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The purpose of this study was to explore the anti-cancer activity and the possible mechanism of Dawa-ul kurkum (Duk) against diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in male Wistar rats. We administered Duk at 3 doses, viz., 75, 150, and 300 mg/kg/day, 2 weeks before the DEN and continued it for 16 weeks. We found that Duk significantly reduced the DEN and 2-AAF induced phenotypical changes in rats and restored the activities of serum markers. Furthermore, Duk counteracted the oxidative stress induced by carcinogens as observed by restoration in the levels of superoxide dismutase (SOD) and catalase (CAT). Duk significantly diminished the levels of malondialdehyde (MDA) in a dose dependent manner and restored the liver microarchitecture as assessed by histopathological studies. The results of immunohistochemical staining showed that Duk inhibited the DEN-induced decrease in the number of cells positive for Bid and Caspase-9. It also reduces the number of cells positive for Cyclin D. This study shows that Duk significantly protects rat liver from hepatocarcinogenesis by regulating oxidative damage and restoring serum markers. The chemopreventive effect of Duk might be through induction of apoptosis.

Hepatocellular carcinoma (HCC) is the third prominent cause of cancer mortality, with increasing prevalence and poor survival worldwide. Being diagnosed at an advanced stage, HCC frequently results in poor prognosis, treatment failure, and recurrence. Post-treatment reactivation and recurrence often amplify the immunosuppressed state induced by HCC pathogenesis. Therefore, stimulating the immune system may be a potential therapy measure for the treatment of HCC. Immune responses of the body may be potentiated by modulation of various effector cells such as B-cells, T-cells, Treg cells, natural killer cells, dendritic cells, cytotoxic T-lymphocytes, and other antigen-presenting cells. microRNAs (small non-coding RNAs) are the regulators of gene expression via translational inhibition or mRNA degradation. Various activities and developmental stages of the immune system are governed by miRNAs and they have a regulative impact on innate and adaptive immune cells in both, healthy and diseased conditions. Their misexpression has been associated with the initiation, development, and metastasis of various cancer types, including HCC. This review summarizes the functional impact of these immuno-miRNAs in the improvement of tumor conditions.

Abstract: Many of the synthetic and herbal drugs, despite their notable in vitro findings, demonstrate insignificant in vivo activity, the majority of the time due to poor bioavailability. As per Biopharmaceutical Classification System (BCS), one of the main concerns is low solubility and/or permeation of drugs resulting in reduced absorption and poor bioavailability. To overcome these issues, various strategies have been adopted, including the use of permeation enhancers which are also known as bioenhancers. Bioenhancers are synthetic or natural compounds that increase the bioavailability of drugs and nutrients such as vitamins, amino acids, minerals, etc., into the systemic circulation and at the site of action for exhibiting improved therapeutic action. By improving bioavailability, bioenhancers can reduce drug dose, decrease the treatment period, and circumvent the problem of drug resistance. Although numerous studies have reported the application of synthetic bioenhancers, plant based bioenhancers can serve as a better alternative owing to their natural origin. Literature reviews have revealed that plant-based bioenhancers have been used in a wide variety of antibiotics, antiviral, and anti-cancer therapeutics. These can be categorized based on their sources and mechanism of action. This review will provide a systematic and detailed overview of the various plant based bioenhancers and their applications.

Cancer immunotherapy is the new generation and widely accepted form of tumour treatment. It is, however, associated with exclusive challenges which include organ-specific inflammation, and single-target strategies. Therefore, approaches that can enhance the efficiency of existing immunotherapies and expand their indications are required for the further development of immunotherapy. Natural products and medicines are stated to have this desired effect on cancer immunotherapy (adoptive immune-cells therapy, cancer vaccines, and immune-check point inhibitors). They refurbish the immunosuppressed tumour microenvironment, which is the primary location of interaction of tumour cells with the host immune system. Various immune cell subsets, via interaction with cytokine/chemokine receptors, are recruited into this microenvironment, and these subsets have roles in tumour progression and treatment responsiveness. This review summarises cytokine/chemokine signalling, types of cancer immunotherapy and the herbal medicine-derived natural products targeting cytokine/chemokines and immune checkpoints. These natural compounds possess immunomodulatory activities and exert their anti-tumour effect by either blocking the interaction or modulating the expression of the proteins linked with immune checkpoint signaling pathways. Some compounds also show a synergistic effect in combination with existing monoclonal antibody drugs to reverse the tumour microenvironment. Additionally, we have also reported some studies about the derivatives and formulations used to overcome the limitations of natural forms. This review can provide important insights for directing future research.

