ETHNOPHARMACOLOGICAL RELEVANCE:Ferula assa-foetida, has been used for centuries as a spice, is well acknowledged as a traditional medicine in Ayurveda, and as a folklore medicine across the globe for its neurological benefits. In recent years, modern pharmacological studies have augmented its potential against various neurological disorders, thus signifying its therapeutic importance against neurological disorders in both ethnic and modern medicinal aspects. AIM OF THE STUDY:We aimed to identify Monoamine oxidase (MAO)-inhibiting sesquiterpene coumarins from Ferula assa-foetida through activity-guided isolation and evaluate them using in vitro and in vivo models relevant to Parkinson's disease (PD). MATERIALS AND METHODS:LC-MS2 was used for the detection of the sesquiterpene coumarins, followed by chromatographic fractionation, and semi-preparative HPLC-mediated purification of the 19 compounds; their structures were established by the combined use of MS, 1D, and 2D NMR techniques. MAO assay identified two active compounds for further study. Toxicity was evaluated in SH-SY5Y cells, Drosophila, and C57BL/6 mice. Effects on mice brain MAO activity and striatal dopamine were examined by LC-MS/HPLC. Finally, neuroprotective effects were validated in an MPTP-induced PD mouse model. RESULTS:LC-MS2 analysis confirmed the presence of naturally occurring sesquiterpene coumarin hybrids with significant structural diversity in Ferula assa-foetida oleo-gum-resin, and 19 compounds were isolated for characterization. After preliminary in vitro MAO assays karatavicinol and farnesiferol C were selected for further evaluation. Both compounds exhibited BBB permeability, inhibited MAO activity in mice brain, and effectively elevated dopamine levels in the striatum. Additionally, these compounds demonstrated their therapeutic potential against PD in a mice model. CONCLUSIONS:The 7 substituted coumarins with the structurally diverse sesquiterpene moieties displayed varying degrees of MAO inhibition. Further detailed investigation on karatavicinol and farnesiferol C confirmed that both compounds holds significant therapeutic potential to address PD related dopamine deficiency, motor incoordination, and neurodegeneration.

BACKGROUND AND PURPOSE:Chemoresistance and tumour relapse pose significant challenges in achieving successful chemotherapy outcomes. Targeting DNA polymerase eta (Pol ƞ)-mediated mutagenic translesion DNA synthesis (TLS) has emerged as a promising strategy for improving chemotherapy. However, the identification of small molecule inhibitors targeting Pol ƞ -mediated TLS with high in vivo efficacy remains a challenge. EXPERIMENTAL APPROACH:The small molecule was identified through in silico screening. Pol η inhibitory potential of the identified small molecule was validated by a fluorescent-based reporter strand displacement assay. Flow cytometry was conducted to analyse the CD44 + CD117 + cancer stem-like cell (CSC) population and live-dead cell population. Xenograft mouse models were used to test the CSC sensitising potential. KEY RESULTS:We screened and identified chrysin as a small-molecule inhibitor that sensitises ovarian cancer stem-like cells to cisplatin treatment by inhibiting Pol ƞ -mediated TLS. Chrysin effectively inhibits Pol ƞ expression, mitigates cancer stem-like cell enrichment and enhances cisplatin-induced cell death both in vitro and in vivo. Furthermore, chrysin treatment reduces spontaneous and cisplatin-induced mutagenesis. Pre-treatment with chrysin attenuates cisplatin-induced haematological toxicity and suppresses tumour growth in human ovarian cancer xenografts. CONCLUSIONS AND IMPLICATIONS:These results establish chrysin as a novel class of TLS inhibitors and highlight its potential as a chemotherapy adjuvant for overcoming chemoresistance and improving treatment outcomes in ovarian cancer.

Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative disorders. Behavioral complexities worsen over time due to progressive dopaminergic (DArgic) neuronal loss at substantia nigra region of brain. Available treatments typically aim to increase dopamine (DA) levels at striatum. DA is degraded by Monoamine oxidase (MAO), thus dietary phytochemicals with MAO inhibitory properties can contribute to elevate DA levels and reduce the ailment. Characterization of naturally occurring dietary MAO inhibitors is inadequate. Based on available knowledge, we selected different classes of molecules and conducted a screening process to assess their potential as MAO inhibitors. The compounds mostly derived from food sources, broadly belonging to triterpenoids (ursane, oleanane and hopane), alkaloid, polyphenolics, monoterpenoids, alkylbenzene, phenylpropanoid and aromatic alcohol classes. Among all the molecules, highest level of MAO inhibition is offered by α-viniferin, a resveratrol trimer. Cell viability, mitochondrial morphology and reactive oxygen species (ROS) generation remained unaltered by 50 μM α-viniferin treatment in-vitro. Toxicity studies in Drosophila showed unchanged gross neuronal morphology, ROS level, motor activity or long-term survival. α-Viniferin inhibited MAO in mice brain and elevated striatal DA levels. PD-related akinesia and cataleptic behavior were attenuated by α-viniferin due to increase in striatal DA. Our study implies that α-viniferin can be used as an adjunct phytotherapeutic agent for mitigating PD-related behavioral deterioration.

Bacterial infections caused by Staphylococcus aureus are one of the growing concerns for human health care management globally. Antibiotic-associated adverse effects and the emergence of bacterial resistant strains necessitate the development of an alternative yet effective approach. Nanoemulsion-based therapy has emerged as a potential therapeutic strategy to combat bacterial infestation. Herein, we designed a cationic metal nanoparticle-conjugated fusogenic nanoemulsion (CFusoN) as a lipid solubilizing nanovesicle for the effective treatment of S. aureus infection with a killing efficiency of 99.999%. The cationic nanoparticle-conjugated nanoemulsion (viz. NECNP) (24.4 ± 2.9 mV) electrostatically bound with the negatively charged bacterial cell membrane (-10.2 ± 3.7 mV) causing alteration of the bacterial surface charge. The fluorometric and flow cytometry studies confirmed the bacterial membrane depolarization and altered cell membrane permeability leading to cell death. The atomic force microscopic studies further demonstrated the damage of the cellular ultrastructure, while the transmission electron microscopic image and membrane lipid solubilization analysis depicted the solubilization of the bacterial membrane lipid bilayer along with the leakage of the intracellular contents. The cell membrane fatty acid analysis revealed that the methyl esters of palmitic acid, stearic acid and octadecadienoic acid isomers were solubilized after the treatment of S. aureus with CFusoN. The bactericidal killing efficiency of CFusoN is proposed to occur through the synergistic efficacy of the targeted attachment of CNP to the bacterial cells along with the lipid solubilization property of NE. Interestingly, NECNP didn't elicit any in vitro hemolytic activity or cytotoxicity against red blood cells (RBCs) and L929 fibroblast cells, respectively, at its bactericidal concentration. Furthermore, a porcine skin wound infection model exhibited the enhanced wound cleansing potency of CFusoN in comparison to the commercially available wound cleansers. The obtained antibacterial activity, biocompatibility and skin wound disinfection efficacy of the NECNP demonstrated the formulation of a cell targeted CFusoN as a promising translatable strategy to combat bacterial infection.

Carex genus contains over 2000 species distributed all around the globe and used for their medicinal and food values. Owing to their traditional and medicinal properties the genus has gained due attention, especially in the last couple of decades which led to the identification of terpenoids, lignans, quinazolinones, phenolic acids, and phenylpropanoids as the major phytochemicals. Besides these several studies reported the therapeutic applications of the extracts and phytochemicals in different experimental conditions. The present review aims to present a comprehensive overview of the present standing of Carex genus that may promote further scientific exploration and their utilization.

