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Abstract Iris kashmiriana belongs to the family Iridaceae and is an important endemic medicinal plant of Kashmir. The current study was designed to determine the phytoconstituents, antioxidant, and cytotoxic potential of ethyl acetate (IRK-ETH) and methanol (IRK-MTH) extracts of Iris kashmiriana flowers. IRK-MTH extract demonstrated maximum radical scavenging activity in DPPH, ABTS, and Superoxide anion radical antioxidant assays with IC50 values of 73.15 μg/ml, 79.05 μg/ml, and 86.52 μg/ml respectively. IRK-ETH and IRK-MTH extracts possessed phenolic (70.9 and 208.5 mgGAE/gdw) and flavonoid (487.7 and 40.55 mgRE/gdw) contents respectively. In MTT assay IRK-ETH demonstrated the highest cytotoxicity towards the MCF-7 cell line with a GI50 value of 49.13 μg/ml. Phase contrast and fluorescence microscopic studies in MCF-7 cells revealed that IRK-ETH extract caused condensation of chromatin, rounding of cells, and nuclear condensation in cells which shows the apoptotic potential of the extract. GCMS analysis for phytochemical characterization revealed the presence of 9 compounds in both extracts which have been reported to possess antibacterial, cytotoxic, and anti-oxidant activities. HPLC analysis confirmed the presence of different polyphenols in both extracts with IRK-MTH extract having maximum polyphenols like epicatechin, rutin, quercetin, vanillic acid, sinapic acid, caffeic acid, chlorogenic acid and ellagic acid. These findings suggest that the flowers of Iris kashmiriana possess very good antioxidant and cytotoxic potential owing to its rich phytoconstituents.

Objective: The objectives of this study were to explore the cytotoxic potential of different fractions (Hexane, chloroform, ethyl acetate and methanol) of Plumbago zeylanica L. root powder. Methodology: In this study, PzMH, PzMC, PzME, and PzMM fractions from the root powder of P. zeylanica were obtained through the cold maceration technique. The cytotoxic properties of these fractions on MG-63 cells were assessed using the MTT assay. The most potent fraction was further analyzed to understand its cytotoxic mechanism. To explore its apoptosis-inducing potential, microscopic and flow cytometric studies were conducted. Additionally, western blot analysis was used to examine the expression levels of proteins associated with apoptotic pathways. Results: PzMH showed the highest cytotoxicity against MG-63 osteosarcoma cells, with a GI50 value of 53.07 µg/ml. Flow cytometric studies revealed an upsurge in reactive oxygen species and disruption of mitochondrial membrane potential. The highest concentration of PzMH fraction (183.48 µg/ml) led to 62 % cell population arrest at G0/G1 stage. The anti-apoptotic protein Bcl2 was downregulated, with p53, cleaved-caspase 9, cleaved-caspase3, Bad and Bax expression upregulated. HPLC analysis revealed the presence of lawsone, p-coumaric acid, plumbagin, and 4-hydroxy benzaldehyde, indicating that the quinone-rich fraction of Plumbago zeylanica L. attenuates the proliferation of MG-63 osteosarcoma cells through the Bax/Bcl-2 pathway. Conclusion: To the best of our current knowledge, this marks the first documented case where the hexane fraction enriched with quinones extracted from the roots of P. zeylanica demonstrates its ability to induce apoptosis by influencing the Bax/Bcl2 pathway.

Tragopogon dubius is commonly consumed as a vegetable and used in traditional medicine for treating inflammatory skin conditions and cutaneous swelling. Despite known pharmacological properties of its leaves and roots, many of its biological characteristics and active phytochemicals remain unexplored. The present study investigates the phytochemical composition, antioxidant, and anticancer properties of methanolic root extracts and isolated fractions (TdRM-1 and TdRM-2) of T. dubius. Utilizing preparative thin-layer chromatography, the crude extract was successfully separated into TdRM-1 and TdRM-2, characterized by GC-MS and FTIR analysis, revealing a diverse range of bioactive compounds including terpenes, flavonoids, and phenolic acids. Qualitative phytochemical screening indicated the presence of carbohydrates, tannins, alkaloids, and other phytoconstituents. Advanced UPLC-ESI-QTOF-MS analysis identified 54 metabolites, significantly contributing to the chemical profiling of the extract. The antioxidant activities of the fractions were quantitatively assessed using ABTS, DPPH, and superoxide radical scavenging assays, where TdRM-2 exhibited superior activity with IC50 values ranging from 51.29 to 60.03 μg/mL. Anticancer potential was evaluated against A549, LN-18, and MCF-7 cancer cell lines, demonstrating that TdRM-2 significantly inhibited cell proliferation with GI50 values as low as 31.62 μg/mL for A549 cells. Additionally, fluorescence microscopy revealed that TdRM-2 induces apoptosis, indicated by changes in nuclear morphology and loss of mitochondrial membrane potential. Annexin V-FITC/PI double staining indicate that the TdRM-2 fractions from T. dubius can significantly inhibit the growth of A-549, LN-18, and MCF-7 cancer cell lines by inducing apoptosis These findings suggest that T. dubius root extracts, particularly the TdRM-2 fraction, hold promising therapeutic potential due to their significant antioxidant and anticancer activities, underpinned by their rich phytochemical composition. This study underscores the importance of T. dubius as a source of natural bioactive compounds with potential health benefits.

