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Pharmaceuticals
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Drug Candidates for the Treatment of Obesity
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Drug Candidates for the Treatment of Obesity

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 17343

Special Issue Editors

Dr. Maria Isabel Cardoso Alonso-Vale

E-Mail Website
Guest Editor
Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
Interests: adipose tissue; obesity; inflammation; fatty acids; mesenchymal stromal cells
Special Issues, Collections and Topics in MDPI journals
Dr. Monica Marques Telles

E-Mail Website
Guest Editor
Department of Physiology/Nutrition Physiology Division, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
Interests: nutraceuticals; obesity; adipose tissue; metabolism; central control of food intake
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

According to the WHO, overweight and obesity have reached an epidemic proportion. It is estimated that one billion people globally will be living with obesity by 2030. This is particularly worrying when considering the obesity-related metabolic risks, predisposing people to type 2 diabetes mellitus, cardiovascular diseases, and some types of cancer, among other pathological conditions. Furthermore, overweight and obesity might impair psychological health and self-esteem, occasionally resulting in anxiety and/or depression. On one hand, it is well-recognized that dietary control and physical activity programmes are the most effective interventions in order to manage obesity and its related disorders. On the other hand, it is also well-known that adherence to the recommended lifestyle modifications is poor. In addition, the pharmacological management of obesity has often been ineffective or associated with important side effects, thus representing an enormous challenge to healthcare professionals. Despite all of the harmful health impacts for individuals with obesity, the high costs to treat obesity and its related disorders are also a matter of concern, and, thus, the development of  new pharmacological therapies for overweight and obesity control has been addressed. Therefore, this Special Issue is focused on new drug candidates for the prevention and treatment of obesity.

Dr. Maria Isabel Cardoso Alonso-Vale
Dr. Monica Marques Telles
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • obesity
  • appetite supressors
  • nutraceuticals
  • plant extracts
  • lipid metabolism
  • high-fat diet
  • adipogenesis

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Published Papers (5 papers)

