Oolong tea polyphenols alleviate cognitive impairment in sleep-deprived mice through the microbiota-gut-brain axis.

Oolong tea polyphenols (OTP) have attracted wide attention due to their ability to reduce inflammatory response, regulate gut microbiota, and improve cognitive function. However, exactly how the gut microbiota modulates nervous system activity is still an open question. We previously expounded that supplementing with OTP alleviated neuroinflammation in circadian rhythm disorder (CRD) mice. Here, we showed that OTP can relieve microglia activation by reducing harmful microbial metabolites lipopolysaccharide (LPS) that alleviate CRD-induced cognitive decline. Mechanistically, OTP suppressed the inflammation response by regulating the gut microbiota composition, including upregulating the relative abundance of Muribaculaceae and Clostridia_UCG-014 and downregulating Desulfovibrio, promoting the production of short-chain fatty acids (SCFAs). Moreover, the use of OTP alleviated intestinal barrier damage and decreased the LPS transport to the serum. These results further inhibited the activation of microglia, thus alleviating cognitive impairment by inhibiting neuroinflammation, neuron damage, and neurotoxicity metabolite glutamate elevation. Meanwhile, OTP upregulated the expression of synaptic plasticity-related protein postsynaptic density protein 95 (PSD-95) and synaptophysin (SYN) by elevating the brain-derived neurotrophic factor (BDNF) level. Taken together, our findings suggest that the OTP has the potential to prevent CRD-induced cognition decline by modulating gut microbiota and microbial metabolites.

Weizmannia coagulans BC99, a Gram-positive, spore-forming, lactic acid-producing bacterium is renowned for its resilience and health-promoting properties, W. coagulans BC99 survives harsh environments, including high temperatures and gastric acidity, enabling effective delivery to the intestines. The consequences of chronic sleep deprivation (SD) include memory deficits and gastrointestinal dysfunction. In this study, a chronic sleep deprivation cognitive impairment model was established by using a sleep deprivation instrument and W. coagulans BC99 was given by gavage for 4 weeks to explore the mechanism by which BC99 improves cognitive impairment in sleep-deprived mice. BC99 improved cognitive abnormalities in novel object recognition tests induced by chronic sleep deprivation and showed behavior related to spatial memory in the Morris water maze test. W. coagulans BC99 reduced the heart mass index of sleep-deprived mice, increased the sleep-related neurotransmitters 5-HT and DA, decreased corticosterone and norepinephrine, and increased alpha diversity and community similarity. It reduced the abundance of harmful bacteria such as Olsenella, increased the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, and promoted the production of short-chain fatty acids (SCFAs). W. coagulans BC99 also inhibits LPS translocation and the elevation of peripheral inflammatory factors by maintaining the integrity of the intestinal barrier and inhibiting the expression of the NLRP3 signaling pathway in the jejunum, thereby inhibiting the NLRP3 inflammasome in the brain of mice and reducing inflammatory factors in the brain, providing a favorable environment for the recovery of cognitive function. The present study confirmed that W. coagulans BC99 ameliorated cognitive impairment in chronic sleep-deprived mice by improving gut microbiota, especially by promoting SCFAs production and inhibiting the NLRP3 signaling pathway in the jejunum and brain. These findings may help guide the treatment of insomnia or other sleep disorders through dietary strategies.

Green Tea, Black Tea, and Oolong Tea Polyphenols Reduce Visceral Fat and Inflammation in Mice Fed High-Fat, High-Sucrose Obesogenic Diets

To investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide. Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 µmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 μg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR). ELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1β, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 µmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05). MT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.

