Search Results (147)

Callistemon citrinus has shown antioxidant and anti-inflammatory properties in certain tissues. However, its impact on the brain remains unproven. This study investigates the effect of C. citrinus extract and phytosomes on the oxidative status of the brains of rats fed a high-fat–fructose diet (HFD). Fifty-four male Wistar rats were randomly divided into nine groups (n = 6). Groups 1, 2, and 3 received a standard chow diet; Group 2 also received the vehicle, and Group 3 was supplemented with C. citrinus extract (200 mg/kg). Groups 4, 5, 6, 7, 8, and 9 received a high-fat diet (HFD). Additionally, groups 5, 6, 7, 8, and 9 were supplemented with orlistat at 5 mg/kg, C. citrinus extract at 200 mg/kg, and phytosomes loaded with C. citrinus at doses of 50, 100, and 200 mg/kg, respectively. Administration was oral for 16 weeks. Antioxidant enzymes, biomarkers of oxidative stress, and fatty acid content in the brain were determined. A parallel artificial membrane permeability assay (PAMPA) was employed to identify compounds that can cross the intestinal and blood–brain barriers. The HFD group (group 4) increased body weight and adipose tissue, unlike the other groups. The brain fatty acid profile showed slight variations in all of the groups. On the other hand, group 4 showed a decrease in the activities of antioxidant enzymes SOD, CAT, and PON. It reduced GSH level, while increasing GPx activity as well as MDA, 4-HNE, and AOPP levels. C. citrinus extract and phytosomes restore the antioxidant enzyme activities and mitigate oxidative stress in the brain. C. citrinus modulates oxidative stress in brain tissue through 1.8-cineole and α-terpineol, which possess antioxidant and anti-inflammatory properties. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

This study aimed to evaluate the effects of C. sinensis extract, orlistat, and their combination on biochemical, hormonal, inflammatory, and oxidative stress parameters in female rats. The extract was characterized by the presence of citric acid, ferulic acid, and quercetin, along with antioxidant activity. Five experimental groups were established: (1) control; (2) obese; (3) orlistat (1.72 mg/kg); (4) C. sinensis extract (7.15 mg/kg); (5) a combination of both treatments. Treatment with the extract, orlistat, or their combination resulted in biochemical parameters (glucose, cholesterol, and triglycerides) that were comparable to the control group and significantly different from the obese group. Notably, only the C. sinensis extract alone restored pro-inflammatory cytokine levels (IL-1β, TNF-α, IL-6, IL-8) to values similar to the control. All treatments improved the activity of antioxidant enzymes catalase and glutathione peroxidase, while a significant increase in superoxide dismutase activity was observed only in the extract group. Among the oxidative damage markers, TBARS was the most responsive to treatment, whereas protein carbonylation was less affected. Histological analysis showed that all treatments promoted structural normalization. These results provide a rationale for further pre-clinical and clinical investigations into the use of C. sinensis extract as an adjunctive therapy for metabolic disorders. Full article

Plantago ovata has been utilized as an effective natural remedy with minimal side effects, offering a promising alternative to synthetic pharmaceuticals. The supercritical fluid extraction (SFE) of Plantago ovata leaves yielded 0.417 g and 0.532 g at 40 °C and 80 °C, respectively. The 40 °C extract exhibited stronger antimicrobial activity, with minimum inhibitory concentrations (MICs) as low as 15.62 µg/mL and minimum bactericidal concentrations (MBCs) as low as 31.25 µg/mL against Bacillus subtilis and Candida albicans. In contrast, the 80 °C extract demonstrated reduced activity, with MICs and MBCs up to 250 and 500 µg/mL, respectively. The 40 °C extract also showed superior lipase inhibition (IC₅₀ = 17.21 µg/mL) compared to the 80 °C extract (IC₅₀ = 26.42 µg/mL), although orlistat remained the most potent (IC₅₀ = 6.02 µg/mL). In addition, cytotoxicity assays revealed stronger effects of the 40 °C extract on Caco-2 colon cancer cells (IC₅₀ = 109.47 µg/mL) compared to the 80 °C extract (IC₅₀ = 174.81 µg/mL). These results suggest that the lower-temperature SFE of P. ovata yields extracts with enhanced antimicrobial, anti-obesity, and anticancer activities, supporting its potential for pharmaceutical and nutraceutical applications. Full article

