Natural Secondary Metabolites Research Articles

Role of natural secondary metabolites as HIF-1 inhibitors in cancer therapy

Role of natural secondary metabolites as HIF-1 inhibitors in cancer therapy

The use of botanicals as pesticides: History, development and emerging challenges

The unrestrained use of artificial pesticides over the years has strictly affected the function and dynamics of the ecosystem. The plants are a valuable store providing natural secondary metabolites that can be used as alternative pesticides that are non- pollutive, inexhaustible, everlasting, locally available, simply accessible, environment-friendly and comparatively profitable. It is against this background that scientists have made relentlessly effort to come up with botanicals that can be used as pesticides. The use of botanicals as pesticides has witnessed a rapid expansion in recent years. Plant extracts like nicotine were some of the earliest agricultural botanicals used as early as 17th century. An increasing number of experiments on bio-pesticides occurred in the rapid institutional growth of agricultural research of the early 20th century. Revival in academic and industrial research with a view to developing bio-pesticides transpired in response to increasing costs related with the overexploitation of artificial chemicals. The emergence of novel bio-pesticides has persistently increased since the mid-1990s. Nowadays more and better botanicals are used as pesticides. However, bio-pesticides or botanicals have their limitations some of which include its slower rate of kill in comparison to orthodox chemical pesticides, shorter persistence in the environment and susceptibility to unfavourable environmental conditions. For effective use of bio-pesticides there is need for knowledge-intensive management systems. Plant protection biologists have a sole duty to facilitate an understanding of bio-pesticide efficacy and as well ensure that innovation and knowledge are properly disseminated towards the progress and implementation of sustainable approaches.

Antimicrobial Potential of Natural Compounds of Zingiberaceae Plants and their Synthetic Analogues: A Scoping Review of In vitro and In silico Approaches.

There has been increased scientific interest in bioactive compounds and their synthetic derivatives to promote the development of antimicrobial agents that could be used sustainably and overcome antibiotic resistance. We conducted this scoping review to collect evidence related to the antimicrobial potential of diverse natural compounds from Zingiberaceae plants and their synthetic derivatives. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews guidelines. The literature search was conducted using PubMed, Web of Science and Scopus electronic databases for relevant studies published from 2012 to 2023. A total of 28 scientific studies fulfilled the inclusion criteria. The authors of these studies implemented in vitro and in silico methods to examine the antimicrobial potency and underlying mechanisms of the investigated compounds. The evidence elucidates the antimicrobial activity of natural secondary metabolites from Zingiberaceae species and their synthetic derivatives against a broad panel of gram-positive and gram-negative bacteria, fungi and viruses. To date, researchers have proposed the application of bioactive compounds derived from Zingiberaceae plants and their synthetic analogues as antimicrobial agents. Nevertheless, more investigations are required to ascertain their efficacy and to broaden their commercial applicability.

Anticancer potential of grifolin in lung cancer treatment through PI3K/AKT pathway inhibition

ObjectiveGrifolin is a natural secondary metabolite isolated from edible fruiting bodies of the mushroom Albatrellus confluens. Grifolin has antitumor activities in several types of cancer. We aimed to determine the effects of grifolin on lung cancer. MethodsWe determined the proliferation, migration, invasion, and apoptosis of lung cancer cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Ethynyl deoxyuridine, colony formation, wound scratch, transwell, flow cytometry, and xenograft mouse assays. Molecular docking evaluated the binding relation between grifolin and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). The levels of PIK3CA, AKT, and p-AKT were measured by western blot. ResultsGrifolin (10, 20, or 40 μM) inhibited the proliferation, migration, and invasion of lung cancer cells, and induced cell cycle arrest and apoptosis. Grifolin also decreased CDK4, CDK6, and CyclinD1 expression and significantly decreased PIK3CA and p-AKT expression in lung cancer cells. These anticancer effects were abolished by 740Y-P. ConclusionsGrifolin regulates the PI3K/AKT pathway, thus inhibiting lung cancer progression.

