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The SARS-CoV-2 outbreak has posed a plethora of problems for the global healthcare system and socioeconomic burden. Despite valiant efforts to contain the COVID-19 outbreak, the situation has deteriorated to the point that there are no viable preventive therapies to treat this disease. The case count has skyrocketed globally due to the newly evolved variants. Despite vaccination drives, the re-occurrence of recent pandemic waves has reinforced the importance of innovation/utilization of immune-booster to achieve appropriate long-term vaccine protection. Plant-derived immuno-adjuvants, which have multifaceted functions, can impede infections by boosting the immune system. Many previous studies have shown that formulation of vaccines using plant-derived adjuvant results in long-lasting immunity may overcome the natural tendency of coronavirus immunity to wane quickly. Plant polysaccharides, glycosides, and glycoprotein extracts have reportedly been utilized as enticing adjuvants in experimental vaccines, such as Advax, Matrix-M, and Mistletoe lectin, which have been shown to be highly immunogenic and safe. When employed in vaccine formulation, Advax and Matrix-M generate long-lasting antibodies, a balanced robust Th1/Th2 cytokine profile, and the stimulation of cytotoxic T cells. Thus, the use of adjuvants derived from plants may increase the effectiveness of vaccines, resulting in the proper immunological response required to combat COVID-19. A few have been widely used in epidemic outbreaks, including SARS and H1N1 influenza, and their use could also improve the efficacy of COVID-19 vaccines. In this review, the immunological adjuvant properties of plant compounds as well as their potential application in anti-COVID-19 therapy are thoroughly discussed.

Amplification of oxidative stress can be utilized as a strategy to attenuate cancer progression by instigating apoptosis. However, the duration of positive response to such therapies is limited, as cancer cells eventually develop resistance. The underlying molecular mechanisms of cancer cells to escape apoptosis under high oxidative stress is unknown. Employing big data, and its integration with transcriptome, proteome and network analysis in six cancer types revealed system-level interactions between DNA damage response (DDR), cell cycle and anti-apoptotic proteins. Cancer system biology is used to elucidate mechanisms for cancer progression, but networks defining mechanisms causing resistance is less explored. Using system biology, we identified DDR hubs between G1-S and M phases that were associated with bad prognosis. The increased expression of DDR network was involved in resistance under high oxidative stress. We validated our findings by combining H2O2 induced oxidative stress and DDR inhibitors in human lung cancer cells to conclude the necessity of targeting a ‘disease-causing network’. Collectively, our work provides insights toward designing strategies for network pharmacology to combat resistance in cancer research.

Gliomas are lethal and aggressive form of brain tumors with resistance to conventional radiation and cytotoxic chemotherapies; inviting continuous efforts for drug discovery and drug delivery. Interestingly, small molecule hybrids are one such pharmacophore that continues to capture interest owing to their pluripotent medicinal effects. Accordingly, we earlier reported synthesis of potent Styryl-cinnamate hybrids (analogues of Salvianolic acid F) along with its plausible mode of action (MOA). We explored iTRAQ-LC/MS-MS technique to deduce differentially expressed landscape of native & phospho-proteins in treated glioma cells. Based on this, Protein-Protein Interactome (PPI) was looked into by employing computational tools and further validated in vitro. We hereby report that the Styryl-cinnamate hybrid, an analogue of natural Salvianolic acid F, alters key regulatory proteins involved in translation, cytoskeleton development, bioenergetics, DNA repair, angiogenesis and ubiquitination. Cell cycle analysis dictates arrest at G0/G1 stage along with reduced levels of cyclin D; involved in G1 progression. We discovered that Styryl-cinnamate hybrid targets glioma by intrinsically triggering metabolite-mediated stress. Various oncological circuits alleviated by the potential drug candidate strongly supports the role of such pharmacophores as anticancer drugs. Although, further analysis of SC hybrid in treating xenografts or solid tumors is yet to be explored but their candidature has gained huge impetus through this study. This study equips us better in understanding the shift in proteomic landscape after treating glioma cells with SC hybrid. It also allows us to elicit molecular targets of this potential drug before progressing to preclinical studies.

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used.

