Hepatoprotective effects of natural drugs: Current trends, scope, relevance and future perspectives.

BACKGROUND: The liver is a well-known player in the metabolism and removal of drugs. Drug metabolizing enzymes in the liver detoxify drugs and xenobiotics, ultimately leading to the acquisition of homeostasis. However, liver toxicity and cell damage are not only related to the nature and dosage of a particular drug but are also influenced by other factors such as aging, immune status, environmental contaminants, microbial metabolites, gender, obesity, and expression of individual genes Furthermore, factors such as drugs, alcohol, and environmental contaminants could induce oxidative stress, thereby impairing the regenerative potential of the liver and causing several diseases. Persons suffering from other ailments and those with comorbidities are found to be more prone to drug-induced toxicities. Moreover, drug composition and drug-drug interactions could further aggravate the risk of drug-induced hepatotoxicity. A plethora of mechanisms are responsible for initiating liver cell damage and further aggravating liver cell injury, followed by impairment of homeostasis, ultimately leading to the generation of reactive oxygen species, immune-suppression, and oxidative stress. OBJECTIVE: To summarize the potential of phytochemicals and natural bioactive compounds to treat hepatotoxicity and other liver diseases. STUDY DESIGN: A deductive qualitative content analysis approach was employed to assess the overall outcomes of the research and review articles pertaining to hepatoprotection induced by natural drugs, along with analysis of the interventions. METHODS: An extensive literature search of bibliographic databases, including Web of Science, PUBMED, SCOPUS, GOOGLE SCHOLAR, etc., was carried out to understand the role of hepatoprotective effects of natural drugs. RESULTS: Bioactive natural products, including curcumin, resveratrol, etc., have been seen as neutralizing agents against the side effects induced by the drugs. Moreover, these natural products are dietary and are readily available; thus, could be supplemented along with drugs to reduce toxicity to cells. Probiotics, prebiotics, and synbiotics have shown promise of improving overall liver functioning, and these should be evaluated more extensively for their hepatoprotective potential. Therefore, selecting an appropriate natural product or a bioactive compound that is free of toxicity and offers a reliable solution for drug-induced liver toxicity is quintessential. CONCLUSIONS: The current review highlights the role of natural bioactive products in neutralizing drug-induced hepatotoxicity. Efforts have been made to delineate the possible underlying mechanism associated with the neutralization process.

Potential of Spirulina platensis as a feed supplement for poultry to enhance growth performance and immune modulation.

Increase in drug resistance as well as ineffective immunization efforts against various pathogens (viruses, bacteria and fungi) pose a significant threat to the poultry industry. Spirulina is one of the most widely used natural ingredients which is becoming popular as a nutritional supplement in humans, animals, poultry and aquaculture. It contains protein, vitamins, minerals, fatty acids, pigments, and essential amino acids. Moreover, it also has considerable quantities of unique natural antioxidants including polyphenols, carotenoids, and phycocyanin. Dietary supplementation of Spirulina can beneficially affect gut microbial population, serum biochemical parameters, and growth performance of chicken. Additionally, it contains polyphenolic contents having antibacterial effects. Spirulina extracts might inhibit bacterial motility, invasion, biofilm formation, and quorum sensing in addition to acting directly on the bacterium by weakening and making the bacterial cell walls more porous, subsequently resulting in cytoplasmic content leakage. Additionally, Spirulina has shown antiviral activities against certain common human or animal viruses and this capability can be considered to exhibit potential benefits against avian viruses also. Spirulan, a calcium-rich internal polysaccharide of Spirulina, is potentially responsible for its antiviral effect through inhibiting the entry of several viruses into the host cells, boosting the production of nitric oxide in macrophages, and stimulating the generation of cytokines. Comparatively a greater emphasis has been given to the immune modulatory effects of Spirulina as a feed additive in chicken which might boost disease resistance and improve survival and growth rates, particularly under stress conditions. This manuscript reviews biological activities and immune-stimulating properties of Spirulina and its potential use as a dietary supplement in poultry to enhance growth, gut health and disease resistance.

Anticancer potential of oroxylin A: from mechanistic insight to synergistic perspectives.