Vitiligo (VL) is associated with several autoimmune diseases, especially Hashimoto's thyroiditis, VL and concomitant Hashimoto's thyroiditis (HT) up to 34% in VL. To assess the predictive value of serum inflammatory factors in guiding treatment response among patients with concurrent VL and concomitant HT. This retrospective study enrolled 67 cases of VL and concomitant HT, and the patients according to treatment outcomes were divided into the unsatisfied group and the satisfied group. The serum thyroid parameters, autoimmune markers, and inflammatory factor levels were analysed and the correlation analysis of serum inflammatory factors was made. The study analysis of serum thyroid parameters showed elevated levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroperoxidase (TPO), and thyroglobulin (Tg) (p < 0.05) in the group with unsatisfactory treatment response. Patients in the unsatisfied group exhibited elevated inflammatory factor levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) (p < 0.05) compared to their counterparts in the satisfied group. Correlation analysis showed that the levels of the above inflammatory factors were significantly negatively correlated with the treatment response. CRP, TNF-α, IL-6, IL-8, IL-10 showed the strongest correlation with VL and concomitant HT, and serum inflammatory factors levels can predict treatment response in patients with VL and concomitant HT.

Changes in serum neuron-specific enolase (NSE) level, S100β protein concentration and inflammatory factor levels and their correlations with cognitive impairment Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in intracranial tumor patients with cognitive impairment were explored. Seventy patients diagnosed with intracranial tumor based on clinical symptoms and computed tomography (CT) images were selected and divided into non-cognitive impairment group (MoCA score ≥26 points, n=44) and cognitive impairment group (MoCA score <26 points, n=26) in accordance with the comprehensive cognitive function evaluation scores. Next, the serum NSE level, S100β protein concentration and inflammatory factor levels were detected, and their relationships with MMSE and MoCA scores were analyzed via Pearsons correlation analysis. The MoCA and MMSE scores in non-cognitive impairment group were higher than those in cognitive impairment group (P<0.05). NSE and S100β levels were higher in non-cognitive impairment group compared with cognitive impairment group (P<0.05). In addition, the levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) were higher in cognitive impairment group than those in non-cognitive impairment group (P<0.05). The levels of patient's serum NSE, S100β protein and inflammatory factors were negatively related to MMSE and MoCA scores (P<0.05). The changes in serum NSE, S100β protein and inflammatory factor levels in patients with cognitive impairment can reflect the severity of the disease to a certain extent and are directly related to cognitive impairment. Accurate and comprehensive assessment of cognitive function of patients and early development of effective and targeted cognitive interventions are of certain clinical practical value for the improvement of prognosis.

Objective A case-control study was conducted to explore the correlation between serum inflammatory factor monitoring and cognitive function, language, and memory ability of Alzheimer's disease (AD) and its clinical significance. Methods Thirty-six patients with AD treated from April 2019 to August 2021 in our hospital were enrolled as the study subjects (AD group), and 30 healthy volunteers from the physical examination center and the AD group with the same sex, age, education, and no complaints of memory loss were enrolled as the control group. Montreal Cognitive Assessment (MoCA) and AD Rating Scale-Cognitive (ADAS-cog) were employed to assess the cognitive function of AD and the control group. The Chinese Standard aphasia Test of China Rehabilitation Research Center (CRRCAE) was employed to assess the language function of AD and NC population. The World Health Organization-University of California, Los Angeles Auditory Word Learning Test (WHO-UCLAAV-LT) scale was employed to evaluate the memory function of AD group and control group. The levels of inflammatory factors in serum of the AD group and control group were detected by enzyme-linked immunosorbent assay (ELISA). The serum inflammatory factors levels were compared between the AD group and the control group, and the correlation between the level of serum inflammatory factors and cognitive function, language, and memory ability in the AD group was analyzed. Results In terms of the demographic data of the two groups, there exhibited no significant difference in gender, age, education level, and other general data (P > 0.05). In terms of cognitive function, MoCA scores were remarkably lower compared to the AD group. In the comparison of memory ability, the scores of long-term delayed recognition, delayed memory, and instantaneous memory in the AD group were remarkably lower (P < 0.05). In the comparison of language ability, the scores of listening comprehension, reading, and naming in the AD group exhibited remarkably lower (P < 0.05). With regard to the levels of serum inflammatory factors, the levels of serum interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and CCL-12 in AD group were remarkably higher, while the level of TNF-β in the AD group was lower compared to the control group. Furthermore, there exhibited no significant correlation between the levels of serum IL-4, IL-6, IL-10, TNF-α, CCL-2, and the total scores, MoCA, and ADAS-cog, but there exhibited a positive relationship between the level of serum TNF-β and the score of MoCA scale. The correlations between IL-4, IL-6, IL-10, TNF-α, TNF-β, CCL-2, and the scores of long-term delayed recognition, delayed memory, and instantaneous memory were analyzed in the AD group. The serum levels of IL-4, IL-6, IL-10, TNF-α, CCL-2, and TNF-β were not remarkably correlated with the scores of long-term delayed recognition, delayed memory, and instantaneous memory. The correlations between IL-4, IL-6, IL-10, TNF-α, TNF-β, CCL-2, and the scores of listening comprehension, reading, and naming were analyzed in the AD group, but with no significant correlation between the serum levels of IL-4, IL-6, IL-10, CCL-2, TNF-α, and TNF-β and the scores of listening comprehension, reading, and naming. Conclusion Compared with the control group, the levels of serum IL-4, IL-6, IL-10, TNF-α, and CCL-2 in patients with AD exhibited remarkably higher, while the level of serum TNF-β exhibited remarkably lower. The level of serum TNF-β was remarkably correlated with cognitive function in patients with AD, which may reflect the severity of cognitive impairment in patients with AD.

