METHODS: A single centre, latin-square cross-over, double masked, randomized controlled clinical trial was conducted on 45 chronic generalized gingivitis subjects who were chosen from the dental clinic of MAHSA University, Malaysia. A total of 45 subjects were randomly assigned into one of the three different groups (n = 15 each) using a computer-generated random allocation sequence: Group A Propolis mouthwash; Group B Chlorhexidine mouthwash; and Group C Placebo mouthwash. Supragingival plaque and gingival inflammation were assessed by full mouth Plaque index (PI) and gingival index (GI) at baseline and after 21 days. The study was divided into three phases, each phase lasted for 21 days separated by a washout period of 15 days in between them. Groups A, B and C were treated with 0.2% Propolis, Chlorhexidine, and Placebo mouthwash, respectively, in phase I. The study subjects were instructed to use the assigned mouthwash twice daily for 1 min for 21 days. On day 22nd, the subjects were recalled for measurement of PI and GI. After phase I, mouthwash was crossed over as dictated by the Latin square design in phase II and III.
RESULTS: At baseline, intergroup comparison revealed no statistically significant difference between Groups A, B and C (p > 0.05). On day 21, one-way ANOVA revealed statistically significant difference between the three groups for PI (p
METHODS: Qualitative study using one-to-one semi-structured interviews conducted with 22 HCPs involved in the care of diabetic patients (6 endocrinologists, 4 general practitioners, 4 nurses and 8 pharmacists). Participants were recruited through general practices, community pharmacies and a diabetic centre in Saudi Arabia. Data were analyzed using thematic analysis.
RESULTS: Five key themes resulted from the analysis. HCPs generally demonstrated negative perceptions toward CAM, particularly regarding their evidence-based effectiveness and safety. Participants described having limited interactions with diabetic patients regarding CAM use due to HCPs' lack of knowledge about CAM, limited consultation time and strict consultation protocols. Participants perceived convenience as the reason why patients use CAM. They believed many users lacked patience with prescribed medications to deliver favourable clinical outcomes and resorted to CAM use.
CONCLUSIONS: HCPs have noted inadequate engagement with diabetic patients regarding CAM due to a lack of knowledge and resources. To ensure the safe use of CAM in diabetes and optimize prescribed treatment outcomes, one must address the communication gap by implementing a flexible consultation protocol and duration. Additionally, culturally sensitive, and evidence-based information should be available to HCPs and diabetic patients.
METHODS: Uncaria gambir extracts at concentrations ranging from 1000 to 7.8 µg/ml and MTA eluates at 4- and 48 h setting times were prepared. 10% dimethyl sulfoxide (DMSO) and culture media were used as positive and negative controls respectively. Cell viability on days 1, 2, 3 and 7 was analysed using Alamar Blue and Live and Dead Cell assay. Any morphological cellular changes were evaluated using transmission electron microscopes (TEM). Data were analysed using a two-way mixed Analysis of Variance (ANOVA).
RESULTS: The interaction between the concentration and exposure time on the fluorescence intensity of Uncaria gambir extract and MTA 48 h was found to be statistically significant (p < 0.001). No cytotoxic effects on the cells were exerted by both MTA 48 h and Uncaria gambir extract at a concentration below 500 µg/mL. TEM analysis and Live and Dead Cell assay for both materials were comparable to the negative control. No significant differences in fluorescent intensity were observed between Uncaria gambir extract at 500 µg/mL and MTA 48 h (p > 0.05).
CONCLUSION: Uncaria gambir extracts at a maximum concentration of 500 μg/mL are non-cytotoxic over time and are comparable to the MTA.
METHODS: The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and β-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods.
RESULTS: The results indicated that there were significant inhibitory effects on all selected inflammatory mediators' release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC-MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers.
CONCLUSIONS: In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.
METHODS: This study was a two-group randomized clinical trial on 69 cancer patients undergoing chemotherapy at Reza Radiotherapy and Oncology Center, Iran in 2018. Patients were randomly divided into intervention and control groups. The intervention group received laughter yoga for four sessions at one-week intervals. Each session consists of one part and lasts for 20-30 min. Patients' health-related quality of life was assessed before and after the laughter yoga sessions using Quality of Life Questionnaire European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) version 3.0. SPSS Statistics (v.20 software was used to conduct Chi-square, independent t-test, Mann-Whitney, Wilcoxon and paired t-tests analyses of the data.