Pterocarpus santalinus heartwood is well acknowledged for its medicinal properties and use in the furniture and handicraft industries. Owing to its medicinal properties, the present investigation aims to isolate and characterize the secondary metabolites from the heartwood. The investigation led to the isolation of one undescribed dehydropterocarpan and eleven known compounds. P. santalinusheartwood is found to be a new source for six compounds. Interestingly, the undescribed dehydropterocarpan is transformed into an artifact, which led us to understand the biosynthetic correlations. The isolated compounds displayed moderate inhibition of α-glucosidase and α-amylase. The enzymatic assay outcome is further complimented with the in silico docking analysis. We have also evaluated the compounds for their drug-likeness properties, which align with the desired characteristics of potential drug candidates.

Dysoxyllum binectariferum is an important medicinal plant known for various biological activities like anti-inflammatory, CNS depressants, contraceptive, analgesic, immunomodulatory, antimalarial, antifeedant, leishmanicidal and antiviral. It is a rich source of rohitukine, a basic skeleton of flavopiridol. Phytochemical investigation of chloroform extracts of Dysoxyllum binectariferum leaves, lead to the isolation of beddomeilactone (1) and two new cycloartane type triterpenoids beddomeilactol (2) and binectarilactone-A (3) with modified A ring. Compounds were assessed for their in-vitro α-glucosidase inhibitory activity. Compound 1 was found to be most potent, showing IC50 of 17.99±0.26 µg/ml which is comparable to the positive control acarbose.

Mammalian flavoenzyme Monoamine oxidase (MAO) resides on the outer mitochondrial membrane (OMM) and it is involved in the metabolism of different monoamine neurotransmitters in brain. During MAO mediated oxidative deamination of relevant substrates, H2O2 is released as a catalytic by-product, thus serving as a major source of reactive oxygen species (ROS). Under normal conditions, MAO mediated ROS is reported to propel the functioning of mitochondrial electron transport chain and phasic dopamine release. However, due to its localization onto mitochondria, sudden elevation in its enzymatic activity could directly impact the form and function of the organelle. For instance, in the case of Parkinson's disease (PD) patients who are on L-dopa therapy, the enzyme could be a concurrent source of extensive ROS production in the presence of uncontrolled substrate (dopamine) availability, thus further impacting the health of surviving neurons. It is worth mentioning that the expression of the enzyme in different brain compartments increases with age. Moreover, the involvement of MAO in the progression of neurological disorders such as PD, Alzheimer's disease and depression has been extensively studied in recent times. Although the usage of available synthetic MAO inhibitors has been instrumental in managing these conditions, the associated complications have raised significant concerns lately. Natural products have served as a major source of lead molecules in modern-day drug discovery; however, there is still no FDAapproved MAO inhibitor which is derived from natural sources. In this review, we have provided a comprehensive overview of MAO and how the enzyme system is involved in the pathogenesis of different age-associated neuropathologic conditions. We further discussed the applications and drawbacks of the long-term usage of presently available synthetic MAO inhibitors. Additionally, we have highlighted the prospect and worth of natural product derived molecules in addressing MAO associated complications.

Talinum triangulare (water leaf) is an important herbaceous vegetable with medicinal importance. It has been used in traditional medicine for the management of diabetes, cancer, stroke, obesity, and measles. Popularly considered a weed, it is an unconventional food plant (UFP) with many nutritional and socio-economic potentials that needs to be rescued for invasive farming. The plant is a reservoir of various phytoconstituents belonging to flavonoids and lignans, alkaloids, and benzoic acid derivatives, which are known for their wide range of pharmacological effects. There is tremendous therapeutic potential in this cosmopolitan leafy vegetable plant, which has antidiabetic, antioxidative, hepatoprotective, and anticancer activity, along with a plethora of other pharmacological activities. This article reviews the traditional uses, phytochemistry, and pharmacology aspects of this underutilized food plant based on an extensive literature search which was available from 1976 to 2024 using a variety of electronic search engines. A network pharmacology-based approach was used for validation of the traditional claims as well as for exploring its therapeutic potential against diabetes for future research directions. This review intends to sensitize the scientific community to further research on this promising plant to bring it to commercial utilization as well as broaden the scope of this underutilized food plant.

