Agricultural Genetic Engineering Research Institute

Known by its scientific name, Cinnamomum verum L., cinnamon is a spice, highly regarded and is utilised in a variety of contexts, including culinary and medical applications. It is vital to cultivate enhanced cinnamon cultivars that display improved qualities, such as larger yield, superior quality, increased disease resistance, and tolerance to a variety of agroclimatic situations. This is because the demand for cinnamon is expanding at an alarming rate. An strategy that is viable for creating improved varieties of cinnamon that have favourable agronomic properties has been made possible by the success that has been made in cinnamon breeding procedures. Cinnamon‘s productivity, quality, and resilience could be improved by the integration of conventional and molecular breeding approaches, as well as through the efficient utilisation of varied germplasm resources. It is absolutely necessary to devote the necessary resources to cinnamon breeding research in order to effectively meet the ever-increasing demand for this highly sought-after spice on a global scale. The objective of this chapter is to provide a complete summary of the latest breakthroughs in breeding procedures that have been utilised for the enhancement of cinnamon. This discussion covers a wide range of topics that are associated with cinnamon breeding, including the investigation of germplasm, the specification of selection criteria, the methods of breeding, and the molecular techniques. In addition, this chapter will shed light on the difficulties that have been experienced in cinnamon breeding research, and it will also offer some insights into the potential opportunities that exist within this particular subject.

This chapter provides an overview of the recent advancements in breeding strategies for saffron (Crocus sativus L.), a highly valuable spice crop known for its unique and vibrant color, distinctive flavor, and various medicinal properties. Saffron production is predominantly dependent on the cultivation of its genetically diverse and economically valuable source, Crocus sativus. The chapter highlights the significance of saffron breeding to address challenges such as low and inconsistent yields, susceptibility to diseases, and changing climatic conditions. It discusses various traditional and modern breeding techniques employed to improve saffron cultivation, focusing on both genetic and agronomic aspects. Traditional breeding methods, including selection, hybridization, and mutation breeding, have played a crucial role in saffron improvement. The chapter outlines how these methods, with advancements in phenotypic and genotypic selection approaches, have contributed to enhancing desirable traits such as improved yield, disease resistance, and increased adaptability to adverse conditions. Furthermore, the chapter delves into the emerging fields of molecular breeding, genomics, and biotechnology, which have opened new avenues for saffron improvement. It explores the utilization of marker-assisted selection (MAS), genotyping-by-sequencing (GBS), and other genomic tools for efficient identification and introgression of beneficial traits. The potential of genetic engineering and transgenic approaches in saffron breeding is also discussed. In addition to genetics, the chapter sheds light on the significance of agronomic practices and cultural management techniques that can contribute to sustainable and enhanced saffron production. It discusses the importance of optimizing irrigation, nutrient management, and crop protection strategies to ensure healthy plant growth and maximum yield. Overall, this chapter provides a comprehensive overview of the recent advances in saffron breeding strategies, encompassing traditional and molecular approaches. It emphasizes the importance of integrating genetic studies with agronomic practices to develop high-yielding and resilient saffron varieties that can meet the increasing global demands sustainably.

Motivated by our recent research progress on the exploitation of s-triazine dendritic platforms as bioactive carriers for well-known anticancer agents and/or targeting ligands, we set out to synthesize new rationally designed dendrimers endowed with MMP-2/9 inhibition potential for halting both breast and liver cancer progression with reduced off-target side effects. New three and four generation s-triazine based dendrimers were developed to incorporate potential ZBGs (Zinc Binding Groups) and carboxyl terminal groups to facilitate direct conjugation of anti-cancer drugs (quercetin) and/or targeting ligands (lactobionic acid) through a biodegradable ester bond. Compared to free quercetin (QUR), MTT assay revealed that all the quercetin-coupled dendrimers displayed better anticancer potential (IC50 = 12.690–29.316, 4.137–29.090 μM) against MCF-7 and HepG-2 cancer cells, respectively within their safe doses (EC100 = 134.35–78.44 μM). Conjugation of lactobionic acid and PEG boosted the anticancer potency against both treated cells, improved apoptosis and down regulated MMP-9 and VEGF gene expression levels in both treated cancer cells. Generally, the more branched G4 dendrimer conjugates exhibited a superior overall anticancer performance compared to their respective G3 analogues, except for their MMP-9 inhibition where G3 conjugate appeared to be more potent and more selective than its G4 analogue.

