Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.

Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.

Development and Validation of Reverse-Phase High-Performance Liquid Chromatography Method for Simultaneous Estimation of Doxorubicin and Clotrimazole.

A reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed to analyze the simultaneous estimation of doxorubicin and clotrimazole. The method was achieved by Nucleodur C18 column with dimension 250 × 4.6 mm (5 µm) using gradient elution. The mobile phase contained 0.2% formic acid (pH 3.2) and acetonitrile. The flow rate was kept at 1.0 mL/min and detection and quantitation of both drugs (doxorubicin and clotrimazole) were achieved using a photodiode array detector at 276 nm, which was the isosbestic point for both drugs. The proposed method was validated according to the current International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use guidelines for specificity, linearity, accuracy, precision, and robustness. The developed method showed a linear response (R2 > 0.999), and was accurate (recoveries 97%-103%), precise (resolution ≤1.0%), sensitive, and specific. Thus, the developed RP-HPLC method for the simultaneous estimation of both drugs was successfully validated and can be utilized for the estimation of these drugs in the formulations being developed.

Hybrids of Benzimidazole-Oxadiazole: A New Avenue for Synthesis, Pharmacological Activity and Recent Patents for the Development of More Effective Ligands.

BACKGROUND: Two significant families of compounds i.e. 1,3,4-oxadiazole and ben-zimidazole, have undergone extensive investigation into their pharmacological characteristics and possible therapeutic applications. Both classes have shown their potential in a variety of ap-plications, and because of their synergistic interactions, they may have an even better therapeutic impact when combined. OBJECTIVES: To produce a specific molecule with potent therapeutic properties, it is now common methods to combine at least two pharmacophores. This facilitates interaction with several targets, enhances biological functions, or eliminates adverse effects associated with them. CONCLUSION: The synthesis of benzimidazole-1,3,4-oxadiazole hybrid compounds has recently involved the use of several synthetic techniques, all of which are detailed in the literature along with the advantages and disadvantages. It has been noted that the structure-activity relationship relates their pharmacological actions to their molecular structure. In order to set the stage for future research, the study aims to provide researchers with an effective toolbox and an under-standing of benzimidazole and 1,3,4-oxadiazole hybrid compounds.

Prospects of chitinase in sustainable farming and modern biotechnology: an update on recent progress and challenges.

Chitinases are multifunctional biocatalysts for the pest control and useful in modern biotechnology and pharmaceutical industries. Chemical-based fungicides and insecticides have caused more severe effects on environment and human health. Many pathogenic fungal species and insects became resistant to the chemical pesticides. The resistant fungi emerged as a multidrug resistant also and less susceptible insects are not possible to control adequately. Chitinases have an immense potential to be exploited as a biopesticide against fungi and insects. The direct use of chitinase in liquid formulation or whole microbial enzyme producing cells, both act as antagonistically against the pests. Chitinase can disintegrate the fungal cell wall and insect integument that holds the chitin as a vital structural component. Moreover, chitinase is applied for the synthesis of pharmaceutically important chitooligosaccharides. Chitinase producing microbes have the huge potential to utilize against the waste management of sea food remains like shells of crustaceans. Chitinase is valuable for the synthesis of protoplasts from industrially important fungi, further it act as the biocontrol agent of malaria and dengue fever causing larvae of mosquitoes. Chitinases also have been successfully used in wine and single cell protein producing industries. Present review is illustrating the updated information on the state of the art of different applications of chitinases in agriculture and biotechnology industry. It also bestows the understanding to the readers about the areas of extensively studied and the field where there is still much left to be done.

Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?

Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.

Lycopene: Sojourn from kitchen to an effective therapy in Alzheimer's disease.

Reports on a significant positive correlation between consumption of carotenoid-rich food and prevention of Alzheimer's disease (AD) led to the investigation of carotenoids for the treatment and prevention of AD. More than 1100 types of carotenoids are found naturally, out of which only around 50 are absorbed and metabolized in human body. Lycopene is one of the most commonly ingested members of fat-soluble carotenoid family that gives vegetables and fruits their red, yellow, or orange color. Lycopene has established itself as a promising therapy for AD owing to its neuroprotective activities, including antioxidant, anti-inflammatory, and antiamyloidogenic properties. In this review, we highlight the various in vitro and preclinical studies demonstrating the neuroprotective effect of lycopene. Also, some epidemiological and interventional studies investigating the protective effect of lycopene in AD have been discussed. Diving deeper, we also discuss various significant mechanisms, through which lycopene exerts its remissive effects in AD. Finally, to overcome the issue of poor chemical stability and bioavailability of lycopene, some of the novel delivery systems developed for lycopene have also been briefly highlighted.

