Hypolipidemic activities of xanthorrhizol purified from centrifugal TLC

Hyperlipidemia is defined as the presence of either hypertriglyceridemia or hypercholesterolemia, which could cause atherosclerosis. Although hyperlipidemia can be treated by hypolipidemic drugs, they are limited due to lack of effectiveness and safety. Previous studies demonstrated that xanthorrhizol (XNT) isolated from Curcuma xanthorrhizza Roxb. reduced the levels of free fatty acid and triglyceride in vivo. However, its ability to inhibit cholesterol uptake in HT29 colon cells and adipogenesis in 3T3-L1 cells are yet to be reported. In this study, XNT purified from centrifugal TLC demonstrated 98.3% purity, indicating it could be an alternative purification method. The IC50 values of XNT were 30.81 ± 0.78 μg/mL in HT29 cells and 35.07 ± 0.24 μg/mL in 3T3-L1 adipocytes, respectively. Cholesterol uptake inhibition study using HT29 colon cells showed that XNT (15 μg/mL) significantly inhibited the fluorescent cholesterol analogue NBD uptake by up to 27 ± 3.1% relative to control. On the other hand, higher concentration of XNT (50 μg/mL) significantly suppressed the growth of 3T3-L1 adipocytes (5.9 ± 0.58%) compared to 3T3-L1 preadipocytes (81.31 ± 0.55%). XNT was found to impede adipogenesis of 3T3-L1 adipocytes in a dose-dependent manner from 3.125 to 12.5 μg/mL, where 12.5 μg/mL significantly suppressed 36.13 ± 2.1% of lipid accumulation. We postulate that inhibition of cholesterol uptake, adipogenesis, preadipocyte and adipocyte number may be utilized as treatment modalities to reduce the prevalence of lipidemia. To conclude, XNT could be a potential hypolipidemic agent to improve cardiovascular health in the future

Xanthorrhizol inhibits cell proliferation, cellular cholesterol uptake in HT29 colon cells and adipogenesis in 3T3-L1 adipocytes

Hyperlipidemia is defined as the presence of either hypertriglyceridemia or hypercholesterolemia, which could cause atherosclerosis, cardiovascular diseases and certain cancers. Although hyperlipidemia can be treated by hypolipidemic drugs, they are limited due to lack of effectiveness and safety. Since flavonoids and tannins have been reported to possess antihyperlipidemic activity, it is believed that phytochemicals isolated from plants may decrease the lipid levels with lower side effects. Previous studies demonstrated that xanthorrhizol (XNT) isolated from Curcuma xanthorrhizza reduced the levels of free fatty acid and triglyceride in vivo. However, antiproliferative activity of XNT and its ability to inhibit cholesterol uptake and adipogenesis are yet to be reported. In this study, the IC50 values of XNT were 15.12 ± 0.68 μg/mL in HT29 cells and 35.07 ± 0.24 μg/mL in 3T3-L1 adipocytes, respectively. Cholesterol uptake inhibition study was conducted in HT29 colon cells using fluorescent cholesterol analogue NBD. The result showed that XNT (15 μg/mL) siginificantly inhibited the cholesterol uptake by up to 37.6 ± 1.53 % relative to control. On the other hand, higher concentration of XNT (50 μg/mL) significantly suppressed the growth of 3T3-L1 adipocytes (5.9 ± 0.58 %) compared to 3T3-L1 preadipocytes (80.42 ± 8.29 %). It was found that XNT (3.125 μg/mL) impeded adipogenesis by reducing lipid content of 3T3-L1 adipocytes for 25.37 ± 3.24 % comparable to positive control (quercetin), 20.07 ± 8.78%. We postulate that inhibition of cholesterol uptake, adipocyte number and adipogenesis may be utilized as treatment modalities to reduce the prevalence of lipidemia. To conclude, XNT could be a potential hypolipidemic agent and further studies could be done on its mechanism of action