RESULTS: The number of participants in intervention and control groups were 34 and 35, there was no significant difference of demographic and disease related characteristics and pre-intervention HRQOL between two groups. In the intervention group, there is significant difference between pre- and post-intervention scores (Mean ± Standard Deviation) of emotional functioning (12.99 ± 10.49), physical functioning (0.78 ± 6.08), role functioning (3.43 ± 7.97), fatigue (-8.82 ± 22.01), pain (-8.33 ± 11.78), sleep disturbance (-15.68 ± 18.77), and global health and quality of life (6.37 ± 5.04) (p
METHODS: Male Sprague Dawley rats weighing 200-250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.
RESULTS: TRF preserved the retinal layer thickness (GCL, IPL, INL and OR; p
METHODS: A cross-sectional study of treated adult chronic disease patients was conducted using the fifth Indonesian Family Life Survey (IFLS-5) database. Descriptive analysis was used to identify the proportion of TM users, while a multivariate logistic regression was used to analyze their characteristics.
RESULTS: This study included 4901 subjects and identified 27.1% as TM users. The highest TM use was in subjects with cancer (43.9%), liver issues (38.3%), cholesterol issues (34.3%), diabetes (33.6%), and stroke (31.7%). Characteristics associated with TM users were a perception of one's current health as unhealthy (OR 2.59, 95% CI 1.76-3.81), low medication adherence (OR 2.49, 95% CI 2.17-2.85), age above 65 years (OR 2.17, 95% CI 1.63-2.90), having higher education (OR 1.64, 95% CI 1.17-2.29), and residence outside of Java (OR 1.27, 95% CI 1.11-1.45).
CONCLUSIONS: Low medication adherence among TM users highlights the potentially irrational use of treatment in chronic diseases. Nevertheless, the longstanding use of TM users indicates the potential for its development. Further studies and interventions are needed to optimize TM use in Indonesia.
METHODS: TC-16 was screened for phytochemicals. Phenolic and flavonoid contents of TC-16 and its individual ingredients were determined, followed by assessment of antioxidant properties using in vitro assays including 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and β-carotene bleaching (BCB) assays. Interactions among the herbs were also investigated by calculating the difference in antioxidant activity and combination index.
RESULTS: Alkaloids, flavonoids, terpenoids, saponins and glycosides were present in TC-16. TC-16 possessed the highest phenolic (46.14 ± 1.40 mg GAE/g) and flavonoid (132.69 ± 1.43 mg CE/g) contents following C. longa. Synergistic antioxidant activity among the herbs was evident in ORAC and BCB assays which uses mainly hydrogen atom transfer-based antioxidant mechanisms.
CONCLUSIONS: TC-16 demonstrated roles in combating free radicals. In a PHF, synergistic interaction among the herbs is observed in some but not all mechanisms. Mechanisms showing synergistic interactions should be highlighted to maximise the beneficial property of the PHF.
AIM: In this study, maceration and Soxhlet extraction of the whole plant of Cassia alata Linn. (leaves, roots, and stem) were performed using four solvents with different polarities, namely n-hexane, ethyl acetate, ethanol and distilled water. The crude extracts were screened using agar well diffusion, colorimetric broth microdilution, grid culture and bacterial growth curve analysis against Staphylococcus aureus. The phytochemicals in the crude extracts were identified using Gas Chromatography-Mass Spectrometry (GC-MS).
RESULTS: Agar-well diffusion analysis revealed that extraction using ethyl acetate showed the largest inhibition zone with an average diameter of 15.30 mm (root Soxhlet extract) followed by 14.70 mm (leaf Soxhlet extract) and 13.70 mm (root maceration extract). The lowest minimum inhibitory and minimum bactericidal concentration in root Soxhlet extract using ethyl acetate was 0.313 and 0.625 µg µL-1, respectively. Our study proved that crude extract of the plant suppressed the growth of S. aureus as evidenced from a significant regression extension (p
METHODS: The fruit powder was macerated using methanol and then partitioned by hexane, ethyl acetate, n-butanol, and water. The fractions were chromatographed on the column chromatography and incorporated with TLC and recrystallization to give pure compounds. The structures of isolated compounds were determined by UV-Visible, FT-IR, MS, proton (1H-NMR), carbon (13C-NMR), and 2D-NMR techniques encompassing HMQC and HMBC spectra. The compounds were evaluated for their ACE inhibitory activity, and the strongest compound was determined by the kinetics enzyme inhibition.