Background: India has been amongst the most affected nations during the SARS CoV2 pandemic, with sparse data on country wide spread of asymptomatic infections and antibody persistence. This longitudinal cohort study was aimed to evaluate SARS CoV2 seropositivity rate as a marker of infection and evaluate temporal persistence of antibodies with neutralization capability and to infer possible risk factors for infection. Methods: Council of Scientific and Industrial Research, India (CSIR) with its more than 40 laboratories and centers in urban and semi urban settings spread across the country piloted the pan country surveillance. 10427 adult individuals working in CSIR laboratories and their family members based on voluntary participation were assessed for antibody presence and stability was analyzed over 6 months utilizing qualitative Elecysys SARS CoV2 specific antibody kit and GENScript cPass SARS CoV2 Neutralization Antibody Detection Kit. Along with demographic information, possible risk factors were evaluated through self to be filled online forms with data acquired on blood group type, occupation type, addiction and habits including smoking and alcohol, diet preferences, medical history and transport type utilized. Symptom history and information on possible contact and compliance with COVID 19 universal precautions was also obtained. Findings:1058 individuals (10.14%) had antibodies against SARS CoV2. A follow up on 346 seropositive individuals after three months revealed stable to higher antibody levels against SARS CoV2 but declining plasma activity for neutralizing SARS CoV2 receptor binding domain and ACE2 interaction. A repeat sampling of 35 individuals, at six months, revealed declining antibody levels while the neutralizing activity remained stable compared to three months. Majority of seropositive individuals (75%) did not recall even one of nine symptoms since March 2020. Fever was the most common symptom with one fourth reporting loss of taste or smell. Significantly associated risks for seropositivity (Odds Ratio, 95% CI, p value) were observed with usage of public transport (1.79, 1.43 to 2∙24, 2.81561x10-6), occupational responsibilities such as security, housekeeping personnel etc. (2.23, 1.92 to 2.59, 6.43969x10-26), non smokers (1.52, 1.16 to 1.99, 0.02) and non vegetarianism (1.67, 1.41 to 1.99, 3.03821x10-8). An iterative regression analysis was confirmatory and led to only modest changes to estimates. Predilections for seropositivity was noted with specific ABO blood groups; O was associated with a lower risk. Interpretation: In a first of its kind study from India, we report the seropositivity in a country wide cohort and identify variable susceptible associations for contacting infection. Serology and Neutralizing Antibody response provides much sought for general insights on the immune response to the virus among Indians and will be an important resource for designing vaccination strategies. Funding: Council of Scientific and Industrial Research, India (CSIR)

Camellia sinensis (tea) is an evergreen plant having bioactive compounds associated with various pharmacological effects, including anti-cancerous activity. These phytochemicals are variedly distributed in plant tissues. A detailed study to understand chemical composition within the economically underutilized tea tissues is required to generate value. Therefore, a comprehensive chemical profiling of underutilized C. sinensis parts [coarse leaves, flowers, fruits (immature); n = 9] was performed by NMR techniques. NMR (1D and 2D) spectroscopy ambiguously identified and quantified fifty-seven metabolites (Coarse leaves: 35, flowers; 42, immature fruits; 45). The statistical analysis showed apparent tissue-specific similarities (26 metabolites) and variations. Further, HPLC-DAD revealed absolute quantification of catechins, caffeine and theanine among the different parts of C. sinensis. Moreover, cytotoxicity studies of tea tissues against colorectal cancer cell lines showed anticancer potentials. This chemical information and anticancer activity of underutilized C. sinensis parts will help to develop value added nutraceutical and cosmeceutical products.

Summary Background & aims Beverages and Non-alcoholic fatty liver disease (NAFLD) both the terms are associated with westernized diet and sedentary lifestyle. Throughout recent decades, dietary changes have boosted demand of beverages to meet the liquid consumption needs, among which rising consumption of several calorie-rich beverages have increased the risk of fatty liver disease. Meanwhile, certain beverages have capacity to deliver many unanticipated health benefits thereby reducing the burden of NAFLD and metabolic diseases. The present review therefore addresses the increasing interconnections between beverages intake among population, dietary patterns and the overall effect of these beverage on the development and prevention of NAFLD. Methods In the present review, some frequently consumed beverage groups have been analyzed in light of their role in the advancement and prevention of NAFLD, including sugar sweetened, hot and alcoholic beverages. The nutritional composition of different beverages makes the progression of NAFLD distinctive. Results The ingestion of sugar-rich beverages has demonstrated the metabolic burden and in all cases, raises the risk of NAFLD, while intake of coffee and tea has decreased this risk without any significant adverse effects. In some cases, low to moderate alcohol intake has been shown to minimize the risk of advanced fibrosis and NAFLD-mortality. Conclusion Together, this review discusses and supports work on new dietary approaches and clinical studies to accomplish nutrition-oriented NAFLD care by improving the drinking habits.