Objectives: We investigated the anticancer activity of the PzMH fraction (hexane fraction) extracted from the roots of Plumbago zeylanica L., an ethnomedicinally significant plant widely distributed in India. Methods: The PzMH fraction was obtained through rigorous extraction and purification processes. In vitro cytotoxicity assays were performed to assess its effects on Ehrlich ascites carcinoma (EAC) cells. Acute toxicity studies were conducted to evaluate its safety profile. An in vivo study was carried out on EAC-bearing Swiss albino mice to assess its anticancer efficacy. Flow cytometric and microscopic analyses were done to examine the induction of cell death by the PzMH fraction. Western blot analysis was used to investigate the molecular mechanisms involved. Results: The PzMH fraction exhibited a significant cytotoxic effect in vitro, resulting in 50% cell death in EAC cells at low concentrations. The calculated GI50 value for the PzMH fraction was 42.74 µg/ml, demonstrating a comparable efficacy to the standard drug 5-fluoro uracil (GI50 = 43.38 µg/ml). The safety of therapeutic doses was confirmed through acute toxicity studies, which yielded an LD50 value of 500 mg/kg body weight. In the in vivo study, the PzMH fraction demonstrated a substantial 79.05% inhibition in the growth of EAC cells at the 300 mg/kg body weight dose of PzMH fraction. Flow cytometric and microscopic analyses revealed distinct apoptotic features in EAC cells treated with the PzMH fraction. Cell cycle analysis showed a significant arrest at the G0/G1 stage following treatment. PzMH treatment elicited a response characterized by escalated levels of cleaved caspases-3 and −9, while concurrently leading to a decreased expression of the Bcl2 protein, as evidenced by Western blot analysis. Conclusions: The current research provides empirical evidence supporting the anticancer activity of the PzMH fraction extracted from P. zeylanica. The observed cytotoxicity, safety, and apoptosis-inducing properties make it a promising candidate for further investigation as a potential cancer therapy. Further exploration of its phytochemical composition, including major compounds such as 4-hydroxybenzaldehyde, trans-cinnamic acid, plumbagin and lawsone, contributes to our understanding of its mechanisms of action.

Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally used to treat rheumatism, fever, asthma, stomach irritation, and inflammatory ailments. The bioactive constituents present in the genus O. include benzoquinones, naphthazarins, alkaloids, phenolic, naphthoquinones, and flavonoids whereas shikonins and onosmins are the most significant. The review compiled contemporary research on O. L., including its distribution, morphology, traditional applications, phytochemistry, ethnopharmacology, and toxicology. This review also highlights a few critical challenges and possible future directions for O. L. research. Modern research has demonstrated a wide range of pharmacological effects of different species of O. L., including anti-diabetic, anticancer, anti-inflammatory, and cardiovascular protective. However, the studies on the O. genus are still not fully explored, therefore, researchers need to discover novel products with their toxicity studies, molecular mechanism, and associated side effects. Future exploration of potent constituents from this genus and clinical trials are required to explore its pharmacological importance.

Adaptation to changing environmental conditions is a driver of plant diversification. Elevational gradients offer a unique opportunity for investigating adaptation to a range of climatic conditions. The use of specialized metabolites as volatile and phenolic compounds is a major adaptation in plants, affecting their reproductive success and survival by attracting pollinators and protecting themselves from herbivores and other stressors. The wormseed Artemisia brevifolia can be found across multiple elevations in the Western Himalayas, a region that is considered a biodiversity hotspot and is highly impacted by climate change. This study aims at understanding the volatile and phenolic compounds produced by A. brevifolia in the high elevation cold deserts of the Western Himalayas with the view to understanding the survival strategies employed by plants under harsh conditions. Across four sampling sites with different elevations, polydimethylsiloxane (PDMS) sampling and subsequent GCMS analyses showed that the total number of volatile compounds in the plant headspace increased with elevation and that this trend was largely driven by an increase in compounds with low volatility, which might improve the plant’s resilience to abiotic stress. HPLC analyses showed no effect of elevation on the total number of phenolic compounds detected in both young and mature leaves. However, the concentration of the majority of phenolic compounds decreased with elevation. As the production of phenolic defense compounds is a costly trait, plants at higher elevations might face a trade-off between energy expenditure and protecting themselves from herbivores. This study can therefore help us understand how plants adjust secondary metabolite production to cope with harsh environments and reveal the climate adaptability of such species in highly threatened regions of our planet such as the Himalayas.

