Molecular Force Research Articles

Elucidation of interactions between myofibrillar proteins and κ-carrageenan as mediated by NaCl level: Perspectives on multiple spectroscopy and molecular docking

The present study was aimed to investigate the intermolecular interaction between myofibrillar proteins (MP) and κ-carrageenan (KC) as mediated by KC concentration (0.1, 0.2, 0.3, and 0.4 %, w/w) and NaCl levels (0.3 and 0.6 M) based on the multiple spectroscopy and molecular docking. The results showed that the incorporation of KC increased the turbidity, zeta-potential, and surface hydrophobicity of MP-KC mixed sols with a dose-dependent manner, as well as significantly decreasing the protein solubility (P < 0.05), which indicated that the interaction between KC and MP promoted the expansion of protein structure and exposed more hydrophobic groups. Fluorescence spectra result revealed that the interaction between MP and KC was a static quenching in the fluorescence quenching process, which affected the aromatic amino acids residue microenvironment of MP. Moreover, the existence of KC decreased the α-helix contents of MP (P < 0.05), contributing to the transformation from random structure to organized configuration of MP. In addition, molecular forces, the molecular docking and thermodynamic parameters indicated that hydrophobic interactions, van der Waals force, and hydrogen bonding were considered as the main interaction forces between MP and KC. Furthermore, 0.6 M NaCl level rendered higher solubility and particle size, as well as lower turbidity and the surface hydrophobicity of MP-KC mixed sols than those with 0.3 M NaCl level (P < 0.05), which promoted the unfolding of MP molecule and subsequently increased the numbers of binding sites between MP and KC, facilitating the intermolecular interactions between MP and KC in mixed sols.

Bioinspired engineered proteins enable universal anchoring strategy for surface functionalization

HypothesisConventional coating strategies and materials for bio-applications with protective, diagnostic, and therapeutic functions are commonly limited by their arduous preparation processes and lack of on-demand functionalities. Herein, inspired by the ‘root-leaf’ structure of grass, a series of novel polyacrylate-conjugated proteins can be engineered with sticky bovine serum albumin (BSA) protein as a ‘root’ anchoring layer and a multifunctional polyacrylate as a ‘leaf’ functional layer for the facile coating procedure and versatile surface functionalities. ExperimentsThe engineered proteins were synthesized based on click chemistry, where the ‘root’ layer can universally anchor onto both organic and inorganic substrates through a facile dip/spraying method with excellent stability in harsh solution conditions, thanks to its multiple adaptive molecular interactions with substrates that further elucidated by molecular force measurements between the ‘root’ BSA protein and substrates. The ‘leaf’ conjugated-polyacrylates imparted coatings with versatile on-demand functionalities, such as resistance to over 99% biofouling in complex biofluids, pH-responsive performance, and robust adhesion with various nanomaterials. FindingsBy synergistically leveraging the universal anchoring capabilities of BSA with the versatile physicochemical properties of polyacrylates, this study introduces a promising and facile strategy for imparting novel functionalities to a myriad of surfaces through engineering natural proteins and biomaterials for biotechnical and nanotechnical applications.

CaAl–NO2 LDH hybrid self-healing microcapsules with chloride triggering: Towards synergistic corrosion resistance

The synergistic corrosion resistance microcapsules (SCRMs) were synthesized by utilizing CaAl–NO2 LDH (NO2-LDH) as chloride trigger and high-performance corrosion inhibitor to hybridize self-healing microcapsules. The morphology, chemical structure and self-healing performance of the microcapsules were characterized. The chloride triggering and corrosion resistance property of the SCRMs were evaluated. The interaction of hybrid wall, NO2-LDH and chloride ion was calculated by first-principles. The findings revealed that the microcapsules show regular spherical with obvious core-wall structure. EDS and chemical structure measurements confirmed that NO2-LDH was successfully embedded within the microcapsule wall. The SCRMs showed excellent corrosion resistance property in simulated chloride-contaminated concrete pore solution (SCPS), and the highest inhibition efficiency was 97.85%. The microcapsule wall was hybridized by NO2-LDH species through chemical pathways. The first-principles calculation results confirmed that Ca and Al species are the main factors for chloride ion immobilization of hybrid wall. The ion exchange process of microcapsules destroys the molecular force of NO2-LDH@ethyl cellulose hybrid wall and improves the mechanical triggering efficiency of microcapsules in cement-based composites.

