Astragalus polysaccharides alleviate tilmicosin-induced toxicity in rats by inhibiting oxidative damage and modulating the expressions of HSP70, NF-kB and Nrf2/HO-1 pathway.

The present study evaluated the toxic effects of Tilmicosin (TIL) on adult rats. The rats received a single subcutaneous injection of TIL at different doses (10, 25, 50, 75 and 100 mg/kg bw). TIL altered the biochemical parameters including liver and kidney function markers, glucose level and lipid profile as well as resulted in histopathological lesions in liver and adrenal glands mostly in rats exposed to 75 and 100 mg/kg bw. Then the role of Astragalus polysaccharide (APS) at 100 and 200 mg/kg bw, in modulating the toxic effects induced by high dose of TIL was evaluated. Single injection of TIL at a dose of 75 mg/kg bw was found to increase the activity of ALT, AST and ALP enzymes, induce the generation of reactive oxygen species (ROS) and decrease the total antioxidant capacity (TAC). TIL upregulated the hepatic mRNA expression of heat shock protein 70 (HSP70) and nuclear factor kappa B (NF-kB) while blocked the Nrf2/HO-1 mediated response. These changes were also associated with increasing tumer necrosis factor-alpha (TNF-α), interlukin1-beta (IL-1ß) and nitric oxide levels. On the other hand, the results indicate that APS has a beneficial role particularly at high level in alleviating the stress and the hepatotoxic effects elicited by TIL injection in rats.

Differential susceptibility of kidneys and livers to proliferative processes and transcriptional level of the genes encoding desmin, vimentin, connexin 43, and nestin in rats exposed to furan.

In this study, we aimed to assess the differential toxic impact, induced by furan exposure, on the liver and kidney tissues by estimating reactive oxygen species (ROS) level, total antioxidant capacity (TAC), oxidative damage, and the tissue injury markers in a male rat model. To explain such impacts, 20 rats were assigned into two groups: a control group, where rats were administered corn oil as a vehicle, and a furan-administered group, where furan was orally administered to rats at a dose of 16 mg/kg b wt/day (five days per week over eight weeks). The transcriptional levels of intermediate filament proteins (desmin, vimentin, nestin, and connexin 43) were assessed by using quantitative real-time polymerase chain reaction (PCR), and the cell proliferation markers (proliferating cell nuclear antigen [PCNA] and proliferation-associated nuclear antigen [Ki-67]) were recognized by immunohistochemical analysis. Furthermore, the ultrastructural changes of liver and kidney were monitored using electron microscopy. Our findings showed that furan exposure could induce hepatic and renal damage to different extents. Furan can increase the ROS content, oxidative damage indices, and liver tissue injury indices but not kidney injury indices. Furthermore, it decreases the TAC in the serum of exposed rats. In addition, furan exposure was associated with changes in the mRNA expression pattern of intermediate filament proteins in both kidney and liver tissues. Moreover, furan enhances the expression of PCNA and Ki-67 in the liver tissues but not in the kidney tissues. The ultrastructure evaluation revealed the incidence of glomerular podocyte degeneration and hepatocyte injury. These results conclusively demonstrate that the deleterious effects of furan are caused by promoting fibrosis and hepatocyte proliferation in liver tissues and triggering podocyte injury in the kidney tissues.

Clarifying of the potential mechanism of Sinisan formula for treatment of chronic hepatitis by systems pharmacology method.

Chronic hepatitis is a general designation class of diseases, which results in different degrees of liver necrosis and inflammatory reaction, followed by liver fibrosis, may eventually develop into cirrhosis. However, the molecular pathogenesis of chronic hepatitis is too complex to elucidate. Herbal medicines, featured with multiple targets and compounds, have long displayed therapeutic effect in treating chronic hepatitis, though their molecular mechanisms of contribution remain indistinct. This research utilized the network pharmacology to confirm the molecular pathogenesis of chronic hepatitis through providing a comprehensive analysis of active chemicals, drug targets and pathways' interaction of Sinisan formula for treating chronic hepatitis. The outcomes showed that 80 active ingredients of Sinisan formula interacting with 91 therapeutic proteins were authenticated. Sinisan formula potentially participates in immune modulation, anti-inflammatory and antiviral activities, even has regulating effects on lipid metabolism. These mechanisms directly or indirectly are involved in curing chronic hepatitis by an interaction way. The network pharmacology based analysis demonstrated that Sinisan has multi-scale curative activity in regulating chronic hepatitis related biological processes, which provides a new potential way for modern medicine in the treatment of chronic diseases.

