Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.

Cancer has become one of the most multifaceted and widespread illnesses affecting human health, causing substantial mortality at an alarming rate. After cardiovascular problems, the condition has a high occurrence rate and ranks second in terms of mortality. The development of new drugs has been facilitated by increased research and a deeper understanding of the mechanisms behind the emergence and advancement of the disease. Numerous preclinical and clinical studies have repeatedly demonstrated the protective effects of natural terpenoids against a range of malignancies. Numerous potential bioactive terpenoids have been investigated in natural sources for their chemopreventive and chemoprotective properties. In practically all body cells, the signaling molecule referred to as signal transducer and activator of transcription 3 (STAT3) is widely expressed. Numerous studies have demonstrated that STAT3 regulates its downstream target genes, including Bcl-2, Bcl-xL, cyclin D1, c-Myc, and survivin, to promote the growth of cells, differentiation, cell cycle progression, angiogenesis, and immune suppression in addition to chemotherapy resistance. Researchers viewed STAT3 as a primary target for cancer therapy because of its crucial involvement in cancer formation. This therapy primarily focuses on directly and indirectly preventing the expression of STAT3 in tumor cells. By explicitly targeting STAT3 in both in vitro and in vivo settings, it has been possible to explain the protective effect of terpenoids against malignant cells. In this study, we provide a complete overview of STAT3 signal transduction processes, the involvement of STAT3 in carcinogenesis, and mechanisms related to STAT3 persistent activation. The article also thoroughly summarizes the inhibition of STAT3 signaling by certain terpenoid phytochemicals, which have demonstrated strong efficacy in several preclinical cancer models.

An Updated Review Summarizing the Anticancer Efficacy of Melittin from Bee Venom in Several Models of Human Cancers.

Apitherapy (using bee products) has gained broad recognition in cancer therapeutics globally. Honeybee venom has a broad range of biological potential, and its utilization is rapidly emerging in apitherapy. Bee products have significant potential to strengthen the immune system and improve human health. Thus, this review is targeted toward recapitulating the chemo-preventive potential of melittin (MEL), which constitutes a substantial portion of honeybee venom. Honeybee venom (apitoxin) is produced in the venom gland of the honeybee abdomen, and adult bees utilize it as a primary colony defense mechanism. Apitoxin comprises numerous biologically active compounds, including peptides, enzymes, amines, amino acids, phospholipids, minerals, carbohydrates, and volatile components. We are mainly focused on exploring the potential of melittin (a peptide component) of bee venom that has shown promising potential in the treatment of several human cancers, including breast, stomach, lung, prostate, ovary, kidney, colon, gastric, esophageal, cervical cancers, melanoma, osteosarcoma, and hepatocellular carcinoma. This review has summarized all potential studies related to the anticancerous efficacy of melittin (apitoxin), its formulations, conjugates, and nano-formulations against several human carcinomas, which would further pave the way for future researchers in developing potent drugs for cancer management.

Updates on the anticancer potential of garlic organosulfur compounds and their nanoformulations: Plant therapeutics in cancer management.

Garlic (Allium sativum L.) possesses numerous pharmacological potential, including antibacterial, antiarthritic, antithrombotic, anticancer, hypoglycemic, and hypolipidemic effects. The anti-cancer action of garlic is likely the best researched of the many advantageous pharmacological effects, and its use offers significant protection against the risk of developing cancer. A few active metabolites of garlic have been reported to be essential in the destruction of malignant cells due to their multi-targeted activities and lack of significant toxicity. The bioactive compounds in garlic having anticancer properties include diallyl trisulfide, allicin, allyl mercaptan diallyl disulfide, and diallyl sulphide. Different garlic-derived constituents and their nanoformulations have been tested for their effects against various cancers including skin, ovarian, prostate, gastric, breast, and lung, colorectal, liver, oral, and pancreatic cancer. The objective of this review is to summarize the antitumor activity and associated mechanisms of the organosulfur compounds of garlic in breast carcinoma. Breast cancer continues to have a significant impact on the total number of cancer deaths worldwide. Global measures are required to reduce its growing burden, particularly in developing nations where incidence is increasing quickly and fatality rates are still high. It has been demonstrated that garlic extract, its bioactive compounds, and their use in nanoformulations can prevent breast cancer in all of its stages, including initiation, promotion, and progression. Additionally, these bioactive compounds affect cell signaling for cell cycle arrest and survival along with lipid peroxidation, nitric oxide synthase activity, epidermal growth factor receptor, nuclear factor kappa B (NF-κB), and protein kinase C in breast carcinoma. Hence, this review deciphers the anticancer potential of garlic components and its nanoformulations against several breast cancer thereby projecting it as a potent drug candidate for efficient breast cancer management.