The roles of probiotics in the gut microbiota composition and metabolic outcomes in asymptomatic post-gestational diabetes women : A randomized controlled trial

Probiotics are widely used as an adjuvant therapy in various diseases. Nonetheless, it is uncertain how they affect the gut microbiota composition and metabolic and inflammatory outcomes in women who have recently experienced gestational diabetes mellitus (post-GDM). A randomized, double-blind, placebo-controlled clinical trial involving 132 asymptomatic post-GDM women was conducted to close this gap (Clinical Trial Registration: NCT05273073). The intervention (probiotics) group received a cocktail of six probiotic strains from Bifidobacterium and Lactobacillus for 12 weeks, while the placebo group received an identical sachet devoid of living microorganisms. Anthropometric measurements, biochemical analyses, and 16S rRNA gene sequencing results were evaluated pre- and post-intervention. After the 12-week intervention, the probiotics group’s fasting blood glucose level significantly decreased (mean difference −0.20 mmol/L; p = 0.0021). The HbA1c, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly different between the two groups (p < 0.05). Sequencing data also demonstrated a large rise in the Bifidobacterium adolescentis following probiotic supplementation. Our findings suggest that multi-strain probiotics are beneficial for improved metabolic and inflammatory outcomes in post-GDM women by modulating gut dysbiosis. This study emphasizes the necessity for a comprehensive strategy for postpartum treatment that includes probiotics to protect post-GDM women from developing glucose intolerance

Xanthorrhizol: a review of its pharmacological activities and anticancer properties

Xanthorrhizol (XNT) is a bisabolane-type sesquiterpenoid compound extracted from Curcuma xanthorrhiza Roxb. It has been well established to possess a variety of biological activities such as anticancer, antimicrobial, anti-inflammatory, antioxidant, antihyperglycemic, antihypertensive, antiplatelet, nephroprotective, hepatoprotective, estrogenic and anti-estrogenic effects. Since many synthetic drugs possess toxic side effects and are unable to support the increasing prevalence of disease, there is significant interest in developing natural product as new therapeutics. XNT is a very potent natural bioactive compound that could fulfil the current need for new drug discovery. Despite its importance, a comprehensive review of XNT’s pharmacological activities has not been published in the scientific literature to date. Here, the present review aims to summarize the available information in this area, focus on its anticancer properties and indicate the current status of the research. This helps to facilitate the understanding of XNT’s pharmacological role in drug discovery, thus suggesting areas where further research is required