Salinity is one of the most important abiotic stress factors affecting wheat production. Salt in the soil is a major environmental stressor that can affect the bacterial community in the rhizosphere of wheat. The bacteria in the plant’s rhizosphere promote growth and stress tolerance, which vary by variety and location. Nevertheless, the soil harbors some of the most diverse microbial communities, while the rhizosphere selectively recruits according to the needs of plants in a complex harmonic regulation. The microbial composition and diversity under normal and saline conditions were assessed by comparing the rhizosphere of wheat with soil using 16S rRNA gene amplicon sequencing, highlighting the number of operational taxonomic units (OTUs). Taxonomic analyzes showed that the bacterial community was predominantly and characteristically composed of the phyla Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia, and Fibrobacteres, representing the usual microbial profile for the rhizosphere of wheat. Idiomarinaceae, Rheinheimera, Halomonas, and Pseudomonas (a strain of Proteobacteria), together with Gracilibacillus (a strain of Firmicutes Bacilli), were recognized as microbial signatures for the rhizosphere microbiome under saline conditions. This was observed even with unchanged soil type and genotype. These patterns occurred despite the same soil type and genotype, with salinity being the only variable. The collective action of these bacterial phyla in the rhizosphere not only improves nutrient availability but also induces systemic resistance in the plants. This synergistic effect improves plant resistance to salt stress and supports the development of salt-tolerant wheat varieties. These microbial signatures could improve our understanding of plant–microbe interactions and support the development of microbiome-based solutions for salt stress.

Wheat production is jeopardized by Puccinia triticina, the pathogen responsible for wheat leaf rust. This study assessed the impact of silver (Ag) and copper (Cu) nanoparticles (NPs) on the control of wheat leaf rust disease and the underlying mechanisms of disease resistance. The application of the two nanoparticles resulted in a reduction of spore germination and an extension of both incubation and latent periods. A common type of infection resulted in a reduction in both the length and width of pustules. It reduced receptivity value (number of pustule cm²) compared to untreated wheat plants by altering the physiological and biochemical responses of wheat plants and cell walls’ physical and mechanical strength. The application of Ag + Cu NPs stimulates the biosynthesis of defense-related molecules crucial for P. triticina inoculation and latent periods. Furthermore, molecular docking studies were conducted to assess the effects of Cu-chitosan nanoparticles (Ag & CuNp) and their mechanisms in disease management.

A novel folic acid-conjugated, iron-based metal framework MIL-101 (Fe) MOF loaded with 1,8-acridinediones (DO8) was developed for targeted photodynamic therapy (PDT).

Macrophomina phaseolina is a soilborne fungus responsible for developing root-rot and charcoal-rot diseases in various plants. Seventeen Bacillus strains were isolated and assessed as potential biocontrol agents to determine their capability to suppress M. phaseolina growth. The KSAM1 isolate demonstrated the highest efficacy in suppressing fungal mycelial growth, achieving an inhibition rate of 38.6%. The 16S rRNA gene sequencing, BLAST analysis, and phylogenetic tree construction demonstrate that KSAM1 is Bacillus velezensis . It is registered in GenBank as B. velezensis strain KSAM1 (Acc# PQ288980). Subsequently, two batch fermentation processes were implemented in an agitated tank bioreactor to optimize agitation and aeration to achieve the highest possible level of culture biomass and secondary metabolite production. The maximum achievable level of the culture biomass was 3.92 g L ⁻¹ , which was achieved at 10.5 hours through the utilization of batch fermentation No. 2. This process involved stirring at rates between 200 and 600 rpm, along with an aeration rate of 1 VVM. This achievement was realized while upholding a steady specific growth rate (µ) of 0.08 h ⁻¹ . The observations indicated that the biomass yield coefficient was established at 0.7 g cells/g glucose. The analysis of bacterial filtrate extract using gas chromatography-mass spectrometry indicated that diisooctyl phthalate was the most bioactive secondary metabolite compound in the chromatogram, accounting for 36.07 percent of the total area. Overall, B. velezensis strain KSAM1 may serve as a biocontrol agent for M. phaseolina , as indicated by the results of the present investigation.