Properties of densities, viscosities, thermodynamics, spectroscopic and theoretical calculations for binary mixtures of N-octyl-2-pyrrolidone and N-dodecyl-2-pyrrolidinon with 1-decanol

Pyrrolidone and long chain alcohols are significant chemical products, which are widely used in petrochemical engineering, biofuels productions, and separations of organic compounds. In this work, the physicochemical data (density and viscosity) of two systems (N-octyl-2-pyrrolidone (NOP) + 1-decanol, N-dodecyl-2-pyrrolidone (NDP) + 1-decanol) were measured at the temperature of 303.15–323.15 K over the entire concentration range and atmosphere pressure. The excess molar volume (VEm), viscosity deviation (Δη) and thermodynamic parameter (ΔG*E) were calculated and correlated by the Redlich-Kister equation. From the point of molecular interaction force and molar volume (ΔVm), the variation trend and fitted results were explained in detail. Subsequently, the spectroscopic analysis including FTIR and UV–vis spectra proved the existence of intermolecular hydrogen bond between OH group of 1-decanol and NCO group of NOP or NDP. The theoretical chemical calculations further confirmed the hydrogen bond interaction.

All-Covalent Nuclease-Resistant and Hydrogel-Tethered DNA Hairpin Probes Map pN Cell Traction Forces.

Cells sense and respond to the physical properties of their environment through receptor-mediated signaling, a process known as mechanotransduction, which can modulate critical cellular functions such as proliferation, differentiation, and survival. At the molecular level, cell adhesion receptors, such as integrins, transmit piconewton (pN)-scale forces to the extracellular matrix, and the magnitude of the force plays a critical role in cell signaling. The most sensitive approach to measuring integrin forces involves DNA hairpin-based sensors, which are used to quantify and map forces in living cells. Despite the broad use of DNA hairpin sensors to study a variety of mechanotransduction processes, these sensors are typically anchored to rigid glass slides, which are orders of magnitude stiffer than the extracellular matrix and hence modulate native biological responses. Here, we have developed nuclease-resistant DNA hairpin probes that are all covalently tethered to PEG hydrogels to image cell traction forces on physiologically relevant substrate stiffness. Using HeLa cells as a model cell line, we show that the molecular forces transmitted by integrins are highly sensitive to the bulk modulus of the substrate, and cells cultured on the 6 and 13 kPa gels produced a greater number of hairpin unfolding events compared to the 2 kPa substrates. Tension signals are spatially colocalized with pY118-paxillin, confirming focal adhesion-mediated probe opening. Additionally, we found that integrin forces are greater than 5.8 pN but less than 19 pN on 13 kPa gels. This work provides a general strategy to integrate molecular tension probes into hydrogels, which can better mimic in vivo mechanotransduction.

A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity

Mechanosensitive (MS) ion channels are a ubiquitous type of molecular force sensor sensing forces from the surrounding bilayer. The profound structural diversity in these channels suggests that the molecular mechanisms of force sensing follow unique structural blueprints. Here we determine the structures of plant and mammalian OSCA/TMEM63 proteins, allowing us to identify essential elements for mechanotransduction and propose roles for putative bound lipids in OSCA/TMEM63 mechanosensation. Briefly, the central cavity created by the dimer interface couples each subunit and modulates dimeric OSCA/TMEM63 channel mechanosensitivity through the modulating lipids while the cytosolic side of the pore is gated by a plug lipid that prevents the ion permeation. Our results suggest that the gating mechanism of OSCA/TMEM63 channels may combine structural aspects of the ‘lipid-gated’ mechanism of MscS and TRAAK channels and the calcium-induced gating mechanism of the TMEM16 family, which may provide insights into the structural rearrangements of TMEM16/TMC superfamilies.