Herbal Immunomodulators - A Remedial Panacea for Designing and Developing Effective Drugs and Medicines: Current Scenario and Future Prospects.

BACKGROUND: Constant exposure to various stressors, such as immune pressure, rapidly increasing population, deleterious changes in the ecosystem, climate change, infection with emerging and re-emerging pathogens, and fast-paced lifestyle, is a critical factor in the globally increasing incidences of immunocompromising health conditions, as well as stress. Synthetic chemotherapeutic agents, which are widely available in the commercial market, may be highly efficacious, but most are immunosuppressive and exert many side effects. METHODS: Herein, we comprehensively reviewed current literature from various scientific databases such as Bentham Science, PubMed, Scopus, Elsevier, Springer, etc. The inclusion/exclusion criteria based on literature with high importance was adopted to analyze and compile salient information from the authentic bibliographic sources. RESULTS: Undoubtedly, the pivotal characteristics of immunostimulants and immunomodulators in the maintenance of the health and productivity of humans, as well as animals, cannot be overlooked. Numerous herbs used in ethnoveterinary medicine can be successfully employed as adjuvant rehabilitators to negate the deleterious effects of chemotherapeutics. The sources of these medicinal remedies are part of long traditions in different regions of the world, such as Indian Ayurveda and Traditional Chinese Medicine, which have been developed through empirical experience. Traditional medicine employs a holistic approach to the prevention of disease, and traditional herbal medicines are a source of many components with a high therapeutic value that are used in modern allopathic medicine. Globally, many studies have been conducted on these herbs and have revealed unique active constituents that activate the innate immune system through the stimulation of macrophages and lymphocytes, and modulation of the cytokine profile, which leads to a state of alertness with a subsequent reduction in the incidence of infection. Immunomodulatory constituents with herbal origins are termed as phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, various bitters, and alkaloids; all these compounds exert vital, multidimensional effects. Efforts have focused on screening plant preparations to identify adjuvant immune properties; furthermore, several potent phytol adjuvants have been experimentally proven to downregulate inflammatory reactions in addition to enhance specific adaptive responses to vaccines. CONCLUSIONS: In summary, this review summarizes the current status and future prospects regarding the immunomodulatory potential of various herbs and plants and their promising utility for designing and developing effective drugs and medicines in safeguarding the health of humans, animals, and poultry.

Medicinal and Therapeutic Potential of Herbs and Plant Metabolites / Extracts Countering Viral Pathogens - Current Knowledge and Future Prospects.

BACKGROUND: Recently, there has been a remarkable progress in the field of antiviral herbal therapy owing to increasing concerns about the development of drug resistance and limited advances in the field of antiviral drug discovery. In almost all countries, medicinal plants have been used widely throughout history for the treatment of diseases and infections as traditional healing remedies due to their broad therapeutic spectrum and minimal or no side effects. As synthetic antiviral drugs are not available against most of the viral agents, hence all possible efforts have been focused on the search for new drugs and complementary/alternative medicines from different herbal formulations. METHODS: We have retrieved the related information from the online published resources (Medline, PubMed, Pub- Med Central, Science Direct and other scientific databases); which were further analyzed and compiled. RESULTS: Medicinal plants contain extractable biochemical and bioactive compounds, which can target certain viruses or can cure or prevent several viral diseases and infections. Despite their long history of use, the research and scientific evidences regarding the use of medicinal plants and natural products as prophylactics, therapeutics, and their health multiple beneficial applications have only gained momentum in past few decades. Many scientific studies have been undertaken, which range from the separation of active substances to the comprehension of the therapeutic mechanisms of antiviral herbs, their potent applications in the neutralization of viral pathogens and clinical trials. Consequently, hundreds of herbs and plant metabolites have been screened, identified, and tested for their antiviral activities; fortunately, some have shown significant medicinal activity in the amelioration or prevention of various viral diseases in both preclinical and clinical studies. CONCLUSION: This review addresses the scientific significance of various herbal formulations of different medicinal plants and their extracts, which have shown promise or been proven effective for the treatment of diseases caused by various viral pathogens, including emerging and re-emerging viruses that infect humans, animals, poultry and fish.

