, effector proteins, and quorum sensing system in this pathogen.

Conclusion: WM36 and its metabolites are shown to be a promising candidates, and an effective approach against typhoid burden.
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http://dx.doi.org/10.7717/peerj.8410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977521PMC
January 2020

Antihyperglycemic effect of rice husk derived xylooligosaccharides in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rat model.

Food Sci Nutr 2020 Jan 9;8(1):428-444. Epub 2019 Dec 9.

Innovation Center for Holistic Health, Nutraceuticals and Cosmeceuticals Faculty of Pharmacy Chiang Mai University Chiang Mai Thailand.

Rice husk (RH) is an agricultural waste obtained from rice milling process. Our previous study demonstrated the optimized process of extracting xylooligosaccharides (XOS), a prebiotic that can support the growth and activity of beneficial gut microbiota, from RH. Accumulated evidences indicate that the composition of gut microbiota is involved in the progression of insulin resistance and diabetes. This study aims to evaluate the antihyperglycemic effect and putative mechanisms of RH-XOS using a diabetic rat model induced by high-fat diet and streptozotocin injection. Diabetic rats were randomly assigned to receive vehicle (DMC), XOS (DM-XOS), metformin (DMM), and a combination of XOS and metformin (DMM-XOS). An additional group of rats were fed with normal diet plus vehicle (NDC) and normal diet plus XOS (ND-XOS). Supplementation with RH-XOS for 12 weeks successfully decreased the fasting plasma glucose, insulin, leptin, and LPS levels in DM-XOS compared with DMC. Likewise, the insulin-stimulated glucose uptake assessed by in vitro study was significantly enhanced in DM-XOS, DMM, and DMM-XOS. The diminished protein expressions of GLUT4 and pAkt as well as pAMPK were significantly modulated in DM-XOS, DMM, and DMM-XOS groups. Interestingly, RH-XOS supplementation reversed the changed gut permeability, elevated the number of beneficial bacteria, both and spp., and increased SCFAs production. Taken together, the results confirm the efficacy of RH-XOS in achieving good glycemic control in diabetes by maintenance of gut microbiota and attenuation of endotoxemia. The findings reveal the benefits of RH-XOS and open an opportunity to improve its value by its development as a nutraceutical for diabetes.
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http://dx.doi.org/10.1002/fsn3.1327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977422PMC
January 2020

Effect of Green Tea Extract During Lactic Acid Bacteria Mediated Fermentation of Morinda citrifolia Linn. (Noni) Fruit Juice.

Pak J Biol Sci 2019 Jan;22(10):486-493

Background And Objective: Fermented noni (Morinda citrifolia L.) fruit juice is considered as one of the health-promoting beverage. The food industries are working on further improvement of fermented noni juice. The objective of the current study was to assess the impact of green tea (GT) extract during the lactic acid bacteria (Lactobacillus plantarum SK15) mediated fermentation of noni fruit juice.

Materials And Methods: The clean-diced noni fruits were blended with sugar, water, 10% SK15 and GT extract. The mixture was kept at 30°C for 25 days. During fermentation, samples were collected. The changes in pH, acidity, alcohol, sugar, pectin content, total phenolic content (TPC), antioxidant capacity (AC), pectin methylesterase (PME) activity and microbial load were assessed.

Results: The fermented noni fruit juice exhibited significantly low pH, sugar and pectin content. TPC and AC were increased after fermentation. The alcohol content, especially methanol volume was increased in all the samples but not exceed the lethal level. The samples with GT extract exhibited superior quality in all measured aspects. Notably, PME activity was suppressed by GT extract, which was reflected in the methanol content of the respective samples when compared to control.

Conclusion: The results suggested that GT extract could be used in the production of fermented plant beverages to prevent the indigenous PME activity (to reduce the methanol formation) and to improve the AC of the product. Further studies are required to know the fate of other phytochemicals and volatile compounds in noni fruit juice during fermentation.
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http://dx.doi.org/10.3923/pjbs.2019.486.493DOI Listing
January 2019

Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol.

Trials 2019 Dec 19;20(1):754. Epub 2019 Dec 19.

Pharmacoepidemiology and Statistics Research Center (PESRC), Chiang Mai University, Chiang Mai, 50200, Thailand.

Background: Current international guidelines recommend the use of a daily topical exit-site antimicrobial to prevent peritoneal dialysis (PD)-related infections. Although nonantibiotic-based therapies are appealing because they may limit antimicrobial resistance, no controlled trials have been conducted to compare topical antimicrobial agents with usual exit-site care for the prevention of PD-related infections among the Thai PD population. We propose a controlled three-arm trial to examine the efficacy and safety of a daily chlorhexidine gluconate-impregnated patch versus mupirocin ointment versus usual exit-site care with normal saline for the prevention of PD-related infections.