Hepatocellular carcinoma (HCC) accounts for about 80-90% of all liver cancers and is found to be the third most common cause of cancer mortality in the Asia-Pacific region. Risk factors include hepatitis B and C virus, cirrhosis, aflatoxin-contaminated food, alcohol, and diabetes. Surgically removing the tumor tissue seems effective but a high chance of recurrence has led to an urgent need to develop novel molecules for the treatment of HCC. Clinical management with sorafenib is found to be effective but it is only able to prolong survival for a few months. Various side effects like gastrointestinal and abdominal pain, hypertension, and hemorrhage are also associated with sorafenib, which calls for the unmet need of effective therapies against HCC. Similarly, the genetic mechanisms behind the occurrence of HCC are still unknown and need to be expounded further for developing newer candidates. Since unearthing the concept of these variants, transcriptomics has revealed the role of noncoding RNAs (ncRNAs) in many cellular, physiological and pathobiological processes. They are also found to be widely associated and abundantly expressed in a variety of cancer. Aberrant expression and mutations are closely related to tumorigenesis and metastasis and hence are classified as novel biomarkers and therapeutic targets for the treatment of cancer, including HCC. Herein, this review summarises the relationship between ncRNAs and hepatocellular carcinoma.

Simple Summary Febrile neutropenia is the serious side-effect associated with myelosuppressive chemotherapy. Filgrastim, the first granulocyte colony-stimulating factor (G-CSF) was approved by the Food and Drug Administration for the treatment of neutropenia. Subsequently, pegfilgrastim (long-acting G-CSF) and filgrastim biosimilars were developed to have comparable efficacy to filgrastim. Therefore, it is necessary to produce a systematic review and meta-analysis that provides evidence that filgrastim is more efficacious than placebo/no-treatment, as it provides evidence on the comparable efficacy of filgrastim versus pegfilgrastim and biosimilar filgrastim. Abstract Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrophil count ANC recovery, depth of ANC nadir (lowest ANC), neutropenia-related hospitalization and other neutropenia-related complications. For filgrastim versus biosimilar filgrastim comparison, the primary efficacy endpoint was the mean difference in duration of severe neutropenia DSN. Results: A total of 56 studies were considered that included data from 13,058 cancer patients. The risk of febrile neutropenia in filgrastim versus placebo/no treatment was not statistically different. The risk ratio for febrile neutropenia was 0.58, a 42% reduction in favor of filgrastim. The most reported adverse event with FIL was bone pain. For pegfilgrastim versus filgrastim, no statistically significant difference was noted. The risk ratio was 0.90 (95% CI 0.67 to 1.12). The overall difference in duration of severe neutropenia between filgrastim and biosimilar filgrastim was not statistically significant. The risk ratio was 1.03 (95% CI 0.93 to 1.13). Conclusions: Filgrastim was effective and safe in reducing febrile neutropenia and related complications, compared to placebo/no treatment. No notable differences were found between pegfilgrastim and filgrastim in terms of efficacy and safety. However, a similar efficacy profile was observed with FIL and its biosimilars.

Reactive oxygen species (ROS) are noxious to cells because their increased level interacts with the body’s defense mechanism. These species also cause mutations and uncontrolled cell division, resulting in oxidative stress (OS). Prolonged oxidative stress is responsible for incorrect protein folding in the endoplasmic reticulum (ER), causing a stressful condition, ER stress. These cellular stresses (oxidative stress and ER stress) are well-recognized biological factors that play a prominent role in the progression of hepatocellular carcinoma (HCC). HCC is a critical global health problem and the third leading cause of cancer-related mortality. The application of anti-oxidants from herbal sources significantly reduces oxidative stress. Kaempferol (KP) is a naturally occurring, aglycone dietary flavonoid that is present in various plants (Crocus sativus, Coccinia grandis, Euphorbia pekinensis, varieties of Aloe vera, etc.) It is capable of interacting with pleiotropic proteins of the human body. Efforts are in progress to develop KP as a potential candidate to prevent HCC with no adverse effects. This review emphasizes the molecular mechanism of KP for treating HCC, targeting oxidative stress.