Growing attention towards rhamnolipids (RLs) biosurfactants with antibacterial, anti-fungal, antivirus and antitumor potentials encourage future research in biotechnology and biomedicine fields. Economic production from waste materials, biodegradability and low toxicity makes RLs perform as green molecules that serve in sustainability and green technologies. This review aims to focus on bioproduction, detection and applications of rhamnolipids in pharmaceuticals, soil bioremediation, agriculture and food industries in addition to future perspectives. This will help to shed light on and update the existing knowledge of feasible and sustainable biosurfactant production depending on the fermentation processes.

Sweet sorghum (Sorghum bicolor L. Moench) is a C4 crop that is characterized by its high photosynthetic efficiency and is specifically bred for its high lignocellulosic biomass in addition to its broad utilization in food, fodder, and biofuel production. Still establishing a robust in vitro tissue culture system for sorghum requires further improvement due to its major limitations in phenolic release and low regeneration rate. In this study, immature inflorescences were employed using three different sweet sorghum varieties (Rex, Ramada, and Sugar Drip) to establish an efficient regeneration system. The study revealed optimal rates of embryogenic callus induction in the varieties Rex (77%), Ramada (93%), and Sugar Drip (94%) from immature inflorescence explants cultured on Murashige and Skoog (MS) medium supplemented with 4.0 or 6.0 mg L−1 2,4-D and 0.2 mg L−1 Kin. The aforementioned concentrations also support the establishment of an embryogenic callus (74%) from a greater inflorescence length (9 to 12 cm) among the three genotypes. The best shoot response, shoot number/explant, and acclimatization process for the three varieties were ascertained following culture on MS medium containing 1.0 mg L−1 IAA, 0.5 mg L−1 BAP, and 0.1 mg L−1 TDZ. Consequently, the rate of shoot induction was 30, 43, and 28% in Rex, Ramada, and Sugar Drip, respectively. In addition, the average shoot number/callus indicated 1.7, 2.9, and 3.0 in Rex, Ramada, and Sugar Drip, respectively. The survival rate of plantlets in the greenhouse, ranging from 79 to 100%, demonstrates the success of the acclimatization process and the effectiveness of the tissue culture protocol. In conclusion, this work will facilitate augmenting the efficiency of sweet sorghum transformation, improving its economical and nutritional values.

The excessive use of antibiotics, including ciprofloxacin (CIP) and tetracycline (TC), poses negative impacts on both human health and ecosystems. In this work, fullerene/magnesium oxide (F/MgO) nanocomposite was prepared and studied as adsorbent for CIP and TC removal. Adding metal oxide to F led to a change in its characteristics which was confirmed by XRD, FTIR, SEM, and TEM. A maximal removal for 50 mg L⁻¹ CIP was 84.6% at 60 min, pH 7, and 0.2 g L⁻¹ of adsorbent dose. 43.6% of 50 mg L⁻¹ of TC adsorbed at 60 min, pH 5, and 1 g L⁻¹ of adsorbent dose. Adsorption thermodynamics elucidated that the adsorption on F/MgO nanocomposite were spontaneous and exothermic, and non-spontaneous and endothermic for CIP and TC, respectively. Pseudo-second-order kinetic model fitted well the adsorption data of CIP and TC. Various coexisting ions had different impacts on the adsorption efficiency of CIP and TC. The competitive adsorption between CIP and TC on the surface of F/MgO nanocomposite was studied. The F/MgO nanocomposite was efficiently reused 5 cycles for CIP and TC removal and remained effective. This work explores a novel adsorbent for the elimination of CIP and TC from aqueous solutions.