Here, in the present work, a new hydroxybenzothiazole derivative (HBT 2) with AIE+ESIPT features was synthesized by Suzuki–Miyora coupling of HBT 1 with 4-formylphenylboronic acid. The AIE and ESIPT features were confirmed by optical, microscopic (AFM) and dynamic light scattering (DLS) techniques. The yellow fluorescent aggregates of HBT 2 can specifically detect Cu2+/Cu+ ions with limits of detection as low as 250 nM and 69 nM. The Job’s plot revealed the formation of a 1:1 complex. The Cu2+ complexation was further confirmed by optical, NMR, AFM and DLS techniques. HBT 2 was also used for the detection of Cu2+ ions in real water samples collected from different regions of Punjab. HBT 2 was successfully used for the bio-imaging of Cu2+ ions in live A549 and its anticancer activity was checked on different cancer cell lines, such as MG63, and HeLa, and normal cell lines such as L929. We successfully utilized HBT 2 to develop security labels for anticounterfeiting applications.

Onosma bracteata Wall. is an important medicinal and immunity-enhancing herbs. This plant is commonly used in the preparation of traditional Ayurvedic drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the present study aimed to investigate the antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human osteosarcoma (MG-63) cells. Among all the fractions isolated from O. bracteata, ethyl acetate fraction (Obea) showed good antioxidant activity in superoxide radical scavenging assay and lipid peroxidation assay with an EC50 value of 95.12 and 80.67 µg/mL, respectively. Silica gel column chromatography of ethyl acetate (Obea) fraction of O. bracteata yielded a pure compound, which was characterized by NMR, FTIR, and HR-MS analysis and was identified as 1,2-benzene dicarboxylic acid, bis (2-methyl propyl) ester (BDCe fraction). BDCe fraction was evaluated for the antiproliferative potential against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung carcinoma A549 cell lines by MTT assay and exhibited GI50 values of 37.53 μM, 56.05 μM, and 47.12 μM, respectively. In MG-63 cells, the BDCe fraction increased the level of ROS and simultaneously decreased the mitochondria membrane potential (MMP) potential by arresting cells at the G0/G1 phase, suggesting the initiation of apoptosis. Western blotting analysis revealed the upregulation of p53, caspase3, and caspase9 while the expressions of p-NF-κB, p-Akt and Bcl-xl were decreased. RT-qPCR studies also showed upregulation in the expression of p53 and caspase3 and downregulation in the expression of CDK2, Bcl-2 and Cyclin E genes. Molecular docking analysis displayed the interaction between BDCe fraction with p53 (−151.13 kcal/mol) and CDK1 (−133.96 kcal/mol). The results of the present work suggest that the BDCe fraction has chemopreventive properties against osteosarcoma (MG-63) cells through the induction of cell cycle arrest and apoptosis via Akt/NF-κB/p53 pathways. This study contributes to the understanding of the utilization of BDCe fraction in osteosarcoma treatment.

Diabetes mellitus (DM) is characterized by impaired insulin secretion or utilization, accompanied by hyperglycemia and glycosuria, as well as by a plethora of DM-induced complications, including nephropathy. The purpose of this investigation was 2-fold: to evaluate the antidiabetic potential of zingerone, and its protective effects against DM-induced nephropathy. It has been reported that oxidative stress is associated with DM and cellular nuclear factor (NF)-κB, tumour necrosis factor (TNF)-α and cyclooxygenase (COX)-2 proteins are overexpressed in DM-triggered nephropathy. The levels of these molecular biomarkers and renal functions were measured in zingerone treated diabetic animals. DM was produced in adult male Wistar rats with streptozotocin/nicotinamide. Zingerone (15, 30 and 60 mg/kg) was administered orally once daily to diabetic rats for 6 consecutive weeks. Significant increase in serum glucose, total cholesterol, low density lipoproteins (LDL), urea, uric acid, creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) was observed in diabetic rats. All these biochemical parameters were significantly reduced in zingerone treated animals in a dose-dependent manner. There was a marked increase in renal levels of thio-barbituric acid reactive substance (TBARS), superoxide anion generation (SAG) and decrease in reduced glutathione (GSH) in diabetic rats. Whereas zingerone treatment showed statistically significant attenuation of all the oxidative stress parameters, in comparison with untreated counterparts. The overexpressed levels of NF-κB, TNF-α and COX-2 proteins in nephropathic rats were attenuated by zingerone. Histological examination of isolated kidneys confirmed the renoprotective effects of zingerone. Our results suggest that the antidiabetic and renoprotective effects of zingerone seem to be due to the combination of different actions: namely antioxidant and anti-inflammatory properties, inhibition of DM-induced oxidative stress by scavenging free radicals, and down-regulation of NF-κB, TNF-α and COX-2 proteins in the kidney tissue.