Probiotic bacteria are increasingly gaining importance in human nutrition owing to their multifaceted health beneficial effects. Studies have also shown that probiotic supplementation is useful in mitigating age-associated oxi-inflammatory stress, immunosenescence, and gut dysbiosis thereby promoting health and longevity. However, our current understanding of the process of aging suggests a strong interrelationship between the accumulation of senescent cells and the development of aging phenotype, including the predisposition to age-related disorders. The present review studies the documented pro-longevity effects of probiotics and highlights how these beneficial attributes of probiotics could be related to the mitigation of cellular senescence. We present a perspective that to fully understand and comprehend the anti-aging characteristics of probiotic bacteria; it is imperative that probiotics or their synbiotic amalgamation with plant polyphenols, be studied under the purview of cellular senescence, that may ultimately help devise probiotic-based anti-senescence strategies.

Context Various factors affect plasma concentrations of antitubercular drugs in different populations so dosing schedule should be adjusted after therapeutic drug monitoring. Aims To study variability in plasma concentrations of Rifampicin and Pyrazinamide with pre and post-meal administration of drugs in tuberculosis patients. Methods and material 52 patients of pulmonary tuberculosis, divided in to two groups, pre and post-meal through systemic randomization. After taking pre-dose sample, drugs were administered according to the group. Samples were withdrawn at 2, 4, 6, and 10 h after drug administration. Analysis of samples was done using HPLC. Results Mean ± 1SD of Cmax of Rifampicin was 7.75 ± 2.82 μg/ml, mean ± 1SD of AUC0–10 was 42.17 ± 17.25 μg h/ml, adjusted Tmax was 4.25 h. In pre-meal samples, the corresponding values were 7.75 ± 2.88 μg/ml, 42.83 ± 18.47 μg h/ml, 3.76 h and in post-meal samples 8.03 ± 2.30 μg/ml, 41.56 ± 16.46 μg h/ml and 4.75 h. Mean ± 1SD of Cmax levels of Pyrazinamide was 54.49 ± 21.86 μg/ml, mean ± 1SD of AUC0–10 was 337.94 ± 124.28 μg h/ml and adjusted Tmax was 3.49 h. In pre-meal samples the corresponding values were 52.00 ± 19.13 μg/ml, 329.96 ± 112.11 μg h/ml, 3.23 h, and in post-meal samples 57.43 ± 23.61 μg/ml, 345.58 ± 136.99 μg h/ml, 3.54 h. Conclusion There is huge variability in the plasma levels of Rifampicin and Pyrazinamide in population of this sub-himalayan region.

Information regarding cellular anti-senescence attributes of probiotic bacteria vis-à-vis modulation of senescence-associated secretory phenotype (SASP) and mTOR signaling is very limited. The present study assessed anti-senescence potential of secretory metabolites of probiotic Lactobacillus fermentum (Lact. fermentum) using H

Background Head and neck squamous-cell carcinoma (HNSCC) ranks sixth among cancers worldwide. Though several molecular mechanisms of tumor initiation and progression of HNSCC are known, others remain unclear. Significance of p38/MAPKAPK2 (Mitogen-activated protein kinase-activated protein kinase-2) pathway in cell stress and inflammation is well established and its role in tumor development is being widely studied. Methods We have elucidated the role of MAPKAPK2 (MK2) in HNSCC pathogenesis using clinical tissue samples, MK2-knockdown (MK2KD) cells and heterotropic xenograft mice model. Results In patient-derived tissue samples, we observed that MK2 is reproducibly overexpressed. Increased stability of cyclin-dependent kinase inhibitor 1B (p27), mitogen-activated protein kinase phosphatase-1 (MKP-1) transcripts and decreased half-life of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) transcripts in MK2KD cells suggests that MK2 regulates their transcript stability. In vivo xenograft experiments established that knockdown of MK2 attenuates course of tumor progression in immunocompromised mice. Conclusion Altogether, MK2 is responsible for regulating the transcript stability and is functionally important to modulate HNSCC pathogenesis. Electronic supplementary material The online version of this article (10.1186/s13046-019-1167-2) contains supplementary material, which is available to authorized users.

