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  1. Bioactivity, phytochemistry studies and subacute in vivo toxicity of ethanolic leaf extract of white mulberry (Morus alba linn.) in female mice
    Fauzi A, Kifli N, Noor MHM, Hamzah H, Azlan A
    J Ethnopharmacol, 2024 May 10;325:117914.
    PMID: 38360381 DOI: 10.1016/j.jep.2024.117914
    ETHNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Morus alba L. leaf extracts (MLE) have been reported for treating hyperglycaemia and diabetes. Phytochemical compounds in the leaves demonstrated the ability to enhance insulin sensitivity and β-cell secretory function, suggesting their potential value in reducing blood glucose and treating diabetes. However, the phytochemical constituents and safety of the herbal medicines need to be verified in each experimental field from different growing areas. Studies on the phytochemistry and toxicity of Morus alba leaves in Southeast Asia, especially in Brunei, have never been investigated.

    AIM OF THE STUDY: This study aimed to investigate the bioactivity and phytochemistry of Morus alba ethanolic leaf extract from Brunei Darussalam and its subacute toxic effects in the Institute of Cancer Research (ICR) female mice.

    MATERIALS AND METHODS: The phenolic yield and antioxidant of the extract were analysed. Meanwhile, liquid chromatography-mass spectrometry and high-performance liquid chromatography were utilised to determine the phenolic compound of the MLE. In the subacute toxicity study, twenty-five female mice were randomly divided into five groups: the control group, which received oral gavage of 5% dimethyl sulfoxide solvent (DMSO), and the MLE treatment group, which received the extract at a dose of 125, 250, 500 and 1000 mg/kg. Physiology, haematology, biochemistry, and histology were evaluated during the study.

    RESULTS: Morus alba leaf depicted total phenolic 10.93 mg gallic acid equivalents (GAE)/g dry weight (DW), flavonoid 256.67 mg quercetin equivalents (QE)/g DW, and antioxidant bioactivity content of 602.03 IC50 μg/mL and 13.21 mg Fe2+/g DW. Twenty compounds in the Morus alba ethanolic leaf extract were identified, with chlorogenic acid (305.60 mg/100 g DW) as the primary compound. As for subacute toxicity in this study, neither mortality nor haematological changes were observed. On the other hand, administration of 500 and 1000 mg/kg MLE resulted in mild hepatocellular injury, as indicated by a significant (p 

  2. Comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. A cheminformatics "proof-of-concept" study
    Moshawih S, Hadikhani P, Fatima A, Goh HP, Kifli N, Kotra V, et al.
    J Mol Graph Model, 2022 Dec;117:108307.
    PMID: 36096064 DOI: 10.1016/j.jmgm.2022.108307
    A Laplacian scoring algorithm for gene selection and the Gini coefficient to identify the genes whose expression varied least across a large set of samples were the state-of-the-art methods used here. These methods have not been trialed for their feasibility in cheminformatics. This was a maiden attempt to investigate a complete comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. This computational "proof-of-concept" study illustrated the combinatorial approach used to explain how the structure of the selected natural products (NPs) undergoes molecular diversity analysis. A virtual combinatorial library (1.6 M) based on 20 anthraquinones and 24 chalcones was enumerated. The resulting compounds were optimized to the near drug-likeness properties, and the physicochemical descriptors were calculated for all datasets including FDA, Non-FDA, and NPs from ZINC 15. UMAP and PCA were applied to compare and represent the chemical space coverage of each dataset. Subsequently, the Laplacian score and Gini coefficient were applied to delineate feature selection and selectivity among properties, respectively. Finally, we demonstrated the diversity between the datasets by employing Murcko's and the central scaffolds systems, calculating three fingerprint descriptors and analyzing their diversity by PCA and SOM. The optimized enumeration resulted in 1,610,268 compounds with NP-Likeness, and synthetic feasibility mean scores close to FDA, Non-FDA, and NPs datasets. The overlap between the chemical space of the 1.6 M database was more prominent than with the NPs dataset. A Laplacian score prioritized NP-likeness and hydrogen bond acceptor properties (1.0 and 0.923), respectively, while the Gini coefficient showed that all properties have selective effects on datasets (0.81-0.93). Scaffold and fingerprint diversity indicated that the descending order for the tested datasets was FDA, Non-FDA, NPs and 1.6 M. Virtual combinatorial libraries based on NPs can be considered as a source of the combinatorial compound with NP-likeness properties. Furthermore, measuring molecular diversity is supposed to be performed by different methods to allow for comparison and better judgment.