Caged xanthone derivatives to promote mitochondria-mediated apoptosis in breast cancer cells

Caged xanthones represent a class of natural secondary metabolites exhibiting significant potential as antitumor agents. These compounds are characterized by their distinct cage-like structures, which offer novel and compelling frameworks for drug design. Nonetheless, there exists a dearth of research focused on the structural modification of these compounds, particularly in relation to their cage-like architectures. This study aims to address this gap by introducing an innovative synthetic method for constructing a novel caged structure that incorporates a widely employed maleimide group. Drawing upon the well-established synthetic approach for dihydroxanthones previously developed within our research group, we successfully synthesized 13 new caged xanthones using the Diels-Alder reaction. Subsequently, we evaluated their anti-proliferative activity against HepG2, A549, and MDA-MB-231 cell lines. The results revealed that compound 10i exhibited IC50 values of 15.86 µM ± 1.29, 19.27 µM ± 1.58, and 12.96 µM ± 0.09 against these cell lines, respectively. Further investigations into the mechanism of action of 10i demonstrated its ability to induce G2/M cell cycle arrest and initiate mitochondria-mediated apoptosis in breast cancer cells.

Feedback regulation of the isoprenoid pathway by SsdTPS overexpression has the potential to enhance plant tolerance to drought stress.

In order to maintain the dynamic physiological balance, plants are compelled to adjust their energy metabolism and signal transduction to cope with the abiotic stresses caused by complex and changeable environments. The diterpenoid natural compound and secondary metabolites, sclareol, derived from Salvia sclarea, has gained significant attention owing to its economic value as a spice material and diverse physiological activities. Here, we focused on the roles and regulatory mechanisms of the sclareol diterpene synthase gene SsdTPS in the resistance of S. sclarea to abiotic stresses. Our results suggested that abiotic stresses could induce the response and upregulation of SsdTPS expression and isoprenoid pathway in S. sclarea. Ectopic expression of SsdTPS conferred drought tolerance in transgenic Arabidopsis, compared with wild-type. Overexpression of SsdTPS enhanced the transcription of ABA signal transduction synthetic regulators and induced the positive feedback upregulating key regulatory genes in the MEP pathway, thereby promoting the increase of ABA content and improving drought tolerance in transgenic plants. In addition, SsdTPS-overexpressed transgenic Arabidopsis improved the responses of stomatal regulatory genes and ROS scavenging enzyme activities and gene expression to drought stress. This promoted the stomatal closure and ROS reduction, thus enhancing water retention capacity and reducing oxidative stress damage. These findings unveil the potentially positive role of SsdTPS in orchestrating multiple regulatory mechanisms and maintaining homeostasis for improved abiotic stress resistance in S. sclarea, providing a novel insight into strategies for promoting drought resistance and cultivating highly tolerant plants.

Liposomal Formulation Improves the Bioactivity of Usnic Acid in RAW 264.7 Macrophage Cells Reducing its Toxicity.

Reactive oxygen species (ROS) production and oxidative stress may be responsible for the onset of several chronic diseases. Usnic acid (UA) is a natural secondary metabolite of lichens with several healthful bioactivities, including antioxidant properties. However, UA is a hydrophobic compound known for its hepatic toxicity. These aspects limit its therapeutic applications. To overcome these drawbacks and improve the pharmacological use of hydrophobic compounds, nanotechnology is widely used. Therefore, the incorporation of UA into appropriate nanocarriers could enhance the bioactivity of UA by increasing its solubility. The aim of this work was to improve the solubility of UA and its bioactivity in the absence of cytotoxicity. In this study, UA loaded liposomes (UA-LP) were developed. The formulations were chemically and physically characterized, and an in vitro release study was performed. Free UA and UA-LP were tested on RAW 264.7 murine macrophages in terms of cytotoxicity, intracellular ROS production, and NO release in the absence or presence of pro-oxidant LPS stimulus. UA-LP showed excellent physical and chemical stability during storage and improved solubility of UA. UA-LP showed an antioxidant effect in the absence of cytotoxicity compared with free UA on LPS-exposed macrophages. For the first time, liposomal formulation improved the beneficial action of UA in terms of solubility and antioxidant activity.