In this study, the anti‐obesity effect of oolong tea polyphenols–phospholipids complex (OTC) was investigated. OTC was prepared with oolong tea polyphenols (OTP) and phospholipids, and exhibited higher stability than OTP in vitro. Then high fat diet‐induced obesity human flora‐associated (HFA) mice model were obtained, and the administration of both OTP and OTC alleviated the changes of the serum and liver levels induced by high fat diet dramatically. The numbers (log10 cell mL−1) of Bifidobacterium and Lactobacillus/Enterococcus spp., Bacteroides‐Prevotella and Clostridium histolyticum in obesity models fed with OTC after 8 weeks were 8.28 ± 0.03, 8.21 ± 0.01, 7.23 ± 0.02, and 7.05 ± 0.03 compared with 8.21 ± 0.02, 8.07 ± 0.02, 7.31 ± 0.02, and 7.10 ± 0.01, respectively, in the control. Together, it confirmed the potential of phospholipids in the promotion of intestinal transport of polyphenols, suggesting OTC may have prebiotic‐like activity to prevent obesity‐related metabolic disorders.Oolong tea polyphenols–phospholipids complex show modulatory effect on the intestinal microbiota of high fat diet‐induced obesity mice model, and may have prebiotic‐like activity contributing to the prevention of obesity.

Oolong tea polyphenols affect the inflammatory response to improve cognitive function by regulating gut microbiota