RESULTS: Based on the spectral data, the isolated compounds were determined as 6,4-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (1), 4,4'-dihydroxy-6-methoxybenzophenone-2-O-β-D-glucopyranoside (2) and mangiferin (3). IC50 values of the isolated compounds 1, 2 and 3 were 0.055, 0.07, and 0.025 mM, respectively.
CONCLUSION: The three compounds have ACE inhibitor and mangiferin demonstrated the best ACE inhibitory activity with competitive inhibition on ACE with the type of inhibition kinetics is competitive inhibition.
METHODS: Human oral cancer cell lines (HSC2, YD10B, YD38, YD9, and YD32) were used in this study. BrdU incorporation, cell cycle and annexin-V/PI staining were all evaluated using flow cytometry to determine the extent to which O. octandra leaf extract inhibits cell proliferation and induces apoptosis. Cell viability and reactive oxygen species (ROS) were also measured in order to investigate the anti-cancer effects of O. octandra extracts. Western blotting was performed to detect cell cycle related protein such as cyclin d1 and cdk4, and to detect apoptosis-related proteins such as Bcl-2, Bcl-XL, Bax, Caspase-9, Cleaved caspase-3, Fas, Caspase-8, and Bid.
RESULTS: Leaf extract of O. octandra reduced oral squamous cell carcinoma (OSCC) cell viability in a dose-dependent manner. Leaf extract of O. octandra has non-toxic in normal keratinocytes. Also, O. octandra extract interrupted the DNA replication via G1 phase arrests, and this effect was independent of ROS generation. In the apoptosis-related experiments, the population of annexin V-positive cells increased upon treatment with O. octandra extract. Furthermore, the expression of anti-apoptotic protein (Bcl-2 and Bcl-xL) was decreased, whereas the expression of cleaved caspase-3 protein was increased in O. octandra-treated OSCC cells.
CONCLUSIONS: The results suggest that a leaf extract of O. octandra inhibited the proliferation of OSCC cells through G1 phase arrest and interrupting DNA replication. The leaf extract of O. octandra could trigger the apoptotic response via caspase 3 activation in OSCC cells. These results suggest that O. octandra has the potential to be developed as an alternative medicine for treating OSCC.
METHODOLOGY: A cross-sectional study was conducted at a university primary care clinic. Patients aged 18 to 80 years old with MetS were recruited. Socio-demographic characteristic, clinical characteristics and information on TCM use and its pattern were recorded in a proforma. Patient's experience of chronic disease conventional care was measured using PACIC-M questionnaire. The comparison of PACIC-M mean score between TCM users and non-users was measured using independent t-test. The factors associated with TCM use were determined by simple logistic regression (SLogR), followed by multiple logistic regression (MLogR).
RESULTS: Out of 394 participants, 381 (96.7%) were included in the final analysis. Of the 381 participants, 255 (66.9%) were TCM users (95% CI 62.7, 71.7). Only 36.9% of users disclosed about TCM use to their health care providers (HCP). The overall mean PACIC-M score was 2.91 (SD ± 0.04). TCM users had significantly higher mean PACIC-M score compared to non-users (2.98 ± 0.74 vs 2.75 ± 0.72, p = 0.01). The independent factors associated with TCM use were being female (Adj. OR 2.50, 95% CI 1.55, 4.06), having high education level (Adj. OR 2.16, 95% CI 1.37, 3.41) and having high overall PACIC-M mean score (Adj. OR 1.49, 95% CI 1.10, 2.03).
CONCLUSION: TCM use was highly prevalent in this primary care clinic. However, the disclosure rate of TCM use to HCP was low. Females, those with high education and high PACIC-M mean score were more likely to use TCM. Further research should explore the reasons for their TCM use, despite having good experience in conventional chronic disease care.
METHODS: OVX rats were treated with TPEE at 125, 250, 500 mg/kg/day, or controls (pomegranate extract, 500 mg/kg/day; estradiol, 25 μg/kg/day) for 12 weeks. Gut microbiota analysis was conducted by extracting the microbial DNA from fecal samples and microbiome taxonomic profiling was carried out by using next-generation sequencing. The levels of serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA) kit. The prediction of functional biomarker of microbiota was performed using PICRUSt to investigate the potential pathways associated with gut health and serum lipid profile regulation. To study the correlation between gut microbiota composition and serum lipid levels, Spearman's correlation coefficients were defined and analyzed. Additionally, gas chromatography-mass spectrometry analysis was conducted to uncover additional physiologically active ingredients.