Cancer stem cells (CSCs) are responsible for chemoresistance and tumor relapse in many solid malignancies, including lung and ovarian cancer. Ellagic acid (EA), a natural polyphenol, exhibits anticancer effects on various human malignancies. However, its impact and mechanism of action on cancer stem-like cells (CSLCs) are only partially understood. In this study, we evaluated the therapeutic potential and underlying molecular mechanism of EA isolated from tropical mango against CSLCs. Herein, we observed that EA treatment reduces the stem-like phenotypes in cancer cells, thereby lowering the cell survival and self-renewal potential of ovarian and lung CSLCs. Additionally, EA treatment limits the populations of lung and ovarian CSLCs characterized by CD133+ and CD44+CD117+, respectively. A mechanistic investigation showed that EA treatment induces ROS generation by altering mitochondrial dynamics, causing changes in the levels of Drp1 and Mfn2, which lead to an increased level of accumulation of DNA damage and eventually trigger apoptosis in CSLCs. Moreover, pretreatment with EA sensitizes CSLCs to cisplatin treatment by enhancing DNA damage accumulation and impairing the DNA repair ability of the CSLCs. Furthermore, EA pretreatment significantly reduces cisplatin-induced mutation frequency and improves drug retention in CSLCs, potentially suppressing the development of acquired drug resistance. Taken together, our results demonstrate an unreported finding that EA inhibits CSLCs by targeting mitochondrial function and triggering apoptosis. Thus, EA can be used either alone or in combination with other chemotherepeutic drugs for the management of cancer.

The present investigation established optimal conditions for ultrasonication-assisted extraction concerning yield and pterostilbene content using response surface methodology (RSM) based on Box-Behnken design (BBD) from the heartwood of Pterocarpus santalinus originating from different geographical locations (sample AP and WB). The influence of extraction temperature (X1: 30-50 degrees C), sonication time (X2: 15-45 min), and solvent/biomass ratio (X3: 20-60) were used as independent input variables resulting in the optimal conditions X1: 42.18, X2: 15.54, X3: 31.58 (sample AP) and X1: 30.00, X2: 31.38, X3: 20.00 (sample WB). Experimentally obtained values of yield 168.375 mg and 20.1 mg and AUC 498354 and 695295, respectively, for sample AP and WB, were in close agreement with those predicted by the RSM-BBD model. Additionally, the samples displayed the potential to inhibit the enzyme alpha-glucosidase.

W. tinctoria, an Indian herb Indrajao, has significant therapeutic potential. While studies have highlighted the anti-inflammatory potential of the leaves and bark of this plant, similar efficacy of the seed-pods remains unexplored. We demonstrate significant anti-inflammatory effects of the hexane fraction (Fr-B) of ethyl acetate extract of the seedpods in reducing lipopolysaccharide and palmitate mediated inflammation in RAW264.7 macrophages and HepG2 cells. GC-MS and NMR profiling of Fr-B revealed the existence of hexadecanoic acid, ethyl hexadecanoate, 9,12-octadecanoic acid, 9,12,15-octadecatrienoic acid, 9,12,15-octadecatrienoic acid ethyl ester, ethyl linoleate and octadecanoic acid ethyl esters.

Flavonoids exhibit several biological activities including inhibition of Monoamine oxidase (MAO), an enzyme that metabolizes several neurotransmitters. Thus, MAO inhibitors are well included in traditional therapeutic practices to fine-tune neuromotor behavior. This study aims to isolate flavonoids from a less explored plant of northeast India, named Indian olive (Elaeocarpus floribundus; Ef, family Elaeocarpaceae), and evaluate their MAO inhibitory properties. Four flavonoids from Ef leaf extract, namely, myricitrin, mearnsitrin, myricetin, and mearnsetin, are taken into consideration. Spectrofluorimetric assay is carried out to determine the MAO inhibitory properties. Next, in vitro and in vivo toxicity studies are performed in neuronal cell line and Drosophila, respectively. Furthermore, MAO inhibition by the selected compounds and their effect on dopamine levels are examined in the mouse brain. We evaluated the therapeutic potential in a mouse model of Parkinson's disease (PD) in terms of behavior, neurotransmitter levels, and dopaminergic neuronal loss. In an in vitro setup, all four compounds inhibited total MAO, whereas myricitrin exhibited some selectivity against MAO-B at 100 μM. Myricitrin and mearnsitrin exhibited no toxicity, in vitro or in vivo. However, only myricitrin inhibited MAO in the mouse brain and elevated dopamine levels. Myricitrin was able to attenuate motor incoordination in the mouse model of PD and improved dopamine levels in the striatum.