  3. Identification and optimization of TDP1 inhibitors from anthraquinone and chalcone derivatives: consensus scoring virtual screening and molecular simulations
    Moshawih S, Goh HP, Kifli N, Darwesh MAE, Ardianto C, Goh KW, et al.
    J Biomol Struct Dyn, 2023 Sep 11.
    PMID: 37697727 DOI: 10.1080/07391102.2023.2256870
    Virtual screening aims to identify and rank compounds with drug/lead-like properties based on their affinity for the protein target. We developed a methodology that integrates structure- and ligand-based screening approaches to enhance hit rates against the TDP1 protein within a database of anthraquinone and chalcone derivatives, followed by evaluation of prioritized compounds through molecular simulations. This technique is particularly useful for training set imbalances. Four screening methods were used: QSAR, pharmacophore, shape similarity, and docking. Each method was individually trained to score compounds, and the scores were fused to create parallel Z-score fusion. The QSAR models exhibited satisfactory R2 values (0.84 to 0.75), whereas the pharmacophoric and shape similarity models demonstrated excellent performance (ROC:0.82-0.88). Docking enrichment analysis identified 6N0D as the optimal TDP1 crystal structure (ROC = 0.73). Remarkably, the consensus scoring method surpassed other screening methods, achieving the highest ROC value of 0.98. Docking screening prioritized compounds with binding modes resembling the co-crystallized ligands, whereas MMGBSA, consensus, and docking produced dynamic simulations that were as stable as the co-crystallized ligands. Additionally, the QSAR-selected compounds exhibited binding modes similar to those of commercially available TDP1 inhibitors. In this study, a strong correlation was found between the inhibitory concentrations and binding energy values of commercialized TDP1 inhibitors, indicating that the top-ranked compounds are expected to have potent inhibitory effects in the nano-/micromolar range. The results of this study establish that consensus scoring can be used as an adaptable mainstay virtual screening methodology, pending subsequent experimental validation for affirmation.Communicated by Ramaswamy H. Sarma.
  4. Fulltext Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A protocol for systematic review
    Chua HM, Moshawih S, Goh HP, Ming LC, Kifli N
    PLoS One, 2023;18(9):e0290948.
    PMID: 37656730 DOI: 10.1371/journal.pone.0290948
    There is still unmet medical need in cancer treatment mainly due to drug resistance and adverse drug events. Therefore, the search for better drugs is essential. Computer-aided drug design (CADD) and discovery tools are useful to streamline the lengthy and costly drug development process. Anthraquinones are a group of naturally occurring compounds with unique scaffold that exert various biological properties including anticancer activities. This protocol describes a systematic review that provide insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment. It was prepared in accordance with the "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 guidelines, and published in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904). Search strategies will be developed based on the combination of relevant keywords and executed in PubMed, Scopus, Web of Science and MedRxiv. Only original studies that employed CADD as primary tool in virtual screening for the purpose of designing or discovering anti-cancer drugs involving anthraquinone scaffold published in English language will be included. Two independent reviewers will be involved to screen and select the papers, extract the data and assess the risk of bias. Apart from exploring the trends and types of CADD methods used, the target proteins of these compounds in cancer treatment will also be revealed in this review. It is believed that the outcome of this study could be utilized to support the ongoing research in similar area with better quality and greater probability of success, consequently optimizing the resources in subsequent in vitro, in vivo, non-clinical and clinical development. It will also serve as an evidence based scientific guide for new research to design novel anthraquinone-derived drug with improved efficacy and safety profile for cancer treatment.
