Integrating network pharmacology with molecular docking to rationalize the ethnomedicinal use of Alchornea laxiflora (Benth.) Pax & K. Hoffm. for efficient treatment of depression.

Background: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (A. laxiflora) has been indicated in traditional medicine to treat depression. However, scientific rationalization is still lacking. Hence, this study aimed to investigate the antidepressant potential of A. laxiflora using network pharmacology and molecular docking analysis. Materials and methods: The active compounds and potential targets of A. laxiflora and depression-related targets were retrieved from public databases, such as PubMed, PubChem, DisGeNET, GeneCards, OMIM, SwissTargetprediction, BindingDB, STRING, and DAVID. Essential bioactive compounds, potential targets, and signaling pathways were predicted using in silico analysis, including BA-TAR, PPI, BA-TAR-PATH network construction, and GO and KEGG pathway enrichment analysis. Later on, with molecular docking analysis, the interaction of essential bioactive compounds of A. laxiflora and predicted core targets of depression were verified. Results: The network pharmacology approach identified 15 active compounds, a total of 219 compound-related targets, and 14,574 depression-related targets with 200 intersecting targets between them. SRC, EGFR, PIK3R1, AKT1, and MAPK1 were the core targets, whereas 3-acetyloleanolic acid and 3-acetylursolic acid were the most active compounds of A. laxiflora with anti-depressant potential. GO functional enrichment analysis revealed 129 GO terms, including 82 biological processes, 14 cellular components, and 34 molecular function terms. KEGG pathway enrichment analysis yielded significantly enriched 108 signaling pathways. Out of them, PI3K-Akt and MAPK signaling pathways might have a key role in treating depression. Molecular docking analysis results exhibited that core targets of depression, such as SRC, EGFR, PIK3R1, AKT1, and MAPK1, bind stably with the analyzed bioactive compounds of A. laxiflora. Conclusion: The present study elucidates the bioactive compounds, potential targets, and pertinent mechanism of action of A. laxiflora in treating depression. A. laxiflora might exert an antidepressant effect by regulating PI3K-Akt and MAPK signaling pathways. However, further investigations are required to validate.

Phytoimmunomodulators: A review of natural modulators for complex immune system.

In the past few decades, the medicinal properties of plants and their effects on the human immune system are being studied extensively. Plants are an incredible source of traditional medicines that help cure various diseases, including altered immune mechanisms and are economical and benign compared to allopathic medicines. Reported data in written documents such as Traditional Chinese medicine, Indian Ayurvedic medicine support the supplementation of botanicals for immune defense reactions in the body and can lead to safe and effective immunity responses. Additionally, some botanicals are well-identified as magical herbal remedies because they act upon the pathogen directly and help boost the immunity of the host. Chemical compounds, also known as phytochemicals, obtained from these botanicals looked promising due to their effects on the human immune system by modulating the lymphocytes which subsequently reduce the chances of getting infected. This paper summarises most documented phytochemicals and how they act on the immune system, their properties and possible mechanisms, screening conventions, formulation guidelines, comparison with synthetic immunity-enhancers, marketed immunity-boosting products, and immune-booster role in the ongoing ghastly corona virus wave. However, it focuses mainly on plant metabolites as immunomodulators. In addition, it also sheds light on the current advancements and future possibilities in this field. From this thorough study, it can be stated that the plant-based secondary metabolites contribute significantly to immunity building and could prove to be valuable medicaments for the design and development of novel immunomodulators even for a pandemic like COVID-19.

The Current Landscape of Bioactive Molecules against DENV: A Systematic Review.

With a 30-fold increase in incidence over the previous 50 years, dengue fever is now the most widespread viral disease transmitted by mosquitoes in the world. The intricate interaction of the human defense system, hereditary predisposition, and specific bitterness elements is more likely to be the pathogenesis of dengue. There are presently no viable treatments for dengue. Synthetic drugs which are used against this ailment also show major side effects. There must be a deeper understanding of the underlying mechanism generating severe symptoms to develop auguring markers, cutting-edge diagnostics, and treatments and finally a well-rounded and secure antiserum. Hence, the aim is to search for safer and more potent drugs derived from plants. Plants or herbs are mainly targeting replication or its enzyme or specific stereotypes, though an exact mechanism of phytoconstituents interfering with the viral replication is still undiscovered. The present attempt provided the update with the objective to bringing up forward pathophysiological eventualities involved in dengue virus along with the naturally derived treatment relevant to provide the impregnable therapy by evading the noxious symptoms for dengue fever. Governor's plum, Cryptocarya chartacea, magnolia berry, and Chinese ginger are such plants exhibiting many effective phytoconstituents against DENV and can be further explored for novel drug discovery by medicinal scientists.

