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Glycyrrhiza uralensis is a traditional herbal medicine with significant bioactivity. This study investigated the effect of G. uralensis crude water extract (GU-CWE) on nitric oxide synthase 2 (NOS2) expression during myogenesis. GU-CWE treatment increased myoblast differentiation by downregulating NOS2 and upregulating myogenic regulatory factors (MYOD, MYOG, and MYH). Notably, this effect was supported by an observed decrease in NOS2 expression in the gastrocnemius tissues of mice treated with GU-CWE. In addition, GU-CWE treatment and NOS2 knockdown were associated with reductions in reactive oxygen species levels. We further elucidate the role of the NOS2 gene in myoblast differentiation, demonstrating that its role was expression dependent, being beneficial at low expression but detrimental at high expression. High NOS2 gene expression induced oxidative stress, whereas its low expression impaired myotube formation. These findings highlight that the modulation of NOS2 expression by G. uralensis can potentially be use for managing muscle wasting disorders.
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Licochalcone B (LicB), a chalcone derived from Glycyrrhiza uralensis and Glycyrrhiza glabra, has received considerable attention due to its diverse pharmacological properties. Accumulated data indicates that LicB has pharmacological effects that include anti-cancer, hepatoprotective, anti-inflammatory, and neuroprotective properties. The action mechanism of LicB has been linked to several molecular targets, such as phosphoinositide 3-kinase/Akt/mammalian target of rapamycin, p53, nuclear factor-κB, and p38, and the involvements of caspases, apoptosis, mitogen-activated protein kinase-associated inflammatory pathways, and anti-inflammatory nuclear factor erythroid 2-related factor 2 signaling pathways highlight the multifaceted therapeutic potential of LicB. This review systematically updates recent findings regarding the pharmacological effects of LicB, and the mechanistic pathways involved, and highlights the potential use of LicB as a promising lead compound for drug discovery.
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The study is a part of a student research project on performance-based evaluation of big data application in health sciences libraries. It presents a theoretical framework of the performance-based evaluation system for health institutes' libraries in the digital environment. The health sciences libraries' systematic approach was judged based on the five main components (data culture, organisational infrastructure, responsibilities, skills and technology competence) of big data analytics (BDA). A comprehensive literature review of the published studies was undertaken related to BDA, including the diffusion of innovation theory, and the theoretical background of the technology acceptance model to produce an application-based big data development framework for the health sciences libraries. The application-based evaluation model integrates BDA in health sciences libraries for improving library services and performance. The study proposed a need for skilled professionals with the knowledge and experience both professionally and technically. Finally, the study proposed a model that will help to measure the organisation's ability to analyse vast amounts of data to empirically validate the association concerning big data analysis and analytical practices in health libraries.
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Big Data , Bibliotecas Médicas , Humanos , Bibliotecas Médicas/tendências , Bibliotecas Médicas/organização & administraçãoRESUMO
This comprehensive analysis explores the rheological parameters and texture profile analysis (TPA) to effect starch solutions for mucoadhesion and assess the impact of micro-nanofibers (MNFs) on these parameters. The surface chemistry of all six samples was examined through the Fourier transform infrared (FTIR) technique. The spectrum of FTIR was recorded in the range of 500-4000 cm-1. The viscosity of different pHs (2-11) and temperatures (20-70 °C) of verious starches, potato, corn, and rice, decreased with the increasing of shear rate, exhibiting shear thinning behavior, which conformed to pseudoplastic fluid.The combination of chitosan and collagen MNFs significantly changed rheological properties, and the sample with the addtion of 1500 µL CC-MNF exhibited a greater viscosity of 59.8 mPa·s at a shear rate of 1.49 s-1. Potato starch emerged as a strong candidate for mucoadhesion due to its low hardness (4.62 ± 0.31 N), high adhesion (0.0322 ± 0.0053 mJ), cohesiveness (0.37 ± 0.03 Ratio), low chewiness (0.66 ± 0.12 mJ), and gumminess (1.69 ± 0.23 N). The inclusion of MNFs, especially collagen/chitosan MNFs showed the potential to further enhance adhesion.