Obesity represents a significant global public health issue, contributing to the rising prevalence of metabolic diseases. One treatment for obesity is orlistat, a drug that inhibits pancreatic lipase. It is widely used due to its efficacy in reducing dietary fat absorption. However, patient adherence to this drug is often hindered by its associated adverse effects. As a result, there is an increasing interest in exploring alternative therapeutic options derived from natural sources, such as plants and algae, particularly extracts and their bioactive compounds. These extracts and compounds have shown potential in inhibiting pancreatic lipase and other markers associated with obesity. Nevertheless, they also present certain limitations, including low bioavailability. In this context, combination therapy involving orlistat and these extracts or their compounds has emerged as a promising strategy. This approach aims to enhance the inhibition of pancreatic lipase and other obesity-related markers, thereby improving therapeutic outcomes and reducing adverse effects associated with treatment. The objective of this review is to analyze the available scientific evidence regarding the combined effects of orlistat and extracts or bioactive compounds in inhibiting various markers related to dyslipidemia and obesity, with the goal of proposing combination therapy as a safe and effective therapeutic option. Full article

Erica spiculifolia Salisb. (formerly Bruckenthalia spiculifolia Benth.) (Balkan heath) is renowned for its traditional usage as a diuretic, anti-inflammatory and antioxidant agent. For the first time, acylquinic acids, flavonoids and numerous proanthocyanidin oligomers were annotated/dereplicated by liquid chromatography–high-resolution mass spectrometry in methanol–aqueous extracts from E. spiculifolia aerial parts harvested at the early and full flowering stage. Chlorogenic acid and proanthocyanidin tetra- and trimer A, B-type together with quercitrin and (+) catechin were the predominant compounds in the semi-quantitative analysis. Neutral triterpenoids, triterpenoid acids and phytosterols were determined in apolar extracts by gas chromatography–mass spectrometry. Triterpenoid acids accounted for 80% of the total triterpenoid content, dominated by ursolic and oleanolic acid, reaching up to 32.2 and 6.1 mg/g dw, respectively. Ursa/olean-2,12-dien-28-oic acids and 3-keto-derivatives together with α-amyrin acetate as a chemotaxonomic marker, α-amyrenone, α- and β-amyrin were evaluated. Total phenolic and flavonoid contents were 83.85 ± 0.89 mg gallic acid equivalents/g and 78.91 ± 0.41 mg rutin equivalents/g, respectively. The extract actively scavenged DPPH and ABTS radicals (540.01 and 639.11 mg Trolox equivalents (TE)/g), possessed high potential to reduce copper and iron ions (660.32 and 869.22 mg TE/g, respectively), and demonstrated high metal chelating capacity (15.57 Ethylenediaminetetraacetic acid equivalents/g). It exhibited prominent anti-lipase (18.32 mg orlistat equivalents/g) and anti-tyrosinase (71.90 mg kojic acid equivalents/g) activity. The extract inhibited α-glucoside (1.35 mmol acarbose equivalents/g) and acetylcholinesterase (2.56 mg galanthamin equivalents/g), and had moderate effects on α-amylase, elastase, collagenase and hyaluronidase. Balkan heath could be recommended for raw material production with antioxidant and enzyme inhibitory properties. Full article

Background/Objectives: In vitro, vancomycin (VAN) and tetrahydrolipstatin (THL) together have been shown to synergistically inhibit Mycobacterium tuberculosis (Mtb), the world’s most infectious killer. The poor oral bioavailability of VAN and THL and predominant tropism of Mtb infection to the lungs and alveolar macrophages make pulmonary administration highly attractive. This study aimed to develop and assess the efficacy of dry powders for inhalation of VAN microparticles embedded with THL. Methods: The dry powders produced by spray-drying, with or without hydrogenated castor oil (HCO), were characterized for their physicochemical properties among others by HPLC-DAD. The fast-screening impactor was used to determine powder aerodynamic properties, and VAN and THL releases were established from the paddle over disk method. Biological activities were assessed in a new M. bovis-infected macrophage model and in Mtb-infected mice. Results and Discussion: The addition of 25% HCO enables co-deposition (fine particle dose) at the desired weight ratio and co-releasing of VAN and THL in aqueous media. Microparticles with 0% to 50% HCO drastically reduced cytoplasmic Mycobacterium bovis survival (99.9% to 62.5%, respectively), with higher efficacy at low HCO concentration. Consequently, VAN/THL with or without 25% HCO was evaluated in Mtb-infected mice. Although no decrease in Mtb lung burden was observed after two weeks of administration, the endotracheal administration of VAN 500 mg/kg and THL 50 mg/kg with 25% HCO administrated three times during five days concomitantly with daily oral rifampicin (10 mg/kg) demonstrated 2-fold bacterial burden reduction compared to the group treated with RIF alone. Conclusions: HCO was crucial for obtaining a fine particle dose at the synergistic weight ratio (VAN/THL 10:1) and for releasing both drugs in aqueous media. With oral administration of the first-line rifampicin, the dry powder VAN/THL/25% HCO was able to exert a potential anti-tubercular effect in vivo in Mtb-infected mice after five days. Full article