Oroxylin A (OA), a well-known constituent of the root of Scutellariae plants, has been used in ethnomedicine already for centuries in treating various neoplastic disorders. However, only recent molecular studies have revealed the different mechanisms behind its action, demonstrating antiproliferative, anti-inflammatory, and proapoptotic effects, restricting also the spread of cancer cells to distant organs. A variety of cellular targets and modulated signal transduction pathways regulated by OA have been determined in diverse cells derived from different malignant tissues. In this review article, these anticancer activities are thoroughly described, representing OA as a potential lead structure for the design of novel more potent anticancer medicines. In addition, co-effects of this natural compound with conventional anticancer agents are analyzed and the advantages provided by nanotechnological methods for more efficient application of OA are discussed. In this way, OA might represent an excellent example of using ethnopharmacological knowledge for designing modern medicines.

Phytosterol: nutritional significance, health benefits, and its uses in poultry and livestock nutrition.

Medicinal plants with active ingredients have shown great potential as natural and sustainable additives in livestock and poultry diets as growth promoters, performance, feed conversion ratio, digestibility of nutrient enhancers, and antioxidants and immune system modulators. Among active ingredients, phytosterols, which are plant-based bio-factors that may be found in seeds, fruits, grains, vegetables and legumes, are thought to be involved in the aforementioned activities but are also widely known in human medicine due to their efficacy in treating diabetes, coronary heart disease, and tumors. Nevertheless, phytosterols can also promote carcinogens production, angiogenesis inhibition, metastasis, infiltration, and cancer cells proliferation. This review focuses on the deepening of the biological role and health benefits of phytosterols and their new potential application in poultry and livestock nutrition.

Celiac disease: Pathogenesis, disease management and new insights into the herbal-based treatments.

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects.

Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice (Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.

The effect of metal-containing nanoparticles on the health, performance and production of livestock animals and poultry.

The application of high doses of mineral feed additives in the form of inorganic salts increases the growth performance of animals, but at the same, due to their low bioavailability, can contaminate the environment. Therefore, there is a need to find a replacement of administering high doses of minerals with an equally effective alternative. The application of lower doses of metal-containing nanoparticles with the same effect on animal production could be a potential solution. In the present review, zinc, silver, copper, gold, selenium, and calcium nanoparticles are discussed as potential feed additives for animals. Production of nanoparticles under laboratory conditions using traditional chemical and physical methods as well as green and sustainable methods - biosynthesis has been described. Special attention has been paid to the biological properties of nanoparticles, as well as their effect on animal health and performance. Nano-minerals supplemented to animal feed (poultry, pigs, ruminants, rabbits) acting as growth-promoting, immune-stimulating and antimicrobial agents have been highlighted. Metal nanoparticles are known to exert a positive effect on animal performance, productivity, carcass traits through blood homeostasis maintenance, intestinal microflora, oxidative damage prevention, enhancement of immune responses, etc. Metal-containing nanoparticles can also be a solution for nutrient deficiencies in animals (higher bioavailability and absorption) and can enrich animal products with microelements like meat, milk, or eggs. Metal-containing nanoparticles are proposed to partially replace inorganic salts as feed additives. However, issues related to their potential toxicity and safety to livestock animals, poultry, humans, and the environment should be carefully investigated.

Antioxidant effects of seaweeds and their active compounds on animal health and production - a review.

Natural antioxidants applied as feed additives can improve not only animals' health and overall performance but also increase their resistance to environmental stress such as heat stress, bad housing conditions, diseases, etc. Marine organisms, for example seaweeds - red, brown, and green macroalgae contain a plethora of biologically active substances, including phenolic compounds, polysaccharides, pigments, vitamins, micro- and macroelements, and proteins known for their antioxidant activity, which can help in the maintenance of appropriate redox status in animals and show pleiotropic effects for enhancing good health, and productivity. The dysregulated production of free radicals is a marked characteristic of several clinical conditions, and antioxidant machinery plays a pivotal role in scavenging the excessive free radicals, thereby preventing and treating infections in animals. Supplementation of seaweeds to animal diet can boost antioxidant activity, immunity, and the gut environment. Dietary supplementation of seaweeds can also enhance meat quality due to the deposition of marine-derived antioxidant components in muscles. The use of natural antioxidants in the meat industry is a practical approach to minimize or prevent lipid oxidation. However, overconsumption of seaweeds, especially brown macroalgae, should be avoided because of their high iodine content. An important point to consider when including seaweeds in animal feed is their variable composition which depends on the species, habitat, location, harvest time, growing conditions such as nutrient concentration in water, light intensity, temperature, etc. This review highlights the beneficial applications of seaweeds and their extracted compounds, which have antioxidant properties as feed additives and impact animal health and production.