Methods/designs: This study is a randomized, double-blind, multicenter, active-controlled, clinical trial. Adult patients aged 18 years or older who have end-stage kidney disease and are undergoing PD will be enrolled at three PD Centers in Thailand. A total of 354 PD patients will be randomly assigned to either the 2% chlorhexidine gluconate-impregnated patch, mupirocin ointment, or usual exit-site care with normal saline dressing according to a computer-generated random allocation sequence. Participants will be followed until discontinuation of PD or completion of 24 months. The primary study outcomes are time to first PD-related infection (exit-site/tunnel infection or peritonitis) event and the overall difference in PD-related infection rates between study arms. Secondary study outcomes will include (i) the rate of infection-related catheter removal and PD technique failure, (ii) rate of nasal and exit-site Staphylococcus aureus colonization, (iii) healthcare costs, and (iv) skin reactions and adverse events. We plan to conduct a cost-utility analysis alongside the trial from the perspectives of patients and society. A Markov simulation model will be used to estimate the total cost and health outcome in terms of quality-adjusted life years (QALYs) over a 20-year time horizon. An incremental cost-effectiveness ratio in Thai Baht and U.S. dollars per QALYs gained will be illustrated. A series of probabilistic sensitivity analyses will be conducted to assess the robustness of the cost-utility analysis findings.

Discussion: The results from this study will provide new clinical and cost-effectiveness evidence to support the best strategy for the prevention of PD-related infections among the Thai PD population.

Trial Registration: ClinicalTrials.gov, NCT02547103. Registered on September 11, 2015.
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http://dx.doi.org/10.1186/s13063-019-3953-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924023PMC
December 2019

Cell-free supernatants from cultures of lactic acid bacteria isolated from fermented grape as biocontrol against Typhi and Typhimurium virulence via autoinducer-2 and biofilm interference.

PeerJ 2019 26;7:e7555. Epub 2019 Aug 26.

Innovation Center for Holistic Health, Nutraceuticals and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.

Background: Typhi and Typhimurium are the causative pathogens of salmonellosis, and they are mostly found in animal source foods (ASF). The inappropriate use of antibiotics enhances the possibility for the emergence of antibiotic resistance in pathogens and antibiotic residue in ASF. One promising alternative to antibiotics in animal farming is the use of lactic acid bacteria (LAB).

Methods: The present study was carried out the cells and/or the cell-free culture supernatants (CFCS) from beneficial LAB against Typhi and Typhimurium. The antibacterial mechanisms of LAB-CFCS as biocontrol agents against both serovars were investigated through the analysis of anti-salmonella growth activity, biofilm inhibition and quorum quenching activity.

Results: Among 146 LAB strains isolated from 110 fermented food samples, the 2 strong inhibitory effect strains (WM33 and WM36) from fermented grapes against both serovars were selected. Out of the selected strains, WM36 was the most effective inhibitor, which indicated Typhi by showing 95.68% biofilm inhibition at 20% biofilm inhibition concentration (BIC) and reduced 99.84% of AI-2 signaling interference. The WM33 was the best to control Typhimurium by producing 66.46% biofilm inhibition at only 15% BIC and 99.99% AI-2 signaling a reduction. The 16S rDNA was amplified by a polymerase chain reaction (PCR). The selected isolates were identified as WM33 and WM36 based on nucleotide homology and phylogenetic analysis.

Conclusion: The metabolic extracts from spp. inhibit serovars with the potential to be used as biocontrol agents to improve microbiological safety in the production of ASF.
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http://dx.doi.org/10.7717/peerj.7555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715067PMC
August 2019

Optimization of alkaline pretreatment and enzymatic hydrolysis for the extraction of xylooligosaccharide from rice husk.

AMB Express 2018 Jul 16;8(1):115. Epub 2018 Jul 16.

Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.