Eriobotrya japonica (Thunb.) Lindl . is an evergreen tree that holds economic significance. It is cultivated for its fruits, leaves and ornamental properties. Its propagation by seeds and cuttings is inefficient due to high heterozygosity, lengthy juvenile phase and reproductive cycle. This study establishes a direct in vitro propagation technique for the plant from the mother tree. The impact of different zinc oxide nanoparticle (ZnO-NP) concentrations on E. japonica ’s in vitro propagation was assessed. Genetic stability of the micropropagated plantlets was also conducted using start codon targeted (SCoT) and sequence-related amplified polymorphism (SRAP) markers to evaluate the protocols’ efficiency. Successful shoot establishment involved 1.0 mg L ⁻¹ 6-benzyladenine (BA) and 0.1 mg L ⁻¹ α-naphthaleneacetic acid (NAA) supplemented to Murashige and Skoog (MS) medium, yielding 80% growth induction, the highest shoot number (3.72) and length (4.84 cm). MS medium with 1.0 mg L ⁻¹ BA and 1.0 mg L ⁻¹ kinetin (Kin) achieved 95% multiplication and optimal shoot number (5.70). Adding 50.0 mg L ⁻¹ ZnO-NPs significantly influenced shoot formation, leading to 100% growth induction, highest shoot number (7.67) and highest shoot length (4.0 cm). Rooting using 1.5 mg L ⁻¹ indole-3-butyric acid (IBA) in half MS medium achieved 100% rooting response and 85% survival for post-greenhouse acclimatization. Genetic stability analysis showed low degree of polymorphism (3.3%) and high percentage of monomorphic bands (96.7%) between donor and micropropagated plants. Dice’s similarity coefficient displayed high similarity (0.992 to 1.000) between sub-cultured and mother plants. An effective method for in vitro propagation of E. japonica was successfully established. ZnO-NPs significantly influence shoot formation and facilitate the mass production of E. japonica plants with desired characteristics.

Background Breast cancer is chemo-resistant and highly metastatic, often resulting in patient mortality. One of the primary factors contributing to the metastasis and chemotherapy resistance is the presence of cancer stem-like cells. We posited that the natural polysaccharide known as 6-glucans, derived from Pleurotus ostreatus, could effectively counteract the chemotherapy resistance associated with cancer stem-like cells in breast cancer. Methods We computationally developed a specific dual combinatorial therapy involving 6-glucans and Paclitaxel (PTX) and tested on preclinical 3D mammosphere human tumor models representing receptor-positive and receptor-negative breast cancer. Using this preclinical 3D spheroid technology, we tested the anti-cancer properties of these predicted treatment combinations on mammospheres containing human breast cancer stem cells. Results Among the 40 distinct combinations examined, computational prediction revealed that the addition of 2.0 mg/mL of 6-glucans to a low dose of 3.0 µg/mL PTX was the sole combination demonstrating a synergistic effect. This optimized synergistic combination therapy displayed a significant inhibitory impact on human cancer epithelial and stem cell migration, evasion, and colony formation. The inclusion of 6-glucans also augmented apoptosis in both breast cancer cells and stem cells, leading to a six-fold reduction in BrdU labeled cells and an increased arrest of cells in the sub-G0 phase. These effects were mediated through mitochondrial dysfunction and the downregulation of associated oncogenes. Conclusion Our study revealed that the computationally predicted 6-glucans-based binary complementary medicine exhibited sequence- and concentration-dependent anticancer synergistic effects.

In light of the fact that climate change has emerged as one of the difficulties confronting the global food system, researchers are obligated to work toward developing fundamental crops, particularly wheat, to combat environmental stress, including drought and salt. In the present study, genetic engineering was used to transfer the Arabidopsis MDAR1 gene, which controls the buildup of ascorbic acid (AsA) to make bread wheat less likely to be sensitive to salt stress. The biolistic bombardment was used to transfer cDNA from the Arabidopsis thaliana plant that encodes MDAR1 into Bobwhite 56 cultivar wheat plants. A molecular investigation was performed on six different transgenic lines to confirm the integration of the transgene, the copy number, and the expression of the transgene. There were one to three copies of the transgene, and there was no association found between the number of copies of the transgene and All the data generated or analyzed during this study are included in this published article [and its supplementary information files].the presence of its expression. Compared to plants that were not transgenic, the amount of ascorbic acid (AsA) that accumulated in the transgenic plants was twice as high. ROS concentrations are significantly lower in transgenic plants compared to non-transgenic plants under both control and salt stress conditions, effectively reducing oxidative stress. By cultivating transgenic T2 plants in a greenhouse, we were able to determine whether they were able to tolerate the potentially damaging effects of salt stress (200 mm). The study concluded that transgenic wheat plants that consistently expressed the MDAR1 gene become tolerant to salt stress with improvement in growth characteristics.