Pharmacognostic studies and thin layer chromatography profile of the aerial parts of Vernonia cinerealess. (Asteraceae)

Vernonia cinerea(VC) Less is synonymously known as Cyanthillium cinereum and Vernonia abbreviate belongs to Asteraceae family. Different parts of the plant are extensively used in traditional medicine for treatment of various disease conditions. However, there was no scientific evaluation of the plant’s pharmacognosy and thin layer chromatography (TLC), which necessitate these studies, to bring out characters that will facilitate its proper identification, standardization and, nature of secondary metabolites in aerial parts of the plant. To carry out detailed pharmacognostic studies and TLC evaluation on the aerial parts of Vernonia cinerea. Aerial plant parts of V. cinerea were studied for their organoleptic, macroscopic, microscopic, physicochemical features and bitterness properties, their elemental and nutritional values were evaluated using standard procedures. In the TLC, reagents were used to evaluate presence of various bioactive constituents in the parts studied. Pharmacognostic studies of aerial parts of VC highlighted features that are diagnostic from microscopic characters and their dimensions, different ergastic substances in the chemomicrocopical study. The elemental analysis showed the presence of macro, micro and trace elements. Nutritionally, there are presence of macro molecules such as carbohydrates, protein and fats. All these will serve as criteria to differentiate it from other species in the same and other families. The TLC profile showed spots of different colour shades after spraying with general and specific reagents and, their Rf values determined. Detailed pharmacognostic studies on the aerial parts of VC showed characters which might be useful to provide information with regard to its identification, standardization and types of phytochemicals present.

Streptomyces Diversity Maps Reveal Distinct High-Specificity Biogeographical and Environmental Patterns Compared to the Overall Bacterial Diversity.

Despite their enormous impact on the environment and humans, the distribution and variety of the biggest natural secondary metabolite producers, the genus Streptomyces, have not been adequately investigated. We developed representative maps from public EMP 16S rRNA amplicon sequences microbiomics data. Streptomyces ASVs were extracted from the EMP overall bacterial community, demonstrating Streptomyces diversity and identifying crucial diversity patterns. Our findings revealed that while the EMP primarily distinguished bacterial communities as host-associated or free-living (EMPO level 1), the Streptomyces community showed no significant difference but exhibited distinctions between categories in EMPO level 2 (animal, plant, non-saline, and saline). Multiple linear regression analysis demonstrated that pH, temperature, and salinity significantly predicted Streptomyces richness, with richness decreasing as these factors increased. However, latitude and longitude do not predict Streptomyces richness. Our Streptomyces maps revealed that additional samplings in Africa and Southeast Asia are needed. Additionally, our findings indicated that a greater number of samples did not always result in greater Streptomyces richness; future surveys may not necessitate extensive sampling from a single location. Broader sampling, rather than local/regional sampling, may be more critical in answering microbial biogeograph questions. Lastly, using 16S rRNA gene sequencing data has some limitations, which should be interpreted cautiously.

Biotechnological production of ectoine: current status and prospects.

Ectoine is an important natural secondary metabolite in halophilic microorganisms. It protects cells against environmental stressors, such as salinity, freezing, drying, and high temperatures. Ectoine is widely used in medical, cosmetic, and other industries. Due to the commercial market demand of ectoine, halophilic microorganisms are the primary method for producing ectoine, which is produced using the industrial fermentation process "bacterial milking." The method has some limitations, such as the high salt concentration fermentation, which is highly corrosive to the equipment, and this also increases the difficulty of downstream purification and causes high production costs. The ectoine synthesis gene cluster has been successfully heterologously expressed in industrial microorganisms, and the yield of ectoine was significantly increased and the cost was reduced. This review aims to summarize and update microbial production of ectoine using different microorganisms, environments, and metabolic engineering and fermentation strategies and provides important reference for the development and application of ectoine.