The p38 mitogen-activated protein kinase (p38MAPK) pathway has been implicated in a variety of pathological conditions including inflammation and metastasis. Post-transcriptional regulation of genes harboring adenine/uridine-rich elements (AREs) in their 3′-untranslated region (3′-UTR) is controlled by MAPK-activated protein kinase 2 (MAPKAPK2 or MK2), a downstream substrate of the p38MAPK. In response to diverse extracellular stimuli, MK2 influences crucial signaling events, regulates inflammatory cytokines, transcript stability and critical cellular processes. Expression of genes involved in these vital cellular cascades is controlled by subtle interactions in underlying molecular networks and post-transcriptional gene regulation that determines transcript fate in association with RNA-binding proteins (RBPs). Several RBPs associate with the 3′-UTRs of the target transcripts and regulate their expression via modulation of transcript stability. Although MK2 regulates important cellular phenomenon, yet its biological significance in tumor progression has not been well elucidated till date. In this review, we have highlighted in detail the importance of MK2 as the master regulator of RBPs and its role in the regulation of transcript stability, tumor progression, as well as the possibility of use of MK2 as a therapeutic target in tumor management.

The role of phosphatidylinositol 3-kinase linked mammalian target of rapamycin (mTOR) pathway hyperactivation is well established in cancer pathogenesis. Several molecules inhibiting mTOR pathway, leading to inhibition of protein synthesis responsible for angiogenesis of tumor cells have emerged out to be potential anticancers. Similar hyperactivation of mTOR pathway has also reported in epilepsy during latent phase, following precipitating injury causing reorganization of neuronal networks and ultimately leading to induction of seizures. The mTOR inhibitors have also found to attenuate pathological changes in the brain associated with epilepsy, primarily suppression of mossy fiber sprouting. At the same time, a few antiepileptic molecules which have been studied against cancer showed anticancer activity, apart from their principal mechanism of action. These studies suggest mTOR signaling pathway to be a common pathogenic link between cancer and epilepsy. It has been found that, anticancer molecules acting on different molecular targets, that ultimately down regulate the expression of mTOR, can also be used in case of epilepsy to reduce its hyperactivation. There are several unexplored anticancer molecules that act by inhibiting mTOR directly or indirectly available which can be explored as antiepileptic in future. Majority of the molecules which are tested as anticancer do not reach the final phases of clinical trials due to less potency and efficacy, and ultimately a few of them reach the market. Since a lot of experimental/safety studies have already been conducted on such molecules, hence it is worthwhile to test these molecules for other disorders that share common pathogenic pathway like epilepsy, provided their pitfalls have been addressed, as proposed in the present review.

Ethnopharmacological relevance Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomas. (Menispermaceae) is one of the most widely used plants in various traditional medicinal systems including “Ayurveda”. The plant is used for the treatment of jaundice, rheumatism, urinary disorder, skin diseases, diabetes and anemia. The phytoconstituents present in the plant belongs to different class of compounds such as alkaloids, diterpenoids lactones, glycosides, steroids, phenol, aliphatic compounds and polysaccharides. Aim of the study The aim of present study was the isolation, structure elucidation, quantification and pharmacological evaluation of secondary metabolites from T. cordifolia for anticancer and immunomodulatory activities. Materials and methods Different extracts and fractions were prepared from the stem of T. cordifolia. Pure molecules were isolated using normal phase chromatography and characterized on the basis of NMR and mass spectroscopic techniques. The anti-cancer and immunomodulatory activities of different extracts, fractions and isolated compounds were evaluated against four different human cancer cell lines, KB (human oral squamous carcinoma), CHOK-1 (hamster ovary), HT-29 (human colon cancer) and SiHa (human cervical cancer) and murine primary cells respectively. A simple, normal phase HPTLC method was also developed for the quantification of three bioactive compounds i.e N-formylannonain (1), 11-hydroxymustakone (5) and yangambin (8) in the stem of T. cordifolia hosted on fifteen different plants. Results Chromatographic purification of different fractions led to the isolation of eight pure molecules i.e N-formylannonain (1), magnoflorine (2), jatrorrhizine (3) palmatine (4), 11-hydroxymustakone (5), cordifolioside A (6), tinocordiside (7) and yangambin (8). All extracts and fractions were active against KB and CHOK-1 cells whereas among the pure molecules palmatine (4) was found to be active against KB and HT-29; tinocordiside (7) against KB and CHOK-1; yangambin (8) against KB cells however N-formylannonain (1) and 11-hydroxymustakone (5), was found active for immunomodulatory activity. HPTLC quantification of three active molecules i.e N-formylannonain (1), 11-hydroxymustakone (5), and yangambin (8) were found in highest quantity in the stem of T. cordifolia hosted on Mangifera indica, however, other two active molecules were not quantified due to their insufficient quantity. Conclusion Eight compounds have been isolated and characterized belonging to different classes. The pharmacological evaluation of extract, fractions and pure molecules revealed the ethnomedicinal value of T. cordifolia for anticancer and immunomodulatory activities.

