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Journal of Ethnopharmacology May 2024Bawei Guben Huashi Jiangzhi Decoction (BGHJ), a traditional Chinese compound formula, comprises eight Chinese medicinal herbs: Codonopsis Radix, Atractylodis...
ETHNOPHARMACOLOGY RELEVANCE
Bawei Guben Huashi Jiangzhi Decoction (BGHJ), a traditional Chinese compound formula, comprises eight Chinese medicinal herbs: Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Cassiae Semen, Lysimachiae Herba, Edgeworthiae Gardner Flos, Oryzae Semen cum Monasco, Nelumbinis Folium, and Alismatis Rhizoma. It has the therapeutic effects of improving digestive and absorptive functions of the gastrointestinal tract, reducing cholesterol levels, and helping to lose weight. Therefore, BGHJ is mainly used to treat spleen-deficient obesity (SDO) clinically.
AIM OF THE STUDY
This study aims to examine the efficacy and mechanism of BGHJ in a model of SDO in rats, as well as the potentially involved constituents entering the blood and differential metabolites.
METHODS
The SDO rat model was replicated utilizing a high-fat and high-sugar diet in conjunction with exhaustive swimming. Subsequently, the rats were subjected to a six-week intervention comprising varying dosages of BGHJ and a positive control, orlistat. To evaluate the efficacy of BGHJ on SDO model rats, we first measured the rats' body weight, body surface temperature, spleen index, as well as biochemical indicators in the serum and colon, and then assessed the pathological state of the colon and liver. Afterward, we analyzed the 16S rDNA gut microbiota, non-targeted serum metabolomics, and serum pharmacology to study the main active components of BGHJ and its action mechanism against SDO model rats. In addition, we constructed a network diagram for overall visualization and analysis, and experimentally verified the predicted results. Finally, we used quantitative polymerase chain reaction (qPCR) to detect the gene expression of proopiomelanocortin (POMC) and neuropeptide Y (NPY) indicators in rat hypothalamic neurons. We quantitatively targeted the detection of neurotransmitters dopamine (DA), acetylcholine (Ach), 5-hydroxytryptamine (5-HT), and noradrenaline (NA) in rat hypothalamus.
RESULTS
The results demonstrated that all dosage regimens of BGHJ exhibited the capacity to moderately modulate parameters including body weight, surface temperature, spleen index, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), 5-HT, interleukin 6 (IL-6) and interleukin 17 (IL-17), while concurrently reducing hepatic lipid droplet deposition and restoring intestinal integrity. Subsequent experimental results showed that we successfully identified 27 blood components of BGHJ and identified 52 differential metabolites in SDO model rats. At the same time, the experiment proved that BGHJ could effectively inhibit the metabolic pathway of arachidonic acid. In addition, BGHJ can also restore the intestinal microbiota composition of SDO model rats. Finally, we also found that BGHJ could regulate the expression of hypothalamic neurons and neurotransmitters.
CONCLUSIONS
The research revealed the main active ingredients of BGHJ and its mechanism against SDO model rats through gut microbiota, non-target serum metabolomics, and serum drug chemistry.