Psoriasis: Interplay between dysbiosis and host immune system.

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.

Advances in designing of polymeric micelles for biomedical application in brain related diseases.

In recent years, unique physicochemical properties of amphiphilic block copolymers have been utilized to design the polymeric micelles for brain-specific delivery of drugs, proteins, peptides and genes. Their unique properties such as nano-size, charge-switching ability, stimuli-responsive cargo release, flexible structure, and self-assembly enable them to overcome limitations of conventional dosage forms that include rapid drug release, drug efflux, and poor brain bioavailability, and poor stability. These limitations hinder their therapeutic efficacy in treating brain diseases. Their ease of functionalization and enhanced penetration and retention effect make them suitable nanocarriers for the diagnosis of various brain diseases. In this context, the present manuscript provides an insight into the progress made in the functionalization of micelles such as the incorporation of stimuli-sensitive moieties in copolymers, conjugation of cargo molecules with the core-forming block via responsive smart linkers, and conjugation of active ligands and imaging moieties with the corona forming block for brain targeting and imaging. Further, the review also expounds on the role of polymeric micelles in delivering neurotherapeutic to the brain. Some patents related to polymeric micelles formulated for brain delivery are also enlisted.

Antimicrobial peptides: A plausible approach for COVID-19 treatment.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected >400 million people globally leading to >5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs). AREAS COVERED: This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed. EXPERT OPINION: Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.

Natural compounds as safe therapeutic options for ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin antagonist, and salicylates are available but are associated with the various limitations and side-effects. None of the above treatments helps to achieve the ultimate goal of the therapy, i.e., maintenance of remission in the long-term. Natural remedies for the treatment of UC show comparatively less side effects as compared to conventional approaches, and affordable. The current review presents details on the role of herbal drugs in the treatment and cure of UC. Google, PubMed, Web of Science, and Scopus portals have been searched for potentially relevant literature to get the latest developments and updated information related to use of natural drugs in the treatment of UC. Natural products have been used over centuries to treat UC. Some of the essential herbal constituents exhibiting antiulcerogenic activity include gymnemic acid (Gymnema sylvestre), shagoal (Zingiber officinale), catechin (Camellia sinensis), curcumin (Curcuma longa), arctigenin (Arctium lappa), and boswellic acid (Boswellia serrata). Although many plant-derived products have been recommended for UC, further research to understand the exact molecular mechanism is still warranted to establish their usefulness clinically.

Orchestration of Obesolytic Activity of Microbiome: Metabiotics at Centre Stage.

Metabiotics have emerged as the safer alternatives to probiotics in last decade. Unlike probiotics that are live microbes, metabiotics are the low molecular weight bioactive metabolites produced by the gut microbiota. While offering a similar profile of health benefits as that of probiotics, metabiotics are free from the risks and uncertain responses associated with administration of live bacteria into the body. Metabiotics have demonstrated substantial effectiveness across the ethnicities, age, gender and nutritional habits in a number of metabolic disorders, including obesity. Obesity is attributed to the offsetting of the energy homeostasis of the body due to a number of genetic, endocrinological, and environmental factors leading to obesity. The obesogenic mechanisms are quite complicated as they result from a complex interplay among a number of factors. Owing to a variety of constituents exerting their action through different pathways, metabiotics offer a pragmatic option for treatment as well as prevention of obesity by addressing heterogeneous aspects of its aetiology. In this review, we categorize various components of metabiotics and discuss their cross-talk with host cells at the molecular level. We also discuss the challenges in understanding these interactions and their potential effects on obesity treatment and prevention strategies. Considering the alarming rise in obesity all over the world, metabiotics offer an attractive non-pharmacological approach to spearhead the strategies being designed to combat the challenges posed by the obesity epidemic.

Sweet pepper and its principle constituent capsiate: functional properties and health benefits.

Capsiate is a non-pungent analogue of capsaicin. It belongs to the family of capsinoids which are esters of vanillyl alcohol with fatty acids while capsaicin belongs to the family of capsaicinoids that are amides of vanillylamine with a variety of branched-chain fatty acids. While capsaicin is extensively reported for plethora of pharmacological actions, capsiate remains much less explored. Extracted from various species of Capsicum plant, the molecule has also been chemically synthesized via a number of synthetic and enzymatic routes. Based on its action on transient receptor potential vanilloid subfamily member 1 receptors, recent research has focused on its potential roles in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. Its toxicity profile has been reported to be much safe. The molecule, however, faces the challenge of low aqueous solubility and stability. It has been commercialized for its use as a weight loss supplement. However, the therapeutic potential of the compound which is much beyond boosting metabolism remains unexplored hitherto. This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. Discussed also are potential future directions for formulation strategies to develop efficient, safe and cost-effective dosage forms of capsiate to explore its role in various disease conditions. The databases investigated include Cochrane library, Medline, Embase, Pubmed and in-house databases. The search terms were "capsiate," "capsinoids," "thermogenesis," and their combinations. The articles were screened for relevance by going through their abstract. All the articles pertaining to physicochemical, physiological, pharmacological and therapeutic effects of capsiate have been included in the manuscript.

