Design and Development of a Non-invasive Opto-Electronic Sensor for Blood Glucose Monitoring Using a Visible Light Source.

Background The management of diabetes is critically dependent on the continuous monitoring of blood glucose levels. Contemporary approaches primarily utilize invasive methods, which often prove to be uncomfortable and can deter patient adherence. There is a pressing need for the development of novel strategies that improve patient compliance and simplify the process of glucose monitoring. Aim and objectives The primary objective of this research is to develop a non-invasive blood glucose monitoring system (NIBGMS) that offers a convenient alternative to conventional invasive methods. This study aims to demonstrate the feasibility and accuracy of using visible laser light at a wavelength of 650 nm for glucose monitoring and to address physiological and technical challenges associated with in vivo measurements. Methods Our approach involved the design of a device that exploits the quantitative relationship between glucose concentration and the refraction phenomena of laser light. The system was initially calibrated and tested using glucose solutions across a range of concentrations (25-500 mg/dL). To get around the problems that come up when people's skin and bodies are different, we combined an infrared (IR) transmitter (800 nm) and receiver that checks for changes in voltage, which are indicative of glucose levels. Results The prototype device was compared with a commercially available blood glucose monitor (Accu-Chek active machine; Roche Diabetes Care, Inc., Mumbai, India). The results demonstrated an average linearity of 95.7% relative to the Accu-Chek machine, indicating a high level of accuracy in the non-invasive measurement of glucose levels. Conclusions The findings suggest that our NIBGMS holds significant promise for clinical application. It reduces the discomfort associated with blood sampling and provides reliable measurements that are comparable to those of existing invasive methods. The successful development of this device paves the way for further commercial translation and could significantly improve the quality of life for individuals with diabetes, by facilitating easier and more frequent monitoring.

Advances on carbon nanomaterials and their applications in medical diagnosis and drug delivery.

Carbon nanomaterials are indispensable due to their unique properties of high electrical conductivity, mechanical strength and thermal stability, which makes them important nanomaterials in biomedical applications and waste management. Limitations of conventional nanomaterials, such as limited surface area, difficulty in fine tuning electrical or thermal properties and poor dispersibility, calls for the development of advanced nanomaterials to overcome such limitations. Commonly, carbon nanomaterials were synthesized by chemical vapor deposition (CVD), laser ablation or arc discharge methods. The advancement in these techniques yielded monodispersed carbon nanotubes (CNTs) and allows p-type and n-type doping to enhance its electrical and catalytic activities. The functionalized CNTs showed exceptional mechanical, electrical and thermal conductivity (3500-5000 W/mK) properties. On the other hand, carbon quantum dots (CQDs) exhibit strong photoluminescence properties with high quantum yield. Carbon nanohorns are another fascinating type of nanomaterial that exhibit a unique structure with high surface area and excellent adsorption properties. These carbon nanomaterials could improve waste management by adsorbing pollutants from water and soil, enabling precise environmental monitoring, while enhancing wastewater treatment and drug delivery systems. Herein, we have discussed the potentials of all these carbon nanomaterials in the context of innovative waste management solutions, fostering cleaner environments and healthier ecosystems for diverse biomedical applications such as biosensing, drug delivery, and environmental monitoring.

Mechanistic analysis of viscosity-sensitive fluorescent probes for applications in diabetes detection.

Diabetes is one of the most detrimental diseases affecting the human life because it can initiate several other afflictions such as liver damage, kidney malfunctioning, and cardiac inflammation. The primary method for diabetes diagnosis involves the analysis of blood samples to quantify the level of glucose, while secondary diagnostic methods involve the qualitative analysis of obesity, fatigue, etc. However, all these symptoms start showing up only when the patient has been suffering from diabetes for a certain period of time. In order to avoid such delay in diagnosis, the development of specific fluorescent probes has attracted considerable attention. Prominent biomarkers for diabetes include abundance of certain analytes in blood serum, e.g., glucose, methylglyoxal, albumin, and reactive oxygen species; high intracellular viscosity; alteration of enzyme functionality, etc. Among these, high viscosity can greatly affect the fluorescence properties of various chromophores owing to the environment sensitivity of fluorescence spectra. In this review article, we have illustrated the application of some prominent fluorophores such as coumarin, BODIPY, xanthene, and rhodamine in the development of viscosity-dependent fluorescent probes. Detailed mechanistic aspects determining the influence of viscosity on the fluorescent properties of the probes have also been elaborated. Fluorescence mechanisms that are directly affected by the high-viscosity heterogeneous microenvironment are based on intramolecular rotations like twisted intramolecular charge transfer (TICT), aggregation-induced emission (AIE), and through-bond energy transfer (TBET). In this regard, this review article will be highly useful for researchers working in the field of diabetes treatment and fluorescent probes. It also provides a platform for the planning of futuristic clinical translation of fluorescent probes for the early-stage diagnosis and therapy of diabetes.

Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance.

The production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation of cancer, through genetic and biological communication with healthy cells. TDSEVs are known to orchestrate the invasion-metastasis cascade via diverse pathways. Regulation of early metastasis processes, pre-metastatic niche formation, immune system regulation, angiogenesis initiation, extracellular matrix (ECM) remodeling, immune modulation, and epithelial-mesenchymal transition (EMT) are among the pathways regulated by TDSEVs. MicroRNAs (miRs) carried within TDSEVs play a pivotal role as a double-edged sword and can either promote metastasis or inhibit cancer progression. TDSEVs can serve as excellent markers for early detection of tumors, and tumor metastases. From a therapeutic point of view, the risk of cancer metastasis may be reduced by limiting the production of TDSEVs from tumor cells. On the other hand, TDSEVs represent a promising approach for in vivo delivery of therapeutic cargo to tumor cells. The present review article discusses the recent developments and the current views of TDSEVs in the field of cancer research and clinical applications.

CAR T cells: engineered immune cells to treat brain cancers and beyond.

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13Rα2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells' promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.

The Emerging Role of HDACs: Pathology and Therapeutic Targets in Diabetes Mellitus.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into four different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate ß cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting novel interventional strategies for metabolic disorders/complications.

One- and Two-Photon-Activated Cysteine Persulfide Donors for Biological Targeting.

Persulfides have been considered as potential signaling compounds similar to the H2S in "S-persulfidation", a sulfur-mediated redox cycle. The research of this sulfur-mediated species is hindered because of the lack of efficient persulfide donors. In this current study, we have developed one- and two-photon-activated persulfide donors based on an o-nitrobenzyl (ONB) phototrigger, which releases the biologically active persulfide (N-acetyl l-cysteine persulfide, NAC-SSH) in a spatiotemporal manner. Next, we have demonstrated the detection of persulfide release both qualitatively and quantitatively using the well-known "turn on" fluorescence probe, that is, monobromobimane, and the trapping agent, that is, 2,4-dinitrofluorobenzene, respectively. Furthermore, we examined the cytotoxicity of synthesized persulfide donors on HeLa cells and the cytoprotective ability in the highly oxidizing cellular environment.

NIR fluorescent organic nanoparticles for photoinduced nitric oxide delivery with self monitoring and real time reporting abilities.

Nitric oxide photodonor (NOD) conjugated perylene tetracarboxylate ester (TPT) based fluorescent organic TPT(NOD)4 nanoparticles (NPs) with aggregation induced NIR emission have shown photoinduced nitric oxide delivery along with a red to green emission transition. Time dependent imaging and dose dependent cytotoxicity studies of these NPs using U87MG cells demonstrate the self monitoring and real time reporting abilities and potential anticancer activity of the system, respectively.

Redox-responsive xanthene-coumarin-chlorambucil-based FRET-guided theranostics for "activatable" combination therapy with real-time monitoring.

A FRET donor-acceptor xanthene-coumarin conjugate has been designed for redox-regulated synergic treatment of photodynamic therapy and chemotherapy with real-time monitoring. The "locked" FRET pair was selectively "unlocked" by biological reducing thiols via rupture of a sacrificial disulfide linker. A distinct change in fluorescence color and selective cancer cell toxicity were observed in vitro.

Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition.

Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. Due to its diverse tissue distribution, P-gp is a novel protective barrier to stop the intake of xenobiotics into the human body. Over-expression of P-gp leads to decreased intracellular accretion of many chemotherapeutic agents thus assisting in the development of MDR. Eventually, the effectiveness of these drugs is decreased. P-gp inhibitors act by altering intracellular ATP levels which are the source of energy and/or by affecting membrane contours to increase permeability. However, the use of synthetic inhibitors is known to cause serious toxicities. For this reason, the search for more potent and less toxic P-gp inhibitors of natural origin is underway. The present review aims to recapitulate the research findings on bioactive constituents of natural origin with P-gp inhibition characteristics. Natural bioactive constituents with P-gp modulating effects offer great potential for semi-synthetic modification to produce new scaffolds which could serve as valuable investigative tools to recognize the function of complex ABC transporters apart from evading the systemic toxicities shown by synthetic counterparts. Despite the many published scientific findings encompassing P-gp inhibitors, however, this article stand alones because it provides a vivid picture to the readers pertaining to Pgp inhibitors obtained from natural sources coupled with their mode of action and structures. It provides first-hand information to the scientists working in the field of drug discovery to further synthesise and discover new P-gp inhibitors with less toxicity and more efficacies.