Bay laurel ( Laurus nobilis ) essential oil is known for its antimicrobial, anti‐inflammatory, and antioxidant properties. This study examined the effects of L. nobilis oil (LN) on Nile tilapia ( Oreochromis niloticus ) under cold stress conditions (16°C). Tilapia (initial weight, 5.02 ± 0.02 g) were acclimatized to 16°C for 14 days before being fed diets containing 0, 0.5, 1.0, 1.5, 2.0, and 2.5 g/kg LN oil for 84 days. The 1.5 g/kg LN oil group exhibited the highest final body weight and weight gain ( p ≤ 0.05), while survival rates peaked at 1 g/kg. Biometric indices and feed efficiency were significantly enhanced, particularly at 1.5 g/kg ( p ≤ 0.05). Histological analysis revealed improved intestinal and hepatic structures in LN‐supplemented groups, although mild alterations were observed at 2.0 and 2.5 g/kg. Blood biochemical analysis showed increased total protein and reduced cholesterol in supplemented groups. Immune responses, including serum lysozyme activity and bacterial inhibition, were significantly enhanced at 1.5 g/kg or higher ( p ≤ 0.05). Antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT), increased ( p ≤ 0.05) with LN oil supplementation, while malondialdehyde (MDA) levels decreased, indicating reduced oxidative stress. Gene expression analysis demonstrated increased insulin‐like growth factor 1 and glucose transporter 4 levels with 1.5 g/kg LN oil, and tumor necrosis factor‐alpha expression decreased at higher dosages. Dietary LN oil, particularly at 1.5 g/kg, enhances growth, immunity, and antioxidant defense in Nile tilapia under cold stress. Future studies should optimize dosages and explore broader applications across species and conditions.

Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and exhibits a limited response to apoptosis-dependent chemotherapeutic drugs (e.g., gemcitabine, Gem). This is mainly attributed to the antioxidant defense system (glutathione and aldehyde dehydrogenase (ALDH) 1A1), which sustains stemness features of cancer stem cells (CSCs) and activated pancreatic stellate cells (PSCs)-generated excess stromal proteins. This dense stroma retards drug delivery. Methods This study established co-spheroid model consisting of mouse PDAC cell line (KPC) and PSCs (1:5) to accurately investigate the anti-PDAC activity of nanocomplex of ferrous oxide nanoparticles-diethyldithiocarbamate (FeO NPs-DE), compared to Gem, using in vitro and in vivo 3D models. Results In vitro and in vivo co-spheroid models demonstrated higher therapeutic efficacy of FeO NPs-DE than Gem. FeO NPs-DE induced selective accumulation of iron-dependent ferroptosis (non-apoptosis)-generated a lethal lipid peroxidation that was potentiated by DE-mediated glutathione and ALDH1A1 suppression. This led to collapse of stemness, as evidenced by down-regulating CSC genes and p-AKT protein expression. Subsequently, gene and/or protein levels of PSC activators (transforming growth factor (TGF)-β, plasminogen activator inhibitor-1, ZEB1, and phosphorylated extracellular signal-regulated kinase) and stromal proteins (collagen 1A2, smooth muscle actin, fibronectin, and matrix metalloproteinase-9) were suppressed. Moreover, DE of nanocomplex enhanced caspase 3-dependent apoptosis with diminishing the main oncogene, BCL-2. Conclusions FeO NPs-DE had a stronger eradicating effect than Gem on primary and metastatic peritoneal PDAC tumors. This nanocomplex-mediated ferroptosis and stemness inhibition provides an effective therapeutic approach for PDAC.