Overcoming hydrolytic degradation challenges in topical delivery: non-aqueous nano-emulsions.

INTRODUCTION: Non-aqueous nano-emulsions (NANEs) are colloidal lipid-based dispersions with nano-sized droplets formed by mixing two immiscible phases, none of which happens to be an aqueous phase. Their ability to incorporate water and oxygen sensitive drugs without any susceptibility to degradation makes them the optimum dosage form for such candidates. In NANEs, polar liquids or polyols replace the aqueous phase while surfactants remain same as used in conventional emulsions. They are a part of the nano-emulsion family albeit with substantial difference in composition and application. AREAS COVERED: The present review provides a brief insight into the strategies of loading water-sensitive drugs into NANEs. Further advancement in these anhydrous systems with the use of solid particulate surfactants in the form of Pickering emulsions is also discussed. EXPERT OPINION: NANEs offer a unique platform for delivering water-sensitive drugs by loading them in anhydrous formulation. The biggest advantage of NANEs vis-à-vis the other nano-cargos is that they can also be prepared without using equipment-intensive techniques. However, the use of NANEs in drug delivery is quite limited. Looking at the small number of studies available in this direction, a need for further research in this field is required to explore this delivery system further.

Discovery and Development of Antibacterial Agents: Fortuitous and Designed.

Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of the investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan, and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

Microfluidic chips: recent advances, critical strategies in design, applications and future perspectives.

Microfluidic chip technology is an emerging tool in the field of biomedical application. Microfluidic chip includes a set of groves or microchannels that are engraved on different materials (glass, silicon, or polymers such as polydimethylsiloxane or PDMS, polymethylmethacrylate or PMMA). The microchannels forming the microfluidic chip are interconnected with each other for desired results. This organization of microchannels trapped into the microfluidic chip is associated with the outside by inputs and outputs penetrating through the chip, as an interface between the macro- and miniature world. With the help of a pump and a chip, microfluidic chip helps to determine the behavioral change of the microfluids. Inside the chip, there are microfluidic channels that permit the processing of the fluid, for example, blending and physicochemical responses. Microfluidic chip has numerous points of interest including lesser time and reagent utilization and alongside this, it can execute numerous activities simultaneously. The miniatured size of the chip fastens the reaction as the surface area increases. It is utilized in different biomedical applications such as food safety sensing, peptide analysis, tissue engineering, medical diagnosis, DNA purification, PCR activity, pregnancy, and glucose estimation. In the present study, the design of various microfluidic chips has been discussed along with their biomedical applications.

Development of mushroom polysaccharide and probiotics based solid self-nanoemulsifying drug delivery system loaded with curcumin and quercetin to improve their dissolution rate and permeability: State of the art.

The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nanocarriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.

Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission.

Recent updates on animal models for understanding the etiopathogenesis of polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.

Exploring role of polysaccharides present in Ganoderma lucidium extract powder and probiotics as solid carriers in development of liquisolid formulation loaded with quercetin: A novel study.

Ganoderma lucidium extract powder (GLEP) contains various polysaccharides which are well known for their antioxidant and anti-inflammatory actions. Probiotics (PB) are well-established for providing a plethora of health benefits. Hence, use of mushroom polysaccharides and probiotics as carriers to solidify liquisolid formulation is anticipated to function as functional excipients i.e. as adsorbent that may provide therapeutic benefits. Quercetin (QUR) has been used as model lipophilic drug in this study. QUR loaded liquisolid compacts (LSCs) were formulated using Tween 80 as solvent. These were further solidified using a combination of PB and GLEP as carriers. Aerosil-200 (A-200) was used as coating agent. The formulation exhibited very good flow characteristics. Dissolution rate of raw QUR was found to be less than 10% in 60 min while in case of QUR loaded LSCs, more than 90% drug release was observed within 5 min. Absence of crystalline peaks of QUR in the DSC and PXRD reports of LSCs and their porous appearance in SEM micrographs indicate that QUR was successfully incorporated in the LSCs. The developed formulation was found to be stable on storage under accelerated stability conditions.

Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant. AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta. MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied. RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner. CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.