  5. Fulltext Overcoming Chemoresistance via Extracellular Vesicle Inhibition
    Hayatudin R, Fong Z, Ming LC, Goh BH, Lee WL, Kifli N
    Front Mol Biosci, 2021;8:629874.
    PMID: 33842540 DOI: 10.3389/fmolb.2021.629874
    With the ever-growing number of cancer deaths worldwide, researchers have been working hard to identify the key reasons behind the failure of cancer therapies so the efficacy of those therapies may be improved. Based on extensive research activities and observations done by researchers, chemoresistance has been identified as a major contributor to the drastic number of deaths among cancer patients. Several factors have been linked to formation of chemoresistance, such as chemotherapy drug efflux, immunosuppression, and epithelial-mesenchymal transition (EMT). Lately, increasing evidence has shed light on the role of extracellular vesicles (EVs) in the regulation of chemoresistance. However, there is limited research into the possibility that inhibiting EV release or uptake in cancer cells may curb chemoresistance, allowing chemotherapy drugs to target cancer cells without restriction. Prominent inhibitors of EV uptake and release in cancer cells have been compiled and contrasted in this review. This is in the hope of sparking greater interest in the field of EV-mediated chemoresistance, as well as to provide an overview of the field for fundamental and clinical research communities, particularly in the field of cancer resistance research. In-depth studies of EV-mediated chemoresistance and EV inhibitors in cancer cells would spur significant improvement in cancer treatments which are currently available.
  6. Fulltext Multiple pathways are responsible for anti-inflammatory and cardiovascular activities of Hordeum vulgare L
    Gul S, Ahmed S, Kifli N, Uddin QT, Batool Tahir N, Hussain A, et al.
    J Transl Med, 2014;12:316.
    PMID: 25428431 DOI: 10.1186/s12967-014-0316-9
    Hordeum vulgare L. (HV or barley) is used by traditional healers to treat various inflammatory and cardiovascular diseases, without the knowledge of pharmacologic rationale behind its actions. This study was designed to explore the potential scientific mechanism(s) that could explain the use of Hordeum vulgare in traditional medicine as a treatment for various inflammatory and cardiovascular diseases.
  7. Fulltext Phytochemicals from Kaempferia angustifolia Rosc. and their cytotoxic and antimicrobial activities
    Tang SW, Sukari MA, Neoh BK, Yeap YS, Abdul AB, Kifli N, et al.
    Biomed Res Int, 2014;2014:417674.
    PMID: 25057485 DOI: 10.1155/2014/417674
    Phytochemical investigation on rhizomes of Kaempferia angustifolia has afforded a new abietene diterpene, kaempfolienol (1) along with crotepoxide (2), boesenboxide (3), 2'-hydroxy-4,4',6'-trimethoxychalcone (4), zeylenol (5), 6-methylzeylenol (6), (24S)-24-methyl-5α-lanosta-9(11), 25-dien-3β-ol (7), sucrose, β-sitosterol, and its glycoside (8). The structures of the compounds were elucidated on the basis of spectroscopic methods (IR, MS, and NMR). Isolation of 6-methylzeylenol (6), (24S)-24-methyl-5α-lanosta-9(11), 25-dien-3β-ol (7), and β-sitosterol-3-O-β-D-glucopyranoside (8) from this plant species has never been reported previously. The spectroscopic data of (7) is firstly described in this paper. Cytotoxic screening indicated that most of the pure compounds tested showed significant activity with (4) showing the most potent activity against HL-60 (human promyelocytic leukemia) and MCF-7 (human breast cancer) cell lines. However, all extracts and most of the pure compounds tested were found to be inactive against HT-29 (human colon cancer) and HeLa (human cervical cancer) cell lines. Similarly, none of the extracts or compounds showed activity in the antimicrobial testing.