Alkaloidal Phytoconstituents for Diabetes Management: Exploring the Unrevealed Potential.

The main characteristic feature of diabetes mellitus is the disturbance of carbohydrate, lipid, and protein metabolism, which results in insulin insufficiency and can also lead to insulin resistance. Both the acute and chronic diabetic cases are increasing at an exponential rate, which is also flagged by the World Health Organization (WHO) and the International Diabetes Federation (IDF). Treatment of diabetes mellitus with synthetic drugs often fails to provide desired results and limits its use to symptomatic treatment only. This has resulted in the exploration of alternative medicine, of which herbal treatment is gaining popularity these days. Owing to their safety benefits, treatment compliance, and ability to exhibit effects without disturbing internal homeostasis, research in the field of herbal and ayurvedic treatments has gained importance. Medicinal phytoconstituents include micronutrients, amino acids, proteins, mucilage, critical oils, triterpenoids, saponins, carotenoids, alkaloids, flavonoids, phenolic acids, tannins, and coumarins, which play a dynamic function in the prevention and treatment of diabetes mellitus. Alkaloids found in medicinal plants represent an intriguing potential for the inception of novel approaches to diabetes mellitus therapies. Thus, this review article highlights detailed information on alkaloidal phytoconstituents, which includes sources and structures of alkaloids along with the associated mechanism involved in the management of diabetes mellitus. From the available literature and data presented, it can be concluded that these compounds hold tremendous potential for use as monotherapies or in combination with current treatments, which can result in the development of better efficacy and safety profiles.

Therapeutic approaches of nutraceuticals in the prevention of Alzheimer's disease.

Alzheimer's disease (AD) is a neurological illness that causes memory loss over time. Currently, available pharmaceutical medicines and products are limited, and they have side effects at a higher price. Researchers and scientists have observed significant effects of nutraceuticals. Various preclinical and clinical studies were investigated for the Anti-Alzheimer's activity of nutraceuticals. The increasing ability of the pathogenesis of AD has led to the analysis of novel therapeutic targets, including the pathophysiological mechanisms and distinct cascades. So, current improvement will show the most adequate and prominent nutraceuticals and suggested concise mechanisms involving autophagy regulation, anti-inflammatory, antioxidant, mitochondrial homeostasis, and others. The effects of nutraceuticals cannot be ignored; it is important to investigate high-quality clinical trials. Given the potential of nutraceuticals to battle AD as multi-targeted therapies, it's vital to evaluate them as viable lead compounds for drug discovery and development. To the best of the authors 'knowledge, modification of blood-brain barrier permeability, bioavailability, and aspects of randomized clinical trials should be considered in prospective investigations. PRACTICAL APPLICATIONS: Advancements in molecular diagnostic and fundamentals have implemented particular usefulness for drug evaluation. An excess of experimental knowledge occurs regarding the effect of nutraceuticals on AD. There are various preclinical and clinical studies that have been done on nutraceuticals. In addition, various substitute inhibit and enhance some pathophysiological levels associated with AD. Nutraceuticals are easily available and have fewer side effects with cost-effective advantages. However, further investigations and clinical trials are required to encourage its effect on disease.

Insights into the Explicit Protective Activity of Herbals in Management of Neurodegenerative and Cerebrovascular Disorders.

The longstanding progressive neurodegenerative conditions of the central nervous system arise mainly due to deterioration, degradation and eventual neuronal cell loss. As an individual ages, the irreversible neurodegenerative disorders associated with aging also begin to develop, and these have become exceedingly prominent and pose a significant burden mentally, socially and economically on both the individual and their family. These disorders express several symptoms, such as tremors, dystonia, loss of cognitive functions, impairment of motor activity leading to immobility, loss of memory and many more which worsen with time. The treatment employed in management of these debilitating neurodegenerative disorders, such as Parkinson's disease (which mainly involves the loss of dopaminergic neurons in the nigrostriatal region), Alzheimer's disease (which arises due to accumulation of Tau proteins causing diffusive atrophy in the brain), Huntington's disease (which involves damage of striatal and spinal neurons, etc.), have several adverse effects, leading to exploration of several lead targets and molecules existing in herbal drugs. The current review highlights the mechanistic role of natural products in the treatment of several neurodegenerative and cerebrovascular diseases such as Parkinson's disease, Alzheimer's disease, ischemic stroke and depression.