Topics: Rats; Animals; Spleen; Multiomics; Serotonin; Obesity; Cholesterol, LDL; Neurotransmitter Agents; Drugs, Chinese Herbal
PubMed: 38296174
DOI: 10.1016/j.jep.2024.117826 -
International Journal of Molecular... Feb 2024Infertility is a modern health problem. Obesity is another expanding health issue associated with chronic diseases among which infertility is also included. This review... (Review)
Review
Infertility is a modern health problem. Obesity is another expanding health issue associated with chronic diseases among which infertility is also included. This review will focus on the effects of weight loss by medical therapy on fertility regarding reproductive hormonal profile, ovulation rates, time to pregnancy, implantation rates, pregnancy rates, normal embryo development, and live birth rates. We comprised medicine already used for weight loss, such as orlistat and metformin, and emerging medical treatments, such as Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA). Their use is not recommended during a planned pregnancy, and they should be discontinued in such cases. The main outcomes of this literature review are the following: modest weight loss after medication and the duration of the treatment are important factors for fertility improvement. The fecundity outcomes upon which medical-induced weight loss provides significant results are the female reproductive hormonal profile, menstrual cyclicity, ovulation and conception rates, and pregnancy rates. Regarding the male reproductive system, the fertility outcomes that feature significant alterations after medically induced weight loss are as follows: the male reproductive hormonal profile, sperm motility, movement and morphology, weight of reproductive organs, and sexual function. The newer promising GLP-1 RAs show expectations regarding fertility improvement, as they have evidenced encouraging effects on improving ovulation rates and regulating the menstrual cycle. However, more human studies are needed to confirm this. Future research should aim to provide answers about whether medical weight loss therapies affect fertility indirectly through weight loss or by a possible direct action on the reproductive system.
Topics: Pregnancy; Humans; Male; Female; Infertility, Female; Sperm Motility; Reproduction; Weight Loss; Glucagon-Like Peptide 1
PubMed: 38339186
DOI: 10.3390/ijms25031909 -
Journal of Biomolecular Structure &... Feb 2024A series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione () designed using molecular hybridization approach were synthesized, structurally...
A series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione () designed using molecular hybridization approach were synthesized, structurally characterized, and explored for their anti-obesity potential inhibition of Pancreatic Lipase (PL). Compound presented the most potent PL inhibitory activity with IC = 2.71 ± 0.31 µM, as compared to the standard drug, Orlistat (IC = 0.99 µM). Kinetic study revealed reversible competitive mode of enzyme inhibition by compound with an inhibitory constant value of 1.19 µM. The most promising compound revealed satisfactory binding mode within the active site of the target protein (human PL, PDB ID: 1LPB). Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analysis were performed for the most promising compound , which showed potent inhibition according to the results of studies. Furthermore, a stable conformation of the 1LPB-ligand suggested the stability of this compound in the dynamic environment. The ADME and toxicity analysis of the compounds were examined using web-based online platforms. Results of studies confirmed the anti-obesity efficacy of compound , wherein oral treatment with compound (30 mg/kg) resulted in a significant reduction in the body weight, BMI, Lee index, feed intake (in Kcal), body fat depots and serum triglycerides. Compound significantly decreased the levels of serum total cholesterol (TC) to 128.6 ± 0.59 mg/dl and serum total triglycerides (TG) to 95.73 ± 0.67 mg/dl as compared to the HFD control group. The present study identified disubstituted TZD derivatives as a new promising class of anti-obesity agents.Communicated by Ramaswamy H. Sarma.
PubMed: 38315459
DOI: 10.1080/07391102.2024.2310799 -
Behavioural Brain Research Mar 2024This study investigates the impact of orlistat on oxidative stress, spatial memory, recognition memory, and hippocampal tissue in obese rats. The study groups were...
This study investigates the impact of orlistat on oxidative stress, spatial memory, recognition memory, and hippocampal tissue in obese rats. The study groups were divided into control, high fat diet-induced obese (HFDIO), HFDIO+orlistat (HFDIO+ORL) groups, each consisting of 8 animals. While control fed with standart diet, HFDIO and HFDIO+ORL fed with high-fat diets for 8 weeks to induce obesity. Then, ORL treated 10 mg/kg for 7 weeks, while control and HFDIO get water. At 16th week, novel object recognition (NOR) and Morris water maze (MWM) tests were performed. TNF-alpha, IL-1beta levels in hippocampal tissue, and total/native thiol/disulphide levels in serum were measured. TNF-alpha level of HFDIO was higher than control, while lower in HFDIO+ORL compared to HFDIO as like IL-1beta level. On the contrary, serum total thiol level was lower in HFDIO than control and higher in HFDIO+ORL compared to the HFDIO, while disulphide level was opposite of the total thiol levels. While recognition index was higher in HFDIO+ORL, in MWM, latency of finding platform in HFDIO was higher than control and latency of HFDIO+ORL was very similar to control in 2-4 days. The HFDIO group demonstrated decrease in time spent in platform zone compared to control, whereas time spent of the HFDIO+ORL was higher than HFDIO. Our study demonstrates that orlistat administration exerts beneficial effects on oxidative stress, spatial memory, recognition memory, and hippocampal tissue in obese rats. It shows that orlistat may have potential therapeutic implications for obesity-related cognitive impairments and hippocampal dysfunction.