  8. Fulltext Phytochemicals from Mangifera pajang Kosterm and their biological activities
    Ahmad S, Sukari MA, Ismail N, Ismail IS, Abdul AB, Abu Bakar MF, et al.
    BMC Complement Altern Med, 2015;15:83.
    PMID: 25887035 DOI: 10.1186/s12906-015-0594-7
    Mangifera pajang Kosterm is a plant species from the mango family (Anacardiaceae). The fruits are edible and have been reported to have high antioxidant content. However, the detailed phytochemical studies of the plant have not been reported previously. This study investigates the phytochemicals and biological activities of different parts of Mangifera pajang.
  9. Fulltext Cancer protective effects of plums: A systematic review
    Bahrin AA, Moshawih S, Dhaliwal JS, Kanakal MM, Khan A, Lee KS, et al.
    Biomed Pharmacother, 2022 Feb;146:112568.
    PMID: 34963086 DOI: 10.1016/j.biopha.2021.112568
    Plums is one of the most cultivated stone fruits due to its fast growing popularity. It has various traditionally recognized health benefits. There are two main commercial types of plums: the European plum (Prunus domestica) and the Japanese plum (Prunus salicina), each having many varieties. Researchers are gathering further evidence of pharmacological effects for plums by scientifically studying its anti-inflammatory, antioxidant properties. A systematic review analysing the literature related to the effects of plums on prevention and treatment of cancer is warranted. This is the first review examining the cancer-related effects of plums. Antioxidation properties of the active constituents of plum were also compared. Scopus, Google Scholar, PubMed, Medxriv and Cochrane Library databases, from their date of inception until July 2021 were utilized. The risk of bias was assessed using CONSORT checklist. A total of 6639 studies were screened and eventually only 54 studies were included. Full-text review of included studies revealed that plum extracts were rich in antioxidants. Overall, most of the studies that fulfilled the eligibility criteria were in vitro and a few clinical studies involving in vivo work. Therefore, it would be beneficial to perform more studies on animals or humans, to confirm that the result obtained from these in vitro studies are able to be extrapolated in a wider range of applications. Further clinical and in vivo studies are warranted to validate plums as a functional food for treatment and prevention of cancer.
  10. Fulltext Licorice: A Potential Herb in Overcoming SARS-CoV-2 Infections
    Ng SL, Khaw KY, Ong YS, Goh HP, Kifli N, Teh SP, et al.
    J Evid Based Integr Med, 2021;26:2515690X21996662.
    PMID: 33787349 DOI: 10.1177/2515690X21996662
    The management of the global pandemic outbreak due to the coronavirus disease (COVID-19) has been challenging with no exact dedicated treatment nor established vaccines at the beginning of the pandemic. Nonetheless, the situation seems to be better controlled with the recent COVID-19 vaccines roll-out globally as active immunisation to prevent COVID-19. The extensive usage and trials done in recent outbreak in China has shown the effectiveness of traditional Chinese Medicines (TCM) in improving the wellbeing of COVID-19 patients. Therefore, COVID-19 Prevention and Treatment guidelines has listed a number of recommended concoctions meant for COVID-19 patients. Licorice, more commonly known as Gancao in Chinese Pinyin, is known as one of the most frequently used ingredients in TCM prescriptions for treatment of epidemic diseases. Interestingly, it is deemed as food ingredient as well, where it is normally used in Western cuisines' desserts and sweets. The surprising fact that licorice appeared in the top 10 main ingredients used in TCM prescriptions in COVID-19 has drawn great attention from researchers in revealing its biological potential in overcoming this disease. To date, there are no comprehensive review on licorice and its benefits when used in COVID-19. Thus, in this current review, the possible benefits, mechanism of actions, safety and limitations of licorice were explored in hope to provide a quick reference guide for its preclinical and clinical experimental set-up in this very critical moment of pandemic.