Ginkgo biloba: A Treasure of Functional Phytochemicals with Multimedicinal Applications.

Ginkgo biloba is an ancient plant species that is thought to provide a variety of health benefits to living organisms and contains plenty of bioactive components, making it a chemically diversified plant. G. biloba has been shown to have a variety of medicinal and pharmacological properties, including anticancer, antidementia, antidiabetic, antiobesity, antilipidemic, antimicrobial, antioxidant, antilipid peroxidation, antiplatelet, anti-inflammatory, hepatoprotective, antidepressant, antiaging, immunomodulatory, antihypertensive, and neuroprotective effects and is frequently used to treat neurological, cardiovascular, and respiratory diseases, such as tardive dyskinesia. Therefore, this review described the therapeutic applications of G. biloba. In addition to describing the therapeutic potential, this review also evaluates the chemical constituents, toxicity, adverse effect, synergistic effect, and the clinical studies of this plant which have been utilized for therapeutic benefits but have demonstrated other consequences. The capacity of G. biloba components to act as free radical scavengers is critical, and combining its extract with other plant extracts has been shown to synergistically boost antioxidant properties. G. biloba used long-term or at high doses that resulted in some adverse effects. Severe drug interactions have also been reported in both animals and humans when combined with other medications. The available data established from both preclinical and clinical studies confirm the potential of G. biloba plant extract in various diseases. Besides, the safety and efficacy of G. biloba continue to require verification through additional experimentation to guide medicinal use.

Allium cepa: A Treasure of Bioactive Phytochemicals with Prospective Health Benefits.

As Allium cepa is one of the most important condiment plants grown and consumed all over the world, various therapeutic and pharmacological effects of A. cepa were reviewed. Onion (Allium cepa) is a high dietary fiber-rich perennial herb that is placed under the family Amaryllidaceae. It contains high concentration of folic acid, vitamin B6, magnesium, calcium, potassium, and phosphorus as well as vitamins and minerals. It is widely used as an antimicrobial agent, but it showed anticancer, antidiabetic, antioxidant, antiplatelet, antihypertensive, and antidepressant effects and neuroprotective, anti-inflammatory, and antiparasitic effects and so on. It is said to have beneficial effects on the digestive, circulatory, and respiratory systems, as well as on the immune system. This review article was devoted to discussing many health benefits and traditional uses of onions in pharmacological perspectives, as well as the safety/toxicological profile. If more detailed research on this perennial herb is conducted, it will open the door to an infinite number of possibilities.