Topics: Rats; Animals; Spatial Memory; Orlistat; Tumor Necrosis Factor-alpha; Hippocampus; Oxidative Stress; Obesity; Diet, High-Fat; Disulfides; Sulfhydryl Compounds
PubMed: 38311071
DOI: 10.1016/j.bbr.2024.114894 -
Scientific Reports Feb 2024Lipase inhibition is one of the directions to control obesity. In vitro assays have confirmed the inhibitory effect of selected xanthophylls, including astaxanthin,...
Lipase inhibition is one of the directions to control obesity. In vitro assays have confirmed the inhibitory effect of selected xanthophylls, including astaxanthin, fucoxanthinol, fucoxanthin, and neoxanthin. Similarly, an in-silico study also demonstrated the successful inhibition of pancreatic lipase by astaxanthin. Unfortunately, the efficacy of these protocols in the emulsion state typical of lipid digestion remains untested. To address this issue, the current study employed the pH-stat test, which mimics lipid digestion in the gastrointestinal tract, to evaluate native and prepared sea buckthorn and rapeseed oils with varying xanthophyll contents from 0 to 1400 mg/kg oil. Furthermore, a molecular docking of zeaxanthin and violaxanthin (commonly found in plant-based foods), astaxanthin (widely distributed in foods of marine origin) and orlistat (approved as a drug) was performed. The in-silico studies revealed comparable inhibitory potential of all tested xanthophylls (variation from - 8.0 to - 9.3 kcal/mol), surpassing that of orlistat (- 6.5 kcal/mol). Nonetheless, when tested in an emulsified state, the results of pH-stat digestion failed to establish the inhibitory effect of xanthophylls in the digested oils. In fact, lipolysis of native xanthophyll-rich sea buckthorn oil was approximately 22% higher than that of the xanthophyll-low preparation. The key insight derived from this study is that the amphiphilic properties of xanthophylls during the digestion of xanthophyll-rich lipids/meals facilitate emulsion formation, which leads to enhanced fat lipolysis.
Topics: Hydrolysis; Orlistat; Emulsions; Molecular Docking Simulation; Xanthophylls; Lipase; Lutein; Lipids; Oils; Digestion
PubMed: 38302772
DOI: 10.1038/s41598-024-53312-9 -
Advances in Pharmacological and... 2024Obesity, characterized by excessive adipose tissue accumulation, has emerged as a crucial determinant for a wide range of chronic medical conditions. The identification...
Obesity, characterized by excessive adipose tissue accumulation, has emerged as a crucial determinant for a wide range of chronic medical conditions. The identification of effective interventions for obesity is of utmost importance. Widely researched antiobesity agents focus on pancreatic lipase, a significant therapeutic target. This study presented the evaluation of ten flavonoid compounds in terms of their inhibitory activities against pancreatic lipase, utilizing both and approaches. The results indicated that all tested compounds demonstrated modest and weaker inhibitory activities compared to the reference compound, orlistat. Among the compounds investigated, F01 exhibited the highest potency, with an IC value of 17.68 ± 1.43 M. The enzymatic inhibition kinetic analysis revealed that F01 operated through a competitive inhibition mechanism with a determined of 7.16 M. This value suggested a moderate binding affinity for the pancreatic lipase enzyme. Furthermore, the associated value was quantified at 0.03272 ΔA·min. studies revealed that F01 displayed a binding mode similar to that of orlistat, despite lacking an active functional group capable of forming a covalent bond with Ser152 of the catalytic triad. However, F01 formed a hydrogen bond with this crucial amino acid. Furthermore, F01 interacted with other significant residues at the enzyme's active site, particularly those within the lid domain. Based on these findings, F01 demonstrates substantial potential as a candidate for further investigations.