In the modern research field, laboratory animals are constantly kept under artificial lighting conditions. However, recent studies have shown the effect of artificial light on animal behavior and metabolism. In the present study on mice, following three weeks of housing in dim light at night (dLAN, 5lux) and complete darkness (DD, 0lux), we monitored the effect on body weight, daily food intake, anxiety-like behavior by employing the open field test, and expression of the period (PER1) gene. We also studied the effect of oral administration of different concentrations of curcumin (50, 100, and 150 mg/kg) for three weeks in the same mice and monitored these parameters. The exposure to dLAN had significantly increased the anxiety-like behavior and body weight possibly through the altered metabolism in mice, whereas exposure to DD caused increased anxiety but no significant difference in weight gain. Moreover, the expression of the PER1 gene involved in sleep was also found to be decreased in the aberrant light conditions (dLAN and DD). Although the treatment of curcumin had no effect on body weight, it ameliorated the anxiety-like behavior possibly by modulating the expression of the PER1 gene. Thus, alteration in the light/dark cycle had a negative effect on laboratory animals on the body weight and emotions of animals. The present study identifies the risk factors associated with artificial lighting systems on the behavior of laboratory animals and the ameliorative effects of curcumin, with a focus on anxiety-like behavior.

Apigenin is being increasingly recognized as a cancer chemopreventive agent. We aimed to investigate the anticancer effects of Apigenin in in-vivo studies to know its present research status and how close or how far it is from the clinics.Several electronic databases such as PubMed, Springer, Cochrane, and ctri.gov.in were searched to fetch the relevant articles. We focused only on published animal studies that reported the anticancer effects of Apigenin against various cancers. Two reviewers independently assessed the risk of bias for each analysis, and the conflicting views were resolved later by consensus.A total of 25 studies focused on the anticancer effects of Apigenin on various cancer types, including liver, prostate, pancreatic, lung, nasopharyngeal, skin, colon, colorectal, colitis-associated carcinoma, head and neck squamous cell carcinoma, leukemia, renal cell carcinoma, Ehrlich ascites carcinoma, and breast cancer were included. Overall, Apigenin reduces tumor volume (SMD=-3.597, 95% CI: -4.502 to -2.691, p 0.001), tumor-weight (SMD=-2.213, 95% CI: -2.897 to -1.529, p 0.001), tumor number (SMD=-1.081, 95% CI: -1.599 to -0.563, p 0.001) and tumor load (SMD=-1.556, 95% CI: -2.336 to -0.776, p 0.001). Further, it has no significant effect on the animal's body-weight (SMD=-0.345, 95% CI: -0.832 to 0.143, p = 0.165). Apigenin exerts anti-tumor effects mainly by inducing apoptosis/cell-cycle arrest.Our analysis suggests that Apigenin has potential anticancer effects against various cancers. However, the poor symmetry of the funnel plot suggested publication bias. Thus, it warrants further research to evaluate the potential of Apigenin alone or as an adjuvant for cancer treatment.

Obesity is a major lifestyle disorder, and it is correlated with several ailments. The prevalence of obesity has elevated over the years, and it has become a global health problem. The drugs presently used for managing obesity have several side effects, such as diarrhea, leakage of oily stools, etc. On the contrary, herbal plants and natural products are considered safe for use because they have lesser side effects. New compounds isolated from medicinal plants are screened and identified to determine their effectiveness and potential in preventing abnormal weight gain. In this review, the medicinal plants and natural materials are surveyed across the literature to cover those that have the potential for managing and controlling weight gain. Furthermore, their mechanism of action, active components, and experimental methodologies are also reviewed. These herbal products can be developed as formulations for therapeutic use in obesity. The herbal plants mentioned in the review are classified based on their mechanism of action, inhibition of pancreatic lipase, and appetite suppression activities. The ability to inhibit pancreatic lipase enzyme has been used to determine the effectiveness of herbal products for the prevention of abnormal weight gain because of its action on dietary fat and suppression of appetite. This review is an attempt to summarize the herbal plants and natural products that can be used to develop formulations effective in controlling weight gain and obesity.