Unraveling the therapeutic potential of natural products in the prevention and treatment of leukemia.

Leukemia is a heterogeneous group of hematological malignancies distinguished by differentiation blockage and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow (BM) and peripheral blood (PB). There are various types of leukemia in which intensive chemotherapy regimens or hematopoietic stem cell transplantation (HSCT) are now the most common treatments associated with severe side effects and multi-drug resistance in leukemia cells. Therefore, it is crucial to develop novel therapeutic approaches with adequate therapeutic efficacy and selectively eliminate leukemic cells to improve the consequences of leukemia. Medicinal plants have been utilized for ages to treat multiple disorders due to their diverse bioactive compounds. Plant-derived products have been used as therapeutic medication to prevent and treat many types of cancer. Over the last two decades, 50 % of all anticancer drugs approved worldwide are from natural products and their derivatives. Therefore this study aims to review natural products such as polyphenols, alkaloids, terpenoids, nitrogen-containing, and organosulfur compounds as antileukemic agents. Current investigations have identified natural products efficiently destroy leukemia cells through diverse mechanisms of action by inhibiting proliferation, reactive oxygen species production, inducing cell cycle arrest, and apoptosis in both in vitro, in vivo, and clinical studies. Current investigations have identified natural products as suitable promising chemotherapeutic and chemopreventive agents. It played an essential role in drug development and emerged as a possible source of biologically active metabolites for therapeutic interventions, especially in leukemia. DATA AVAILABILITY: Data will be made available on request.

Unravelling the Influence of Nutrition and Mental Stress on Immune Response.

The review article reveals the role of mental as well as biological phenomena working behind immunity. In recent times, irresistible illnesses and inflammation have been thought to be hereditary or the result of the natural working mechanism of the human body in response to the pathogenic variables working inside the human system. In the past few years, the importance of psychological adjustments, mental well-being and eating habits has been studied and shown to have a marked effect on immunity. Psychoneuroimmunology considers that mental disorders are strongly interrelated with the resistant reaction. Besides, the immunological components control the wellbeing of the individual. Psychosocial mediations help reduce disease severity and enhance the functioning of the immune system. Nutrition plays a vital role in immunity and thus has an influence on our mental health.

Biomedical and Antioxidant Potentialities in Chilli: Perspectives and Way Forward.

Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.

Potential Therapeutic Role of Mesenchymal-Derived Stem Cells as an Alternative Therapy to Combat COVID-19 through Cytokines Storm.

Medical health systems continue to be challenged due to newly emerging COVID-19, and there is an urgent need for alternative approaches for treatment. An increasing number of clinical observations indicate cytokine storms to be associated with COVID-19 severity and also to be a significant cause of death among COVID-19 patients. Cytokine storm involves the extensive proliferative and hyperactive activity of T and macrophage cells and the overproduction of pro-inflammatory cytokines. Stem cells are the type of cell having self-renewal properties and giving rise to differentiated cells. Currently, stem cell therapy is an exciting and promising therapeutic approach that can treat several diseases that were considered incurable in the past. It may be possible to develop novel methods to treat various diseases by identifying stem cells' growth and differentiation factors. Treatment with mesenchymal stem cells (MSCs) in medicine is anticipated to be highly effective. The present review article is organized to put forward the positive arguments and implications in support of mesenchymal stem cell therapy as an alternative therapy to cytokine storms, to combat COVID-19. Using the immunomodulatory potential of the MSCs, it is possible to fight against COVID-19 and counterbalance the cytokine storm.

Unveiling Antioxidant and Antiproliferative Effects of Prosopis juliflora Leaves against Human Prostate Cancer LNCaP Cells.