PubMed: 38298460
DOI: 10.1155/2024/6655996 -
International Journal of Obesity (2005) May 2024This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg...
OBJECTIVES
This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC).
METHODS
Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime.
RESULTS
From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained.
CONCLUSION
Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.
Topics: Humans; Cost-Benefit Analysis; Canada; Middle Aged; Obesity; Female; Anti-Obesity Agents; Male; Orlistat; Quality-Adjusted Life Years; Liraglutide; Diabetes Mellitus, Type 2; Bupropion; Naltrexone; Glucagon-Like Peptides
PubMed: 38291203
DOI: 10.1038/s41366-024-01467-w -
Diabetes, Obesity & Metabolism May 2024To characterize factors associated with the receipt of anti-obesity medication (AOM) prescription and fill.
AIM
To characterize factors associated with the receipt of anti-obesity medication (AOM) prescription and fill.
MATERIALS AND METHODS
This retrospective cohort study used electronic health records from 1 January 2015 to 30 June 2023, in a large health system in Ohio and Florida. Adults with a body mass index ≥30 kg/m who attended ≥1 weight-management programme or had an initial AOM prescription between 1 July 2015 and 31 December 2022, were included. The main measures were a prescription for an AOM (naltrexone-bupropion, orlistat, phentermine-topiramate, liraglutide 3.0 mg and semaglutide 2.4 mg) and an AOM fill during the study follow-up.
RESULTS
We identified 50 678 adults, with a mean body mass index of 38 ± 8 kg/m and follow-up of 4.7 ± 2.4 years. Only 8.0% of the cohort had AOM prescriptions and 4.4% had filled prescriptions. In the multivariable analyses, being a man, Black, Hispanic and other race/ethnicity (vs. White), Medicaid, traditional Medicare, Medicare Advantage, self-pay and other insurance types (vs. private insurance) and fourth quartile of the area deprivation index (vs. first quartile) were associated with lower odds of a new prescription. Hispanic ethnicity, being a man, Medicaid, traditional Medicare and Medicare Advantage insurance types, liraglutide and orlistat (vs. naltrexone-buproprion) were associated with lower odds of AOM fill, while phentermine-topiramate was associated with higher odds. Among privately insured individuals, the insurance carrier was associated with both the odds of AOM prescription and fill.
CONCLUSIONS
Significant disparities exist in access to AOM both at the prescribing stage and getting the prescription filled based on patient characteristics and insurance type.
Topics: Aged; Adult; Humans; United States; Orlistat; Retrospective Studies; Topiramate; Naltrexone; Liraglutide; Anti-Obesity Agents; Medicare Part C; Phentermine
PubMed: 38287140
DOI: 10.1111/dom.15473 -
Circulation. Heart Failure Feb 2024Utilization patterns of bariatric surgery among older patients with heart failure (HF), and the associations with cardiovascular outcomes, are not well known.
BACKGROUND
Utilization patterns of bariatric surgery among older patients with heart failure (HF), and the associations with cardiovascular outcomes, are not well known.
METHODS
Medicare beneficiaries with HF and at least class II obesity from 2013 to 2020 were identified with Medicare Provider Analysis and Review 100% inpatient files and Medicare 5% outpatient files. Patients who underwent bariatric surgery were matched to controls in a 1:2 ratio (matched on exact age, sex, race, body mass index, HF encounter year, and HF hospitalization rate pre-surgery/matched period). In an exploratory analysis, patients prescribed pharmacotherapies with weight loss effects (semaglutide, liraglutide, naltrexone-bupropion, or orlistat) were identified and matched to controls with a similar strategy in addition to HF medical therapy data. Cox models evaluated associations between weight loss therapies (as a time-varying covariate) and mortality risk and HF hospitalization rate (calculated as the rate of HF hospitalizations following index HF encounter per 100 person-months) during follow-up.
RESULTS
Of 298 101 patients with HF and body mass index ≥35 kg/m, 2594 (0.9%) underwent bariatric surgery (45% men; mean age, 56.2 years; mean body mass index, 51.5 kg/m). In propensity-matched analyses over a median follow-up of 4.7 years, bariatric surgery was associated with lower risk of all-cause mortality (HR, 0.55 [95% CI, 0.49-0.63]; <0.001), greater reduction in HF hospitalization rate (rate ratio, 0.72 [95% CI, 0.67-0.77]; <0.001), and lower atrial fibrillation risk (HR, 0.78 [95% CI, 0.65-0.93]; =0.006). Use of pharmacotherapies with weight loss effects was low (4.8%), with 96.3% prescribed GLP-1 (glucagon-like peptide-1) agonists (semaglutide, 23.6%; liraglutide, 72.7%). In propensity-matched analysis over a median follow-up of 2.8 years, patients receiving pharmacotherapies with weight loss effects (versus matched controls) had a lower risk of all-cause mortality (HR, 0.82 [95% CI, 0.71-0.95]; =0.007) and HF hospitalization rate (rate ratio, 0.87 [95% CI, 0.77-0.99]; =0.04).
CONCLUSIONS
Bariatric surgery and pharmacotherapies with weight loss effects are associated with a lower risk of adverse outcomes among older patients with HF and obesity; however, overall utilization remains low.
Topics: Male; Humans; Aged; United States; Middle Aged; Female; Heart Failure; Liraglutide; Medicare; Obesity; Bariatric Surgery; Weight Loss; Retrospective Studies
PubMed: 38275114
DOI: 10.1161/CIRCHEARTFAILURE.122.010453 -
The Journal of Nutritional Biochemistry Apr 2024Mitochondrial dysfunction is one of the triggers for obesity-induced neuron apoptosis. Thinned young apple is getting more attention on account of the extensive...
Mitochondrial dysfunction is one of the triggers for obesity-induced neuron apoptosis. Thinned young apple is getting more attention on account of the extensive biological activities because of rich polyphenols and polysaccharides. However, the neuroprotective effect of thinned young apple powder (YAP) is still unclear. The aim of the present study was to investigate the preventive effect of YAP on obesity-induced neuronal apoptosis. C57BL/6J male mice were divided into 5 groups, control (CON), high fat diet (HFD), HFD + orlistat (ORL), HFD + low-dose young apple powder (LYAP) and HFD + high-dose young apple powder (HYAP) groups and intervened for 12 weeks. It was found that the YAP effectively reduced body weight gain. Importantly, the levels of pro-apoptosis protein were lower in LYAP and HYAP groups than the HFD group, such as Bak/Bcl2 and cleaved caspase3/caspase3. Pathway analysis based on untargeted metabolomics suggested that YAP alleviated obesity-induced neuronal apoptosis by three main metabolic pathway including arginine metabolism, citrate cycle (TCA cycle) and glutathione metabolism. Meanwhile, YAP improved the protein expression of mitochondrial respiratory chain complex, maintained the homeostasis of TCA cycle intermediates, protected the balance of mitochondrial dynamics and alleviated lipid accumulation. In addition, the levels of several antioxidants in cerebral cortex were higher in HYAP group than the HFD group like superoxide dismutase (SOD) and catalase (CAT). In summary, YAP supplementation suppressed neuronal apoptosis in the cerebral cortex of HFD-induced obesity mice by improving mitochondrial function and inhibiting oxidative stress.
Topics: Mice; Male; Animals; Malus; Powders; Mice, Inbred C57BL; Obesity; Mitochondria; Oxidative Stress; Diet, High-Fat; Apoptosis; Cerebral Cortex
PubMed: 38266689
DOI: 10.1016/j.jnutbio.2024.109588