Determining mechanisms to establish an initial infection and form intracellular complexes for accumulation and movement of RNA plant viruses are important areas of study in plant virology. The impact of these findings on the basic understanding of plant molecular virology and its application in agriculture is significant. Studies with tobacco mosaic virus (TMV) and related tobamoviruses often provide important foundational knowledge for studies involving other viruses. Topics discussed here include capsid disassembly, establishment of a virus replication complex (VRC), and transport of the VRCs or virus components within the cell to locations at the plasmodesmata for intercellular virus RNA (vRNA) movement. Seminal findings with TMV and related tobamoviruses include detecting co-translational disassembly of the vRNA from the virus rod, full sequencing of genomic vRNA and production of infectious transcript for genetic studies determining virus components necessary for intercellular movement, and biochemical and cell biological studies determining the host factors, protein and membrane, needed for replication and movement. This review highlights many of the studies through the years on TMV and selected tobamoviruses that have impacted not only our understanding of tobamovirus accumulation and movement but also that of other plant viruses.

Background: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPAs) are useful tools for rheumatoid arthritis (RA). The presence of ACPAs against citrullinated proteins (CPs), especially citrullinated fibrinogen (cFBG), seems to be a useful serological marker for diagnosing RA. RA patients’ sera were found to be enriched in exosomes that can transmit many proteins. Exosomes have been found to express citrullinated protein such as cFBG. Objective: We conducted this study in two stages. In the first phase, we aimed to evaluate the association between autoantibodies and risk factors. In the next step, ACPA-positive serum samples from the first phase were subjected to exosomal studies to explore the presence of cFBG, which is a frequent target for ACPAs. Methods: We investigated the autoantibodies in one hundred and sixteen Saudi RA patients and correlated with host-related risk factors. Exosomes were extracted from patients’ sera and examined for the presence of cFBG using monoclonal antibodies. Results: The study reported a high female-to-male ratio of 8:1, and seropositive RA (SPRA) was more frequent among included RA patients. The frequency and the levels of ACPAs were similar in both genders. Autoantibodies incidences have a direct correlations with patient age, while the average titers decreased as the age increased. Further, the highest incidence and levels of autoantibodies were reported in patients with RA duration between 5 and 10 years. Smoking and family history have no impact on autoantibody, except for ACPAs titers among smokers’ RA. Our analysis of serum exosomes revealed that about 50% of SPRA patients expressed cFBG. Conclusions: The female-to-male ratio is 8:1, which is higher than the global ratio. We can conclude that patients’ age and disease duration contribute to the autoantibodies, particularly RF and anti-MCV, whereas smoking and family history had no effects on autoantibodies. We detected cFBG in all exosomes from SPRA patients; thus, we suggest that the precise mechanism of exosomes in RA pathogenesis can be investigated to develop effective treatment strategies.

The classic antipsychotic drug haloperidol is known to possess neurotoxic effects in experimental animals. The aim is to investigate neuronal injury, liver damage, and genotoxicity effects of haloperidol and their possible modulation by treatment with α-lactalbumin (Lacprodan® α-10) in the rat. Lacprodan® α-10 (100 or 200 mg/kg) was concurrently given with haloperidol (1.5 mg/kg) for 2 weeks. Compared with the saline control group, rats treated with only haloperidol exhibited significantly decreased reduced glutathione concentration and superoxide dismutase activity along with raised malondialdehyde levels in both brain and liver tissue. Additionally, haloperidol caused significant structural and numerical chromosomal aberrations, increased hepatic DNA fragmentation and DNA damage of peripheral blood lymphocytes. Oral administration of Lacprodan® α-10 in a dose of 200 mg/kg resulted in a significant increase in reduced glutathione concentration and decreased lipid peroxidation (malondialdehyde) in brain and liver tissue. Moreover, Lacprodan® α-10 (100–200 mg/kg) resulted in a significant increase in superoxide dismutase activity compared to the haloperidol control group. Lacprodan® α-10 ameliorated the gentotoxcity and DNA damage caused by haloperidol. The histological assessment showed that haloperidol caused degenerated neurocytes, and pericellular vacuolation. The liver exhibited significant damage with necrosis of hepatocytes, focal area of lymphocyte infiltration and hemorrhage in between hepatocytes. These changes were markedly ameliorated by treatment with Lacprodan® α-10 (200 mg/kg). Lacprodan® α-10 can prevent the neurotoxic and genotoxic/DNA damage caused by the haloperidol. Therefore, Lacprodan® α-10 is likely to prove of value in reducing these adverse effects in patients treated with haloperidol.

Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness.