Potential Of Natural Products Research Articles

Investigating Potential Anti-Bacterial Natural Products Based on Ayurvedic Formulae Using Supervised Network Analysis and Machine Learning Approaches

Objectives: This study implements a multi-dimensional methodology to systematically identify potential natural antibiotics derived from the medicinal plants utilized in Ayurvedic practices. Methods: Two primary analytical techniques are employed to explore the antibiotic potential of the medicinal plants. The initial approach utilizes a supervised network analysis, which involves the application of distance measurement algorithms to scrutinize the interconnectivity and relational patterns within the network derived from Ayurvedic formulae. Results: 39 candidate plants with potential natural antibiotic properties were identified. The second approach leverages advanced machine learning techniques, particularly focusing on feature extraction and pattern recognition. This approach yielded a list of 32 plants exhibiting characteristics indicative of natural antibiotics. A key finding of this research is the identification of 17 plants that were consistently recognized by both analytical methods. These plants are well-documented in existing literature for their antibacterial properties, either directly or through their bioactive compounds, which suggests a strong validation of the study’s methodology. By synergizing network analysis with machine learning, this study provides a rigorous and multi-faceted examination of Ayurvedic medicinal plants, significantly contributing to the identification of natural antibiotic candidates. Conclusions: This research not only reinforces the potential of traditional medicine as a source for new therapeutics but also demonstrates the effectiveness of combining classical and contemporary analytical techniques to explore complex biological datasets.

MicroRNA dynamics, PTEN/PI3K/AKT signaling, and their relationship to breast cancer: prospects for pharmaceuticals and natural product application.

Globally, Breast Cancer (BC) is the most frequent cancer in women and has a major negative impact on the physical and emotional well-being of its patients as well as one of the most common cancers to be diagnosed. Numerous studies have been published to identify various molecular pathways, including PI3K/AKT/PTEN. Moreover, growing evidence suggests that miRNAs have been found to play a vital role in the growth and carcinogenesis of tumors. Because of their crucial in the development and course of the illness, all other molecular variables, molecular pathways and microRNAs have gained recognition as important therapeutic targets in BC due to growing interest among researchers in utilizing synthetic drugs and natural products to target these signaling pathway with encouraging outcomes in vivo, in vitro and preclinical trials in recent years. We searched PUBMED, Science Direct, google scholar, Embase and Scopus for article published from the inception of each database to May 30, 2024. We discussed PI3K/PTEN/AKT signaling pathway and microRNA activities with breast cancer cell line. In addition, this review covered a wide range of potential drug and natural products as targeted therapies that are linked to downregulating ER-α expression and activity, inhibiting proliferation, migration, metastasis and angiogenesis, inducing apoptosis, cell cycle arrest and sensitizing breast cancer cells. Many studies have been conducted, but as of right now, there are not enough articles to fully explain the treatment and research of breast cancer. We also need more and more studies on breast cancer from a variety of perspectives. Future scientist will find it easier to consider breast cancer treatment after reading this article presentation. So, the review focuses on our understanding of the roles that microRNA and PI3/PTEN/AKT signaling pathways play in regulating BC. Furthermore, we emphasized the potential therapeutic benefits of newly discovered inhibitors and the use of natural compounds in alone or combinations during preclinical trials.

Diabetic Wound Healing: Factors, Mechanisms, and Treatment Strategies Using Herbal Components.

Managing diabetic wounds is a significant challenge for healthcare professionals since severe complications and delayed recovery greatly impact the patients' quality of life. This article aimed to explore various factors affecting diabetic wound healing, the mechanism of wound healing, and potential natural products having wound healing capability. It focuses on mechanisms of action and the therapeutic effectiveness of the compounds employed in the management of diabetic wounds. The review discusses the function of nutrition in wound healing, emphasizing the significance of consuming adequate amounts of protein, energy, lipids, amino acids, vitamins, minerals, and water to promote healing. Several herbs, including Rosmarinus officinalis, Carica papaya, Aloe vera, Annona squamosa, and Punica granatum, are being tested for wound healing qualities in diabetes circumstances. These plants have a variety of modes of action, including antioxidant, anti-inflammatory, antibacterial, and immunomodulatory activities that help to speed up wound healing, stimulate collagen formation, and promote tissue regeneration. The variety of action mechanisms seen in natural products, especially in plants, offers hope for the treatment of diabetic wounds. It may also be possible to improve healing results and the quality of life of diabetes individuals with chronic wounds by including these herbal treatments in wound care programs.