A p-Hydroxyphenacyl-Benzothiazole-Chlorambucil Conjugate as a Real-Time-Monitoring Drug-Delivery System Assisted by Excited-State Intramolecular Proton Transfer.

Among the well-known phototriggers, the p-hydroxyphenacyl (pHP) group has consistently enabled the very fast, efficient, and high-conversion release of active molecules. Despite this unique behavior, the pHP group has been ignored as a delivery agent, particularly in the area of theranostics, because of two major limitations: Its excitation wavelength is below 400 nm, and it is nonfluorescent. We have overcome these limitations by incorporating a 2-(2'-hydroxyphenyl)benzothiazole (HBT) appendage capable of rapid excited-state intramolecular proton transfer (ESIPT). The ESIPT effect also provided two unique advantages: It assisted the deprotonation of the pHP group for faster release, and it was accompanied by a distinct fluorescence color change upon photorelease. In vitro studies showed that the p-hydroxyphenacyl-benzothiazole-chlorambucil conjugate presents excellent properties, such as real-time monitoring, photoregulated drug delivery, and biocompatibility.

Fluorene-morpholine-based organic nanoparticles: lysosome-targeted pH-triggered two-photon photodynamic therapy with fluorescence switch on-off.

Nanocarrier-mediated photodynamic therapy (PDT) is an effective tool for anti-tumour treatment due to the targeted and image-guided delivery of photosensitizers (PSs) to diseased tissues. These nanocarriers range from inorganic, ceramic, polymeric to biological nanoparticles (NPs). Such PS-grafted bicomponent nanocarriers have limitations like (i) difficulty in surface modification, (ii) lower loading percentages of the therapeutic agent, (iii) unstable physical encapsulation, etc. By any means, if we can prepare PSs directly as NPs then we can surpass the above drawbacks. Hence, we synthesised new two-photon fluorene-functionalised morpholine (Fluo-Mor)-based organic NPs that showed strong fluorescence and profound photodynamic therapy (PDT) activity only in acidic medium. Such a pH-responsive appearance of fluorescence enables Fluo-Mor NPs for the real time monitoring of photodynamic therapeutic activity selectively in low-pH organelles viz. lysosome. Cytotoxicity of Fluo-Mor NPs was monitored using time-dependent and dose-dependent cancer cell viability assay and confocal imaging.

Coumarin-containing-star-shaped 4-arm-polyethylene glycol: targeted fluorescent organic nanoparticles for dual treatment of photodynamic therapy and chemotherapy.

Single component fluorescent organic polymeric nanoparticles (NPs) have been synthesized based on a star shaped 4-arm PEG containing coumarin chromophore for the concomitant employment of photodynamic therapy (PDT) and chemotherapy synergistically to wipe out tumour cells with a high efficiency. Polymeric NPs are emerging as the most promising nanoparticulates in the area of drug delivery systems due to their ability to overcome the disadvantages like premature and imprecise control over the drug release, lack of loading capacity etc. Among polymeric NPs, star shaped branched polymers have attracted great attention mainly due to their multiple functionalization properties. Hence, herein we have made use of a multi-arm PEG, functionalized with a targeting unit biotin and a coumarin fluorophore for site-specific and image guided synergic treatment of cancer cells. The anticancer drug chlorambucil is released by the coumarin chromophore in a photocontrolled manner. In addition to that, coumarin also generated singlet oxygen upon irradiation with UV/vis light (≥365 nm) with a moderate quantum yield of ∼0.37. In vitro application of thus prepared organic polymeric nanoparticles (PEG-Bio-Cou-Cbl) in the HeLa cell line shows a reduction of cell viability by up to ∼5% in the case of a combined treatment of PDT and chemotherapy whereas analogous organic polymeric NPs without the chemotherapeutic drug (PEG-Bio-Cou) result in ∼49% cell viability by means of PDT process only.

Ameliorative effect of water spinach, Ipomea aquatica (Convolvulaceae), against experimentally induced arsenic toxicity.