Stem cells are becoming increasingly popular in public lexicon owing to their prospective applications in the biomedical and therapeutic domains. Extensive research has found various independent stem cell systems fulfilling specific needs of plant development. Plant stem cells are innately undifferentiated cells present in the plant's meristematic tissues. Such cells have various commercial uses, wherein cosmetic manufacture involving stem cell derivatives is the most promising field at present. Scientific evidence suggests anti-oxidant and anti-inflammatory properties possessed by various plants such as grapes (Vitis vinifera), lilacs (Syringa vulgaris), Swiss apples (Uttwiler spatlauber) etc. are of great importance in terms of cosmetic applications of plant stem cells. There are widespread uses of plant stem cells and their extracts. the products so formulated have a varied range of applications which included skin whitening, de-tanning, moisturizing, cleansing etc. Despite all the promising developments, the domain of plant stem cells remains hugely unexplored. This article presents an overview of the current scenario of plant stem cells and their applications in humans.

Heavy metal neurotoxicity is one of the major challenges in today’s era due to the large scale and widespread mechanisation of the production. However, the causative factors responsible for neurotoxicity are neither known nor do we have the availability of therapeutic approaches to deal with it. One of the major causative agents of neurotoxicity is a non-essential transition heavy metal, Cadmium (Cd), that reaches the central nervous system (CNS) through the nasal mucosa and olfactory pathway causing adverse structural and functional effects. In this study, we explored the neuroprotective efficacy of plant derived Curcumin which is reported to have pleiotropic biological activity including anti-oxidant, anti-inflammatory, anti-apoptotic, anti-carcinogenic and anti-angiogenic effects. Four different concentrations of curcumin (20, 40, 80 and 160 mg/kg of the body weight) were used to assess the behavioural, biochemical, hippocampal proteins (BDNF, CREB, DCX and Synapsin II) and histological changes in Swiss Albino mice that were pre-treated with Cd (2.5 mg/kg). The findings showed that Cd exposure led to the behavioural impairment through oxidative stress, reduction of hippocampal neurogenesis associated proteins, and degeneration of CA3 and cortical neurons. However, treatment of different curcumin concentrations had effectively restored the behavioural changes in Cd-exposed mice through regulation of oxidative stress and up-regulation of hippocampal proteins in a dose-dependent manner. Significantly, a dose of 160 mg/kg body weight was found to be glaringly effective. From this study, we infer that curcumin reverses the adverse effects of neurotoxicity induced by Cd and promotes neurogenesis.

Neurological disorders are one of the major problems that we are facing in today's fast paced world. Scientific advancements have had a tremendous impact on our life span, and humans today are managing to live far longer than their predecessors; however, with the rise of an aging population, there has also been an escalation in age-related neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Even though several synthetic drugs are available for the treatment of these diseases, most of them are only capable of warding off certain symptoms and, in fact, achieve very little to prevent the underlying causes of neurodegeneration. Under examination, it has been revealed that many of these diseases share similar underlying cellular and biochemical imbalances. There is increasing evidence that consumption of saffron, a spice derived from the flower of Crocus sativus plant, has various therapeutic effects. Saffron has been used since the seventh century for medical purposes and still continues to be used in some forms of traditional medicine. Researchers have discovered over 150 compounds in saffron which have neuroprotective effects. The bioactive molecules of saffron such as crocin, picrocrocin, and safranal have strong antioxidant effects on brain cells. Saffron has also been shown to improve the learning and memory capacity. It is also capable of reducing glutathione (GSH) and allaying oxidative stress. Researchers have reported that saffron has reversed the neurotoxicity caused by many toxic xenobiotics. Since saffron is a natural product and there are no side effects like synthetic drugs, it can be used as a novel therapeutic agent for neurodegenerative diseases.

Saffron, the stigma of Crocus sativus L., has a long history for being used in food industry (flavoring and aromatic agent), in textile industries (dyes), and for therapeutic and medicinal purposes. Medicinal uses of saffron can be attributed to the active metabolites such as crocin, crocetin, picrocrocin, and safranal present in it, which exhibit antihypertensive, anticonvulsant, antidepressant, antitussive, antigenototoxic, anxiolytic, aphrodisiac, antioxidant, anticancer, antiinflammatory, antinociceptive, and muscle relaxant activity. The liver is a critical organ of the human body. It supports metabolism, digestion, detoxification, vitamin storage, and immunity among other functions. According to various studies conducted on animal models and liver cell lines to assess the activity of saffron on the liver, it has been observed that saffron and its active components play a significant role as hepatoprotective agent via its antioxidant and radical scavenging activity, genoprotective and chemopreventive activity, inhibition of cell proliferation, induction of apoptosis, prevention of lipid peroxidation and antiinflammatory processes in fatty liver disease, liver cancer, hyperlipidemia, and hepatotoxicity. This chapter covers various activities of saffron on the liver with emphasis on liver cancer and the possible mechanism involved in it.