Herbal medications or formulations are regularly recommended by clinicians as a potential therapeutic method for a variety of human ailments, including cancer. Although Prosopis juliflora extracts have shown promise in anticancer activity, the effects on prostate cancer and the accompanying molecular mechanisms of action are still unexplored. This research aims at the antioxidant, antiproliferative, and apoptosis-inducing properties of Prosopis juliflora methanolic leaves extract in human prostate cancer LNCaP cells. The antioxidant ability of the extract was assessed using the DPPH (2, 2-diphenyl-2-picrylhydrazyl) and two additional reducing power tests. Antitumor activity was determined using MTT cell viability tests and LDH cytotoxicity assays. The probable mechanism of apoptotic cell death was further investigated utilizing a caspase-3 activation assay and qRT-PCR mRNA expression investigations of apoptotic-related genes. The results revealed that the methanol extract of Prosopis juliflora leaves contains alkaloids, flavonoids, tannins, glycosides, and phenols, all of which have substantial antioxidant activity. In vitro anticancer tests demonstrated that extract therapy resulted in a dose-dependent reduction in cell viability of LNCaP prostate cancer cells, but normal HaCaT cells showed no cytotoxic effects. Furthermore, plant extract therapy increased caspase-3 activation and mRNA expression of apoptotic-related genes, suggesting that this could be a mechanism for cancer cell growth suppression. The significance of Prosopis juliflora as a source of new antioxidant compounds against prostate cancer was emphasized in the current study. However, more study is needed to demonstrate the efficacy of Prosopis juliflora leaves extract in the treatment of prostate cancer.

Moringa oleifera Plant as potent alternate to Chemical Coagulant in Water Purification

Abstract Quality of groundwater is threatened due to pollution by industrial, domestic and agricultural waste. A large number of populations are residing in rural areas which are unable to afford high cost water purifiers due to their low income as well as limited awareness. However, limited availability of fresh water has become a critical issue in developing countries. Around 1.2 billion population is deprived of affordable and safe water for their domestic need. Additionally, chemical coagulants which are nowadays being used for water purification pose severe and numerous health hazards to human. Thus utilization of easily accessible natural coagulant for water purification might offer a sustainable, practical and cost effective solution to the current alarming situation in developing countries. Several experimental findings have shown strong efficiency of Moringa oleifera plant extracts obtained from different solvents in the improvement of water quality parameters including physicochemical (such as pH, hardness, turbidity, metallic impurities, total dissolved solid) and biological (E.coli count) parameter. We have also highlighted the limitations and advantages of chemical coagulation in water purification. Altogether, this review summarizes one such miracle tree which has shown significant potential as a natural coagulant and its associated underlying mechanism in water purification process.

Rutin (Bioflavonoid) as Cell Signaling Pathway Modulator: Prospects in Treatment and Chemoprevention.

Cancer is a complex ailment orchestrated by numerous intrinsic and extrinsic pathways. Recent research has displayed a deep interest in developing plant-based cancer therapeutics for better management of the disease and limited side effects. A wide range of plant-derived compounds have been reported for their anticancer potential in the quest of finding an effective therapeutic approach. Rutin (vitamin P) is a low-molecular weight flavonoid glycoside (polyphenolic compound), abundantly present in various vegetables, fruits (especially berries and citrus fruits), and medicinal herbs. Numerous studies have delineated several pharmacological properties of rutin such as its antiprotozoal, antibacterial, anti-inflammatory, antitumor, antiviral, antiallergic, vasoactive, cytoprotective, antispasmodic, hypolipidemic, antihypertensive, and antiplatelet properties. Specifically, rutin-mediated anticancerous activities have been reported in several cancerous cell lines, but the most common scientific evidence, encompassing several molecular processes and interactions, including apoptosis pathway regulation, aberrant cell signaling pathways, and oncogenic genes, has not been thoroughly studied. In this direction, we attempted to project rutin-mediated oncogenic pathway regulation in various carcinomas. Additionally, we also incorporated advanced research that has uncovered the notable potential of rutin in the modulation of several key cellular functions via interaction with mRNAs, with major emphasis on elucidating direct miRNA targets of rutin as well as the process needed to transform these approaches for developing novel therapeutic interventions for the treatment of several cancers.