Research Advances in Clinical Applications, Anticancer Mechanism, Total Chemical Synthesis, Semi-Synthesis and Biosynthesis of Paclitaxel.

Paclitaxel, a natural secondary metabolite isolated and purified from the bark of the Taxus tree, is considered one of the most successful natural anticancer drugs due to its low toxicity, high potency and broad-spectrum anticancer activity. Taxus trees are scarce and slow-growing, and with extremely low paclitaxel content, the contradiction between supply and demand in the market is becoming more and more intense. Therefore, researchers have tried to obtain paclitaxel by various methods such as chemical synthesis, artificial culture, microbial fermentation and tissue cell culture to meet the clinical demand for this drug. This paper provides a comprehensive overview of paclitaxel extraction, combination therapy, total synthesis, semi-synthesis and biosynthesis in recent years and provides an outlook, aiming to provide a theoretical basis and reference for further research on the production and application of paclitaxel in the future.

The Interplay of Genital Herpes with Cellular Processes: A Pathogenesis and Therapeutic Perspective.

Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular processes, from harnessing host machinery for replication to subverting antiviral defenses like autophagy and programmed cell death, exemplifies the intricate interplay at the heart of its pathogenesis. While the biomedical community has extensively researched antiviral interventions, the efficiency of these strategies in managing HSV-2 remains suboptimal. Recognizing this, attention has shifted toward leveraging host cellular components to regulate HSV-2 replication and influence the cell cycle. Furthermore, innovative interventional strategies-including drug repurposing, microbivacs, connecting the host microbiome, and exploiting natural secondary metabolites-are emerging as potential game changers. This review summarizes the key steps in HSV-2 pathogenesis and newly discovered cellular interactions, presenting the latest developments in the field, highlighting existing challenges, and offering a fresh perspective on HSV-2's pathogenesis and the potential avenues for its treatment by targeting cellular proteins and pathways.

Modulation of hypoxia-inducible factor-1 signaling pathways in cancer angiogenesis, invasion, and metastasis by natural compounds: a comprehensive and critical review.

Tumor cells employ multiple signaling mediators to escape the hypoxic condition and trigger angiogenesis and metastasis. As a critical orchestrate of tumorigenic conditions, hypoxia-inducible factor-1 (HIF-1) is responsible for stimulating several target genes and dysregulated pathways in tumor invasion and migration. Therefore, targeting HIF-1 pathway and cross-talked mediators seems to be a novel strategy in cancer prevention and treatment. In recent decades, tremendous efforts have been made to develop multi-targeted therapies to modulate several dysregulated pathways in cancer angiogenesis, invasion, and metastasis. In this line, natural compounds have shown a bright future in combating angiogenic and metastatic conditions. Among the natural secondary metabolites, we have evaluated the critical potential of phenolic compounds, terpenes/terpenoids, alkaloids, sulfur compounds, marine- and microbe-derived agents in the attenuation of HIF-1, and interconnected pathways in fighting tumor-associated angiogenesis and invasion. This is the first comprehensive review on natural constituents as potential regulators of HIF-1 and interconnected pathways against cancer angiogenesis and metastasis. This review aims to reshape the previous strategies in cancer prevention and treatment.

A Multi-Label Learning Framework for Predicting Chemical Classes and Biological Activities of Natural Products from Biosynthetic Gene Clusters.