Onosma bracteata Wall. (Boraginaceae) is a highly valuable medicinal herb that is used for the treatment of fever, bronchitis, asthma, rheumatism, stomach irritation, and other inflammatory disorders. The present study aims to explore the hepatoprotective potential of ethanolic extract (Obeth) from O. bracteata aerial parts against carbon tetrachloride (CCl4) which causes hepatic damage in the male Wistar rats. Obeth showed effective radical quenching activity with an EC50 of 115.14 and 199.33 µg/mL in superoxide radical scavenging and lipid peroxidation analyses respectively along with plasmid DNA protective potential in plasmid nicking assay. The Obeth modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC50 10.48 µg/0.1 mL/plate) in TA100 strain of Salmonella typhimurium. In in vivo studies, pretreatment of Obeth (50, 100, and 200 mg/kg) had the potential to normalize the biochemical markers aggravated by CCl4 (1mL/kg b.wt.) including liver antioxidative enzymes. Histopathological analysis also revealed the restoration of CCl4-induced liver histopathological alterations. Immunohistochemical studies showed that the treatment of Obeth downregulated the expression levels of p53 and cyclin D in hepatocytes. and downregulation in the Western blotting analysis revealed the downregulation of p-NF-kB, COX-2, and p53. HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in Obeth. The present investigation establishes the hepatoprotective and chemopreventive potential of O. bracteata against CCl4-induced hepatotoxicity via antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells.

Cassia fistula L. is a highly admirable traditional medicinal plant used for the treatment of various diseases and disorders. The present study was performed to divulge the antioxidant, antiproliferative, and apoptosis-inducing efficacy of fractions from C. fistula leaves. The hexane (CaLH fraction), chloroform (CaLC fraction), ethyl acetate (CaLE fraction), n-butanol (CaLB fraction), and aqueous (CaLA fraction) were sequentially fractionated from 80% methanolic (CaLM extract) of C. fistula leaves. The CaLE fraction was fractionated using column chromatography to yield a pure compound, which was characterized as Epiafzelechin (CFL1) based on 1H, 13C, and DEPT135 NMR. Among these fractions, CaLE and isolated CFL1 fractions exhibited an effective antioxidant potential in Ferric ion reducing power, (2,2’-azino-bis (3-ethylbenzothiazoline -6-sulfonic acid)) cation radical scavenging, and nitric oxide radical scavenging assays. Epiafzelechin was investigated for its antiproliferative effects against MG-63 (osteosarcoma), IMR-32 (neuroblastoma), and PC-3 (prostate adenocarcinoma), and was found to inhibit cell proliferation with a GI50 value of 8.73, 9.15, and 11.8 μM respectively. MG-63 cells underwent apoptotic cell death on treatment with Epiafzelechin as the cells showed the formation of apoptotic bodies, enhanced reactive oxygen species (ROS) generation, mitochondrial membrane depolarization along with an increase in early apoptotic cell population analyzed using Annexin V-FITC/PI double staining assay. Cells showed cell cycle arrest at the G0/G1 phase accompanied by a downregulation in the expression levels of p-Akt (Protein kinase B), p-GSK-3β (Glycogen synthase kinase-3 beta), and Bcl-xl (B-cell lymphoma-extra large) proteins. RT-PCR (Real time-polymerase chain reaction) analysis revealed downregulation in the gene expression level of β-catenin and CDK2 (cyclin-dependent kinases-2) while it upregulated the expression level of caspase-8 and p53 genes in MG-63 cells.