Identification of potential natural product inhibitors against the Mpro enzyme of Covid-19: a computational study

Identification of potential natural product inhibitors against the Mpro enzyme of Covid-19: a computational study

Identification of Potential Inhibitors of TGFβR1 for the Treatment of Cancer through Structure-Based Virtual Screening and Molecular Dynamics Simulations.

Globally, cancer is one of the leading causes of death. Resistance to conventional medications, such as chemotherapy and radiation, continues to be a significant challenge in the treatment of cancer despite the availability of numerous medicines. Therefore, the highest priority is to hunt for new therapeutic agents. Transforming growth factor-beta is a pivotal regulatory cytokine that exerts significant influence over cellular processes, particularly emphasizing its role in facilitating and modulating cell proliferation. TGF-β receptor 1, identified as the most promising active site of the TGF-β signaling, is a potent drug target site that has garnered wide attention for developing new anticancer agents. The present investigation investigates the potential natural products as TGFβR1 inhibitors. The SB431542 complexed TGFβR1 protein model was used to screen the natural product database to obtain a compound with high binding potential. NPC247629 has emerged as the best-scored compound among all the screened compounds, demonstrating the highest affinity towards the TGFβR1 regarding docking score -17.54 kcal/mol. The all-atoms MD simulation study indicated that all proposed hits are retained inside the receptor in dynamic states. Additionally, principal component and free energy landscape analysis were performed to explore the binding mechanism of top-hit natural products. The best-screened hits, NPC247629 and NPC60735, have excellent binding affinity and hold a massive potential for TGFβR1 inhibition, paving the way for promising future investigations in cancer treatment.

Commentary on the Obtention of Semi-Synthetic Derivatives from Natural Products for Medicinal Applications: Advances, Challenges, and Perspectives.

Plants have historically been a primary source of medicines due to their diverse molecular and structural composition. Plant metabolism, comprising primary and secondary processes, produces primary metabolites crucial for growth and secondary metabolites, or natural products (NPs), with specific biological functions. These small molecules are instrumental in pharmacology for their ability to penetrate biological barriers and interact with intracellular targets. The structural complexity and limited availability of NPs have led to research focusing on enhancing their diversity through semi-synthesis. In this commentary, examples of various semisynthetic derivatives of NPs obtained through different synthetic strategies, such as organic semi-synthesis or combinatorial chemistry, are cited. Additionally, the importance of developing hybrid molecules based on the combination of two or more distinct pharmacophores is emphasized. This strategy has been widely implemented to obtain new multitarget drugs applicable to the treatment of multifactorial neurodegenerative diseases, where stimulating the cholinergic system by modulating different therapeutic targets is crucial. However, challenges, such as structural complexity, raw material availability, and the need for precise synthetic methods, persist. Innovations in synthetic routes, sustainable harvesting, and biotechnological advances are critical to overcoming these barriers. The integration of omics technologies, green chemistry principles, and global collaboration is essential to maximize the potential of NPs in drug development, ensuring sustainable and efficient production of new therapeutics.

MetaCGRP is a high-precision meta-model for large-scale identification of CGRP inhibitors using multi-view information

Migraine is considered one of the debilitating primary headache conditions with an estimated worldwide occurrence of approximately 14–15%, contributing highly to factors responsible for global disability. Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays a crucial role in the pathophysiology of migraines and thus, its inhibition can help relieve migraine symptoms. However, conventional process of CGRP drug development has been laborious and time-consuming with incurred costs exceeding one billion dollars. On the other hand, machine learning (ML)-based approaches that are capable of accurately identifying CGRP inhibitors could greatly facilitate in expediting the discovery of novel CGRP drugs. Therefore, this study proposes a novel and high-accuracy meta-model, namely MetaCGRP, that can precisely identify CGRP inhibitors. To the best of our knowledge, MetaCGRP is the first SMILES-based approach that has been developed to identify CGRP inhibitors without the use of 3D structural information. In brief, we initially employed different molecular representation methods coupled with popular ML algorithms to construct a pool of baseline models. Then, all baseline models were optimized and used to generate multi-view features. Finally, we employed the feature selection method to optimize the multi-view features and determine the best feature subset to enable the construction of the meta-model. Both cross-validation and independent tests indicated that MetaCGRP clearly outperforms several conventional ML classifiers, with accuracies of 0.898 and 0.799 on the training and independent test datasets, respectively. In addition, MetaCGRP in conjunction with molecular docking was utilized to identify five potential natural product candidates from Thai herbal pharmacopoeia and analyze their binding affinity and interactions to CGRP. To facilitate community-wide efforts in expediting the discovery of novel CGRP inhibitors, a user-friendly web server for MetaCGRP is freely available at https://pmlabqsar.pythonanywhere.com/MetaCGRP.