The role of increased tissue senescent cell (SC) burden in driving the process of ageing and associated disorders is rapidly gaining attention. Amongst various plausible factors, impairment in immune functions is emerging as a critical regulator of known age-associated accumulation of SC. Immune cells dysfunctions with age are multi-faceted and are uniquely attributed to the independent processes of immunosenescence and cellular senescence which may collectively impair immune system mediated clearance of SC. Moreover, being functionally and phenotypically heterogenic, immune cells are also liable to be affected by senescence microenvironment in other tissues. Therefore, strategies aimed at improving immunosenescence and cellular senescence in immune cells can have pleiotropic effects on ageing physiology including the accumulation of SC. In this regard, nutraceutical's immunomodulatory attributes are well documented which may have implications in developing nutrition-oriented immunotherapeutic approaches against SC. In particular, the three diverse sources of bioactive ingredients, viz., phytochemicals, probiotic bacteria and omega-3-fatty acids have shown promising anti-immunosenescence and anti-cellular senescence potential in immune cells influencing aging and immunity in ways beyond modest stimulation of immune responses. The present narrative review describes the preventive and therapeutic attributes of phytochemicals such as polyphenols, probiotic microbes and omega-3-fatty acids in influencing the emerging nexus of immunosenescence, cellular senescence and SC during aging. Outstanding questions and nutraceuticals-based pro-longevity and niche research areas have been deliberated. Further research using integrative approaches is recommended for developing nutrition-based holistic immunotherapeutic strategies for 'healthy ageing'.

Aim Emerging studies have shown that application of low concentration of bioactive phytomolecules can confer anti-proliferative effects on tumour cells by inducing senescence pathways. The alkaloid berberine is recognized for its anti-cancer attributes but its potential to induce senescence in tumour cells is least understood. Materials and methods The present work assessed the mechanisms pertaining to dose-dependent anti-proliferative effects of berberine in the perspective of senescence and inflammation using human non-small cell lung cancer cell line (A549). Key findings Amongst the different tested bioactive phytomolecules, berberine treatment suppressed the proliferation of A549 cells regardless of the concentration applied. Application of low doses of berberine induced a weak SA-β-gal activity and p21WAF1 expression but did not show evidence of SASP activation due to absence of NF-κB activation and expression of proinflammatory genes. However, treatment with higher dose of berberine showed no evidence of SA-β-gal activity or p21WAF1 expression, but instead induced apoptosis and suppressed the expression of cell cyclins. The proliferative capacity of berberine treated cells was at par with control cells and no SA-β-gal activity could be observed in first generation of berberine treated cells. mTOR pathway showed no distinct activation on account of berberine treatment thereby further emphasizing that low dose of berberine induced quiescence and not senescence in A549 cells. Significance Taken together, our observations indicate that despite its strong anti-proliferative effects, low dose berberine treatment may only induce transient changes akin to quiescence that needs to be considered before implying pro-senescence attributes of berberine in cancer therapeutics.