Background/Objectives: Obesity is a major health concern that can lead to various chronic diseases. Little is known about the anti-obesity effect of a standardized hot water extract from the stems of Ipomoea batatas (WIB). This study aimed to evaluate the therapeutic potential of WIB as a natural alternative to conventional anti-obesity treatments by assessing its effects on body weight, fat accumulation, and key metabolic biomarkers in a high-fat diet-induced obesity model. Methods: A high-fat diet (HFD) induced obesity in C57BL/6 mice. The mice were then treated orally with either orlistat (positive control) or WIB. Changes in body weight, food intake, and fat weight were measured, along with blood lipid profiles and adipokines. Western blot analyses were conducted to determine protein levels in each tissue. H&E staining in white adipose tissue and liver, and the gut microbiota composition were analyzed. Results: WIB treatment significantly reduced body weight and fat mass compared to the HFD group and demonstrated comparable effects to orlistat. WIB improved blood lipid profiles and adipokine levels. H&E staining revealed reduced fat accumulation in the white adipose tissue and liver. Also in those tissues, WIB restored expression levels of sterol regulatory element-binding protein-1 (SREBP-1) and CCAAT/enhancer-binding protein α (C/EBPα) and increased AMP-activated protein kinase (AMPK) phosphorylation. In brown adipose tissue, WIB enhanced AMPK phosphorylation and upregulated thermogenic-related proteins, including peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), sirtuin 1 (SIRT1), uncoupling protein-1 (UCP-1), and cytochrome C oxidase subunit 4 (COX-IV). Analysis of gut microbiota revealed that WIB normalized β-diversity and reversed HFD-induced phyla imbalances (notably in Bacteroidetes, Firmicutes, and Proteobacteria). Conclusions: By reducing adiposity under the conditions tested in a murine model, improving metabolic markers, and favorably modulating gut microbiota, WIB demonstrates potential in mitigating obesity-related risks. These findings suggest that WIB may serve as a promising natural substance for the management of obesity. Further studies are warranted to confirm its efficacy and explore the potential underlying mechanisms in overweight or obese humans as a health supplement to help manage or prevent obesity. Full article

Obesity is a growing global health challenge, necessitating effective treatment options beyond lifestyle interventions. This narrative review explores established and emerging pharmacotherapies for weight management, including parenteral agents like Liraglutide, Semaglutide, Setmelanotide, and Tirzepatide, as well as peroral medications such as Phentermine, Phentermine/Topiramate, Bupropion/Naltrexone, Orlistat, and Metformin. Newer treatments like Cagrilintide and Bimagrumab show promise for enhancing weight loss outcomes. Parenteral GLP-1 receptor agonists demonstrate superior efficacy compared to traditional peroral medications, with gastrointestinal side effects being the most common. Artificial intelligence presents intriguing opportunities to enhance weight loss strategies; however, its integration into clinical practice remains investigational and requires rigorous clinical validation. While current anti-obesity medications deliver significant benefits, future research must determine the efficacy, safety, and cost-effectiveness of AI-driven approaches. This includes exploring how AI can complement combination therapies and tailor personalized interventions, thereby grounding its potential benefits in robust clinical evidence. Future directions will focus on integrating AI into clinical trials to refine and personalize obesity management strategies. Full article