MicroRNAs (miRNAs, miRs) are short, endogenously initiated, non-coding RNAs that bind to target mRNAs, leading to the degradation or translational suppression of respective mRNAs. They have been reported as key players in physiological processes like differentiation, cellular proliferation, development, and apoptosis. They have gained importance as gene expression regulators in the immune system. They control antibody production and release various inflammatory mediators. Abnormal expression and functioning of miRNA in the immune system is linked to various diseases like inflammatory disorders, allergic diseases, cancers etc. As compared to the average human genome, miRNA targets the genes of immune system quite differently. miRNA appeared to regulate the responses related to both acquired and innate immunity of the humans. Several miRNAs importantly regulate the transcription and even, dysregulation of inflammation-related mediators. Many miRNAs are either upregulated or downregulated in various inflammatory and infectious diseases. Hence, modifying or targeting the expression of miRNAs might serve as a novel strategy for the diagnosis, prevention, and treatment of various inflammatory and infectious conditions.

When a plant experiences water stress, one of the early signs is the control of water loss through its stomata. These responses are more closely linked to soil moisture content than to leaf water status, which remains constant. Stomata actually respond to chemical or hormonal signals produced by the dehydrating roots. The most important hormonal signal in this regard is ABA, which has been very well observed in dehydrating roots and circulating in plants under water deficit conditions. ABA is thought to produce its effect through its interaction with other chemicals like jasmonic acid (JA), cytokinins, auxin and ethylene. They produce their effect through ion exchange, cytoskeletal reorganization, metabolite production, modulation of gene expression and post-translational modification of proteins. ABA and JA are positive regulators of stomatal closure, auxins and cytokinins are negative regulators and the role of ethylene dependent on the tissue and its condition. Here, we would like to give a brief account of various signaling components involved in opening and closing of stomata during water deficit, especially with reference to the hormonal signals. We will also discuss the role of various ion channels, transporters, and pumps localized in the plasma membrane for influx and efflux of solutes and thus providing help in stomatal function. The role of ER proteins calnexin (CNX) and calreticulin (CRT) as Ca 2 + binding chaperones in mediating drought stress signaling has also been discussed.

Cancer is a disorder which has noted a significant rise in incidence worldwide and continues to be the largest cause of mortality. It has a dramatic impact on human life expectancy and quality of life in spite of the increase in technology and the treatments available for cancer patients. These new therapeutic options being chemotherapy, radiotherapy, photolytic therapy and catalytic therapy are known to have many adverse reactions and also no better positive outcomes than before. Hence, research is now focused more on utilizing the vast repertoire of traditional medicinal knowledge i.e. the use of flora for treatment of cancer rather than the use of chemicals. One such herb is the Crocus sativus L., commonly known as Saffron, rich in carotenoids - crocin, crocetin and safranal. Various studies have been carried out over the past few years to confirm the anti-cancer properties of saffron, both in vivo using animal models and in vitro using human malignant cell lines on various types of cancers with positive results. The proposed mechanism of actions has also been worked upon. This review is aimed to provide a brief overview on the anti-tumor potential of saffron focusing on the molecular mechanism involved.

A high prevalence of vitamin D deficiency has been found in Saudi Arabia, which can be directly attributed to inadequate exposure of sunlight largely due to religious practices and lifestyle. The poor dietary intake of vitamin D further adds to this problem. Various researchers have proved vitamin D deficiency to be linked with increased incidences of cancer, diabetes, and autoimmune and cardiovascular diseases. Recently, scientists have found an association of vitamin D deficiency with reduced testosterone levels. This can be attributed to increasing incidences of male infertility in Saudi Arabia. The rising incidences of infertility in Saudi males can be attributed to their decreasing vitamin D levels. Taking adequate measures to overcome the vitamin D deficiency can improve their sexual vigor.

Depending on plant species, floral senescence varies. It can be seen in the form of wilting or withering. Both of these results correspond to different physiological phenomena. While wilting happens due to loss of turgor pressure, it corresponds to a slow dehydration process and a change in color. Most of the flower senescence corresponds to petal senescence, where the petals get detached from the plants. The time gap from the onset of senescence until its visible symptoms varies profusely among species to species. In this chapter, we have emphasized the various events that occur during flower senescence, which include structural changes, oxidative changes, and changes at the level of nucleic acids and proteins.