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Research

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15 pages, 2206 KiB  
Article
Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells
by Ivana Cacciatore, Sonia Spalletta, Annalisa Di Rienzo, Vincenzo Flati, Erika Fornasari, Laura Pierdomenico, Piero Del Boccio, Silvia Valentinuzzi, Erica Costantini, Elena Toniato, Stefano Martinotti, Carmela Conte, Antonio Di Stefano and Iole Robuffo
Pharmaceuticals 2023, 16(3), 340; https://doi.org/10.3390/ph16030340 - 22 Feb 2023
Cited by 3 | Viewed by 2463
Abstract
(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives (CD1-3 [...] Read more.
(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives (CD1-3) that are able to reduce both adipogenesis and the inflammatory status often associated with the progression of the obesity disease. (2) Methods: The synthesis of CD1-3 was performed using classical procedures in a solution phase. Biological studies were performed on three cell lines: 3T3-L1, WJ-MSCs, and THP-1. The anti-adipogenic properties of CD1-3 were evaluated using western blotting and densitometric analysis by assessing the expression of obesity-related proteins, such as ChREBP. The anti-inflammatory effect was estimated by measuring the reduction in TNF-α expression in CD1-3-treated THP-1 cells. (3) Results: CD1-3—obtained through a direct linkage between the carboxylic moiety of anti-inflammatory drugs (Ibuprofen, Flurbiprofen, and Naproxen) and the hydroxyl group of carvacrol—have an inhibitory effect on the accumulation of lipids in both 3T3-L1 and WJ-MSCs cell cultures and an anti-inflammatory effect by reducing TNF- α levels in THP-1 cells. (4) Conclusions: Considering the physicochemical properties, stability, and biological data, the CD3 derivative—obtained by a direct linkage between carvacrol and naproxen—resulted in the best candidate, displaying anti-obesity and anti-inflammatory effects in vitro. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Obesity)
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25 pages, 10639 KiB  
Article
Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic–Oleic Acid-Induced Steatosis in HepG2 Cells
by Salah Abdalrazak Alshehade, Raghdaa Hamdan Al Zarzour, Michael Mathai, Nelli Giribabu, Atefehalsadat Seyedan, Gurjeet Kaur, Fouad Saleih Resq Al-Suede, Amin Malik Shah Abdul Majid, Vikneswaran Murugaiyah, Hassan Almoustafa and Mohammed Abdullah Alshawsh
Pharmaceuticals 2023, 16(1), 109; https://doi.org/10.3390/ph16010109 - 11 Jan 2023
Cited by 5 | Viewed by 3794
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Orthosiphon aristatus (Blume) Miq, a traditional plant in South Asia, has previously been shown to attenuate obesity and hyperglycaemic conditions. Eight weeks of feeding C57BL/6 mice with the standardized O. [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Orthosiphon aristatus (Blume) Miq, a traditional plant in South Asia, has previously been shown to attenuate obesity and hyperglycaemic conditions. Eight weeks of feeding C57BL/6 mice with the standardized O. aristatus extract (400 mg/kg) inhibited the progression of NAFLD. Liver enzymes including alanine aminotransferase and aspartate transaminase were significantly reduced in treated mice by 74.2% ± 7.69 and 52.8% ± 7.83, respectively. Furthermore, the treated mice showed a reduction in serum levels of glucose (50% ± 5.71), insulin (70.2% ± 12.09), total cholesterol (27.5% ± 15.93), triglycerides (63.2% ± 16.5), low-density lipoprotein (62.5% ± 4.93) and atherogenic risk index relative to the negative control. Histologically, O. aristatus reversed hepatic fat accumulation and reduced NAFLD severity. Notably, our results showed the antioxidant activity of O. aristatus via increased superoxide dismutase activity and a reduction of hepatic malondialdehyde levels. In addition, the levels of serum pro-inflammatory mediators (IL-6 and TNFα) decreased, indicating anti-inflammatory activity. The aqueous, hydroethanolic and ethanolic fractions of O. aristatus extract significantly reduced intracellular fat accumulation in HepG2 cells that were treated with palmitic–oleic acid. Together, these findings suggest that antioxidant activities are the primary mechanism of action of O. aristatus underlying the anti-NAFLD effects. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Obesity)
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14 pages, 2764 KiB  
Article
Ginkgo biloba Extract Stimulates Adipogenesis in 3T3-L1 Preadipocytes
by Fernanda Malanconi Thomaz, Jussara de Jesus Simão, Viviane Simões da Silva, Meira Maria Forcelini Machado, Lila Missae Oyama, Eliane Beraldi Ribeiro, Maria Isabel Cardoso Alonso Vale and Monica Marques Telles
Pharmaceuticals 2022, 15(10), 1294; https://doi.org/10.3390/ph15101294 - 20 Oct 2022
Cited by 6 | Viewed by 2667
Abstract
Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation [...] Read more.
Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation in preadipocytes. 3T3-L1 preadipocytes were differentiated for 7 days into adipocytes without (control group) and with GbE at 1.0 mg/mL. Lipid content and gene expression were analyzed on day 7 (D7) by Oil Red O staining and PCR Array Gene Expression. Western blotting analysis of the key adipogenesis markers was evaluated during the differentiation process at days 3 (D3), 5 (D5), and 7 (D7). GbE increased lipid content and raised the gene expression of the main adipogenesis markers. Key proteins of the differentiation process were modulated by GbE, since C/EBPβ levels were decreased, while C/EBPα levels were increased at D7. Regarding the mature adipocytes’ markers, GbE enhanced the levels of both FABP4 at D5, and perilipin at D3 and D5. In summary, the present findings showed that GbE modulated the adipogenesis pathway suggesting that the treatment could accelerate the preadipocyte maturation, stimulating the expression of mature adipocyte proteins earlier than expected. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Obesity)
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14 pages, 2393 KiB  
Article
Palmitoleic Acid Acts on Adipose-Derived Stromal Cells and Promotes Anti-Hypertrophic and Anti-Inflammatory Effects in Obese Mice
by Jussara J. Simão, Maysa M. Cruz, Fernanda M. Abdala, Andressa Bolsoni-Lopes, Lucia Armelin-Correa and Maria Isabel C. Alonso-Vale
Pharmaceuticals 2022, 15(10), 1194; https://doi.org/10.3390/ph15101194 - 28 Sep 2022
Cited by 8 | Viewed by 2735
Abstract
Adipose tissue (AT) secretes adipokines, modulators of low-grade chronic inflammation in obesity. Molecules that induce the emergence of new and functional adipocytes in AT can alleviate or prevent inflammatory and metabolic disorders. The objective of this study was to investigate the role of [...] Read more.
Adipose tissue (AT) secretes adipokines, modulators of low-grade chronic inflammation in obesity. Molecules that induce the emergence of new and functional adipocytes in AT can alleviate or prevent inflammatory and metabolic disorders. The objective of this study was to investigate the role of palmitoleic acid (n7) in 3T3-L1 and primary pre-adipocyte differentiation and AT inflammation. C57BL/6j mice were submitted to a control or high-fat diet (HFD) for 8 weeks, and treated with n7 for 4 weeks. Mice consuming a HFD presented an increase in body weight, epididymal (Epi) fat mass, and Epi adipocytes size. N7 treatment attenuated the body weight gain and completely prevented the hypertrophy of Epi adipocytes, but not the increment in Epi mass induced by the HFD, suggesting a greater adipocytes hyperplasia in animals treated with n7. It was agreed that n7 increased 3T3-L1 proliferation and differentiation, as well as the expression of genes involved in adipogenesis, such as Cebpa, Pparg, aP2, Perilipin, and Scl2a4. Furthermore, n7 decreased the inflammatory cytokines Mcp1, Tnfa, Il6, Cxcl10, and Nos2 genes in Epi vascular stromal cells, but not in the whole AT. These findings show that n7 exerts anti-hypertrophic effects in adipocytes which influence the surrounding cells by attenuating the overexpression of pro-inflammatory cytokines triggered by a HFD. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Obesity)
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Review