Natural products (NP) or secondary metabolites, as a class of small chemical molecules that are naturally synthesized by chromosomally clustered biosynthesis genes (also called biosynthetic gene clusters, BGCs) encoded enzymes or enzyme complexes, mediates the bioecological interactions between host and microbiota and provides a natural reservoir for screening drug-like therapeutic pharmaceuticals. In this work, we propose a multi-label learning framework to functionally annotate natural products or secondary metabolites solely from their catalytical biosynthetic gene clusters without experimentally conducting NP structural resolutions. All chemical classes and bioactivities constitute the label space, and the sequence domains of biosynthetic gene clusters that catalyse the biosynthesis of natural products constitute the feature space. In this multi-label learning framework, a joint representation of features (BGCs domains) and labels (natural products annotations) is efficiently learnt in an integral and low-dimensional space to accurately define the inter-class boundaries and scale to the learning problem of many imbalanced labels. Computational results on experimental data show that the proposed framework achieves satisfactory multi-label learning performance, and the learnt patterns of BGCs domains are transferrable across bacteria, or even across kingdom, for instance, from bacteria to Arabidopsis thaliana. Lastly, take Arabidopsis thaliana and its rhizosphere microbiome for example, we propose a pipeline combining existing BGCs identification tools and this proposed framework to find and functionally annotate novel natural products for downstream bioecological studies in terms of plant-microbiota-soil interactions and plant environmental adaption.

An Outlook on Pathological Pathways of Diabetes and Molecular Mechanisms of Anti-diabetic Phytobioactives

Background & Purpose: Diabetes is a disease that has affected many people worldwide. According to the World Health Organization, approximately 80% of humans still rely on conventional or folk medicament in developed countries. The effectiveness of herbal medicines was credited to the phytochemical components. Objective: This review aims to highlight the pathological pathways of diabetes and the antidiabetic mechanism of phytochemicals. Materials and Methods: This organized search was compiled from the databases such as PubMed, Scopus, Embase, ScienceDirect, Web of Science, and Google Scholar till February 2023. Results: Inflammatory and oxidative stress are mainly two examples of pathological pathways of diabetes that are explored. The reported antidiabetic phytochemicals work by increasing insulin secretion, lowering hepatic glucose output, controlling specific enzymes, and utilizing other mechanisms. For instance, studies on α-glucosidase inhibitors, modulation peroxisome proliferator-activated receptor-α, hypolipidaemic activity, antioxidants, inhibition of glycolytic enzymes like phosphoenolpyruvate carboxykinase, improvement of glycosylated haemoglobin and increased expression of glucose transporters have been conducted. Conclusion: Many natural secondary metabolites (phytochemicals) have significant potential for the manufacture of marketable, new, and efficient anti-diabetic medicines which can be used for clinical purposes.

Screening of Antiviral Efficacy of Few Seaweeds of Tamil Nadu Coast

Lately there has been a lot of interest worldwide in studies on the antiviral activities of marine natural secondary metabolites, notably marine polysaccharides. It has been established that polysaccharides made from marine sources and their derivatives have antiviral effects against potent viruses. Agricultural, biological, food, and pharmaceutical industries all make extensive use of goods obtained from algae. The most well-known chemical components found in algae are polysaccharides, which have been the subject of a variety of studies because of their varied bioactivities. Polysaccharides made from algae have recently risen to the top of pharmaceutical research due to their fascinating antiviral potential. Currently, COVID-19 can be prevented with vaccination, but the brown alga Sargassum wightii has several bioactive compounds that have the following qualities and may be a better option. S. wightii is one of the marine algae species that is rich in sulfated polysaccharides, the secondary metabolites which have antiviral action and the capacity to prevent viral proliferation. Fucoidan, a long-chain sulfated polysaccharide found in various brown algae, has potent antiviral effects. Additionally, sulfated polysaccharides from green algae (such as ulvans) and red algae (such as carrageenan), and lectins from red algae (such as griffithsin) have antiviral therapeutic agents against coronaviruses and other viruses. This research focuses on screening seaweeds for possible antiviral compounds to treat viral infections notably COVID-19.

Cryopreservation of bioflavonoid-rich plant sources and bioflavonoid-microcapsules: emerging technologies for preserving bioactivity and enhancing nutraceutical applications.