Effects of xanthorrhizol on 3T3-L1 adipocyte hyperplasia and hypertrophy

According to the National Health and Morbidity Survey (NHMS) 2015, 47.7% of the Malaysian population are either obese or overweight. The increased obesity prevalence has caused major health problems such as cardiovascular diseases and diabetes. Although several anti-obesity drugs have been developed, they are limited due to adverse side effects such as stroke, myocardial infarction, and depression. These circumstances have increased the demand for effective and safe anti-obesity agents. Previous studies demonstrated that xanthorrhizol (XNT) reduced the levels of serum free fatty acid and triglyceride in vivo, but the detailed anti-obesity activities and its related mechanisms are yet to be reported. In this study, crude oil containing XNT was extracted from Curcuma xanthorrhiza Roxb. by supercritical fluid carbon dioxide extraction. It was further purified by column chromatography and centrifugal thin layer chromatography (TLC). The presence of XNT in each eluate was identified by TLC. The purity of XNT was determined by gas chromatography-mass spectrometry (GC-MS) analysis, whilst its structure was confirmed by proton and carbon nuclear magnetic resonance (NMR) spectral analysis. Next, the IC50 value of XNT was determined by MTT assay. The mode of cell death was further evaluated by annexin V/7-AAD staining for early apoptosis and TUNEL assay for late apoptosis, respectively. The mechanisms involved were determined by quantitative ELISA analysis of caspase-3 and PARP-1 proteins. On the other hand, the ability of XNT to inhibit adipogenesis was examined by oil red O (ORO) staining and glycerol-3-phosphate dehydrogenase (GPDH) activity. The mechanisms involved were evaluated by quantitative ELISA analysis of PPARγ and FAS proteins. The ability of XNT to induce lipolysis was investigated by quantifying the glycerol amount. The mechanisms were examined by quantitative ELISA analysis of leptin and insulin proteins. Statistical significance was analyzed by one-way ANOVA, where p < 0.05 was considered significantly different. Thus, this study aims to evaluate XNT’s abilities to induce apoptosis, impede adipogenesis, and stimulate lipolysis employing 3T3-L1 adipocytes. In this study, XNT purified from centrifugal TLC demonstrated 98.3% purity, and the structure was confirmed by 1H and 13C NMR spectral analysis. The IC50 value of XNT in 3T3-L1 adipocytes was 35 ± 0.24 μg/mL. The loss of cell viability was due to 20.01 ± 2.77% of early apoptosis and 24.13 ± 2.03% of late apoptosis (p < 0.05). XNT elicited apoptosis via up-regulation of caspase-3 and cleaved PARP-1 protein expression for 4.09-fold and 3.12-fold, respectively. Moreover, XNT decreased adipocyte differentiation and GPDH activity in a dose-dependent manner from 3.13 to 12.5 μg/mL. The highest inhibition of adipogenesis was 36.13 ± 3.64% (p < 0.05). The GPDH activity was reduced to 52.26 ± 4.36% by XNT (p < 0.05). It was found that XNT reduced adipocyte formation by impairing the expression of PPARγ to 0.36-fold and FAS to 0.38-fold, respectively. On the other hand, XNT increased glycerol release by 45.37 ± 6.08% compared to control (p < 0.05). During lipolysis, XNT up-regulated the leptin protein for 2.08-fold but down-regulated the protein level of insulin to 0.36-fold (p < 0.05). These results indicated that XNT reduced the volume of adipocytes through modulation of leptin and insulin. To conclude, XNT exerted its anti-obesity mechanisms by suppression of adipocyte hyperplasia through induction of apoptosis (regulation of caspase-3 and PARP-1) and inhibition of adipogenesis (regulation of PPARγ and FAS) whilst reduction of adipocyte hypertrophy through stimulation of lipolysis (regulation of leptin and insulin). Thus, XNT could be developed as a potential anti-obesity agent in the future

The Roles of Probiotics in the Gut Microbiota Composition and Metabolic Outcomes in Asymptomatic Post-Gestational Diabetes Women: A Randomized Controlled Trial

Probiotics are widely used as an adjuvant therapy in various diseases. Nonetheless, it is uncertain how they affect the gut microbiota composition and metabolic and inflammatory outcomes in women who have recently experienced gestational diabetes mellitus (post-GDM). A randomized, double-blind, placebo-controlled clinical trial involving 132 asymptomatic post-GDM women was conducted to close this gap (Clinical Trial Registration: NCT05273073). The intervention (probiotics) group received a cocktail of six probiotic strains from Bifidobacterium and Lactobacillus for 12 weeks, while the placebo group received an identical sachet devoid of living microorganisms. Anthropometric measurements, biochemical analyses, and 16S rRNA gene sequencing results were evaluated pre- and post-intervention. After the 12-week intervention, the probiotics group’s fasting blood glucose level significantly decreased (mean difference −0.20 mmol/L; p = 0.0021). The HbA1c, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly different between the two groups (p Bifidobacterium adolescentis following probiotic supplementation. Our findings suggest that multi-strain probiotics are beneficial for improved metabolic and inflammatory outcomes in post-GDM women by modulating gut dysbiosis. This study emphasizes the necessity for a comprehensive strategy for postpartum treatment that includes probiotics to protect post-GDM women from developing glucose intolerance

The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease

The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (−7.9 ± 0.44, p 0.0001) and TNF-α (−0.96 ± 0.25, p 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: −34.51 ng/mL ± 18.38, p p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes