-
Journal of Medicine and Life Sep 2023Obesity is a world health concern and a serious risk factor for several chronic diseases. is a plant with reported anti-obesity properties. However, the preclinical...
Obesity is a world health concern and a serious risk factor for several chronic diseases. is a plant with reported anti-obesity properties. However, the preclinical anti-obesity effect of ethanolic extract of Iraqi has not been studied yet. This study aimed to evaluate the preclinical anti-obesity properties of Iraqi extract, alone or in combination with orlistat, on high-fat diet-induced obesity in male rats. Male rats were divided into five groups: control, induction, ethanolic extract of Iraqi (250 mg/kg and 500 mg/kg), orlistat (Xenical) alone (10 mg/kg), and a combination of the extract (250 mg/kg) with Xenical. The rats were fed a high-fat diet to induce obesity, and treatments were given orally for 8 weeks. Body weight, food intake, serum lipid profile, and liver enzymes were measured. Administration of ethanolic extract of Iraqi (250 mg/kg and 500 mg/kg), Xenical alone (10 mg/kg), and combination with the extract (250 mg/kg) for 8 weeks significantly reduced body weight, food intake, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and liver enzymes (aspartate transaminase and alanine transaminase) when compared to the induction group. The ethanolic extract of Iraqi showed anti-obesity effects and could be a potential therapeutic agent in managing obesity. However, further studies are needed to evaluate its clinical efficacy and safety.
Topics: Rats; Animals; Orlistat; Diet, High-Fat; Hibiscus; Iraq; Plant Extracts; Obesity; Body Weight; Cholesterol
PubMed: 38107717
DOI: 10.25122/jml-2023-0140 -
Obesity Surgery Mar 2024Many individuals search for obesity treatment options on the Internet. We aimed to analyze the popularity of pharmacological and surgical obesity treatment methods...
PURPOSE
Many individuals search for obesity treatment options on the Internet. We aimed to analyze the popularity of pharmacological and surgical obesity treatment methods searched by Google users.
MATERIAL AND METHODS
We used Google Trends to identify topics representing the following: recommended surgical methods (n = 9), recommended pharmacological methods (n = 10), and not recommended pharmacological methods (n = 34). The data was generated for 2004-2022 and 2020-2022. Relative search volume (RSV) was adjusted using "Gastric bypass surgery" as a benchmark. We analyzed the geographical and temporal trends of the topics.
RESULTS
In 2004-2022, the topics representing recommended surgical methods numerically gained the most popularity among Google users, but in 2020-2022 the recommended drugs exceeded other obesity treatment methods. The most popular individual topics since 2004 were "flaxseed," "Spirulina," "Carnitine," "Bariatric surgery," and "Orlistat." The most dynamic increases of searches since 2004 were observed for "Sleeve gastrectomy," "Curcumin," "Psyllium," and "Bupropion/Naltrexon." Since 2018, topics representing GLP-1 analogs such as "Semaglutide" and "Saxenda" revealed exponential increases in RSV, causing that "Semaglutide" to become the fourth most popular topic in 2020-2022.
CONCLUSIONS
Google users across the world were the most interested in topics representing bariatric surgery, but recently recommended drugs for the treatment of obesity gained the most attention. The most popular individual topics were dietary supplements with uncertain effects on weight loss.
Topics: Humans; Obesity, Morbid; Search Engine; Retrospective Studies; Obesity; Bariatric Surgery
PubMed: 38103152
DOI: 10.1007/s11695-023-06971-y -
Frontiers in Endocrinology 2023Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and...
INTRODUCTION
Pharmacological therapy is recommended as a second-line alternative to reverse obesity. Currently, five anti-obesity drugs (AODs) have been approved by the U.S. Food and Drug Administration (FDA) for chronic weight management. The aim of this paper is to investigate the pharmacoeconomic evaluation of AODs through a systematic review with a special focus on methodological considerations.
METHODS
We searched the general and specific databases to identify the primary pharmacoeconomic evaluation of AODs.
RESULTS
A total of 18 full-text articles and three conference abstracts were included in this review. Most of the economic assessments were still about Orlistat. And the observations we could make were consistent with the previous systematic review. A few studies were on the combined therapies (i.e. PHEN/TPM ER and NB ER) compared to different comparators, which could hardly lead to a generalized summary of the cost-effectiveness. Most recently, pharmacoeconomic evidence on the newest GLP 1 RA approved for the indication of obesity or obesity with at least one comorbidity emerged gradually. Modelling-based cost-utility analysis is the major type of assessment method. In the modelling studies, a manageable number of the key health states and the state transitions were structured to capture the disease progression. In particular, the principal structure of the decision model adopted in the three studies on the newly approved drug was nearly the same, which enables more in-depth comparisons and generalizations of the findings.
CONCLUSION
This study provided an up-to-date overview of the strengths and areas for improvement in the methodological design of the pharmacoeconomic evaluation of the licensed drugs for chronic weight management. Future modelling evaluations would benefit from a better understanding of the long-term weight loss effects of the current therapeutic options and the weight rebound process after the discontinuation of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302648, identifier CRD42022302648.
Topics: United States; Humans; Anti-Obesity Agents; Economics, Pharmaceutical; Obesity; Orlistat; Comorbidity
PubMed: 38027186
DOI: 10.3389/fendo.2023.1254398 -
Journal of Traditional and... Nov 2023Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal...
BACKGROUND AND AIM
Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway.
EXPERIMENTAL PROCEDURE
The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN.
RESULTS AND CONCLUSION
The most frequent Chinese medicine component in XLW was . Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.
PubMed: 38020547
DOI: 10.1016/j.jtcme.2023.05.008 -
Journal For Immunotherapy of Cancer Nov 2023Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply...
BACKGROUND
Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages.
METHODS
In this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection.
RESULTS
FABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1-/- mice consistently showed attenuation. The FABP1-/- group's relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo.
CONCLUSIONS
ScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.
Topics: Animals; Humans; Mice; Carcinoma, Hepatocellular; Fatty Acid-Binding Proteins; Immunosuppressive Agents; Liver Neoplasms; Mice, Inbred C57BL; Orlistat; PPAR gamma; RNA; Tumor Microenvironment
PubMed: 38007237
DOI: 10.1136/jitc-2023-007030 -
Obesity Pillars Dec 2022/Objectives: Obesity is a risk factor for COVID-19 infection severity and mortality. Anti-obesity medications (AOM) are effective for weight loss. However, weight loss...
BACKGROUND
/Objectives: Obesity is a risk factor for COVID-19 infection severity and mortality. Anti-obesity medications (AOM) are effective for weight loss. However, weight loss outcomes with AOM during the COVID-19 pandemic are yet to be described.
SUBJECTS
/Methods: Between January 1, 2016, and June 30, 2021, a total of 966 patients were prescribed long-term FDA-approved AOMs at the Mayo Clinic. From these patients, 711 patients did not meet inclusion criteria. A total of 255 patients were included.
INTERVENTIONS/METHODS
We performed a retrospective systematic review of electronic medical records and included patients who started a long-term FDA-approved AOM. We excluded patients with history of bariatric procedure, AOM prescription with lorcaserin, orlistat, semaglutide (approved for weight loss after the pandemic), or phentermine (short-term AOM), those taking ≥2 AOMs, <3 months of prescribed AOM, and/or pregnancy. Analysis was divided by 1)preCOVID-19: those who started an AOM before COVID-19 restrictions, 2)COVID-19: those who started an AOM during first quarter of 2020 after the establishment of COVID-19 restrictions. Our primary endpoint was the total body weight loss percentage (%TBWL) at 3, 6, and 12 months after AOM initiation.
RESULTS
There was a statistical difference in TBWL% between the preCOVID-19 and COVID-19 group: 5.3 ± 3.5% vs 4 ± 3.0% (95% CI -2.4 to -0.2; p = 0.02) and 9.7 ± 7.2% vs 6.2 ± 4.7% (95% CI -5.7 to -1.3; p = 0.002) at 3 and 12 months, respectively. At 6 months, the TBWL% was 7.1 for the preCOVID-19 group compared to 6.2% for the COVID-19 (95% CI -2.5 to 0.7; p = 0.25).
CONCLUSION
With the possible exception of liraglutide, this study shows that weight loss outcomes to AOMs were inferior when prescribed during the routine clinical practice throughout COVID-19 pandemic, compared to the outcomes observed prior to the COVID-19 pandemic.
PubMed: 37990666
DOI: 10.1016/j.obpill.2022.100046 -
Molecules (Basel, Switzerland) Oct 2023has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk...
has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk medicine. From the leaves of , ten new monoterpenoid glycosides named ligurobustosides T (), T (), T (), T (), T (), T (), F (), T (), T (), and E (), together with five known ones (, , , , ), were separated and identified using the spectroscopic method and chemical method in this research. The results of biological tests exhibited that the fatty acid synthase (FAS) inhibitory action of compound (IC: 4.38 ± 0.11 μM) was as strong as orlistat (IC: 4.46 ± 0.13 μM), a positive control; the α-glucosidase inhibitory actions of compounds - and -, and the α-amylase inhibitory actions of compounds - were medium; the ABTS radical scavenging capacities of compounds - and - (IC: 6.27 ± 0.23 ~ 8.59 ± 0.09 μM) were stronger than l-(+)-ascorbic acid (IC: 10.06 ± 0.19 μM) served as a positive control. This research offered a theoretical foundation for the leaves of to prevent diabetes and its complications.