Rice husk (RH) is the major agricultural waste obtained during rice hulling process, which can be a sustainable source of xylooligosaccharide (XOS). The current study deals with the production of XOS from Thai rice husk using alkaline pretreatment and enzyme hydrolysis method. The response surface methodology consisted of central composite design and Box-Behnken design was employed to achieve the maximum response in alkaline pretreatment and XOS production, respectively. The optimum conditions for alkaline pretreatment to recover maximum xylan yield were 12-18% of alkaline concentration, the temperature at 110-120 °C, and steaming time for 37.5-40 min. The FTIR results suggested that the extracted sample was the xylan fraction. The maximum XOS production of 17.35 ± 0.31 mg XOS per mL xylan was observed in the run conditions of 6.25 mg enzyme per g xylan, 9 h of incubation time, and 5% of xylan. The results revealed that the xylan extracted from RH by using an effective base couple with the steam application and the enzymatic hydrolysis help to maximize the yield of XOS, which can be further used in functional foods and dietary supplements.
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http://dx.doi.org/10.1186/s13568-018-0645-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047951PMC
July 2018

Lactobacillus paracasei HII01, xylooligosaccharides, and synbiotics reduce gut disturbance in obese rats.

Nutrition 2018 10 20;54:40-47. Epub 2018 Mar 20.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. Electronic address:

Objectives: The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation.

Methods: Male Wistar rats were fed with either a normal or high-fat diet that contained 19.77% and 59.28% energy from fat, respectively, for 12 wk. Then, the high-fat diet rats were fed daily with a 10 colony forming unit of the probiotic HII01, 10% prebiotic XOS, and synbiotics for 12 wk. The metabolic parameters, serum lipopolysaccharide levels, fecal Firmicutes/Bacteroidetes ratios, levels of Enterobacteriaceae, Bifidobacteria, and gut proinflammatory cytokine gene expression were quantified.

Results: The consumption of probiotic L. paracasei HII01, prebiotic XOS, and synbiotics for 12 wk led to a decrease in metabolic endotoxemia, gut dysbiosis (a reduction in the Firmicutes/Bacteroidetes ratio and Enterobacteriaceae), and gut inflammation in obese-insulin resistant rats.

Conclusions: Pro-, pre-, and synbiotics reduced gut dysbiosis and gut inflammation, which lead to improvements in metabolic dysfunction in obese-insulin resistant rats.
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http://dx.doi.org/10.1016/j.nut.2018.03.005DOI Listing
October 2018

Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats.

J Neuroinflammation 2018 Jan 9;15(1):11. Epub 2018 Jan 9.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

Background: Chronic high-fat diet (HFD) consumption caused not only obese-insulin resistance, but also cognitive decline and microglial hyperactivity. Modified gut microbiota by prebiotics and probiotics improved obese-insulin resistance. However, the effects of prebiotics, probiotics, and synbiotics on cognition and microglial activity in an obese-insulin resistant condition have not yet been investigated. We aimed to evaluate the effect of prebiotic (Xyloolidosaccharide), probiotic (Lactobacillus paracasei HII01), or synbiotics in male obese-insulin resistant rats induced by a HFD.

Methods: Male Wistar rats were fed with either a normal diet or a HFD for 12 weeks. At week 13, the rats in each dietary group were randomly divided into four subgroups including vehicle group, prebiotics group, probiotics group, and synbiotics group. Rats received their assigned intervention for an additional 12 weeks. At the end of experimental protocol, the cognitive functioning of each rat was investigated; blood and brain samples were collected to determine metabolic parameters and investigate brain pathology.

Results: We found that chronic HFD consumption leads to gut and systemic inflammation and impaired peripheral insulin sensitivity, which were improved by all treatments. Prebiotics, probiotics, or synbiotics also improved hippocampal plasticity and attenuated brain mitochondrial dysfunction in HFD-fed rats. Interestingly, hippocampal oxidative stress and apoptosis were significantly decreased in HFD-fed rats with all therapies, which also decreased microglial activation, leading to restored cognitive function.

Conclusions: These findings suggest that consumption of prebiotics, probiotics, and synbiotics restored cognition in obese-insulin resistant subjects through gut-brain axis, leading to improved hippocampal plasticity, brain mitochondrial function, and decreased microglial activation.
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http://dx.doi.org/10.1186/s12974-018-1055-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761137PMC
January 2018

Assessment of changes in the content of anthocyanins, phenolic acids, and antioxidant property of Saccharomyces cerevisiae mediated fermented black rice bran.

AMB Express 2017 Dec 5;7(1):114. Epub 2017 Jun 5.

Innovation Center for Holistic Health, Nutraceuticals and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.