Hyperlipidemia, marked by high levels of fats in the blood, is a major risk factor for non-communicable diseases such as type 2 diabetes, cardiovascular diseases, and cancer. It has been linked to the action of reactive oxygen species and the formation of advanced glycation end products. Current treatments for hyperlipidemia, like orlistat, simvastatin, and atorvastatin, often present undesirable side effects, prompting the need for new therapeutic agents that are safer, more effective, cost-efficient, and have fewer side effects. In this context, new compounds, specifically propano- and butanosulfonic acids with 9-substituted quinobenzothiazinyl substituents, were synthesized through reactions with 9-substituted quinobenzothiazines and propane sultone or butane sultone. These novel quinobenzothiazine derivatives were verified using ¹H NMR, ¹³C NMR, and HR-MS techniques. The research focused on assessing these compounds for their toxicity, ability to prevent glycation, antioxidant properties, and their potential to combat hyperlipidemia. Toxicity was evaluated on the 3T3 L1 fibroblast cell line using the MTT assay. The capacity to prevent glycation was tested with bovine serum albumin–methylglyoxal and bovine serum albumin–glucose systems. This study measured total reactive oxygen species in the 3T3 L1 cell line using 2′,7′-dichlorodihydrofluorescein diacetate staining, and antioxidant capacity was assessed through DPPH scavenging and metal ion chelation tests. The effectiveness against hyperlipidemia was determined by targeting cholesterol esterase and pancreatic lipase activities, with concentrations of the compounds 5 to 12 ranging from 0.0245 to 0.268 μM. Standard drugs such as orlistat, simvastatin, statins, and aminoguanidine were used as positive controls in various assays. Additionally, computational docking studies with AutoDock Vina were performed. The resulting findings indicated that the compounds were non-toxic to cells, effectively inhibited key enzymes related to hyperlipidemia, and showed significant antioxidant properties, including the prevention of advanced glycation end-product formation. Compounds 11 and 12 demonstrated the highest activity levels. These promising results highlight the potential of new quinobenzothiazine derivatives as lead compounds for the development of antihyperlipidemic drugs, although further research is necessary to confirm their efficacy and safety. Full article

Obesity increases the risk of anovulation, insulin resistance, hyperandrogenism, and endometrial dysfunction, resulting in women with infertility and increasing preconceptional and pregnancy complications. Bariatric surgery has been described as the most effective intervention for obesity, with improved fertility outcomes. However, its invasive nature increases the potential of nutritional deficiencies and the need for a delayed conception post-surgery. On the other hand, pharmacological treatments such as glucagon-like-peptide 1 receptor agonists offer non-invasive alternatives with promising results in body weight, improving insulin sensitivity and restoring ovarian function. However, their use must be discontinued before conception due to potential fetal risks. Other available pharmacological treatment options encompass topiramate, phentermine, and Orlistat. The choice of treatment must be individualized considering cost-effectiveness, accessibility, obesity severity, reproductive goals, and associated risks within each patient. A multidisciplinary approach is essential to optimize metabolic and reproductive health in obesity and infertility. This review will examine the impact on metabolism when comparing surgical and pharmacological interventions for weight loss in women with infertility. Full article

Adolescent obesity is a growing global health problem all around the world. We reviewed the use of complementary and alternative medicine (CAM) for adolescent obesity, examining improvements in BMI or any metabolic indices of obesity. We performed a PubMed and Scopus search for articles on CAM treatments in adolescents aged 12–17 years, and included all studies with subjects in that age range. Out of 226 PubMed articles and 14 Scopus articles, 28 articles from PubMed and 1 article from Scopus fit our criteria. Most CAM studies that showed some improvement in BMI were acupuncture- or yoga-based. Yoga-based interventions showed a BMI reduction of 1–2 points, which is similar to results achieved in studies based on physical activity and Orlistat, a weak anti-obesity medication; meanwhile, acupuncture-based studies showed a slightly higher BMI reduction of 2–4 points, similar to that achieved with Liraglutide, a GLP-1 agonist that is a good anti-obesity medication. Herbs and supplements showed improvement in metabolic markers of obesity. Stress interventions in mind–body interventions, music skip-rope exercise, and creative drama in physical activity-based interventions also showed improvement in BMI. Although many of the studies reviewed were RCTs, the small sample size of those RCTs is a limiting factor. There may be a role for investigating this topic in larger populations to generate more effective conclusions. Full article

Introduction and Objective: Obesity has increased worldwide, and existing anti-obesity medications have treatment limitations that diminish their overall benefits. This study aimed to investigate the effects of orlistat in combination with Elettaria cardamomum “Cardamom” (CAR) extract on working memory, recognition memory, anxiety, and inflammation within hippocampal tissue. Methods: Mice were categorized into two groups: a control group (CD) and a cafeteria diet (CAF) group induced with obesity (CAF) for 10 weeks. The groups were then subdivided into a CAF group treated with orlistat (CAF-ORL), a CAF group treated with orlistat and Elettaria cardamomum (CAF-ORL-CARD), and a group that continued on the CAF. The CAF-ORL group received orlistat at a dosage of 10 mg/kg/day for four weeks, while the CAF-ORL-CARD group received 10 mg/kg/day of orlistat and 500 mg/kg of CAR extract via oral gavage. In the 14th week, various assessments were conducted, including the novel object recognition (NOR) test, Y maze test, marble-burying test (MBT), open-field test, and TNF-α levels in the hippocampus. Result: TNF-α levels in the hippocampal tissue of the CAF group were elevated compared to the CD group (p < 0.01), whereas the CAF-ORL group exhibited reduced TNF-α levels compared to the CAF group (p < 0.01). Moreover, TNF-α levels in the CAF-ORL-CARD group were significantly lower than in the CAF-ORL group (p < 0.01). The recognition index was notably higher in the CAF-ORL group compared to the CAF group (p < 0.01) and higher in the CAF-ORL-CARD group compared to the CAF-ORL group (p < 0.01). However, there were no changes in the open-field test and Y maze test (p > 0.05). Conclusions: Orlistat combined with CAR has positive effects on neuroinflammation and memory, suggesting that this combination may offer potential therapeutic benefits for cognitive impairments and hippocampal dysfunction associated with obesity. Full article