Triterpenes are naturally occurring derivatives biosynthesized following the isoprene rule of Ruzicka. The triterpenes have been reported to possess a wide range of therapeutic applications including anti-viral properties. In this review, the recent studies (2010–2020) concerning the anti-viral activities of triterpenes have been summarized. The structure activity relationship studies have been described as well as brief biosynthesis of these triterpenes is discussed.

Ferula assa-foetida, containing organosulfides is widely used in Indian cuisine and traditionally claimed to have several medicinal properties including anticancer properties. Ferula oil enriched with organosulfides displayed significant inhibition of the cell growth in-vitro against SKOV3 and A549 cancer cells in a dose-dependent manner. This prompted us to investigate and delineate the compounds responsible for the activity. In this endeavor, the employed GC/GC-MS analysis resulted in the indecisive outcome. This led to the development of an expedient isocratic RP-HPLC method for the separation and purification of four major compounds which were further unambiguously characterised as (-)-E-2-butyl propenyl disulfide, (-)-Z-2-butyl propenyl disulfide, (-)-1-(methylthio)propyl(E)-1-propenyl disulfide, and (-)-1-(methylthio)propyl(Z)-1-propenyl disulfide employing 1H, 13C, and 2 D NMR. The isolated compounds were further evaluated for their potential against SKOV3 and A549 cell lines where a trisulfide has displayed better activity.

In the last two decades, intensive research has been carried out to improve the survival rates of cancer patients. However, the development of chemoresistance that ultimately leads to tumor relapse poses a critical challenge for the successful treatment of cancer patients. Many cancer patients experience tumor relapse and ultimately die because of treatment failure associated with acquired drug resistance. Cancer cells utilize multiple lines of self-defense mechanisms to bypass chemotherapy and radiotherapy. One such mechanism employed by cancer cells is translesion DNA synthesis (TLS), in which specialized TLS polymerases bypass the DNA lesion with the help of monoubiquitinated proliferating cell nuclear antigen. Among all TLS polymerases (Pol eta, Pol iota, Pol kappa, REV1, Pol zeta, Pol mu, Pol lambda, Pol nu, and Pol theta), DNA polymerase eta (Pol eta) is well studied and majorly responsible for the bypass of cisplatin and UV-induced DNA damage. TLS polymerases contribute to chemotherapeutic drug-induced mutations as well as therapy resistance. Therefore, targeting these polymerases presents a novel therapeutic strategy to combat chemoresistance. Mounting evidence suggests that inhibition of Pol eta may have multiple impacts on cancer therapy such as sensitizing cancer cells to chemotherapeutics, suppressing drug-induced mutagenesis, and inhibiting the development of secondary tumors. Herein, we provide a general introduction of Pol eta and its clinical implications in blocking acquired drug resistance. In addition; this review addresses the existing gaps and challenges of Pol eta mediated TLS mechanisms in human cells. A better understanding of the Pol eta mediated TLS mechanism will not merely establish it as a potential pharmacological target but also open possibilities to identify novel drug targets for future therapy.