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Quitosana , Nanofibras , Reologia , Amido , Amido/química , Viscosidade , Quitosana/química , Nanofibras/química , Adesividade , Soluções , Temperatura , Colágeno/química , Solanum tuberosum/químicaRESUMO
Skeletal muscle (SM) mass and strength maintenance are important requirements for human well-being. SM regeneration to repair minor injuries depends upon the myogenic activities of muscle satellite (stem) cells. However, losses of regenerative properties following volumetric muscle loss or severe trauma or due to congenital muscular abnormalities are not self-restorable, and thus, these conditions have major healthcare implications and pose clinical challenges. In this context, tissue engineering based on different types of biomaterials and scaffolds provides an encouraging means of structural and functional SM reconstruction. In particular, biomimetic (able to transmit biological signals) and several porous scaffolds are rapidly evolving. Several biological macromolecules/biomaterials (collagen, gelatin, alginate, chitosan, and fibrin etc.) are being widely used for SM regeneration. However, available alternatives for SM regeneration must be redesigned to make them more user-friendly and economically feasible with longer shelf lives. This review aimed to explore the biological aspects of SM regeneration and the roles played by several biological macromolecules and scaffolds in SM regeneration in cases of volumetric muscle loss.
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Materiais Biocompatíveis , Músculo Esquelético , Regeneração , Engenharia Tecidual , Alicerces Teciduais , Humanos , Materiais Biocompatíveis/química , Substâncias Macromoleculares/química , Músculo Esquelético/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
This article has focused on collagen-gelatin, the gelation process, as well as blend interaction between collagen/gelatin with various polysaccharides to boost mucoadhesion and gastric retention. The interaction between mucoadhesive materials and mucin layers is of significant interest in the development of drug delivery systems and biomedical applications for effective targeting and prolonged time in the gastrointestinal tract. This paper reviews the current advancement and mucoadhesive properties of collagen/gelatin and different polysaccharide complexes concerning the mucin layer and interactions are briefly highlighted. Collagen/gelatin and polysaccharide blends biocompatible and biodegradable, the complex biomolecules have shown encouraging mucoadhesive properties due to their cationic nature and ability to form hydrogen bonds with mucin glycoproteins. The mucoadhesion mechanism was attributed to the electrostatic interactions between the positively charged amino (NH2) groups of blend biopolymers and the negatively charged sialic acid residues present in mucin glycoprotein. At the end of this article, the encouraging prospect of collagen/polysaccharide complex and mucin glycoprotein is highlighted.
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Colágeno , Mucosa Gástrica , Gelatina , Polissacarídeos , Gelatina/química , Polissacarídeos/química , Colágeno/química , Humanos , Animais , Mucosa Gástrica/metabolismo , Mucinas/química , Mucinas/metabolismo , AdesividadeRESUMO
The interaction between mucoadhesive materials and mucin layers is of significant interest in the development of drug delivery systems and biomedical applications for effective targeting and prolonged stay in the gastrointestinal tract. In this article, the current advancement and mucoadhesive properties of chitosan concerning the stomach mucin layer and its interactions have been briefly addressed. Chitosan a biocompatible polysaccharide exhibited promising mucoadhesive properties attributed to its cationic nature and ability to establish bonds with mucin glycoproteins. The mucoadhesion mechanism is ascribed to the electrostatic interactions between the positively charged amino (NH2) groups of chitosan and the sialic acid residues in mucin glycoprotein which carry a negative charge. The article provides a succinct overview of prior uses, current trends, and recent advancements in chitosan-based gastric-targeted delivery systems. We look forward to further innovations and emerging research related to chitosan-based methods of delivery that may increase the chitosan suitability for use in novel therapeutic approaches.
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Quitosana , Mucinas Gástricas , Quitosana/química , Sistemas de Liberação de Medicamentos , EstômagoRESUMO
Cultured meat (CM) is an alternative protein food and is produced by cultivating muscle satellite (stem) cells (MSCs) derived from livestock animals (bovine, chickens, and porcine) through myogenesis leading to generate muscle mass. Myostatin (MSTN) is well well-known negative regulator of myogenesis, and in the present study, in silico screening of natural compounds was performed to identify MSTN inhibitors. Interestingly, quercetin was found to inhibit MSTN (binding energy -7.40 kcal/mol), and this was further validated by a 100 ns molecular dynamics simulation. Quercetin was added to culture media to boost myogenesis, and its potent antioxidant property helped maintain media pH. Furthermore, quercetin increased the myotube thickness and length, increased MSC differentiation, and upregulated the gene and protein expressions of myoblast determination protein 1 (MYOD), Myogenin (MYOG), and Myosin heavy chains (MYH) in vitro. In addition, quercetin inhibited the activities of MSTN, activin receptor type-2B (ACVR2B), and SMAD2 and 3, and thus significantly enhanced MSC differentiation and myotube formation. Overall, this study shows that quercetin might be useful for enhancing large-scale CM production. It is hoped that this study provides a starting point for research in the CM area aimed to enhancing product quality, nutritional values, and the efficacy of large-scale production.