  11. Fulltext Do Lipid-based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?
    Loh JS, Tan LKS, Lee WL, Ming LC, How CW, Foo JB, et al.
    Cancers (Basel), 2021 Oct 25;13(21).
    PMID: 34771511 DOI: 10.3390/cancers13215346
    Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.
  12. Fulltext Levofloxacin: Insights Into Antibiotic Resistance and Product Quality
    Izadi E, Afshan G, Patel RP, Rao VM, Liew KB, Meor Mohd Affandi MMR, et al.
    Front Pharmacol, 2019;10:881.
    PMID: 31474853 DOI: 10.3389/fphar.2019.00881
    Counterfeit and substandard medicines are recognized as one of serious threats to public health. The product quality of antibacterial medicine will compromise patients' recovery and increase the chance of antibacterial resistance. The review aims to provide a summary of low quality levofloxacin issues and the risk factors as well as suggesting the aspects of product quality that need to be regulated strictly. Quality of the active ingredient, levofloxacin, has an important role to contribute to successful therapy. The poor quality of raw material, directly and indirectly, causes treatment failure as the presence of insufficient dose, mislabeled content, and poor dissolution characteristics can lead to lower bioavailability. Identifying and reporting these factors can potentially help in improving the quality of drug marketed in various developing countries and may also reduce the incidences of treatment failure. Dissolution test is used for testing the dissolution profiles and the rate of drug release from solid formulation such as oral formulations, thus providing information regarding the in vivo performance of a formulation and its bioequivalence. On the other hand, quality-testing procedures are used for comparing the quality of products.
  13. Fulltext Mobile Health Apps on COVID-19 Launched in the Early Days of the Pandemic: Content Analysis and Review
    Ming LC, Untong N, Aliudin NA, Osili N, Kifli N, Tan CS, et al.
    JMIR Mhealth Uhealth, 2020 09 16;8(9):e19796.
    PMID: 32609622 DOI: 10.2196/19796
    BACKGROUND: Mobile health (mHealth) app use is a major concern because of the possible dissemination of misinformation that could harm the users. Particularly, it can be difficult for health care professionals to recommend a suitable app for coronavirus disease (COVID-19) education and self-monitoring purposes.

    OBJECTIVE: This study aims to analyze and evaluate the contents as well as features of COVID-19 mobile apps. The findings are instrumental in helping health care professionals to identify suitable mobile apps for COVID-19 self-monitoring and education. The results of the mobile apps' assessment could potentially help mobile app developers improve or modify their existing mobile app designs to achieve optimal outcomes.

    METHODS: The search for the mHealth apps available in the android-based Play Store and the iOS-based App Store was conducted between April 18 and May 5, 2020. The region of the App Store where we performed the search was the United States, and a virtual private network app was used to locate and access COVID-19 mobile apps from all countries on the Google Play Store. The inclusion criteria were apps that are related to COVID-19 with no restriction in language type. The basic features assessment criteria used for comparison were the requirement for free subscription, internet connection, education or advisory content, size of the app, ability to export data, and automated data entry. The functionality of the apps was assessed according to knowledge (information on COVID-19), tracing or mapping of COVID-19 cases, home monitoring surveillance, online consultation with a health authority, and official apps run by health authorities.

    RESULTS: Of the 223 COVID-19-related mobile apps, only 30 (19.9%) found in the App Store and 28 (44.4%) in the Play Store matched the inclusion criteria. In the basic features assessment, most App Store (10/30, 33.3%) and Play Store (10/28, 35.7%) apps scored 4 out of 7 points. Meanwhile, the outcome of the functionality assessment for most App Store apps (13/30, 43.3%) was a score of 3 compared to android-based apps (10/28, 35.7%), which scored 2 (out of the maximum 5 points). Evaluation of the basic functions showed that 75.0% (n=36) of the 48 included mobile apps do not require a subscription, 56.3% (n=27) provide symptom advice, and 41.7% (n=20) have educational content. In terms of the specific functions, more than half of the included mobile apps are official mobile apps maintained by a health authority for COVID-19 information provision. Around 37.5% (n=18) and 31.3% (n=15) of the mobile apps have tracing or mapping and home monitoring surveillance functions, respectively, with only 17% (n=8) of the mobile apps equipped with an online consultation function.