Comparative investigation of various modification methods on Trachypenaeus Curvirostris surimi gel: Gelling properties, rheological behaviors and structure characteristics.

The aim of this study was to compare the investigations of various contents of egg white protein (2.0%-8.0%, EWP), microbial transglutaminase (0.1%-0.4%, MTGase), and konjac glucomannan (0.5%-2.0%, KGM) on the gelling properties and rheological behavior of Trachypenaeus Curvirostris shrimp surimi gel (SSG), and assessed the modification mechanisms through the analysis of structure characteristics. The findings suggested that all modified SSG samples (expect SSG-KGM2.0% ) had the higher gelling properties and the denser network structure than those of unmodified SSG. Meanwhile, EWP could give SSG a better appearance than MTGase and KGM. Rheological results showed that SSG-EWP6% and SSG-KGM1.0% had the highest G' and G″, demonstrating that the formation of higher levels of elasticity and hardness. All modifications could increase gelation rates of SSG along with the reduction of G″ during the degeneration of protein. According to the FTIR results, three modification methods changed SSG protein conformation with the increasing α-helix and β-sheet contents and the decreasing of random coil content. LF-NMR results indicated that more free water could be transformed into immobilized water in the modified SSG gels, which contributed to improve the gelling properties. Furthermore, molecular forces showed that EWP and KGM could further increase the hydrogen bonds and hydrophobic interaction in SSG gels, while MTGase could induce the formation of more disulfide bonds. Thus, compared with another two modifications, EWP modified SSG gels showed the highest gelling properties.

Experimental characterisation of the dilation angle of polymers

Despite the wide use of Drucker-Prager plasticity-based models on polymers, the experimental measurement of the dilation angle, a critical parameter to fully describe the plastic potential, has been rarely reported in existing literature. This paper shows, for the first time, the experimental characterisation of the dilation angle of polymers over a wide range of plastic strain. These measurements were obtained from uniaxial compression experiments conducted on poly(methyl methacrylate) (PMMA) and an untoughened epoxy resin. The calculation of the dilation angle relied on the measurements of the compressive force and the strain components obtained via Digital Image Correlation (DIC). Lower values of dilation angle were obtained for the epoxy resin, suggesting that resistance to volumetric change during plastic deformation could be associated to molecular structure and internal forces. The methodology and results presented in this study can be applied to different types of materials and employed for developing and validating constitutive models that incorporate plastic dilation.

Development of mechanosensitive synthetic cells for biomedical applications

The ability of cells to sense and respond to their physical environment plays a fundamental role in a broad spectrum of biological processes. As one of the most essential molecular force sensors and transducers found in cell membranes, mechanosensitive (MS) ion channels can convert mechanical inputs into biochemical or electrical signals to mediate a variety of sensations. The bottom-up construction of cell-sized compartments displaying cell-like organization, behaviors, and complexity, also known as synthetic cells, has gained popularity as an experimental platform to characterize biological functions in isolation. By reconstituting MS channels in the synthetic lipid bilayers, we envision using mechanosensitive synthetic cells for several medical applications. Here, we describe three different concepts for using ultrasound, shear stress, and compressive stress as mechanical stimuli to activate drug release from mechanosensitive synthetic cells for disease treatments.