BackgroundHypothermia is associated with many adverse clinical outcomes in pediatric patients, and thus, it is important to find an effective and safe method for preventing peri-operative hypothermia and its associated adverse outcomes in pediatric patients. This study aimed to investigate the effect of forced-air warming blankets with different temperatures on changes in the transforming growth factor-β (TGF-β), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels in children undergoing surgical treatment for developmental displacement of the hip (DDH).MethodsThe study included 123 children undergoing surgery for DDH under general anesthesia. The patients were randomly assigned to three groups, using a random number table: the 32, 38, and 43°C groups according to the temperature setting of the forced-air warming blankets. For each patient, body temperature was recorded immediately after anesthesia induction and intubation (T0), at initial incision (T1), at 1 h after incision (T2), at 2 h after incision (T3), at the end of surgery (T4), immediately upon return to the ward after surgery (T5), and then at 12 h (T6), 24 h (T7), 36 h (T8), and 48 h (T9) after the surgery. The serum levels of TGF-β, TNF-α, IL-1β, and IL-10 were measured at T0 and T4 for all groups.ResultsThe number of patients with fever in the 38°C group was significantly less than those in the 32 and 43°C groups (χ2 = 6.630, P = 0.036). At T0, the body temperatures in the 38 and 43°C groups were significantly higher than that in the 32°C group (F = 17.992, P < 0.001). At T2, the body temperature was significantly higher in the 43°C group than those in the 32 and 38°C groups (F = 12.776, P < 0.001). Moreover, at T4, the serum levels of TGF-β (F = 3286.548, P < 0.001) and IL-10 (F = 4628.983, P < 0.001) were significantly increased in the 38°C group, and the serum levels of TNF-α (F = 911.415, P < 0.001) and IL-1β (F = 322.191, P < 0.001) were significantly decreased in the 38°C group, compared with the levels in the 32 and 43°C groups.ConclusionForce-air warming blankets set at 38°C maintained stable body temperature with less adverse outcome and effectively inhibited the inflammatory response in pediatric patients undergoing surgery for DDH.Clinical trial registrationChiCTR1800014820; http://www.chictr.org.cn/showproj.aspx?proj=25240.

Objective To observe the effect of alinastatin on the treatment of severe acute pancreatitis and level of the serum inflammatory factors. Methods Eighty-six patients with severe acute pancreatitis were randomly divided into observation group and control group, with 43 cases in each group. The control group was given common treatment, the observation group underwent the conventional treatment combined with ulinastatin. Acute physiology and chronic health evaluation (APACHEⅡ), clinical symptoms disappeared time, serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-8(IL-8) were compared between two groups after 7 d of treatment. Results After 7 d of treatment, the APACHE Ⅱ score of observation group was 8.93±2.47, which was significantly lower than that of control group (11.61±2.58, P<0.01). The disappearing time of abdominal pain, bloating, nausea, vomiting and other clinical symptoms in observation group were shorter than those in control group. The levels of TNF-α, IL-6 and IL-8 in the two groups after treatment significantly decreased (P<0.01), and the levels of all inflammatory factors in observation group were significantly lower than those in control group after treatment (P<0.01). Conclusions Ulinastatin in the treatment of severe acute pancreatitis can rapidly improve the clinical symptoms, reduce levels of serum inflammatory factors, with significant clinical effect. Key words: Ulinastatin; Severe acute pancreatitis; Inflammatory factors

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in addition to the general therapy can significantly lower the levels of serum MIF and IL-6, reduce the degree of carotid atherosclerosis to some extent and improve neurological impairment and the prognosis of patients with AIS.

The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.

The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

Oolong tea, as well as the polyphenols it contains, has been shown to alter physiological processes related to glucose regulation. As part of a double blinded randomized crossover design study, 19 overweight and obese men (BMI 25‐34, ages 25‐64 years) consumed a controlled diet at weight maintenance along with 5 treatment beverages: 1) oolong tea, 2) oolong tea with added catechins, 3) oolong tea with added oolong tea polyphenols, 4) water with caffeine (matched for caffeine content of oolong tea) and 5) water. Each subject consumed four 350 ml servings (1400 ml/day) of the treatment beverages per day with breakfast, lunch, mid‐afternoon and dinner for four days. On the fifth day, after a 12 hour fast, subjects consumed a mixed meal tolerance test breakfast (450 kcals, 85 g carbohydrate, 10 g fat, 8 g protein) along with the treatment beverage. Biomarkers, glucose, insulin, triglycerides and the homeostasis model assessment of insulin resistance (HOMA‐IR), were measured every 30 minutes during a four hour period. Results showed no significant postprandial changes in glucose, insulin, triglycerides and HOMA‐IR after consumption of the treatment beverages. Consumption of the oolong tea treatments had no adverse effects on glucoregulatory biomarkers in overweight and obese men.Supported by US Department of Agriculture and Suntory Corporation, Osaka, Japan