Medicinal plants used against hepatic disorders in Bangladesh: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver disease is a major cause of illness and death worldwide which accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. That's why it is seeking the researchers' attention to find out the effective treatment strategies. Phytochemicals from natural resources are the main leads for the development of noble hepatoprotective drugs. The majority of the natural sources whose active compounds are currently employed actually have an ethnomedical use. Ethnopharmacological research is essential for the development of these bioactive compounds. These studies not only provide scientific evidence on medicinal plants utilized for particular therapeutic purposes, but they also ensure cultural heritage preservation. Plenty of experimental studies have been well-documented that the ethnomedicinal plants are of therapeutics' interest for the advanced pharmacological intervention in terms of hepatic disorders. AIM OF THE STUDY: This study summarizes the processes of hepatotoxicity induced by various toxins and explores identified hepatoprotective plants and their phytoconstituents, which can guide the extraction of novel phytochemical constituents from plants to treat liver injury. This review aimed to summarize the hepatoprotective activity of Bangladeshi medicinal plants where the bioactive compounds may be leads for the drug discovery in future. MATERIALS AND METHODS: Literature searches in electronic databases, such as Web of Science, Science Direct, SpringerLink, PubMed, Google Scholar, Semantic Scholar, Scopus, BanglaJOL, and so on, were performed using the keywords 'Bangladesh', 'ethnomedicinal plants', 'Hepatoprotective agents' as for primary searches, and secondary search terms were used as follows, either alone or in combination: traditional medicine, medicinal plants, folk medicine, liver, hepatitis, therapeutic uses, and anti-inflammatory. Besides, several books, including the book entitled "Medicinal plants of Bangladesh: chemical constituents and uses" authored by Abdul Ghani, were carefully considered, which contained pharmacological properties and phytoconstituents of many medicinal plants growing and traditionally available in Bangladesh. Among them, the most promising plant species with their latest therapeutic effects against hepatic disorders were deeply considered in this review. RESULTS: The results of this study revealed that in most cases, therapy using plant extracts stabilized altered hepatic biochemical markers induced by hepatotoxins. Initially, we investigated 32 plant species for hepatoprotective activity, however after extensive literature searching; we observed that 20 plants offer good pharmacological evidence of hepatoprotective function. Consequently, most bioactive compounds derived from the herbs including berberine, thymoquinone, andrographolide, ursolic acid, luteolin, naringenin, genistein, quercetin, troxerutin, morin, epigallocatechin-3-gallate, chlorogenic acid, emodin, curcumin, resveratrol, capsaicin, ellagic acid, etc. are appeared to be effective against hepatic disorders. CONCLUSIONS: Flavonoids, phenolic acids, monoterpenoids, diterpenoids, triterpenoids, alkaloids, chromenes, capsaicinoids, curcuminoids, and anthraquinones are among the phytoconstituents were appraised to have hepatoprotective activities. All the actions displayed by these ethnomedicinal plants could make them serve as leads in the formulation of drugs with higher efficacy to treat hepatic disorders.

A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

Egypt's COVID-19 Recent Happenings and Perspectives: A Mini-Review.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected countries across the world. While the zoonotic aspects of SARS-CoV-2 are still under investigation, bats and pangolins are currently cited as the animal origin of the virus. Several types of vaccines against COVID-19 have been developed and are being used in vaccination drives across the world. A number of countries are experiencing second and third waves of the pandemic, which have claimed nearly four million lives out of the 180 million people infected globally as of June 2021. The emerging SARS-CoV-2 variants and mutants are posing high public health concerns owing to their rapid transmissibility, higher severity, and in some cases, ability to infect vaccinated people (vaccine breakthrough). Here in this mini-review, we specifically looked at the efforts and actions of the Egyptian government to slow down and control the spread of COVID-19. We also review the COVID-19 statistics in Egypt and the possible reasons behind the low prevalence and high case fatality rate (CFR%), comparing Egypt COVID-19 statistics with China (the epicenter of COVID-19 pandemic) and the USA, Brazil, India, Italy, and France (the first countries in which the numbers of patients infected with COVID-19). Additionally, we have summarized the SARS-CoV-2 variants, vaccines used in Egypt, and the use of medicinal plants as preventive and curative options.

Therapeutic potential of indole alkaloids in respiratory diseases: A comprehensive review.

BACKGROUND: Indole alkaloids are very promising for potential therapeutic purposes and appear to be particularly effective against respiratory diseases. Several experimental studies have been performed, both in vivo and in vitro, to evaluate the effectiveness of indole alkaloids for the management of respiratory disorders, including asthma, emphysema, tuberculosis, cancer, and pulmonary fibrosis. PURPOSE: The fundamental objective of this review was to summarize the in-depth therapeutic potential of indole alkaloids against various respiratory disorders. STUDY DESIGN: In addition to describing the therapeutic potential, this review also evaluates the toxicity of these alkaloids, which have been utilized for therapeutic benefits but have demonstrated toxic consequences. Some indole alkaloids, including scholaricine, 19-epischolaricine, vallesamine, and picrinine, which are derived from the plant Alstonia scholaris, have shown toxic effects in non-rodent models. METHODS: This review also discusses clinical studies exploring the therapeutic efficacy of indole alkaloids, which have confirmed the promising benefits observed in vivo and in vitro. RESULTS: The indole alkaloidal compounds have shown efficacy in subjects with respiratory diseases. CONCLUSION: The available data established both preclinical and clinical studies confirm the potential of indole alkaloids to treat the respiratory disorders.