LagNet: Deep Lagrangian Mechanics for Plug-and-Play Molecular Representation Learning

Molecular representation learning is a fundamental problem in the field of drug discovery and molecular science. Whereas incorporating molecular 3D information in the representations of molecule seems beneficial, which is related to computational chemistry with the basic task of predicting stable 3D structures (conformations) of molecules. Existing machine learning methods either rely on 1D and 2D molecular properties or simulate molecular force field to use additional 3D structure information via Hamiltonian network. The former has the disadvantage of ignoring important 3D structure features, while the latter has the disadvantage that existing Hamiltonian neural network must satisfy the “canonial” constraint, which is difficult to be obeyed in many cases. In this paper, we propose a novel plug-and-play architecture LagNet by simulating molecular force field only with parameterized position coordinates, which implements Lagrangian mechanics to learn molecular representation by preserving 3D conformation without obeying any additional restrictions. LagNet is designed to generate known conformations and generalize for unknown ones from molecular SMILES. Implicit positions in LagNet are learned iteratively using discrete-time Lagrangian equations. Experimental results show that LagNet can well learn 3D molecular structure features, and outperforms previous state-of-the-art baselines related molecular representation by a significant margin.

Physicochemical origins of prokaryotic and eukaryotic organisms.

Origins research currently rests on a vitalistic foundation and requires reconceptualization. From a cellular perspective, prokaryotic cells grow and divide in stable, colloidal processes, throughout which the cytoplasm remains crowded (concentrated) with closely interacting proteins and nucleic acids. Their functional stability is ensured by repulsive and attractive non-covalent forces, especially van der Waals forces, screened electrostatic forces, and hydrogen bonding (hydration and the hydrophobic effect). On average, biomacromolecules are crowded at above 15% volume fraction, surrounded by up to 3 nm layer of aqueous electrolyte at ionic strength above 0.01 molar; they are energized by biochemical reactions coupled to nutrient environments. During cellular growth, non-covalent molecular forces and biochemical reactions stabilize the cytoplasm as a two-phase, colloidal system comprising vectorially structured cytogel and dilute cytosol. From a geochemical perspective, Earth's rotation kept prebiotic molecules in continuous cyclic disequilibria in Usiglio-type intertidal pools, rich in potassium and magnesium ions, the last cations to precipitate from evaporatig seawater. These ions impart biochemical functionality to extant proteins and RNAs. The prebiotic molecules were repeatedly purified by phase separation in response to tidal drying and rewetting; they were chemically evolving as briny, carbonaceous inclusions in tidal sediments until the crowding transition allowed chemical evolution to proceeed toward Woesian progenotes, the Last Universal Common Ancestors (LUCAs) and the first prokaryotes. These cellular and geochemical processes are summarized as a jigsaw puzzle of the emerging and evolving prokaryotes. Their unavoidable cyclic fusions and rehydrations along Archaean coastlines initiated the emergence of complex Precambrian eukaryotes.

Experimental study on the effect of high water cut on the emulsifying properties of crude oil

Most waterflooding oilfields have entered the high water cut stage, but significant amounts of crude oil remain in the formation. Therefore, understanding the emulsifying characteristics of crude oil with high water content is crucial. This study investigates the effects of shear time, shear rate, temperature, water content, and re-emulsification at high water content on the emulsifying properties of crude oil. Results indicate that shear time, temperature, and water content play a role in enhancing the emulsifying capacity of crude oil. Additionally, the initial water content of the emulsion affects the solubilization ability of crude oil; lower initial water content leads to stronger solubilization ability, while higher total water content leads to weaker solubilization capacity. Under an optical microscope, the morphology of the emulsion was observed, revealing that an increase in water content resulted in an increase in particle size and quantity of emulsion droplets, leading to more uniform droplets. However, at high water content, the particle size of emulsion decreased, the number of droplets decreased, and the droplets became uneven. Furthermore, the particle size of re-emulsified emulsion was smaller than that of the emulsion with the same moisture content, indicating that re-emulsification can lead to instability. The interfacial characteristics of the emulsion were also analyzed, showing that an increase in water content caused an increase in interfacial tension and expansion modulus of emulsion compared to crude oil. Finally, the study elucidates the influence mechanism of high-water content on the emulsifying performance of crude oil, which includes the destruction of molecular forces on and between interfaces, weakening the steric hindrance effect. Unstable film and non-uniform droplets can promote coalescence and fragmentation of droplets, limiting the emulsifying performance of crude oil. The results of this study provide a better understanding of the formation and fracture process of emulsion under high water cut conditions, offering a theoretical basis for further enhanced oil recovery.