RESULTS: TPEE-treated OVX rats showed significant reduction in serum triglycerides (TG), total cholesterols (TCHOL), and LDL/VLDL levels but increase in HDL level. The alteration in the pathways involve in metabolism was the most common among the other KEGG categories. Particularly, TPEE also significantly reduced the relative abundance of sequences read associated with inflammatory bowel disease (IBD) and the peroxisome proliferator-activated receptor (PPAR) signalling pathway. TPEE intervention was seen to reduce the Firmicutes to Bacteroidetes (F/B) ratio in the OVX rats, denoting a reduction in microbial dysbiosis in the OVX rats. Correlation analysis at the phylum level revealed that Bacteriodetes and Proteobacteria were strongly correlated with serum TG, TCHOL and HDL levels. At the species level, Bifidobacterium pseudolongum group was seen to positively correlate with serum HDL level and negatively correlated with serum AST, ALT, LDL/VLDL, TCHOL, and TG levels.
CONCLUSIONS: TPEE treatment showed therapeutic benefits by improving the intestinal microbiota composition which strongly correlated with the serum lipid and cholesterol levels in the OVX rats.
METHODS: PCOS was induced in rats except for normal control by administering LTZ at 1 mg/kg/day for 21 days. Methanolic extract of F. deltoidea leaf was then orally administered to the PCOS rats at the dose of 250, 500, or 1000 mg/kg/day, respectively for 15 consecutive days. Lipid profile was measured enzymatically in serum. The circulating concentrations of reproductive hormone and antioxidant enzymes were determined by ELISA assays. Ovarian and uterus histomorphometric changes were further observed by hematoxylin and eosin (H&E) staining.
RESULTS: The results showed that treatment with F. deltoidea at the dose of 500 and 1000 mg/kg/day reduced insulin resistance, obesity indices, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), malondialdehyde (MDA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to near-normal levels in PCOS rats. The levels of high-density lipoprotein cholesterol (HDL), estrogen, and superoxide dismutase (SOD) are also similar to those observed in normal control rats. Histomorphometric measurements confirmed that F. deltoidea increased the corpus luteum number and the endometrial thickness.
CONCLUSIONS: F. deltoidea can reverse PCOS symptoms in female rats by improving insulin sensitivity, antioxidant activities, hormonal imbalance, and histological changes. These findings suggest the potential use of F. deltoidea as an adjuvant agent in the treatment program of PCOS.
METHODS: Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model.
RESULTS: As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of - 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents.
CONCLUSIONS: This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.
METHOD: The extracts were prepared using Soxhlet apparatus for ethanol and hexane extracts while the water extracts were freeze-dried. In vitro cytotoxic activities of B. frutescens extracts of various concentrations (20 to 160 μg/mL) at 24, 48, and 72 hours time points were studied using MTT in chemically induced hypoxic condition and in 3-dimensional in vitro cell culture system. An initial characterisation of B. frutescens extracts was carried out using Fourier-transform Infrared- Attenuated Total Reflection (FTIR-ATR) to determine the presence of functional groups.
RESULTS: All leaf extracts except for water showed IC50 values ranging from 23 -158 μg/mL. Hexane extract showed the lowest IC50 value (23 μg/mL), indicating its potent cytotoxic activity. Among the branch extracts, only the 70% ethanolic extract (B70) showed an IC50 value. The hexane leaf extract tested on 3- dimensional cultured cells showed an IC50 value of 17.2 μg/mL. The FTIR-ATR spectroscopy analysis identified various characteristic peak values with different functional groups such as alcohol, alkenes, alkynes, carbonyl, aromatic rings, ethers, ester, and carboxylic acids. Interestingly, the FTIR-ATR spectra report a complex and unique profile of the hexane extract, which warrants further investigation.
CONCLUSION: Adaptation of tumour cells to hypoxia significantly contributes to the aggressiveness and chemoresistance of different tumours. The identification of B. frutescens and its possible role in eliminating breast cancer cells in hypoxic conditions defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.
METHODS: This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.
RESULTS: The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir was Lactobacillus hilgardii followed by Lactobacillus harbinensis, Acetobacter lovaniensis, Lactobacillus satsumensis, Acetobacter tropicalis, Lactobacillus zeae, and Oenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.
CONCLUSIONS: This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.