Topics: Ligustrum; Glycosides
PubMed: 37959693
DOI: 10.3390/molecules28217274 -
Foods (Basel, Switzerland) Oct 2023Black garlic, also known as fermented garlic, is a useful food that may have therapeutic benefits. The aim of this study was to analyze the impact of fermented garlic...
BACKGROUND
Black garlic, also known as fermented garlic, is a useful food that may have therapeutic benefits. The aim of this study was to analyze the impact of fermented garlic and orlistat therapy on obese rats.
METHODS
A total of 40 male albino rats (245-250 g) were fed either an HFD ( = 32) or a normal diet ( = 8) for 6 weeks; therefore we randomly assigned the rats into: group I (normal diet), group II (HFD), groups III and IV (HFD with fermented garlic), and group V (orlistat for) 6 weeks. Two different dosages of fermented garlic (481.2 mg/kg and 963.3 mg/kg) were administered. Afterward, blood was collected, body weight was measured, and tissue was collected for further analysis.
RESULTS
Both the orlistat and black garlic groups showed a significant reduction in BMI, lipid profiles, and insulin levels compared with the baseline. The orlistat group showed significant elevation ( < 0.005) in body weight, organ weight, lipids, and liver parameters, with histopathological findings. The administration of black garlic improved the inflammatory markers with all other parameters.
CONCLUSION
The fermented garlic and orlistat reinstated all of the investigated parameters significantly ( < 0.05), especially body weight and lipid profiles, and induced histopathological changes compared to the drug orlistat. Additionally, it showed anti-obesity-related therapeutic impacts compared with the orlistat drug. Black garlic provides a reliable and effective treatment for obesity compared to orlistat.
PubMed: 37959027
DOI: 10.3390/foods12213905 -
European Journal of Pharmaceutical... Jan 2024Enabling formulations, such as lipid-based formulations (LBFs), are means to deliver challenging-to-formulate, poorly soluble drugs. LBFs may be composed of lipids,...
Enabling formulations, such as lipid-based formulations (LBFs), are means to deliver challenging-to-formulate, poorly soluble drugs. LBFs may be composed of lipids, surfactants and/or cosolvents and can be classified depending on the proportions of the components and the hydrophilicity of the surfactant according to the Lipid Formulations Classification System, ranging from type I (very lipophilic) to type IV (hydrophilic). In cases where drug solubility in LBFs does not suffice, e.g. for preclinical toxicity studies, supersaturated LBFs can be used in order to increase the drug load. However, the effect of digestion on drug absorption from supersaturated type I formulations (consisting exclusively of lipids) still remains relatively unexplored and unclear. In the present study, the impact of lipid digestion on absorption of cinnarizine-loaded supersaturated lipid-based formulations of type I was investigated in rats by pre-dosing of the lipase inhibitor orlistat. The lipid chain length and the drug dose were varied by testing medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), both supersaturated and non-supersaturated. Due to the physical instability of supersaturated formulations of cinnarizine, i.e. a potential of precipitation of cinnarizine, the impact of the addition of the amphiphilic polymer Soluplus®, as a potential precipitation inhibitor, was also investigated. The supersaturated systems resulted in a 2.3 - 3.3-fold higher Area Under the Curve (AUC, not dose-normalized) and 1.4 - 2.2-fold higher maximum plasma concentration (C, not dose-normalized) than non-supersaturated formulations (statistically significant with p = 0.05), whereas the addition of Soluplus® did not reveal any benefit. Results indicated that lipase inhibition affected the in vivo performance of LBFs: Co-administration of the lipase inhibitor significantly reduced C and AUC (both to 33-39 %, not dose-normalized) for the LCT formulations and, though not significant, a similar trend was observed for the AUC of the MCT formulations (to 53-87 %), suggesting a higher dependency on lipolysis for LCT. Also, t tended to decrease to 20-60 % when compared to the animals not dosed with orlistat but lacking statistical significance. Without lipase inhibition, the LCT in general lead to better absorption of cinnarizine as compared to MCT, with 1.2-1.7-fold higher AUC and 1.4-1.8-fold higher C, but without showing statistical significance. Overall, the study revealed that lipolysis plays a major role in drug absorption from supersaturated lipid-based formulations type I.
Topics: Rats; Animals; Cinnarizine; Orlistat; Pharmaceutical Preparations; Triglycerides; Solubility; Surface-Active Agents; Lipase; Digestion; Administration, Oral
PubMed: 37951315
DOI: 10.1016/j.ejps.2023.106634 -
Biological & Pharmaceutical Bulletin 2023This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma...
This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.
Topics: Animals; Female; Rats; Carcinoma, Hepatocellular; Diethylnitrosamine; Estrogens; Fatty Acid Synthases; Interleukin-6; Liver; Liver Neoplasms; Receptors, Estrogen
PubMed: 37914358
DOI: 10.1248/bpb.b23-00342