Immunometabolic aspects of chronic nonspecific inflammation in obesity

The disappointing results of epidemiological studies in recent years continue to attract the attention of scientists to obesity - one of the most acute medical and social problems of our time. In the last few decades, adipose tissue has been regarded as an immunobiological and endocrine organ that secretes a large number of hormones, adipokines and growth factors that play an important role in regulating energy homeostasis and a variety of immune processes. The latest results of molecular genetic, immunometabolic, morphological and microbiological studies force scientists to approach the study of this complex issue from different angles. One of them is a change in the work of the immune system in conditions of overweight, which is based on the formation of chronic nonspecific inflammation. The presented review examines the pathogenetic mechanisms of the formation of the inflammatory process against the background of obesity, in the development of which several stages are currently conditionally distinguished: adipocyte hypertrophy, hypoxia, adipocyte necrosis, cellular infiltration and the formation of fibrosis. The article also analyzes modern scientific data on the relationship of chronic inflammation with complications of obesity and the physiological characteristics of the child's body, which can be an important link in the formation of metabolic disorders. In addition, the authors discuss the possible connection of the formation of various obesity phenotypes with a violation of the implementation of certain immune mechanisms – an area in which there is currently a significant amount of disagreement and unresolved issues. Further study of the phenotypes of obesity is one of the key points underlying the formation of metabolic disorders in this disease.

Study on the Hydroconversion Law of Coal-Based Heavy Fractions with Different Catalyst Contents Based on an Improved Separation Method.

Heavy fractions (e.g., asphaltene and resin) can easily be subjected to physical aggregation and chemical coking reaction through molecular force in the process of lightweight processing and use of coal tar (CT), such that the normal processing and use can be affected. In this study, hydrogenation experiments were performed by regulating the catalyst to oil ratio (COR), while the heavy fractions of the hydrogenated products were extracted based on a novel separation method (e.g., the resin with a poor separation effect and rare existing research). The samples were analyzed through Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. On that basis, the composition and structure characteristics of heavy fractions and the law of hydrogenation conversion were investigated. As indicated by the results, with the rise of the COR, the saturates, aromatics, resins, and asphaltenes (SARA) contents indicated the law of increasing the content of saturate, decreasing the content of other fractions, as well as sharply decreasing the content of asphaltene. Moreover, with the increase of the reaction condition, the relative molecular weight, the content of the hydrogen bonded functional groups and C-O groups, the carbon skeleton properties, the number of aromatic rings, and the stacking structure parameters were progressively reduced. In comparison with resin, asphaltene was characterized by large aromaticity and more aromatic rings, short and less alkyl side chains, as well as more complex heteroatoms on the surface of the heavy fractions. The results achieved in this study are expected to lay a solid basis for the relevant theoretical research and facilitate the industrial use process of CT processing.

Molecular Force Imaging Reveals That Integrin-Dependent Mechanical Checkpoint Regulates Fcγ-Receptor-Mediated Phagocytosis in Macrophages.

Macrophages are a type of immune cell that helps eliminate pathogens and diseased cells. Recent research has shown that macrophages can sense mechanical cues from potential targets to perform effective phagocytosis, but the mechanisms behind it remain unclear. In this study, we used DNA-based tension probes to study the role of integrin-mediated forces in FcγR-mediated phagocytosis. The results showed that when the phagocytic receptor FcγR is activated, the force-bearing integrins create a "mechanical barrier" that physically excludes the phosphatase CD45 and facilitates phagocytosis. However, if the integrin-mediated forces are physically restricted at lower levels or if the macrophage is on a soft matrix, CD45 exclusion is significantly reduced. Moreover, CD47-SIRPα "don't eat me" signaling can reduce CD45 segregation by inhibiting the mechanical stability of the integrin barrier. These findings demonstrate how macrophages use molecular forces to identify physical properties and combine them with biochemical signals from phagocytic receptors to guide phagocytosis.