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20 pages, 3195 KiB  
Review
Pharmacological Treatments and Natural Biocompounds in Weight Management
by Amin Gasmi, Pavan Kumar Mujawdiya, Amine Nehaoua, Mariia Shanaida, Yuliya Semenova, Salva Piscopo, Alain Menzel, Volodymyr Voloshyn, Olena Voloshyn, Volodymyr Shanaida and Geir Bjørklund
Pharmaceuticals 2023, 16(2), 212; https://doi.org/10.3390/ph16020212 - 30 Jan 2023
Cited by 8 | Viewed by 4469
Abstract
The obesity pandemic is one of society’s most urgent public health concerns. One-third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming [...] Read more.
The obesity pandemic is one of society’s most urgent public health concerns. One-third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming years. Generally, the treatment strategy for obese patients is largely patient-centric and needs dietary, behavioral, pharmacological, and sometimes even surgical interventions. Given that obesity cases are rising in adults and children and lifestyle modifications have failed to produce the desired results, the need for medical therapy adjunct to lifestyle modifications is vital for better managing obesity. Most existing or past drugs for obesity treatment target satiety or monoamine pathways and induce a feeling of fullness in patients, while drugs such as orlistat are targeted against intestinal lipases. However, many medications targeted against neurotransmitters showed adverse events in patients, thus being withdrawn from the market. Alternatively, the combination of some drugs has been successfully tested in obesity management. However, the demand for novel, safer, and more efficacious pharmaceutical medicines for weight management does exist. The present review elucidates the current understanding of the available anti-obesity medicines of synthetic and natural origin, their main mechanisms of action, and the shortcomings associated with current weight management drugs. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Obesity)
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