Cypermethrin induced toxicities in fish and adverse health outcomes: Its prevention and control measure adaptation.

Pesticides are being widely employed in the modern agriculture, though in different quantities, across the globe. Although it is useful for crops yield enhancement, however, there are the serious environment, health and safety related concerns for aquatic and terrestrial living biomes that include humans, animals, and plants. Various in practice and emerging pesticides adversely affect the survival, development and biological systems stability. Several research efforts have been made to highlight the bio-safety and toxicological features of toxicants through risk assessment studies using different animal models, e.g., different fish species. Among several pesticides, cypermethrin is extensively used in agriculture and households, and the reported concentrations of this pesticide in different water bodies including rivers and streams, soil and even in rainwater are threatening. Consequently, cypermethrin is considered for risk assessment studies to know about its deep and different level of toxicological effects subject to its dose, exposure time and route. The cypermethrin existence/persistence in the environment is posing a severe threat to humans as well as another non-target terrestrial and aquatic organism. Herein, the toxic effects of pesticides, with special reference to cypermethrin, on fish, the mode of toxicity, concerns regarding public health and harmful impacts on human beings are comprehensively reviewed. The information is also given on their appropriate control and prevention strategies.

Erythrocytes as a biological model for screening of xenobiotics toxicity.

Erythrocytes are the main cells in circulation. They are devoid of internal membrane structures and easy to be isolated and handled providing a good model for different assays. Red blood cells (RBCs) plasma membrane is a multi-component structure that keeps the cell morphology, elasticity, flexibility and deformability. Alteration of membrane structure upon exposure to xenobiotics could induce various cellular abnormalities and releasing of intracellular components. Therefore the morphological changes and extracellular release of haemoglobin [hemolysis] and increased content of extracellular adenosine triphosphate (ATP) [as signs of membrane stability] could be used to evaluate the cytotoxic effects of various molecules. The nucleated RBCs from birds, fish and amphibians can be used to evaluate genotoxicity of different xenobiotics using comet, DNA fragmentation and micronucleus assays. The RBCs could undergo programmed cell death (eryptosis) in response to injury providing a useful model to analyze some mechanisms of toxicity that could be implicated in apoptosis of nucleated cells. Erythrocytes are vulnerable to peroxidation making it a good biological membrane model for analyzing the oxidative stress and lipid peroxidation of various xenobiotics. The RBCs contain a large number of enzymatic and non-enzymatic antioxidants. The changes of the RBCs antioxidant capacity could reflect the capability of xenobiotics to generate reactive oxygen species (ROS) resulting in oxidative damage of tissue. These criteria make RBCs a valuable in vitro model to evaluate the cytotoxicity of different natural or synthetic and organic or inorganic molecules by cellular damage measures.

Rosmarinic acid: modes of action, medicinal values and health benefits.

The supplementation of livestock rations with herbs containing bioactive components, such as rosmarinic acid (RA), have shown promising results as a natural feed additive in promoting growth, productive and reproductive performance, feed utilization, fertility, anti-oxidant status and immunologic indices. Furthermore, RA reportedly reduces the risks of various animal diseases and mitigates side effects of chemical and synthetic drugs. RA is a natural polyphenol present in several Lamiaceae herbs like Perilla frutescens, and RA is becoming an integral component of animal nutrition as it counters the effect of reactive oxygen species induced in the body as a consequence of different kinds of stressors. Studies have further ascertained the capability of RA to work as an anti-microbial, immunomodulatory, anti-diabetic, anti-allergic, anti-inflammatory, hepato- and renal-protectant agent, as well as to have beneficial effects during skin afflictions. Additionally, RA is favored in meat industries due to enhancing the quality of meat products by reportedly improving shelf-life and imparting desirable flavor. This review describes the beneficial applications and recent findings with RA, including its natural sources, modes of action and various useful applications in safeguarding livestock health as well as important aspects of human health.