Plants have been the basis of traditional medicine since the dawn of civilizations. Different plant parts possess various phytochemicals, playing important roles in preventing and curing diseases. Scientists, through extensive experimental studies, are playing an important part in establishing the use of phytochemicals in medicine. However, there are still a large number of medicinal plants which need to be studied for their phytochemical profile. In this study, the objective was to isolate phytochemicals from bark of Bauhinia variegata L. and to study them for their antioxidant and cytotoxic activities. The bark was extracted with methanol, followed by column chromatography and thus isolating kaempferol, stigmasterol, protocatechuic acid-methyl ester (PCA-ME) and protocatechuic acid (PCA). 2,2-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) and 2, 2’-diphenyl-1-picrylhydrazyl radical (DPPH) radical scavenging assays were utilized for assessment of antioxidant activity, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye reduction assay was used to determine cytotoxic activity against C-6 glioma rat brain, MCF-7 breast cancer, and HCT-15 colon cancer cell lines. The compounds were found to have significant antioxidant and cytotoxic activity. Since there is a considerable increase in characterizing novel chemical compounds from plant parts, the present study might be helpful for chemotaxonomic determinations, for understanding of medicinal properties as well as for the quality assessment of herbal supplements containing B. variegata bark, thus establishing its use in traditional medicine.

Heavy metals (including Cadmium) are being entered into the environment through various sources and cause toxicity to plants. Response of Brassica juncea L. var. RLC-1 was evaluated after exposing them to different concentration of cadmium (Cd) for seven days. Seeds of B. juncea were treated with different concentrations of Cd like 0.2−0.6 mM for 7 days, allowing them to grow in Petri-dishes, and seedlings were examined for different physiological responses. Following exposure to Cd, in the seedlings of B. juncea, growth parameters (root and shoot length), stress markers (lipid peroxidation and H2O2 content), secondary metabolites, photosynthetic pigments, and ion analysis, were estimated along with enzymatic and non-enzymatic antioxidants. We observed a significant reduction in root and shoot length after Cd treatment as compared to control seedlings. Malondialdehyde and H2O2 contents were increased accompanied by enhanced Cd uptake. Activities of antioxidative enzymes were also significantly altered following Cd exposure to the seedlings of B. juncea. Conclusively, we suggest that Cd exposure to the seedlings triggered an induction of several defense responses in B. juncea including major metabolites.

Abstract  Brassinosteroids are of universal occurrence in plants. They have been reported to affect plant growth and development through a spectrum of physiological responses. Recently they are reported to confer resistance in plants against a number of biotic and abiotic stresses. In the present study, a brassinosteroid was isolated from Aegle marmelos Correa. (Rutaceae) which was characterized to be 24-epibrassinolide (EBL) using various spectroscopic techniques (TLC and ESI-MS analysis). It was evaluated for the antigenotoxicity against maleic hydrazide (MH) induced genotoxicity in Allium cepa chromosomal aberration assay. It was shown that the percentage of chromosomal aberrations induced by maleic hydrazide (0.01%) declined significantly with 24-epibrassinolide treatment. EBL (10−7 M) proved to be the most effective concentration with 91.8% inhibition. This is the first report on the isolation of 24-epibrassinolide from Aegle marmelos and its antigenotoxic effects against MH employing Allium cepa chromosomal aberration assay. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is an exceptionally aggressive disease, the treatment of which has largely been unsuccessful due to higher resistance offered by pancreatic cancer cells to conventional approaches such as surgery, radiation and/or chemotherapy. The aberration of Ras oncoprotein has been linked to the induction of multiple signaling pathways and to the resistance offered by pancreatic cancer cells to apoptosis. Therefore, there is a need for development of new and effective chemotherapeutic agents which can target multiple pathways to induce responsiveness of pancreatic cancer cells to death signals. In this study, human pancreatic adenocarcinoma cells AsPC-1 were used to investigate the effect of Lupeol on cell growth and its effects on the modulation of multiple Ras-induced signaling pathways. Lupeol caused a dose-dependent inhibition of cell growth as assessed by MTT assay and induction of apoptosis as assessed by flow cytometry, fluorescence microscopy and western blotting. Lupeol treatment to cells was found to significantly reduce the expression of Ras oncoprotein and modulate the protein expression of various signaling molecules involved in PKCα/ODC, PI3K/Akt and MAPKs pathways along with a significant reduction in the activation of NFκB signaling pathway. Our data suggest that Lupeol can adopt a multi-prong strategy to target multiple signaling pathways leading to induction of apoptosis and inhibition of growth of pancreatic cancer cells. Lupeol could be a potential agent against pancreatic cancer, however, further in-depth in vivo studies are warranted. [ABSTRACT FROM AUTHOR]