In pursuit of developing anti-aging or age-delaying strategies, nutritional interventions have long been considered promising candidates. However, emerging advances in the understanding of the causes and effects of senescence per se have enhanced the prospects of a more focused approach in the exploration of therapies aimed at the modulation of aging. The aim of this study was to review recent developments on the molecular basis of aging and provide evidence that regulation of the mechanistic target of rapamycin (mTOR), senescence-associated secretory phenotype (SASP), and apoptotic pathways could be the key mechanistic targets of prospective senescence modulatory interventions. The emerging role of nutraceuticals in specifically targeting these molecular aspects of senescence are reviewed with the rationale of identifying novel opportunities and challenges in formulating food- and nutrition-based anti-aging therapies.

The phytochemical epigallocatechin gallate (EGCG) has been reported to alleviate age-associated immune disorders and organ dysfunction. However, information regarding the mechanistic role of EGCG in the suppression of cellular senescence is limited. The present study thus assessed the effects and underlying mechanisms of EGCG in the inhibition of senescence as well as its potential to selectively eliminate senescent cells (senolytics) using 3T3-L1 preadipocytes. Premature senescence was established in cells by repeated exposure of H2O2 at a sub-lethal concentration (150 μM). H2O2 treated cells showed characteristic senescence-associated features including increased cell size, senescence-associated β-galactosidase activity (SA-β-gal), development of senescence-associated secretory phenotype (SASP), activation of reactive oxygen species (ROS) and pathways, DNA damage as well as induction of cell cycle inhibitors (p53/p21WAF1/p16INK4a). In addition, a robust activation of PI3K/Akt/mTOR and AMPK pathways was also observed in H2O2 treated cells. Presence of EGCG (50 and 100 μM) showed significant downregulation of PI3K/Akt/mTOR and AMPK signaling along with the suppression of ROS, iNOS, Cox-2, NF-κB, SASP and p53 mediated cell cycle inhibition in preadipocytes. In addition, EGCG treatment also suppressed the accumulation of anti-apoptotic protein Bcl-2 in senescent cells thereby promoting apoptosis mediated cell death. Our results collectively show that EGCG acts as an mTOR inhibitor, SASP modulator as well as a potential senolytic agent thereby indicating its multi-faceted attributes that could be useful for developing anti-aging or age-delaying therapies.

Needles of seven cultivated clones (C1 - C7) of Juniperus communis at lower altitude and three wild Juniperus species (J. communis, J. recurva and J. indica) at higher altitudes were investigated comparatively for their essential oils (EOs) yields, chemical composition, cytotoxic and antibacterial activities. The EOs yields varied from 0.26 to 0.56% (v/w) among samples. Sixty-one volatile components were identified by gas chromatography-mass spectrometry (GC/MS) and quantified using gas chromatography GC (FID) representing 82.5 - 95.7% of the total oil. Monoterpene hydrocarbons (49.1 - 82.8%) dominated in all samples (α-pinene, limonene and sabinene as major components). Principal component analysis (PCA) of GC data revealed that wild and cultivated Juniperus species are highly distinct due to variation in chemical composition. J. communis (wild species) displayed cytotoxicity against SiHa (human cervical cancer), A549 (human lung carcinoma) and A431 (human skin carcinoma) cells (66.4 ± 2.2%, 74.4 ± 1.4% and 57.4 ± 4.0%), respectively, at 200 μg/ml. EOs exhibited better antibacterial activity against Gram-positive bacteria than against Gram-negative bacteria with the highest zone of inhibition against Staphylococcus aureus MTCC 96 (19.2 ± 0.7) by clone-7. As per the conclusion of the findings, EOs of clone-2, clone-5 and clone-7 can be suggested to the growers of lower altitude, as there is more possibility of uses of these EOs in food and medicinal preparations.

Clematis gouriana (Ranunculaceae), a perennial herb, is used by the local inhabitants of the western Himalayan region for its medicinal properties. Major bioconstituents of C. gouriana leaves using different solvent extracts were obtained and analysed. The results revealed promising contents of phenolics (from 18.19 ± 0.10 to 22.17 ± 0.10 mg g(-1)) as gallic acid and flavonoids (from 2.83 ± 0.01 to 6.52 ± 0.08 mg g(-1)) as quercetin equivalent in different extracts. Aqueous acetone extract showed higher antioxidant activity with IC50 value of 129.11 and 25.35 μg mL(-1) against DPPH and ABTS free radicals, respectively. Antioxidant yield ranged from 16.87 ± 0.27 to 24.48 ± 0.13 mg g(-1) of Trolox equivalent in different extracts as measured by the FRAP assay. Furthermore, ethylacetate extract exhibited strong in vitro cytotoxicity against Chinese hamster ovary and glioma cell lines. Proximate composition (proteins, fats, ash and minerals) of C. gouriana leaves was also assessed. Results demonstrated the potential of C. gouriana bioconstituents as nutraceuticals.