A tile model of circuit topology for self-entangled biopolymers

Building on the theory of circuit topology for intra-chain contacts in entangled proteins, we introduce tiles as a way to rigorously model local entanglements which are held in place by molecular forces. We develop operations that combine tiles so that entangled chains can be represented by algebraic expressions. Then we use our model to show that the only knot types that such entangled chains can have are 3_1, 4_1, 5_1, 5_2, 6_1, 6_2, 6_3, 7_7, 8_{12} and connected sums of these knots. This includes all proteins knots that have thus far been identified.

Brittleness mechanism of pork meatballs revealed from molecular structure to macroscopic performance

AbstractMeatballs are manufactured with great craftsmanship, but the brittle quality of meatballs is not resistant to frozen storage, which limits the large‐scale promotion of meatballs for transportation. Meanwhile, the ‘brittle mechanism’ of meatballs is still unclear and it is difficult to solve the scientific problem of brittle quality loss of meatballs from the root. This study revealed the mechanism underlying the brittleness of pork meatballs gel. In this study, the rheological properties, textural quality, molecular forces and microstructure of meatballs were characterized using fresh meat (FsM group), ambient meat group, frozen meat group, and ground meat group. The results showed that the FsM group presented better sensorial characteristics. The rheological properties of the FsM group exhibited higher storage modulus (G′) and loss modulus (G″), indicating better viscoelastic properties. The results of textural determination reflected that the FsM group showed improved brittleness quality and the brittleness was supported by hydrophobic interactions and disulfide bonds. The FsM group with good brittleness quality formed a ‘large cavity’ microstructure. The correlations analysis revealed a correlation between the texture properties of meatballs and their protein molecular forces. Our findings clearly provide new insights into the mechanism underlying the brittleness of meatballs.

Contact interaction model of liquid and solid phases

The work implements the approach formulated by B.V. Deryagin, which states for replacing the Coulomb and molecular (dispersion) forces with a system of tensions obtained on the basis of the mechanics of continuum equations using an incompressible liquid model. Interphasal activity modeling is considered from the standpoint of the equilibrium equations of mechanics of continuum using an incompressible liquid model and representing the interfacial tension tensor as a combination of spherical and deviatoric components. Analytical expressions are obtained for the components of the tension tensor depending on the wetting conditions of a solid surface with a liquid. Intermolecular interaction is determined by the value of the internal pressure of the liquid, which is variable over the interfacial layer thickness. The anisotropy of the interfacial tension tensor in the liquid-solid interfacial layer is expressed by the representation of the spherical and deviatoric components combination, which provides the equilibrium conditions for the interfacial layer. The authors propose to consider the adhesive contact as an external force effect of a solid surface on the volume phase of a liquid, leading to the formation of an interfacial tension tensor with components that are variable over the layer thickness. The authors established the nonlinear nature of the interfacial pressure distribution over the layer thickness, due to the difference in interfacial pressures in the liquid and solid phases in the direct contact zone. It is shown that the surface phenomena specificity is due to the deformation of the liquid volume in the interfacial layer, which leads to a change in intermolecular distances in different directions, which occurs with any kind of force acting on the volume phase of the liquid. The law of intermolecular forces distribution of a liquid depending on the distance is established based on the study results of a sitting drop. Expressions are obtained for determining the long-range interaction radius of liquid molecules and the thickness of the liquid-solid interfacial layer, which give a result that fits into the known estimates of the values of these quantities.