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids' shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids' bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

T-2 toxin induces cardiotoxicity by activating ferroptosis and inhibiting heme oxygenase-1

T-2 toxin, a natural secondary sesquiterpenoid metabolite produced by numerous strains of Fusarium fungi, is prevalent in both contaminated food and the environment. T-2 toxin is known to be highly toxic to the cardiovascular system, but the precise mechanisms that lead to T-2 toxin-induced cardiotoxicity are not yet fully understood. Recent findings indicate that ferroptosis is a pivotal factor in cardiovascular damage and exhibits a strong correlation with the detrimental impacts of T-2 toxin. The present study was designed to examine the involvement of ferroptosis in T-2 toxin-induced cardiac injury. Male mice and human cardiomyocytes were subjected to T-2 toxin for 24 h to induce acute cardiotoxicity for in vivo and in vitro studies, respectively. Our results demonstrated that T-2 toxin increased reactive oxygen species production, malondialdehyde, and decreased glutathione/oxidized glutathione and adenosine triphosphate levels. Furthermore, T-2 toxin was observed to activate ferroptosis, as evidenced by an increase in iron (Fe2+) concentration and upregulation of prostaglandin endoperoxide synthase 2, downregulation of glutathione peroxidase 4 and ferritin heavy chain 1, as well as ferroptotic morphological alterations. Inhibition of ferroptosis by Liproxstatin-1 reversed T-2 toxin-induced cardiac injury. Additionally, the downregulation of heme oxgenase-1 (HO-1) expression by T-2 toxin exacerbates ferroptosis and oxidative damage, which can be further aggravated by HO-1 inhibition with Sn-protoporphyrin. These findings provide novel insights into the mechanism of T-2 toxin-induced cardiotoxicity and suggest that targeting ferroptosis and HO-1 may represent a promising cardioprotective strategy against T-2 toxin.

Impacts of Plant-derived Secondary Metabolites for Improving Flora in Type 2 Diabetes.

Diabetes has become a problem that plagues public healthcare systems. Recent studies have shown that intestinal flora exerts positive therapeutic effects on metabolic diseases, and plant-derived secondary metabolites are safe, effective and easy to prepare and also have an impact on intestinal flora and diabetes; these drugs have rarely been reviewed before as a class of drugs for diabetes, especially focusing on the intestinal flora. Therefore, studying the relationship between plant-derived secondary metabolites and diabetes mellitus is crucial. The objective of this study is to summarize and investigate the therapeutic mechanism of drugs extracted from natural plants effects on type 2 diabetes mellitus. The relationship between flora and type 2 diabetes was investigated by reviewing the recent experimental literature, and the pathways available for natural plant-derived secondary metabolites in the treatment of type 2 diabetes were summarized. The therapeutic mechanisms of common plant-derived secondary metabolites for type 2 diabetes were summarized with a focus on the prebiotic efficacy of natural plant-derived secondary metabolites and the modulation of intestinal flora, and the mechanisms through which plantderived secondary metabolites treat type 2 diabetes via effects on intestinal flora are further reviewed. Common plant-derived secondary metabolites can play a role in regulating bacteria in the intestinal tract by enriching beneficial bacteria and removing harmful bacteria to achieve their therapeutic effect on type 2 diabetes. In addition, due to their excellent ability to regulate intestinal flora, plant-derived secondary metabolites may also have excellent efficacy in cancer and obesity, among other diseases.

Saikosaponin D exerts cytotoxicity on human endometrial cancer ishikawa cells by inducing apoptosis and inhibiting metastasis through MAPK pathways.

Saikosaponin D (SSD) is one of plant secondary metabolic active substance with effective anti-tumor ability; however, the toxicity of Saikosaponin D on human endometrial cancer Ishikawa cells is still unclear. Our results revealed that SSD displayed cytotoxicity on the Ishikawa cell with an IC50 = 15.69 μM, but was non-toxic to the human normal cell line HEK293. SSD could upregulate p21 and Cyclin B to keep cells in the G2/M stage. In addition, it activated the death receptor and mitochondrion routes to induce apoptosis in Ishikawa cells. The transwell chamber and wound healing results showed that SSD inhibited the cell migration and invasion. In addition, we found that it was closely related to the MAPK cascade pathway, and it could mediate the three classical MAPK pathways to block cell metastasis. In conclusion, SSD could be potentially beneficial as a natural secondary metabolite in preventing and treating endometrial carcinoma.