BACKGROUND: Ipomea aquatica (Convolvulaceae) is traditionally used against Arsenic (As) poisoning in folk medicines in India. The present study was designed to explore the therapeutic role of aqueous extract of I. aquatica (AEIA) against As-intoxication. METHODS: AEIA was chemically standardized by spectroscopic and chromatographic analysis. The cytoprotective role of AEIA was measured on isolated murine hepatocytes. The effect on redox status were measured after incubating the hepatocytes with NaAsO2 (10 µM) + AEIA (400 µg/ml). The protective effect of AEIA (400 µg/ml) in expressions of apoptotic proteins were estimated in vitro. The protective role of AEIA was measured by in vivo assay in mice. Haematological, biochemical, As bioaccumulation and histological parameters were evaluated to ensure the protective role of AEIA (100 mg/kg) against NaAsO2 (10 mg/kg) intoxication. RESULTS: Phytochemical analysis revealed presence of substantial quantities of phenolics, flavonoids, saponins and ascorbic acid in AEIA. Incubation of murine hepatocytes with AEIA (0-400 µg/ml) + NaAsO2 (10 µM) exerted a concentration dependent cytoprotective effect. Incubation of murine hepatocytes with NaAsO2 (10 µM, ~ IC50) induced apoptosis via augmenting oxidative stress. NaAsO2 treated hepatocytes exhibited significantly (p < 0.01) enhanced levels of ROS production, lipid peroxidation and protein carbonylation with concomitant depletion of antioxidant enzymes (p < 0.05-0.01) and GSH (p < 0.01) levels. However, AEIA (400 µg/ml) + NaAsO2 (10 µM) could significantly (p < 0.05-0.01) reinstate the aforementioned parameters to near-normal status. Besides, AEIA (400 µg/ml) could significantly counteract (p <0.05-0.01) ROS mediated alteration in the expressions of apoptotic proteins viz. Bcl-2, BAD, Cyt C, Apaf 1, caspases, Fas and Bid. In in vivo bioassay, NaAsO2 (10 mg/kg) treatment in mice caused significantly (p < 0.05-0.01) elevated As bioaccumulation, ATP levels, DNA fragmentations and oxidative stress in the liver, kidney, heart, brain and testes along with alteration in cytoarchitecture of these organs. In addition, the serum biochemical and haematological parameters were significantly (p < 0.05-0.01) altered in the NaAsO2-treated animals. However, concurrent administration of AEIA (100 mg/ml) could significantly reinstate the NaAsO2-induced pathogenesis. CONCLUSION: Presence of substantial quantities of dietary antioxidants within AEIA would be responsible for overall protective effect.

Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response.

BACKGROUND: Abroma augusta L. (Malvaceae) leaf is traditionally used to treat diabetes in India and Southern Asia. Therefore, current study was performed to evaluate the protective effect of defatted methanol extract of A. augusta leaves (AA) against type 2 diabetes mellitus (T2DM) and its associated nephropathy and cardiomyopathy in experimental rats. METHODS: Antidiabetic activity of AA extracts (100 and 200 mg/kg, p.o.) was measured in streptozotocin-nicotinamide induced type 2 diabetic (T2D) rat. Fasting blood glucose level (at specific interval) and serum biochemical markers (after sacrifice) were measured. Redox status, transcription levels of signal proteins (NF-κB and PKCs), mitochondria dependent apoptotic pathway (Bad, Bcl-2, caspase cascade) and histological studies were performed in kidneys and hearts of controls and AA treated diabetic rats. RESULTS: Phytochemical screening of extracts revealed the presence of taraxerol, flavonoids and phenolic compounds in the AA. T2D rats showed significantly (p < 0.01) elevated fasting blood glucose level. Alteration in serum lipid profile and release of membrane bound enzymes like lactate dehydrogenase and creatine kinase, which ensured the participation of hyperlipidemia and cell membrane disintegration in diabetic pathophysiology. T2DM caused alteration in the serum biochemical markers related to diabetic complications. T2DM altered the redox status, decreased the intracellular NAD and ATP concentrations in renal and myocardial tissues of experimental rats. Investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation of NF-κB and increase in the concentrations of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in the renal and cardiac tissues. The activation of mitochondria dependent apoptotic pathway was observed in renal and myocardial tissues of the T2D rats. However, Oral administration of AA at the doses of 100 and 200 mg/kg body weight per day could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological studies also supported the protective characteristics of AA. CONCLUSIONS: Results suggest that AA could offer prophylactic role against T2DM and its associated reno- and cardio- toxicity.

Bioautography and its scope in the field of natural product chemistry.

Medicinal plants, vegetables and fruits are the sources of huge number of bioactive lead/scaffolds with therapeutic and nutraceutical importance. Bioautography is a means of target-directed isolation of active molecules on chromatogram. Organic solvents employed in chromatographic separation process can be completely removed before biological detection because these solvents cause inactivation of enzymes and/or death of living organisms. They offer a rapid and easy identification of bioactive lead/scaffolds in complex matrices of plant extracts. Bioautography is a technique to isolate hit(s)/lead(s) by employing a suitable chromatographic process followed by a biological detection system. This review critically describes the methodologies to identify antimicrobial, antioxidant, enzyme inhibitor lead/scaffolds by employing bioautography. A significant number of examples have been incorporated to authenticate the methodologies.