Ethnopharmacological relevance: Pterocarpus santalinus, an ancient folk medicine, is endemic to the eastern ghats of south India, and the heartwood is prescribed since time immemorial for the mitigation of inflammatory disorders in traditional practice and ayurvedic system of medicines. Aim of the study: This review aims to provide collective pieces of information of the traditional uses, phytochemicals, and pharmacological facets of P. santalinus, with an intuition for promoting future research to explore its pharmaceutical potential as a therapeutic agent against modern maladies. Material and methods: Extensive literature search was performed to collate the data by using various electronic search engines. A network pharmacology-based approach is incorporated for validation of traditional claims orbiting around anti-inflammatory properties and directed its future exploration against obesity, ovarian inflammation, ovarian folliculogenesis, and inflammatory breast cancer. Results: In a nutshell, the present review encompasses the phytochemistry, pharmacology of this species intending to sensitize the scientific community for future research on this promising plant. Nearly 85 chemical constituents are reported from the plants wherein bark and leaves are enriched with the lupane and oleanane class of triterpene while sesquiterpenes and polyphenolic compounds are predominantly present in the heartwood of the plant. Although phytochemical investigations are being reported since the mid-twentieth century however there has been recent interest in the evaluation of biological activities such as anti-inflammatory, antioxidant, anti-cancer, anti-viral, etc. Conclusion: In conclusion, a systematic phytochemical analysis and pharmacological exploration in close collaboration for establishing the therapeutic potential of the chemical constituents present in P. santalinus is recommended to substantiate the traditional claims for bringing it into the mainstream pharmaceutical and commercial utilization.

Plants are the oxygen support for our planet and all living things They can be considered as of As mothers take care of a child, Plants do the same for all human beings and animals Medicinal plants have therapeutic properties that produce a beneficial pharmacological effect on the animal and human body In recent years plants are surveyed as new drugs and gain attention to the discovery of new bioactive compounds Hippocrates quoted Let thy be thy medicine, and thy medicine shall be thy food The flavor, aroma, taste, and nutritional properties make the Cinnamon offers a wide range of health benefits The present study explores the connection between the Cinnamon plant and medicine, our food, modern science

Proteases play a crucial role during tumor initiation, progression, and metastasis and through their ability to promote cell division and proliferation or via promoting the invasion of adjacent tissues. The human whole genome consists of > 569 proteolytic enzyme-coding genes, among which many of the proteases form integrated functional networks. Thus it is important to use global strategies for the analysis of this class of enzymes. A large body of research shows that around 30 proteases have firm tumor-suppressive activity. In this book chapter, we confer recent knowledge on the multidimensional impact of tumor-suppressive proteases in various types of cancers. Additionally, we highlight known mechanisms through which tumor-suppressive proteases display antitumor properties. Herein, an attempt has been made to divide the pro- and antitumorigenic proteases so that we can quickly identify friend and foe proteolytic enzymes in the war against cancer. Further, illumination of the function of proteolytic enzymes in cancer will help us to formulate an effective strategy and novel protease-based medicines for clinical utility.

The present study of mint variety-CIM-Karnti demonstrated for cultivation of Madhepura district of Bihar. Mint is an essential oil bearing plant. Oil and its derivatives are extensively used in food, pharmaceutical, perfumery and flavouring industry. During the study period, 55 farmers of mint cultivation have been demonstrated on the farmer’s field of five villages under Madhepura district of Bihar during 2018-19. The primary data were collected from the selected farmer’s field. Simple analytical tools and technique has been used for data analysis and for carried out the cost of cultivation according different cost concepts. The multiple linear production function was used to evaluate the resource use efficiency in the production of mint. It was observed that medium level adoption of mint cultivation has been found higher followed by high and low level adoption. The total cost of cultivation and gross return has been found Rs. 52,804 /- and Rs. 1, 59,268/- ha-1, respectively. The net return on cost A1, C, Rs. 1,06,464/- and Rs. 90,640/-ha-1. The benefit cost ratio has been observed 2.02 and 1.32 at cost A1 and Cost C, respectively. The independent variables like sucker and nursery raising, manures and fertilizers and distillation charges were positive indicating significant impact on the returns from mint crop in the study area. Thus, profitable returns through cultivation of mint may attract large number of farmers to cultivate this crop to enhance their income and employment in the study area with integrated farming traditional crops.