The phytochemical and biological investigation of Cissampelos pareira leads to the isolation of one new isoquinoline alkaloid (7) along with six known isoquinoline alkaloids, namely, magnoflorine (1), magnocurarine (2), cissamine (3), curine (4), hayatinine (5) and cycleanine (6). Magnoflorine (1) and magnocurarine (2) were isolated for the first time from C. pareira. A new, rapid, simple and sensitive UPLC method was developed for simultaneous quantification of five pure compounds (1-5). Seasonal variation study revealed higher content of these compounds during the rainy season. The chloroform (CPCF) and n-butanol (CPBF) fractions showed cytotoxic efficacy against KB cells. Among pure compounds, hayatinine (5) was found to be most active against KB and A549, while, cycleanine (6) against KB cells.

Nanocomposites of plant cellulose nanocrystals (CNCs) were developed by binding model proteins BSA and HSA onto CNCs by physical adsorption and chemical conjugation methods The spectroscopy and microscopy studies confirmed the protein binding onto CNCs. Phosphate buffer saline (pH=4.0, 7.4) and simulated gastric and intestinal fluids (SGF/SIF; pH=1.1/6.5) showed maximum protein release of ∼62% over a period of time. The released proteins were found to retain both structural integrity as well as≥90% of bioactivity. Further, these cytocompatible nanocomposites showed ∼58-85% cholesterol release from HUVEC whereas no selectivity was observed for HCAEC. It is speculated that due to the presence of combination of shuttles (albumins) and sinks (CNCs and albumins), these prepared nanocomposites with increased cholesterol effluxing ability may serve as a potential candidate for future biomedical applications in pharmaceuticals.

Oxygen (OA systematic search in PubMed and SciFinder for the literature on HIF-1 biology and therapeutic importance in cancer was carried out.This review highlights the initial description as well as the recent insights into HIF-1 biology and regulation. We have focused on emerging data regarding varied classes of HIF-1 target genes affecting various levels of crosstalk among tumorigenic pathways. We have emphasized on the fact that HIF-1 acts as a networking hub coordinating activities of multiple signaling molecules influencing tumorigenesis. Emerging evidences indicate role of many HIF-induced proteomic and genomic alterations in malignant progression by mediating a myriad of genes stimulating angiogenesis, anaerobic metabolism and survival of cancer cells in OBetter understanding of the crucial role of HIF-1 in carcinogenesis could offer promising new avenues to researchers and aid in elucidating various open issues regarding the use of HIF-1 as an anticancer therapeutic target. In spite of large efforts in this field, many questions still remain unanswered. Hence, future investigations are necessary to devise, assess and refine methods for translating previous research efforts into novel clinical practices in cancer treatment.

Eleven constituents were characterised by gas chromatography-mass spectrometry analysis, and five molecules were isolated using column chromatography. The in vitro study of the extract and isolated molecules against KB and SiHa cell lines revealed oleanolic acid (1) and oleic acid (2) as potent cytotoxic molecules with potential anticancer activity. The IC50 values of n-hexane extract (CPHF), oleanolic acid (1) and oleic acid (2) were >300, 56.08 and 70.7 μg/mL (μM), respectively, against KB cell lines and >300, 47.24 and 80.2 μg/mL (μM), respectively, against SiHa cell lines.