Beneficial health applications and medicinal values of Pedicularis plants: A review.

Pedicularis plants (Orobanchaceae), popularly known as lousewort, are found in Asia, Europe, and North America, and have been used in Sowa-Rigpa, the Himalayan art of healing and a traditional system of medicine for treating various ailments in humans. A comprehensive compilation on this valuable medicinal plant is not available, however. The present extensive review provides insight into the salient medicinal properties of Pedicularis plants with respect to various health issues and diseases. Our previous studies on Pedicularis plants from the Changthang region of Ladakh (India) and research advances leading to new developments in this field have prompted this review. The information presented here has been compiled and analyzed from authenticated published resources available on Medline, Pubmed, Pubmed Central, Science Direct, and other scientific databases. The Pedicularis genus consists of approximately 600 species (83 of which are found in India), with commonly reported species being Pedicularis longiflora Rudolph, P. bicornuta Klotzsch, P. oederi Vahl, P. cheilanthifolia, and P. pectinata. The major phytoconstituents of the Pedicularis sp. are phenols, phenylethanoids, phenylpropanoids, flavonoids, iridoids, lignans, and alkaloids, among others. The existing literature highlights that these compounds possess antioxidant, immunomodulatory, anti-inflammatory, antidiabetic, antibacterial, antifungal, analgesic, antitumor, hepatoprotective, neuroprotective, muscle-relaxing, antifatigue, diuretic, antipyretic, antithrombus, antihemolysis, and DNA-repairing properties. This medicinal herb is used in the treatment of leucorrhoea, fevers, sterility, rheumatism, general debility, collapse, and urinary problems, and for revitalizing the blood circulation, improving digestion, and maintaining vitality. This review emphasizes the various medicinal aspects of Pedicularis sp. plants containing a variety of phytoconstituents. Besides phenols, terpenoids, flavonoids, lignans, tannins, iridoid, and phenylpropanoid glycosides are among the active constituents responsible for multiple health effects. However, further extensive research is required to characterize the various phytoconstituents of Pedicularis to explore their modes of action at a molecular level and identify other beneficial applications that can exploit the tremendous medicinal potential of this important herb.

In vitro antioxidant activities of resveratrol, cinnamaldehyde and their synergistic effect against cyadox-induced cytotoxicity in rabbit erythrocytes.

This study was conducted to explore the potential benefits of using cinnamaldehyde (CIN), resveratrol (RES) separately or in combination on cyadox (CYA)-induced alterations in isolated rabbit erythrocytes. Erythrocytes suspensions were partitioned into 7 groups (5 replicates/group), 1st kept as control treated with phosphate buffered saline (PBS) with dimethyl sulphoxide (DMSO); 2nd group was subjected to CYA (40 µg/ml), 3rd group was incubated with CIN (40 µM), 4th group was subjected to RES (40 µM), 5th group was co-exposed to CYA (40 µg/ml) and CIN (40 µM), 6th group was co exposed to CYA (40 µg/ml) and RES (40 µM), and 7th group was exposed to CYA in combination with both CIN and RES at the same indicated concentrations. The reaction mixtures of different groups were incubated at 37 °C for 3 h with gentle shaking every 15 minutes. Our results revealed that exposure to CYA caused a significant decrease (linear and quadratic) in superoxide dismutase (SOD) and catalase (CAT) activities and the contents of reduced glutathione (GSH) and glutathione transferase (GST). Incubation of erythrocytes with CYA increased GSSG content, GSSG/GSH ratio, malonaldehyde (MDA) and protein carbonyl (PrC) concentrations while it decreased the total protein (TP). CYA also lead to hemolysis and energy depletion of erythrocytes beside activation of caspase cascades, suggesting the pro-oxidant effect CYA that could be implicated in eryptosis. CIN and RES were able to inverse these hazardous effects of CYA. However, CIN was more effective than RES, their combination showed a positive synergistic effect in protecting the cells against oxidative injury caused by CYA.