Studies on phytochemical properties and bioactivities of rice bran revealed the wealth of natural complex antioxidant compounds. The composition and the properties of the rice bran get altered after fermentation by several microbes. This study was designed to optimize the black rice bran fermentation conditions for the total anthocyanin (ACN) content, total antioxidant properties, and relative activity of β-glucosidase (BGS) by Saccharomyces cerevisiae. The Box-Behnken design and response surface methodology was employed to achieve the maximum response in fermentation. The kinetic analysis of HPLC based phytochemical determination and bioconversion of ACN, and in vitro antioxidant assays were performed during fermentation. The optimum pH, temperature and NaCl concentration to achieve maximum ACN content, antioxidant capacity, and BGS activity were pH 4.0, 40 °C, and 0.5%, respectively. Bioconversion of cyanidin-3-glucoside and peonidin-3-glucoside to cyanidin and peonidin was recorded at a significant level, respectively. The maximum activity of BGS on rice bran was noticed at 24 h of fermentation. The results suggested that phytochemical content was not changed significantly, whereas the antioxidant properties of rice bran were slightly enhanced after 24 h of fermentation. Additional detailed in vivo evaluation is required to explain the impact of submerged fermentation on the bioactivity of rice bran.
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http://dx.doi.org/10.1186/s13568-017-0411-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459781PMC
December 2017

Germinated Thai Black Rice Extract Protects Experimental Diabetic Rats from Oxidative Stress and Other Diabetes-Related Consequences.

Pharmaceuticals (Basel) 2016 Dec 28;10(1). Epub 2016 Dec 28.

Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

: Diabetes mellitus (DM), particularly type 2 DM (T2DM), is one of the most common metabolic disorder worldwide. The prevention measures and treatment strategies for DM are improving steadily. The current study explains the impact of germination on phytochemical content of Thai black rice (BR), and the influence of germinated BR extract (GBRE) supplementation on diabetic conditions in rats. : BR was germinated and the phenolic, anthocyanin, and γ-aminobutyric acid (GABA) content of the extract were analyzed using HPLC and spectrophotometric methods. Streptozotocin-induced diabetic rats were supplemented with high and low doses of GBRE. The plasma glucose, insulin, cholesterol, triglyceride levels, antioxidant status, and antioxidant enzyme levels of treated animals were assessed using ELISA and spectrophotometric methods. : Germination enhanced the GABA content of BR, and GBRE intervention improved the total antioxidant capacity and antioxidant enzymes levels in diabetic rats. The plasma glucose, cholesterol, triglyceride levels, insulin resistance and glucose tolerance were reduced, and the degree of insulin secretion in rat plasma was significantly increased upon GBRE treatment. Both pre and post-treatment approaches showed the anti-diabetic ability of GBRE. In most of the analyzed parameters, GBRE was quite equal to the performance of drug-metformin. : GBRE supplementation helps prevent and manage the consequences of DM.
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http://dx.doi.org/10.3390/ph10010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374407PMC
December 2016

Unpolished Thai Rice Prevents Aberrant Crypt Foci Formation through the Invovement of ?catenin and COX2 Expression in AzoxymethaneTreated Rats.

Asian Pac J Cancer Prev 2016 ;17(7):3551-8

Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand Email :

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world, with chronic inflammation and diet as major causes in its development. Chemopreventive effects of natural dietary products have been the focus of studies for prevention over the past decade. This study was conducted to determine the effects of unpolished Thai rice during precancerous stage through the involvement of ?catenin, cyclooxygenase2 (COX2) expression and inflammatory cytokines focusing on azoxymethane (AOM)induced aberrant crypt foci (ACF)related to CRC. Male Sprague Dawley rats received two injections of AOM (15 mg/kg body weight) at weeks 4 and 5 while rats were treated with 20% or 70% unpolished Thai rice. The rats were sacrificed at week 38 and the colons removed for aberrant crypt foci (ACF) identification. Histopathologic changes, immunohistochemical analysis of ?catenin and COX2 expression, and cytokine expression of proinflammatory and antiinflammatory markers were determined. The administration of unpolished Thai rice significantly and dose dependently decreased the total number of ACF and the percentages of ACF with highgrade dysplasia. Interestingly, unpolished Thai rice suppressed the expression of βcatenin and COX2. In addition, it also altered proinflammatory (IL6 and IFNγ) and antiinflammatory (IL 10) markers. The results suggested that unpolished Thai rice may provide a promising dietary intake for prevention during precancerous stage of CRC development, through the involvement of βcatenin and COX2 expression, and also modulate inflammatory cytokinesrelated to CRC.
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January 2017

Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

Pharm Biol 2016 Sep 21;54(9):1596-605. Epub 2016 Jan 21.

a Health Product Research and Development Unit , Faculty of Pharmacy, Chiang Mai University , Chiang Mai , Thailand ;

Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary administration of inulin reduces the formation of preneoplastic lesions in the colon, possibly by altering the microecology and microbial activities on carcinogenesis.
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http://dx.doi.org/10.3109/13880209.2015.1110597DOI Listing
September 2016