Background/Objectives: Obesity has reached pandemic proportions, with predictions suggesting that, by 2030, over 1.5 billion people will be affected. Pancreatic lipase (PL), the enzyme primarily responsible for the absorption of dietary lipids, presents a potential target for obesity management. However, while porcine pancreatic lipase (PPL) is commonly used as the enzyme source for screening potential inhibitors, its effect on human pancreatic lipase (HPL) is rarely reported. This work aimed to screen the inhibitory effects of a library of flavonoids with different functional groups on the activity of PL from the human pancreas (triacylglycerol acyl hydrolase, EC 3.1.1.3) and compare it to the effects of the porcine pancreas (type II, EC 3.1.1.3), establishing, whenever possible, a structure–activity relationship. Methods: The inhibitory effects of a library of 48 flavonoids with different hydroxy, glycosyl, rutinosyl, galloyl, and extended alkyl groups were evaluated against PPL and HPL. The kinetic parameters and inhibitory mechanisms of the most active flavonoids were determined, and in silico docking studies of the more potent flavonoids were also performed, using the active site of HPL. Results/Conclusions: Variations in enzyme catalytic activity were observed depending on the source of the enzyme. The inhibitory effect was particularly influenced by the presence of extended alkyl groups at the C-3 of the C-ring and the C2=C3 double bond of the C-ring and the presence of a pyrogallol group at the C-2′, C-3′ and C-4′ of the B-ring. Docking results showed a strong correlation between docking scores and observed inhibitory activities, highlighting the critical role of specific substituents on the flavonoid backbone in enhancing detailed interaction dynamics with key amino acids. Compounds 28, 29, and 30, with alkyl groups, showed the highest docking scores, interacting with residues HIS151, PHE215, ARG256, and HIS263. Further analysis also revealed that specific substituents improved pocket occupancy and formed additional interactions with residues TYR114, PRO180, ILE209, and PHE215, which are crucial for inhibition. These binding characteristics closely mimic those observed with orlistat, reinforcing their mechanistic similarities in inhibiting HPL and validating their inhibitory activities. Full article

Hypertension, type 2 diabetes (T2D), and obesity raise an individual’s risk of suffering from diseases associated with metabolic syndrome (MS). In humans, enzymes that play a role in the prevention and development of MS include angiotensin converting enzyme (ACE-1) associated with hypertension, α-amylase associated with T2D, and lipase linked to the development of obesity. Seaweeds are a rich source of bioactives consisting of proteins/peptides, polysaccharides, and lipids. This study examined the potential of seaweed-derived bioactives from Alaria esculenta, Ulva lactuca, and Palmaria palmata as inhibitors of ACE-1, α-amylase, and lipase. In vitro enzyme inhibitory assays were used to quantify the bioactivity of the seaweed extracts and compare their half-maximal inhibitory (IC₅₀) values to recognised positive control enzyme inhibitory drugs captopril© (an ACE-1 inhibitor), acarbose (an α-amylase inhibitor), and orlistat (a lipase inhibitor). Three seaweed extracts displayed enzyme inhibitory activities equal to, or more effective than, the reference positive control drugs. These were P. palmata peptides (ACE-1 IC₅₀ 94.29 ± 3.07 µg/mL, vs. captopril© 91.83 ± 2.68 µg/mL); A. esculenta polyphenol extract (α-amylase IC₅₀ 147.04 ± 9.72 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL, and lipase IC₅₀ 106.21 ± 6.53 µg/mL vs. orlistat 139.74 ± 9.33 µg/mL); and U. lactuca polysaccharide extract (α-amylase IC₅₀ 168.06 ± 10.53 µg/mL vs. acarbose 185.67 ± 12.48 µg/mL). Proximate analysis also revealed that all three seaweeds were a good source of protein, fibre, and polyunsaturated essential fatty acids (PUFAs). These findings highlight the potential of these seaweeds in the management of diseases associated with MS and as foods. Full article