    CONCLUSIONS: Most iOS-based apps incorporate infographic mapping of COVID-19 cases, while most android-based apps incorporate home monitoring surveillance features instead of providing focused educational content on COVID-19. It is important to evaluate the contents and features of COVID-19 mobile apps to guide users in choosing a suitable mobile app based on their requirements.

  14. Fulltext Phytochemical and Therapeutic Potential of Citrus grandis (L.) Osbeck: A Review
    Anmol RJ, Marium S, Hiew FT, Han WC, Kwan LK, Wong AKY, et al.
    J Evid Based Integr Med, 2021 10 19;26:2515690X211043741.
    PMID: 34657477 DOI: 10.1177/2515690X211043741
    Citrus grandis or Citrus maxima, widely recognized as Pomelo is widely cultivated in many countries because of their large amounts of functional, nutraceutical and biological activities. In traditional medicine, various parts of this plant including leaf, pulp and peel are used for generations as they are scientifically proven to have therapeutic potentials and safe for human use. The main objective of this study was to review the different therapeutic applications of Citrus grandis and the phytochemicals associated with its medicinal values. In this article different pharmacological properties like antimicrobial, antitumor, antioxidant, anti-inflammatory, anticancer, antiepileptic, stomach tonic, cardiac stimulant, cytotoxic, hepatoprotective, nephroprotective, and anti-diabetic activities of the plant are highlighted. The enrichment of the fruit with flavonoids, polyphenols, coumarins, limonoids, acridone alkaloids, essential oils and vitamins mainly helps in exhibiting the pharmacological activities within the body. The vitamins enriched fruit is rich in nutritional value and also has minerals like calcium, phosphorous, sodium and potassium, which helps in maintaining the proper health and growth of the bones as well as the electrolyte balance of the body. To conclude, various potential therapeutic effects of Citrus grandis have been demonstrated in recent literature. Further studies on various parts of fruit, including pulp, peel, leaf, seed and it essential oil could unveil additional pharmacological activities which can be beneficial to the mankind.
  15. Fulltext Coriandrum sativum L.: A Review on Ethnopharmacology, Phytochemistry, and Cardiovascular Benefits
    Mahleyuddin NN, Moshawih S, Ming LC, Zulkifly HH, Kifli N, Loy MJ, et al.
    Molecules, 2021 Dec 30;27(1).
    PMID: 35011441 DOI: 10.3390/molecules27010209
    Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The cardiovascular benefits of C. sativum have not been summarized before, hence this review aims to further evaluate and discuss its effectiveness in cardiovascular diseases, according to the recent literature. An electronic search for literature was carried out using the following databases: PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews. Articles were gathered from the inception of the database until August 2021. Moreover, the traditional uses and phytochemistry of coriander were surveyed in the original resources and summarized. As a result, most of the studies that cover cardiovascular benefits and fulfilled the eligibility criteria were in vivo, while only a few were in vitro and clinical studies. In conclusion, C. sativum can be deemed a functional food due to its wide range of cardiovascular benefits such as antihypertensive, anti-atherogenic, antiarrhythmic, hypolipidemic as well as cardioprotective effects.
  16. Fulltext Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management
    Shaik Mohamed Sayed UF, Moshawih S, Goh HP, Kifli N, Gupta G, Singh SK, et al.
    Front Pharmacol, 2023;14:1182937.
    PMID: 37408757 DOI: 10.3389/fphar.2023.1182937
    Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.
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