Effect of the exposure period and concentration of aqueous and alcoholic zingiber (Zingiber officinale) extract on the mean of mortality for hydatid cyst's protocolises.

To determine the anti-protocolises effect of aqueous and alcoholic zingiber extract. The present experimental study was conducted from 01, July 2021 to 15. December, 2021 at the College of Education for Pure Sciences, Iraq, and comprised 25mg/mL, 50mg/mL, 100mg/mL and 200mg/mL concentrations of both aqueous and alcoholic extracts of zingiber officinale that were prepared and used in vitro on hydatid cyst protocolises with 10min, 20min, 30min, 40min, 50min and 60min exposure times. The data was analysed using statistical package for the social sciences (SPSS) version 10 by using ANOVA and t- test to determine the differences between groups. The concentration of 200mg/ml was more efficient against the protocolises for aqueous extract, while the alcoholic extract was effective at both 100mg/ml and 200mg/ml concentrations. There was a positive relationship of the degree of killing with both exposure time and concentration. Zingiber officinale could be a potential bioactive natural product and its active constituents could be isolated and used as anti-protoscolex without any side effects.

Triple negative breast cancer migration is modified by mitochondrial metabolism alteration induced by natural extracts of C. spinosa and P. alliacea

Tumor metabolism is a crucial aspect of cancer development, and mitochondria plays a significant role in the aggressiveness and metastasis of tumors. As a result, mitochondria have become a promising therapeutic target in cancer treatment, leading to the development of compounds known as mitocans. In our group, we have consolidated the search of anticancer therapies based on natural products derived from plants, obtaining extracts such as P2Et from Caesalpinia spinosa and Anamu-SC from Petiveria alliacea, which have been shown to have antitumor activities in different cancer models. These extracts, due to their complex molecular composition, can interfere with multiple functions during tumor progression. To better understand how these natural products operate (P2Et and Anamu-SC), we constructed a model using 4T1 murine breast cancer cells with reduced expression of genes associated with glycolysis (Hexokinase-2) and mitochondrial function (Cqbp). The results indicate that the cells were more sensitive to the Anamu-SC extract, showing significant decreases in glucose consumption, ATP production, and oxygen consumption rate. Additionally, we observed changes in mitochondrial function, which reduced the cells’ ability to migrate, particularly when C1qbp was silenced. This triple-negative breast cancer model allows us to identify potential natural products that can modulate tumor cell metabolism.

Integrative Network Pharmacology Unveils Limonia acidissima as a Potential Natural Product for Targeting Cancer

Cancer remains a formidable health challenge worldwide, with complex molecular mechanisms driving its initiation, progression, and therapeutic resistance. In this study, we employed bioinformatics analyses to elucidate the molecular underpinnings of cancer biology, focusing on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Our GO analysis revealed the enrichment of key biological processes such as protein phosphorylation, regulation of programmed cell death, and transmembrane receptor signaling pathways, underscoring the critical roles of signaling cascades and regulatory mechanisms in tumorigenesis. Similarly, molecular functions such as protein kinase activity and ATP binding were identified as significantly enriched, highlighting the importance of protein kinases and molecular interactions in cancer development and progression. The KEGG pathway analysis further delineated dysregulated signaling pathways associated with cancer, including the MAPK and PI3K-Akt signaling pathways, implicating these pathways as central regulators of cancer progression. These findings deepen our understanding of cancer biology and offer potential targets for therapeutic intervention. Integrating multi-omics data and systems biology approaches may provide deeper insights into the intricate networks underlying cancer pathogenesis, paving the way for developing more effective treatments for cancer patients.