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BACKGROUND: Myostatin (MSTN) inhibition has demonstrated promise for the treatment of diseases associated with muscle loss. In a previous study, we discovered that Glycyrrhiza uralensis (G. uralensis) crude water extract (CWE) inhibits MSTN expression while promoting myogenesis. Furthermore, three specific compounds of G. uralensis, namely liquiritigenin, tetrahydroxymethoxychalcone, and Licochalcone B (Lic B), were found to promote myoblast proliferation and differentiation, as well as accelerate the regeneration of injured muscle tissue. PURPOSE: The purpose of this study was to build on our previous findings on G. uralensis and demonstrate the potential of its two components, Licochalcone A (Lic A) and Lic B, in muscle mass regulation (by inhibiting MSTN), aging and muscle formation. METHODS: G. uralensis, Lic A, and Lic B were evaluated thoroughly using in silico, in vitro and in vivo approaches. In silico analyses included molecular docking, and dynamics simulations of these compounds with MSTN. Protein-protein docking was carried out for MSTN, as well as for the docked complex of MSTN-Lic with its receptor, activin type IIB receptor (ACVRIIB). Subsequent in vitro studies used C2C12 cell lines and primary mouse muscle stem cells to acess the cell proliferation and differentiation of normal and aged cells, levels of MSTN, Atrogin 1, and MuRF1, and plasma MSTN concentrations, employing techniques such as western blotting, immunohistochemistry, immunocytochemistry, cell proliferation and differentiation assays, and real-time RT-PCR. Furthermore, in vivo experiments using mouse models focused on measuring muscle fiber diameters. RESULTS: CWE of G. uralensis and two of its components, namely Lic A and B, promote myoblast proliferation and differentiation by inhibiting MSTN and reducing Atrogin1 and MuRF1 expressions and MSTN protein concentration in serum. In silico interaction analysis revealed that Lic A (binding energy -6.9 Kcal/mol) and B (binding energy -5.9 Kcal/mol) bind to MSTN and reduce binding between it and ACVRIIB, thereby inhibiting downstream signaling. The experimental analysis, which involved both in vitro and in vivo studies, demonstrated that the levels of MSTN, Atrogin 1, and MuRF1 were decreased when G. uralensis CWE, Lic A, or Lic B were administered into mice or treated in the mouse primary muscle satellite cells (MSCs) and C2C12 myoblasts. The diameters of muscle fibers increased in orally treated mice, and the differentiation and proliferation of C2C12 cells were enhanced. G. uralensis CWE, Lic A, and Lic B also promoted cell proliferation in aged cells, suggesting that they may have anti-muslce aging properties. They also reduced the expression and phosphorylation of SMAD2 and SMAD3 (MSTN downstream effectors), adding to the evidence that MSTN is inhibited. CONCLUSION: These findings suggest that CWE and its active constituents Lic A and Lic B have anti-mauscle aging potential. They also have the potential to be used as natural inhibitors of MSTN and as therapeutic options for disorders associated with muscle atrophy.
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Chalconas , Fibras Musculares Esqueléticas , Miostatina , Camundongos , Animais , Miostatina/metabolismo , Simulação de Acoplamento Molecular , Diferenciação Celular , Fibras Musculares Esqueléticas/metabolismo , Proliferação de Células , Músculo Esquelético/metabolismoRESUMO
Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.
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Petrochemical-based synthetic plastics poses a threat to humans, wildlife, marine life and the environment. Given the magnitude of eventual depletion of petrochemical sources and global environmental pollution caused by the manufacturing of synthetic plastics such as polyethylene (PET) and polypropylene (PP), it is essential to develop and adopt biopolymers as an environment friendly and cost-effective alternative to synthetic plastics. Research into bioplastics has been gaining traction as a way to create a more sustainable and eco-friendlier environment with a reduced environmental impact. Biodegradable bioplastics can have the same characteristics as traditional plastics while also offering additional benefits due to their low carbon footprint. Therefore, using organic waste from biological origin for bioplastic production not only reduces our reliance on edible feedstock but can also effectively assist with solid waste management. This review aims at providing an in-depth overview on recent developments in bioplastic-producing microorganisms, production procedures from various organic wastes using either pure or mixed microbial cultures (MMCs), microalgae, and chemical extraction methods. Low production yield and production costs are still the major bottlenecks to their deployment at industrial and commercial scale. However, their production and commercialization pose a significant challenge despite such potential. The major constraints are their production in small quantity, poor mechanical strength, lack of facilities and costly feed for industrial-scale production. This review further explores several methods for producing bioplastics with the aim of encouraging researchers and investors to explore ways to utilize these renewable resources in order to commercialize degradable bioplastics. Challenges, future prospects and Life cycle assessment of bioplastics are also highlighted. Utilizing a variety of bioplastics obtained from renewable and cost-effective sources (e.g., organic waste, agro-industrial waste, or microalgae) and determining the pertinent end-of-life option (e.g., composting or anaerobic digestion) may lead towards the right direction that assures the sustainable production of bioplastics.