Medicinal Plants, Phytochemicals, and Herbs to Combat Viral Pathogens Including SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), is the most important health issue, internationally. With no specific and effective antiviral therapy for COVID-19, new or repurposed antiviral are urgently needed. Phytochemicals pose a ray of hope for human health during this pandemic, and a great deal of research is concentrated on it. Phytochemicals have been used as antiviral agents against several viruses since they could inhibit several viruses via different mechanisms of direct inhibition either at the viral entry point or the replication stages and via immunomodulation potentials. Recent evidence also suggests that some plants and its components have shown promising antiviral properties against SARS-CoV-2. This review summarizes certain phytochemical agents along with their mode of actions and potential antiviral activities against important viral pathogens. A special focus has been given on medicinal plants and their extracts as well as herbs which have shown promising results to combat SARS-CoV-2 infection and can be useful in treating patients with COVID-19 as alternatives for treatment under phytotherapy approaches during this devastating pandemic situation.

Bromelain a Potential Bioactive Compound: A Comprehensive Overview from a Pharmacological Perspective.

Bromelain is an effective chemoresponsive proteolytic enzyme derived from pineapple stems. It contains several thiol endopeptidases and is extracted and purified via several methods. It is most commonly used as an anti-inflammatory agent, though scientists have also discovered its potential as an anticancer and antimicrobial agent. It has been reported as having positive effects on the respiratory, digestive, and circulatory systems, and potentially on the immune system. It is a natural remedy for easing arthritis symptoms, including joint pain and stiffness. This review details bromelain's varied uses in healthcare, its low toxicity, and its relationship to nanoparticles. The door of infinite possibilities will be opened up if further extensive research is carried out on this pineapple-derived enzyme.

Plant-Based Indole Alkaloids: A Comprehensive Overview from a Pharmacological Perspective.

Plant-based indole alkaloids are very rich in pharmacological activities, and the indole nucleus is considered to contribute greatly to these activities. This review's fundamental objective is to summarize the pharmacological potential of indole alkaloids that have been derived from plants and provide a detailed evaluation of their established pharmacological activities, which may contribute to identifying new lead compounds. The study was performed by searching various scientific databases, including Springer, Elsevier, ACS Publications, Taylor and Francis, Thieme, Wiley Online Library, ProQuest, MDPI, and online scientific books. A total of 100 indole compounds were identified and reviewed. The most active compounds possessed a variety of pharmacological activities, including anticancer, antibacterial, antiviral, antimalarial, antifungal, anti-inflammatory, antidepressant, analgesic, hypotensive, anticholinesterase, antiplatelet, antidiarrheal, spasmolytic, antileishmanial, lipid-lowering, antimycobacterial, and antidiabetic activities. Although some compounds have potent activity, some only have mild-to-moderate activity. The pharmacokinetic profiles of some of the identified compounds, such as brucine, mitragynine, 7-hydroxymitragynine, vindoline, and harmane, were also reviewed. Most of these compounds showed promising pharmacological activity. An in-depth pharmacological evaluation of these compounds should be performed to determine whether any of these indoles may serve as new leads.

Potential role of important nutraceuticals in poultry performance and health - A comprehensive review.

Antibiotics use in poultry as a growth promoter leads to the propagation of antibiotic-resistant microorganisms and incorporation of drug residues in foods; therefore, it has been restricted in different countries. There is a global trend to limit the use of antibiotics in the animal products. Prevention of the antibiotics use in the poultry diets led to the reduction in the growth performance. Consequently, there is a high demand for natural substances that lead to the same growth enhancement and beneficially affect poultry health. These constituents play essential roles in regulating the normal physiological functions of animals including the protection from infectious ailments. Nutraceuticals administration resulted beneficial in both infectious and noninfectious diseases. Being the natural components of diet, they are compatible with it and do not pose risks associated with antibiotics or other drugs. Nutraceuticals are categorized as commercial additives obtained from natural products as an alternative feed supplement for the improvement of animal welfare. This group includes enzymes, synbiotics, phytobiotics, organic acids and polyunsaturated fatty acids. In the present review, the summary of various bioactive ingredients that act as nutraceuticals and their mode of action in growth promotion and elevation of the immune system has been presented.