Background Plant-based traditional system of medicine continues to play an important role in healthcare. In order to find new potent source of bioactive molecules, we studied the cytotoxic activity of the essential oils from the flowers and leaves of Callistemon citrinus. This is the first report on anticancer potential of essential oils of C. citrinus. Methods Cytotoxicity of essential oil was evaluated using sulfo-rhodamine B (SRB) assay against human lung carcinoma (A549), rat glioma (C-6), human colon cancer (Colo-205) and human cervical cancer (SiHa) cells. Apoptosis induction was evaluated by caspase-3/7 activity which was further confirmed by western blotting. Percentage cell apoptosis was determined by Annexin V based dead cell assay followed by DNA content as cell cycle analysis against A549 and C-6 cells. While 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to check the toxicity against normal human peripheral blood mononuclear cells (PBMCs), the immunomodulatory activity on mouse splenocytes was evaluated using SRB assay. Results The GC and GC-MS analysis of these essential oils revealed high content of α-pinene (32.3%), limonene (13.1%) and α-terpineol (14.6%) in leaf sample, whereas the flower oil was dominated by 1,8-cineole (36.6%) followed by α-pinene (29.7%). The leaf oil contained higher amount of monoterpene hydrocarbons (52.1%) and sesquiterpenoids (14%) as compared to flower oil (44.6% and 1.2%, respectively). However, the flower oil was predominant in oxygenated monoterpenes (43.5%). Although both leaf and flower oils showed highest cytotoxicity on A549 cells (61.4%±5.0 and 66.7%±2.2, respectively), only 100 μg/mL flower oil was significantly active against C-6 cells (69.1%±3.1). Interestingly, no toxicity was recorded on normal cells. Conclusion Higher concentration of 1,8-cineole and/or synergistic effect of the overall composition were probably responsible for the efficacy of flower and leaf oils against the tested cells. These oils may form potential source of natural anti-cancer compounds and play important role in human health.

The pathogenic mechanism of dengue virus infection is related to the host responses within target cells, and therefore we assessed intracellular changes in stress proteins following dengue virus infection. This study provides evidence that Hsp70 helps in viral multiplication by suppressing the type 1 interferon response. Dengue virus infection in human monocytic THP-1 cells led to overexpression of Hsp70, which also acts as a chaperone. The functional role of Hsp70 in dengue virus multiplication was identified by downregulating the Hsp70 gene with its specific siRNA duplexes, which led to a decrease in viral RNA copy numbers in cellular supernatants and intracellular viral load. It also resulted in an increased IFN-α level, which mediates its antiviral effect through double-stranded RNA-induced protein kinase-PKR. Collectively these results suggest that an increased level of Hsp70 expression in dengue-virus-infected THP-1 cells assists in viral replication by escaping the antiviral effect of type 1 interferon.

Rhodiola imbricata is a medicinal plant having immunostimulating properties. The anti-proliferative effects of Rhodiola aqueous extract (RAE), were studied in human erythroleukemic cell line K-562 using MTT cell proliferation assay. The proliferation of K-562 was significantly decreased after 72h incubation with RAE at 100 and 200microg/ml. However, almost no suppressive effects could be detected in normal human peripheral blood lymphocytes or mouse macrophage cell line RAW-264.7. RAE was also found to induce intracellular reactive oxygen species (ROS) in K-562 cells at 200microg/ml when incubated overnight. The increased ROS generation may cause apoptosis, which was observed in AnnexinV-FITC and propidium iodide (PI) staining of cells treated with RAE for 72h in K-562 cells. Moreover, RAE arrested cell cycle progression in G2/M phase in early and late period of exposure. The anti-cancer activity of RAE was also confirmed by increased NK cell cytotoxicity. These observations suggest that aqueous extract of R. imbricata rhizome has very potent anti-cancer activities, which might be useful in leukemia cancer treatment.

Modulation of immune response to alleviate diseases has long since been of interest. Plant extracts have been widely investigated for their possible immunomodulatory properties. We have evaluated the immunomodulatory activity of aqueous extract of Rhodiola rhizome in human peripheral blood mononuclear cells (PBMCs) and mouse macrophage cell line RAW 264.7. The Rhodiola extract was found to stimulate production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in human PBMCs as well as RAW 264.7 cell line. It also increased production of nitric oxide synergistically in combination with lipopolysaccharide (LPS) in RAW 264.7. Rhodiola at 250 microg/ml increased the p-IkappaB expression in human PBMCs. Aqueous extract of Rhodiola (250 microg/ml) also activated the nuclear translocation of NF-kappaB in human PBMCs, which is comparable to the positive stimulant LPS. Thus, our present study suggests that Rhodiola most likely activates proinflammatory mediators via phosphorylated inhibitory kB and transcription factor NF-kB. Our study demonstrates immunostimulatory potential of aqueous extract of Rhodiola rhizome, that can be used for upregulation of immune response in patients with inadequate functioning of the immune system.