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Compostagem , Plásticos , Humanos , Biopolímeros/química , Tecnologia , Resíduos IndustriaisRESUMO
Ginseng is usually consumed as a daily food supplement to improve health and has been shown to benefit skeletal muscle, improve glucose metabolism, and ameliorate muscle-wasting conditions, cardiovascular diseases, stroke, and the effects of aging and cancers. Ginseng has also been reported to help maintain bone strength and liver (digestion, metabolism, detoxification, and protein synthesis) and kidney functions. In addition, ginseng is often used to treat age-associated neurodegenerative disorders, and ginseng and ginseng-derived natural products are popular natural remedies for diseases such as diabetes, obesity, oxidative stress, and inflammation, as well as fungal, bacterial, and viral infections. Ginseng is a well-known herbal medication, known to alleviate the actions of several cytokines. The article concludes with future directions and significant application of ginseng compounds for researchers in understanding the promising role of ginseng in the treatment of several diseases. Overall, this study was undertaken to highlight the broad-spectrum therapeutic applications of ginseng compounds for health management.
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Diabetes Mellitus , Doenças Neurodegenerativas , Panax , Humanos , Obesidade , Inflamação/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
The enzyme dipeptidyl peptidase 4 (DPP4) is a potential therapeutic target for type 2 diabetes (T2DM). Many synthetic anti-DPP4 medications are available to treat T2DM. The need for secure and efficient medicines has been unmet due to the adverse side effects of existing DPP4 medications. The present study implemented a combined approach to machine learning and structure-based virtual screening to identify DPP4 inhibitors. Two ML models were trained based on DPP4 IC50 datasets. The ML models random forest (RF) and multilayer perceptron (MLP) neural network showed good accuracy, with the area under the curve being 0.93 and 0.91, respectively. The natural compound library was screened through ML models, and 1% (217) of compounds were selected for further screening. Structure-based virtual screening was performed along with positive control sitagliptin to obtain more specific and selective leads for DPP4. Based on binding affinity, drug-likeness properties, and interaction with DPP4, Z-614 and Z-997 compounds showed high binding affinity and specificity in the catalytic pocket of DPP4. Finally, the stability conformation of the DPP4 enzyme complex was checked by a molecular dynamics (MD) simulation. The MD simulation showed that both compounds bind better in the catalytic pocket, but the Z-614 compound altered the DPP4 native conformation. Therefore, Z-614 showed a high deviation in the backbone. This combined approach (ML and structure-based) study reported that Z-997 binds most stably to DPP4 in their catalytic pocket with a binding free energy of -70.3 kJ/mol, suggesting its therapeutic potential as a treatment option for T2DM disease.Communicated by Ramaswamy H. Sarma.
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Androgenic alopecia (AGA) is a dermatological disease with psychosocial consequences for those who experience hair loss. AGA is linked to an increase in androgen levels caused by an excess of dihydrotestosterone in blood capillaries produced from testosterone by 5α-reductase type II (5αR2), which is expressed in scalp hair follicles; 5αR2 activity and dihydrotestosterone levels are elevated in balding scalps. The diverse health benefits of flavonoids have been widely reported in epidemiological studies, and research interest continues to increase. In this study, a virtual screening approach was used to identify compounds that interact with active site residues of 5αR2 by screening a library containing 241 flavonoid compounds. Here, we report two potent flavonoid compounds, eriocitrin and silymarin, that interacted strongly with 5αR2, with binding energies of -12.1 and -11.7 kcal/mol, respectively, which were more significant than those of the control, finasteride (-11.2 kcal/mol). Molecular dynamic simulations (200 ns) were used to optimize the interactions between compounds and 5αR2 and revealed that the interaction of eriocitrin and silymarin with 5αR2 was stable. The study shows that eriocitrin and silymarin provide developmental bases for novel 5αR2 inhibitors for the management of AGA.
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Lumpy skin disease (LSD) is a contagious viral transboundary disease listed as a notifiable disease by the World Organization of Animal Health (WOAH). The first case of this disease was reported in Pakistan in late 2021. Since then, numerous outbreaks have been documented in various regions and provinces across the country. The current study primarily aimed to analyze samples collected during LSD outbreaks in cattle populations in the Sindh and Punjab provinces of Pakistan. Phylogenetic analysis was conducted using partial sequences of the GPCR, p32, and RP030 genes. Collectively, the LSDV strains originating from outbreaks in Pakistan exhibited a noticeable clustering pattern with LSDV strains reported in African, Middle Eastern, and Asian countries, including Egypt, the Kingdom of Saudi Arabia, India, China, and Thailand. The precise reasons behind the origin of the virus strain and its subsequent spread to Pakistan remain unknown. This underscores the need for further investigations into outbreaks across the country. The findings of the current study can contribute to the establishment of effective disease control strategies, including the implementation of a mass vaccination campaign in disease-endemic countries such as Pakistan.
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Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Surtos de Doenças/veterinária , Doença Nodular Cutânea/epidemiologia , Vírus da Doença Nodular Cutânea/genética , Paquistão/epidemiologia , FilogeniaRESUMO
BACKGROUND: Cellulase is an important bioprocessing enzyme used in various industries. This study was conducted with the aim of improving the biodegradation activity of cellulase obtained from the Bacillus subtilis AG-PQ strain. For this purpose, AgO and FeO NPs were fabricated using AgNO3 and FeSO4·7H2O salt respectively through a hydro-thermal method based on five major steps; selection of research-grade materials, optimization of temperature, pH, centrifuge, sample washed with distilled water, dry completely in the oven at the optimized temperature and finally ground for characterization. The synthesized NPs were characterized by scanning electron microscope (SEM), energy dispersive X-ray (EDX), and X-ray diffraction (XRD) to confirm the morphology, elemental composition, and structure of the sample respectively. The diameter of the NPs was recorded through SEM which lay in the range of 70-95 nm. RESULTS: Cultural parameters were optimized to achieve better cellulase production, where incubation time of 56 h, inoculum size of 5%, 1% coconut cake, 0.43% ammonium nitrate, pH 8, and 37 °C temperature were found optimal. The enhancing effect of AgO NPs was observed on cellulase activity (57.804 U/ml/min) at 50 ppm concentration while FeO NPs exhibited an inhibitory effect on cellulase activity at all concentrations. Molecular docking analysis was also performed to understand the underlying mechanism of improved enzymatic activity by nanocatalysts. CONCLUSION: This study authenticates AgO NPs as better nanocatalysts for improved thermostable cellulase biodegradation activity with the extraordinary capability to be potentially utilized in bioethanol production.
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The regenerative ability of skeletal muscle (SM) in response to damage, injury, or disease is a highly intricate process that involves the coordinated activities of multiple cell types and biomolecular factors. Of these, extracellular matrix (ECM) is considered a fundamental component of SM regenerative ability. This review briefly discusses SM myogenesis and regeneration, the roles played by muscle satellite cells (MSCs), other cells, and ECM components, and the effects of their dysregulations on these processes. In addition, we review the various types of ECM scaffolds and biomaterials used for SM regeneration, their applications, recent advances in ECM scaffold research, and their impacts on tissue engineering and SM regeneration, especially in the context of severe muscle injury, which frequently results in substantial muscle loss and impaired regenerative capacity. This review was undertaken to provide a comprehensive overview of SM myogenesis and regeneration, the stem cells used for muscle regeneration, the significance of ECM in SM regeneration, and to enhance understanding of the essential role of the ECM scaffold during SM regeneration.
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Skeletal muscle (SM) plays a vital role in energy and glucose metabolism by regulating insulin sensitivity, glucose uptake, and blood glucose homeostasis. Impaired SM metabolism is strongly linked to several diseases, particularly type 2 diabetes (T2D). Insulin resistance in SM may result from the impaired activities of insulin receptor tyrosine kinase, insulin receptor substrate 1, phosphoinositide 3-kinase, and AKT pathways. This review briefly discusses SM myogenesis and the critical roles that SM plays in insulin resistance and T2D. The pharmacological targets of T2D which are associated with SM metabolism, such as DPP4, PTB1B, SGLT, PPARγ, and GLP-1R, and their potential modulators/inhibitors, especially natural compounds, are discussed in detail. This review highlights the significance of SM in metabolic disorders and the therapeutic potential of natural compounds in targeting SM-associated T2D targets. It may provide novel insights for the future development of anti-diabetic drug therapies. We believe that scientists working on T2D therapies will benefit from this review by enhancing their knowledge and updating their understanding of the subject.