A targeted, image-guided and dually locked photoresponsive drug delivery system.

We have developed a new targeted image-guided photoresponsive drug delivery system (DDS) based on a dual locking strategy. Excitation of the DDS by fluorescent light results in the first unlocking and activation of the drug, and allows real-time monitoring of the prodrug. Extended irradiation results in a second unlocking, giving drug release within cancer cells.

Coumarin-benzothiazole-chlorambucil (Cou-Benz-Cbl) conjugate: an ESIPT based pH sensitive photoresponsive drug delivery system.

We have developed an ESIPT based drug delivery system (DDS), Cou-Benz-Cbl conjugate, by incorporating a benzothiazole group at the 8th position of the 7-hydroxy-coumarin moiety for pH sensitive fluorescence properties and photocontrolled release of the anticancer drug chlorambucil. The Cou-Benz-Cbl conjugate exhibited unique photophysical properties like good absorbance at around 350 nm, a large Stokes shift (∼151 nm) and pH sensitive fluorescence properties. The pH sensitive fluorescence properties of the Cou-Benz-Cbl conjugate can be ascribed to an ESIPT turn "on and off" mechanism. At physiological pH, the ESIPT gets turned "off" and a blue fluorescence of the coumarin moiety was observed, but at acidic pH, the ESIPT gets turned "on" and a green fluorescence was noted. Photolysis of the Cou-Benz-Cbl conjugate using UV light of wavelength ≥365 nm resulted in the efficient release of the anticancer drug chlorambucil. Cellular uptake studies revealed that the Cou-Benz-Cbl conjugate was easily internalized inside the cancer cells. Further, an MTT assay showed that the Cou-Benz-Cbl conjugate has a good biocompatibility and low cytotoxicity towards the MDA-MB-231 cell line, whereas upon exposure to UV light, the Cou-Benz-Cbl conjugate exhibited enhanced cytotoxicity compared to the free drug due to the effective release of the anticancer drug chlorambucil inside the cancer cell.

Bioautography and its scope in the field of natural product chemistry / 药物分析学报

Medicinal plants, vegetables and fruits are the sources of huge number of bioactive lead/scaffolds with therapeutic and nutraceutical importance. Bioautography is a means of target-directed isolation of active molecules on chromatogram. Organic solvents employed in chromatographic separation process can be completely removed before biological detection because these solvents cause inactivation of enzymes and/or death of living organisms. They offer a rapid and easy identification of bioactive lead/scaffolds in complex matrices of plant extracts. Bioautography is a technique to isolate hit(s)/lead(s) by employing a suitable chromatographic process followed by a biological detection system. This review critically describes the methodologies to identify antimicrobial, antioxidant, enzyme inhibitor lead/scaffolds by employing bioautography. A significant number of examples have been incorporated to authenticate the methodologies.

Signal transducer and oxidative stress mediated modulation of phenylpropanoid pathway to enhance rosmarinic acid biosynthesis in fungi elicited whole plant culture of Solenostemon scutellarioides.

This study aimed to improve rosmarinic acid (RA) production in the whole plant culture of Solenostemon scutellarioides through elicitation with phytopathogenic fungi. Amongst selected fungi, Aternaria alternata caused significant elevation (p<0.05-0.01) in RA accumulation (∼1.3-1.6-fold) between 25 and 100 µg l(-1). However, elicitation at the dose of 50 µg l(-1) has been found to be most effective and intracellular RA content reached almost ∼1.6-fold (p<0.01) higher in day 7. Therefore, A. alternata (50 µg l(-1)) was selected for mechanism evaluation. A significant elevation of intercellular jasmonic acid was observed up to day 6 after elicitation with A. alternata (50 µg l(-1)). A significant increase in tissue H2O2 and lipid peroxidation coupled with depletion of antioxidant enzymes superoxide dismutase and catalase indicated augmented oxidative stress associated with biotic interaction. Preceding the elicitor-induced RA accumulation, a notable alteration in the specific activities of biosynthetic enzymes namely PAL and TAT was recorded, while, no significant change in the activities of RAS was observed. HPPR activity was slightly improved in elicited plant. Therefore, it could be concluded that A. alternata elicited the biosynthesis of rosmarinic acid via signal transduction through jasmonic acid coupled with elicitor induced oxidative stress and associated mechanism.