LAP2β transmits force to upregulate genes via chromatin domain stretching but not compression.

There is increasing evidence that force impacts almost every aspect of cells and tissues in physiology and disease including gene regulation. However, the molecular pathway of force transmission from the nuclear lamina to the chromatin remain largely elusive. Here we employ two different approaches of a local stress on cell apical surface via an RGD (Arg-Gly-Asp)-coated magnetic bead and whole cell deformation at cell basal surface via uniaxial or biaxial deformation of a fibronectin-coated flexible polydimethylsiloxane substrate. We find that nuclear protein LAP2β mediates force transmission from the nuclear lamina to the chromatin. Knocking down LAP2β increases spontaneous movements of the chromatin by reducing tethering of the chromatin and substantially inhibits the magnetic bead-stress or the substrate-deformation induced chromatin domain stretching and the ensuing dihydrofolate reductase (DHFR) gene upregulation. Analysis of DHFR gene-containing chromatin domain alignments along or perpendicular to the direction of the stretching/compressing reveals that the chromatin domain must be stretched and not compressed in order for the gene to be rapidly upregulated. Together these results suggest that external-load induced rapid transcription upregulation originates from chromatin domain stretching but not compressing and depends on the molecular force transmission pathway of LAP2β. STATEMENT OF SIGNIFICANCE: How force regulates gene expression has been elusive. Here we show that the orientation of the chromatin domain relative to the stress direction is crucial in determining if the chromatin domain will be stretched or compressed in response to a cell surface loading. We also show that nuclear protein Lap2b is a critical molecule that mediates force transmission from the nuclear laminar to the chromatin to regulate gene transcription. This study reveals the molecular force transmission pathway for force-induced gene regulation.

Iridoids from Morinda lucida, (Benth.) Rubiaceae, produced analgesic and anti-inflammatory activities via agonism at the kappa and delta opioid receptors, inhibition of COX-2 besides elevation of CAT and SOD activities.

Pain and inflammation are the major symptoms of almost every human disease. Herbal preparations from Morinda lucida are used to treat pain and inflammation in traditional medicine. However, the analgesic and anti-inflammatory activities of some of its chemical constituents are not known. The aim of this study is to evaluate the analgesic and anti-inflammatory activities and possible mechanisms of these activities of iridoids from Morinda lucida. The compounds were isolated using column chromatography and characterized by NMR spectroscopy and LC-MS. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema. Whereas, the analgesic activity was assessed in the hot plate and acetic acid-induced writhing assays. Mechanistic studies were conducted using pharmacological blockers, determination of antioxidant enzymes, lipid peroxidation, and docking studies. The iridoid, ML2-2 exhibited inverse dose-dependent anti-inflammatory activity (42.62% maximum at 2 mg/kg p. o). ML2-3 produced dose-dependent anti-inflammatory activity (64.52% maximum at 10 mg/kg p. o.). Anti-inflammatory activity of diclofenac sodium was 58.60% at 10 mg/kg p. o. Furthermore, ML2-2 and ML2-3 produced analgesic activity (P < 0.01) of 44.44 ± 5.84 and 54.18 ± 19.01%. at 10 mg/kg p. o. respectively in the hot plate assay and 64.88 and 67.44% in the writhing assay. ML2-2 significantly elevated catalase activity. However, ML2-3 elevated SOD and catalase activity significantly. In the docking studies, both iridoids formed stable crystal complexes with delta and kappa opioid receptors, and the COX-2 enzyme with very low free binding energies (ΔG) from -11.2 to -14.0 kcal/mol. However, they did not bind with the mu opioid receptor. The lower bound RMSD of most of the poses were found to be ≤ 2. Several amino acids were involved in the interactions through various inter molecular forces. These results indicate that ML2-2 and ML2-3 possessed very significant analgesic and anti-inflammatory activities via acting as both delta and kappa opioid receptor agonist, elevation of anti-oxidant activity and inhibition of COX-2.