Metabolic engineering of artificially modified transcription factor SmMYB36-VP16 for high-level production of tanshinones and phenolic acids

Tanshinones and phenolic acids are the two main chemical constituents in Salvia miltiorrhiza, which are used clinically for the treatment of hypertension, coronary heart disease, atherosclerosis, and many other diseases, and have broad medicinal value. The efficient synthesis of the target products of these two metabolites in isolated plant tissues cannot be achieved without the regulation and optimization of metabolic pathways, and transcription factors play an important role as common regulatory elements in plant tissue metabolic engineering. However, most of the regulatory effects are specific to one class of metabolites, or an opposing regulation of two classes of metabolites exists. In this study, an artificially modified transcription factor, SmMYB36-VP16, was constructed to enhance tanshinones and phenolic acids in Salvia miltiorrhiza hair roots simultaneously. Further in combination with the elicitors dual-screening technique, by applying the optimal elicitors screened, the tanshinones content in the transgenic hairy roots of Salvia miltiorrhiza reached 6.44 mg/g DW, which was theoretically 6.08-fold that of the controls without any treatment, and the content of phenolic acids reached 141.03 mg/g DW, which was theoretically 5.05-fold that of the controls without any treatment. The combination of artificially modified transcriptional regulatory and elicitors dual-screening techniques has facilitated the ability of plant isolated tissue cell factories to produce targeted medicinal metabolites. This strategy could be applied to other species, laying the foundation for the production of potential natural products for the medicinal industry.

Therapeutic Potential of Rosa davurica Pall. Root Extract as an Antidiabetic Agent: A Comprehensive Analysis from Molecular Mechanisms to In Vivo Efficacy.

Rosa davurica Pall. is widely used in traditional oriental herbal therapy, but its components and molecular mechanisms of action remain unclear. This study investigates the antidiabetic potential of Rosa davurica Pall. root extract (RDR) and elucidates its underlying molecular mechanisms with in vitro and in vivo models. Data from the current study show that RDR exhibits strong antioxidant activity and glucose homeostasis regulatory effects. It significantly impacts glucose homeostasis in C2C12 skeletal muscle cells by inhibiting α-glucosidase activity. Further molecular mechanistic studies revealed that RDR promoted glucose uptake by phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC), but not Phosphatidylinositol 3-kinase (PI 3-kinase)/Akt in C2C12 skeletal muscle cells. These actions increased the expression and translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. In addition, RDR treatment in the STZ-induced diabetic rats remarkably improved the low body weight, polydipsia, polyphagia, hyperglycemia, and islet architecture and increased the insulin/glucose ratio. The liver (ALT and AST) and kidney marker enzyme (BUN and creatinine) levels were restored by RDR treatment as well. Phytochemical analysis identified eight major constituents in RDR, crucial for its antioxidant and antidiabetic activity. Through the molecular docking of representative glucose transporter GLUT4 with these compounds, it was confirmed that the components of RDR had a significantly high binding score in terms of structural binding. These findings from the current study highlight the antidiabetic effects of RDR. Collectively, our data suggest that RDR might be a potential pharmaceutical natural product for diabetic patients.

Potential skin anti-aging effects of main phenolic compounds, tremulacin and tremuloidin from Salix chaenomeloides leaves on TNF-α-stimulated human dermal fibroblasts

The genus Salix spp. has long been recognized as a healing herb for its use in treating fever, inflammation, and pain relief, as well as a food source for its nutritional value. In this study, we aimed to explore the potential bioactive natural products in the leaves of Salix chaenomeloides, commonly known as Korean pussy willow, for their protective effects against skin damage, including aging. Utilizing LC/MS-guided chemical analysis of the ethanol extract of S. chaenomeloides leaves, with a focus on major compounds, we successfully isolated two main phenolic compounds, tremulacin (1) and tremuloidin (2). Subsequently, we investigated the protective effects of tremulacin (1) and tremuloidin (2) in TNF-α-stimulated human dermal fibroblasts (HDFs). The results revealed that both tremulacin (1) and tremuloidin (2) inhibited TNF-α-stimulation-induced ROS, suppressed matrix metalloproteinase-1 (MMP-1) expression, and enhanced collagen secretion. This implies that both tremulacin (1) and tremuloidin (2) hold promise as preventive agents against photoaging-induced skin aging. Furthermore, we assessed the activity of mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and heme oxygenase 1 (HO-1) to elucidate the mechanism of photoaging inhibition by tremuloidin (2), which exhibited superior efficacy. We found that tremuloidin (2) inhibited ERK and p38 phosphorylation and notably suppressed COX-2 expression while significantly upregulating HO-1 expression. These findings suggest potent anti-inflammatory and antioxidant properties of tremuloidin (2), positioning it as a potential candidate for combating photoaging-induced skin aging.

Identification of potential natural product derivatives as CK2 inhibitors based on GA-MLR QSAR modeling, synthesis and biological evaluation

Identification of potential natural product derivatives as CK2 inhibitors based on GA-MLR QSAR modeling, synthesis and biological evaluation

Improvement of glucolipid metabolism and oxidative stress via modulating PI3K/Akt pathway in insulin resistance HepG2 cells by chickpea flavonoids

Chickpea (Cicer arietinum L.) is a significant dietary source of flavonoids and the hypoglycemic activity were investigated in this study. Firstly, total twenty nine chickpea flavonoids were identified by UPLC-MS/MS with ononin, cyanidin-3-O-glucoside, astragalin, cynaroside, kaempferol-3-O-rutinoside, biochanin A, and daidzin being the most abundant among them. Our results demonstrated that chickpea flavonoids regulated glucose metabolism and lipid metabolism, and reduced oxidative stress in insulin resistance HepG2 cells. Furthermore, insulin resistance was ameliorated by chickpea flavonoids through the activation of insulin receptor substrate1 (IRS1), phosphoinositide 3-kinase (PI3K), and phosphorylated protein kinase B (Akt) in HepG2 cells. More importantly, key differential metabolites include L-tryptophan, L-tyrosine, l-glutamine and linoleic acid were reserved by chickpea flavonoids and correlated with glucolipid metabolism and oxidative stress in IR-HepG2 cells. In conclusion, these results indicated that chickpea flavonoids might act as potential natural products regulating insulin resistance in HepG2 cells.

Navel orange peel essential oil inhibits the growth and progression of triple negative breast cancer

BackgroundTriple Negative Breast Cancer (TNBC) is a particular type of breast cancer with the highest mortality rate. Essential oils are concerned more and more as potential anti-cancer drugs.MethodsTNBC cells were treated with different concentrations of navel orange peel essential oil (NOPEO), and then a variety of experiments were performed to investigate the changes in the growth and progression of TNBC cells. MTT assay was performed to detect the proliferation of TNBC cells. The changes of cell cycle and apoptosis were analyzed by FACS. In order to explored the migration of TNBC cells, scratch wound assay was carried out. Western blotting and qPCR were used to examine the expression of proteins and mRNA of related genes. Furthermore, RNA-seq was used to analyze the altered genes and explored the possible signal pathway.ResultsNOPEO demonstrated dose- and time-dependent suppression of TNBC cell growth. TNBC cells showed an increased percentage of G2/M-phase cells and the protein levels of CyclinB1 and CyclinD1 were decreased after NOPEO treatment. The apoptotic cells were increased in the NOPEO treated TNBC cells. The migration mobility was significantly inhibited by NOPEO. In total, 1376 genes were found to be up-regulated and 1335 genes were down-regulated after NOPEO treatment. According to KEGG and GO pathways, the differentially expressed genes were related to MAPK, Jak/stat and FoxQ signaling pathways.ConclusionThis investigation explored the bio-activity and molecular mechanisms of NOPEO against TNBC cells. These results indicated that NOPEO could suppress TNBC growth and migration perhaps via the MAPK and Jak/stat signaling pathways, which may provide theoretical reference for anticancer drug development. NOPEO may be a potential natural product for the chemotherapeutic of TNBC.

AI-based prediction of protein–ligand binding affinity and discovery of potential natural product inhibitors against ERK2

Determination of protein–ligand binding affinity (PLA) is a key technological tool in hit discovery and lead optimization, which is critical to the drug development process. PLA can be determined directly by experimental methods, but it is time-consuming and costly. In recent years, deep learning has been widely applied to PLA prediction, the key of which lies in the comprehensive and accurate representation of proteins and ligands. In this study, we proposed a multi-modal deep learning model based on the early fusion strategy, called DeepLIP, to improve PLA prediction by integrating multi-level information, and further used it for virtual screening of extracellular signal-regulated protein kinase 2 (ERK2), an ideal target for cancer treatment. Experimental results from model evaluation showed that DeepLIP achieved superior performance compared to state-of-the-art methods on the widely used benchmark dataset. In addition, by combining previously developed machine learning models and molecular dynamics simulation, we screened three novel hits from a drug-like natural product library. These compounds not only had favorable physicochemical properties, but also bound stably to the target protein. We believe they have the potential to serve as starting molecules for the development of ERK2 inhibitors.

The Role of Natural Products in Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus and potentially leads to significant visual impairment and blindness. The complex mechanisms involved in the pathological changes in DR make it challenging to achieve satisfactory outcomes with existing treatments. Diets conducive to glycemic control have been shown to improve outcomes in diabetic patients, thus positioning dietary interventions as promising avenues for DR treatment. Investigations have demonstrated that natural products (NPs) may effectively manage DR. Many types of natural compounds, including saponins, phenols, terpenoids, flavonoids, saccharides, alkaloids, and vitamins, have been shown to exert anti-inflammatory, antioxidant, anti-neovascular, and antiapoptotic effects in vivo and in vitro. Nevertheless, the clinical application of NPs still faces challenges, such as suboptimal specificity, poor bioavailability, and a risk of toxicity. Prospective clinical studies are imperative to validate the therapeutic potential of NPs in delaying or preventing DR.

In Vitro Bioactivities and In Silico ADME Profile for Potential Biological Target Prediction of Selected Phytochemicals Using Six Nepeta Species

AbstractSeveral Nepeta species, used in traditional uses, represent sources of valuable phytochemical composition, as well as in vitro biological and in silico clinical activities. In the present study, the antioxidant and DNA protective properties of methanol: chloroform (1 : 1) extracts of six Nepeta species were evaluated by comparison with standards. In HPLC‐MS/MS analysis, the main components of the extracts were identified as rosmarinic acid, caffeic acid, chlorogenic acid, shikimic acid, and scutellarin. In the GC‐FID analysis, the highest components were palmitate and cis‐11‐eicosenoic acid. N. aristata has the greatest total phenol and flavonoid contents. N. baytopii, N. aristata, N. italica, N. stenantha, and N. nuda exhibited the highest antioxidant activities. The N. nuda, N. aristata, N. italica, and N. trachonitica extracts were shown to have the most potent DNA protection activity. According to the result of the GC‐FID and HPLC‐MS/MS analysis of Nepeta extracts, ADMET studies of the main components of the extracts were performed. It was evaluated that palmitic acid had BBB permeability, but oleic acid was toxic. The in vitro and in silico results confirmed that Nepeta L. extracts are potential natural products.

Natural products act as game-changer potentially in treatment and management of sepsis-mediated inflammation: A clinical perspective

BackgroundSepsis, a life-threatening condition resulting from uncontrolled host responses to infection, poses a global health challenge with limited therapeutic options. Due to high heterogeneity, sepsis lacks specific therapeutic drugs. Additionally, there remains a significant gap in the clinical management of sepsis regarding personalized and precise medicine. PurposeThis review critically examines the scientific landscape surrounding natural products in sepsis and sepsis-mediated inflammation, highlighting their clinical potential. MethodsFollowing the PRISMA guidelines, we retrieved articles from PubMed to explore potential natural products with therapeutic effects in sepsis-mediated inflammation. Results434 relevant in vitro and in vivo studies were identified and screened. Ultimately, 55 studies were obtained as the supporting resources for the present review. We divided the 55 natural products into three categories: those influencing the synthesis of inflammatory factors, those affecting surface receptors and modulatory factors, and those influencing signaling pathways and the inflammatory cascade. ConclusionNatural products' potential as game-changers in sepsis-mediated inflammation management lies in their ability to modulate hallmarks in sepsis, including inflammation, immunity, and coagulopathy, which provides new therapeutic avenues that are readily accessible and capable of undergoing rapid clinical validation and deployment, offering a gift from nature to humanity. Innovative techniques like bioinformatics, metabolomics, and systems biology offer promising solutions to overcome these obstacles and facilitate the development of natural product-based therapeutics, holding promise for personalized and precise sepsis management and improving patient outcomes. However, standardization, bioavailability, and safety challenges arise during experimental validation and clinical trials of natural products.