A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits.

Hesperidin, a phytoactive compound, is an abundant and economical dietary bioflavonoid possessing numerous biological and medicinal benefits. Several studies have strongly proven the significant chemotherapeutic potential of hesperidin. Therefore, this review aims to bring together the existing studies demonstrating hesperidin as a potential anticancer agent with its mode of action reported in the therapeutic strategies for numerous cancer types. Hesperidin acts via modulating multiple pathways involving cell cycle arrest, apoptosis, antiangiogenic, antimetastatic and DNA repair in various cancer cells. Hesperidin has been reported to alter several molecular targets related to carcinogenesis, such as reactive nitrogen species, cellular kinases, transcription factors, reactive oxygen species, drug transporters, cell cycle mediators and inflammatory cytokines. Collectively, this review provides significant insights for the potential of hesperidin to be a strong and promising candidate for pharmaceuticals, functional foods, dietary supplements, nutraceuticals and geared toward the better management of carcinoma.

Jab1 Inhibition by Methanolic Extract of Moringa Oleifera Leaves in Cervical Cancer Cells: A Potent Targeted Therapeutic Approach.

Modern research propounded that alteration in signaling pathways have shown strong connection with the progression of cervical cancer and modulation of these pathways by natural compounds could be a better treatment approach for the management of cervical cancer. Additionally, inhibitory role of methanolic extract of Moringa oleifera leaves against Jab1 has not been elucidated yet. Therefore, we have elucidated the inhibitory potential of MMLE against Jab1 in cervical cancer by analyzing several In Vitro assays. The MMLE treatment in cervical cancer cells showed decreased cell growth in a dose and time dependent manner. Furthermore, MMLE treated cervical cells have also depicted enhanced nuclear condensation (apoptotic induction potential) confirmed by Hoechst analysis. RT-PCR results clearly illustrated the inhibitory potential of MMLE against Jab1 via down regulating its expression. Conversely, a significant increase in p27 expression was also reported which could explain the cells growth arrest at G0/G1 phase. Additionally, enhanced ROS production and caspase-3 activation explains one of the possible mechanisms behind the inhibitory potential of MMLE against Jab1 in cervical cancer cells (HeLa). Thus our experimental findings may pave a potent phyto compound for targeting a crucial signalosome (Jab1) in cervical cancer.

Study to Investigate the Potential of Combined Extract of Leaves and Seeds of Moringa oleifera in Groundwater Purification.

Several parts of the Moringa oleifera plant have revealed incredible potential for water quality improvement. However, the purification potential of a combined leaf and seed extract of Moringa oleifera plants remains unexplored. To the best of our knowledge, this research would be the first to work towards exploiting the combined potential of a leaf and seed extract of the Moringa oleifera plant in the process of water purification. In this study, we investigated the combined effectiveness of the leaf and seed extract in the purification of groundwater. The jar test method was used to analyze the effectiveness of Moringa plant extract (in combination) on different quality parameters of groundwater. Treatment with the combined plant extract (seed and leaf) resulted in significant improvement of various physicochemical (hardness, pH, turbidity, Total Dissolved Solid (TDS), and metallic impurities) and biological parameters (E.coli count) over individual seed and leaf extracts in groundwater samples. Experimental findings have strongly shown the enhanced purification efficacy of the hexane extract of combined plant materials in comparison to the individual extracts, thereby providing us with a potent natural coagulant that could combat the side effects of chemical coagulants.

Moringa oleifera methanolic leaves extract induces apoptosis and G0/G1 cell cycle arrest via downregulation of Hedgehog Signaling Pathway in human prostate PC-3 cancer cells.

The inadequacy of effective treatment approaches for prostate cancer enlightens the crucial necessity for the search and emergence of novel and multitasking anticancer substances. Several experimental studies suggested the role of natural compounds in prostate cancer growth inhibition by Hedgehog signaling modulation. In the current study, we suggested the anticancer and apoptosis inducing effects of Moringa oleifera (M. oleifera) were linked to downregulation of Hedgehog pathway in PC-3 prostate cancer cells. We found that M. oleifera leaves methanolic extract exhibited significant anticancerous potential by inducing ROS-mediated apoptosis and activation of caspase-3 activity in prostate cancer. We also observed a dose-dependent G0/G1 cell cycle arrest as well as significant alteration in mRNA expression of apoptosis related and Hedgehog signaling pathway genes by M. oleifera extract treatment. Altogether, these experimental findings demonstrated that M. oleifera may exert antiproliferative apoptosis inducing effects by Hedgehog signaling pathway downregulation. PRACTICAL APPLICATIONS: Moringa oleifera plant, a rich nutrional source, has extensive range of pharmacological applications including antioxidant, anti-inflammatory, and anticancer activity. To best of our knowledge, this could be the first intensive report which presented the inhibitory potential of M. oleifera leaves extract against PC-3 prostate cancer cells via targeting key molecules of Hedgehog signaling. Decreased mRNA expression of GLI1 transcription factor and SMO protein of Hedgehog signaling pathway may be involved in antiproliferative effects of M. oleifera leaves extract against prostate cancer cells. Our study suggested that M. oleifera supplementation might be beneficial for the development and improvement of targeted therapeutic strategies in prostate cancer cells.

Elucidation of the potential of Moringa oleifera leaves extract as a novel alternate to the chemical coagulant in water treatment process.

In recent years, several studies have been developed to search for sustainable and eco-friendly natural coagulants as an alternative to inorganic and synthetic coagulants to obtain drinking water. Despite the performance and cost-effectiveness of these coagulants, they require pH and alkalinity adjustments, they generate high volumes of sludge, and their residuals in treated water (e.g., aluminum) are linked with neurodegenerative diseases such as Alzheimer's, as well as neurotoxic and carcinogenic effects. Moringa oleifera seeds had shown better coagulation properties but have numerous limitations which have prompted us to find better alternatives. To the best part of my knowledge, utilization of its leaves extract obtained from different organic solvents in water purification has rarely been reported. Our findings clearly revealed that M. oleifera leaves hexane extract has significantly improved the water quality parameters including pH (8.2-7.1), TDS (512-221), hardness (246-138), turbidity (15.6-6.1), fluoride (2.3-1.1), and Escherichia coli count (315-41) whereas alum effectively improved these parameters at a dose of 50 mg/L. Moringa oleifera showed significant removal capability in comparison to alum but slightly at higher dose, thus our results strongly supported the efficacy of M. oleifera leaves extracts as better alternative to chemical coagulant in water purification. PRACTITIONER POINTS: Chemical coagulants pose severe side effects to humans such as neurodegenerative diseases. Use of Moringa oleifera leaves as natural coagulants in water purification is a cost-effective approach due to its easy availability throughout the year. Moringa oleifera leaves exhibited significant coagulating efficiency by improving water quality parameters including pH, turbidity, total dissolved solids, fluoride, hardness, and E. coli count.

Kinetics of adsorptive removal of DEClP and GB on impregnated Al2O3 nanoparticles.

Nanoparticles of AP-Al(2)O(3) (aero-gel produced alumina) have been produced by an alkoxide based synthesis involving aluminum powder, methanol, toluene and water. Thus produced alumina nanoparticles were characterized and the data indicated the formation of nanoparticles of alumina in the size range of 2-30 nm with high surface area (375 m(2)/g). Thereafter, these nanoparticles were impregnated with reactive chemicals. Adsorptive removal kinetics for DEClP (diethylchlorophosphate) and GB (isopropylmethylphosphonofluoridate, sarin) was monitored by GC-FID (gas chromatograph coupled with flame ionization detector) technique and found to be following pseudo first order reaction kinetics. Among impregnated AP-Al(2)O(3) nanoparticles based sorbent systems AP-Al(2)O(3) impregnated with 9-molybdo-3-vanadophosphoric acid (10%, w/w) was found to be the most reactive with least half-life values of 7 and 30 min for the removal of DEClP and GB, respectively, whereas unimpregnated AP-Al(2)O(3) nanoparticles showed the best adsorption potential among all studied systems. In addition to this, hydrolysis reaction {identified using GC/MS (gas chromatograph coupled with mass spectrometer) technique} was found to be the route of degradation of DEClP and GB on impregnated alumina nanoparticles.