The therapeutic role of nutraceuticals targeting the Nrf2/HO-1 signaling pathway in liver cancer.

Liver cancer (L.C.) is the most common cause of cancer death in the United States and the fifth most common globally. The overexpression of nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) caused by oxidative stress has been associated with tumor growth, aggressiveness, treatment resistance, and poor prognosis. Nutraceuticals that inhibit Nrf2/HO-1 signaling may become the most effective strategy to treat liver cancer. Phytochemicals found in fruits and vegetables, also known as nutraceuticals, tend to emerge as chemopreventive agents, with the added benefit of low toxicity and high nutritional values. This paper reviews the present scientific knowledge of the Nrf2/HO-1 signaling as a possible target molecule for chemotherapeutic agents, its basic control mechanisms, and Nrf2/HO-1 inducers produced from natural products that might be employed as cancer chemopreventive drugs. The growing interest in the contribution of the Nrf2/ARE/HO-1 signaling in the development of liver cancer and the Use of nutraceuticals to treat liver cancer by targeting Nrf2/ARE/HO-1. PRACTICAL APPLICATIONS: An increase in Nrf2 expression indicates that Nrf2 is the most important player in liver cancer. Cancer patients are more resistant to chemotherapy because of this erroneous Nrf2 signaling. Furthermore, an increasing body of evidence indicates that activation of the Nrf2/HO-1 pathway results in the production of phase II detoxifying and antioxidant enzymes, which serve a defense purpose in cells. As a consequence, treating liver cancer. This master regulator may be a possibility. Nutraceuticals that reduce Nrf2/HO-1 signaling may be the most effective strategy for preventing liver cancer. The methods of action of numerous natural substances are examined in this article.

Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends.

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer's disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.

Perception of Individuals with Diabetes about Efficacy and Safety of Complementary and Alternative Medicines (CAM) in the Jazan Region, Saudi Arabia.

Background: CAM is widely accepted for the management of diabetes, and CAM users from many countries showed positive perception towards its use. However, little is known about the perception of individuals with diabetes in Saudi Arabia. Objectives: This study was aimed to assess the perception of the individuals with diabetes of Jazan region in Saudi Arabia towards CAM. Methods: An online, anonymous cross-sectional survey was designed and conducted between September 5 and December 31, 2021. Data were collected using 19-item self-report survey from the individuals with diabetes of the Jazan region. Results: A total of 359 validated responses were received. Approximately, 34% of the participants reported using CAM with modern medicine to control diabetes. Most of the participants reported that CAM is affordable, accessible, acceptable, and effective. Of the study sample, 28% reported using herbal medicine to control diabetes. Significantly, higher percentages of CAM users reported media (42% vs 27%) and friends/family (31% vs 27%) as the primary sources of information about CAM as compared to non-CAM users. Individuals who used CAM for diabetes showed significantly more positive perception (ß = 2.386; p=0.001) than those who did not use CAM in the adjusted analysis. Similarly, students had a significantly higher positive perception towards CAM (ß = 4.121; p=0.013) compared to employed individuals. Conclusion: A quarter of the sample of individuals with diabetes used herbal medicine to control diabetes. Individuals who ever used CAM for diabetes showed positive perception towards CAM. However, there is a need of healthcare workers to be involved in educating the individuals with diabetes and the general public in order to use CAM more effectively and safely.

Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents.

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher's opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

Understanding the role of "sunshine vitamin D" in Parkinson's disease: A review.

Next to Alzheimer's disease, Parkinson's disease constitutes the second most widespread neurological disorder, primarily affecting the older population. Its symptoms are noticeable with advancing age including tremors, postural imbalance, and slow movements, and over time, these symptoms get aggravated, progressing to osteoporosis, osteopenia, and risk of fractures. These symptoms correlate to low bone density and hence weakened bones; thus, vitamin D proves to be an intricate component of the pathogenesis of the disease. Moreover, lower serum concentrations of vitamin D have been found in diseased subjects. Supplementation with vitamin D can retard the aggravation of non-motor as well as motor symptoms of Parkinson's disease that include cognitive improvement along with the decline in risk of fractures. Also, vitamin D is extremely crucial for brain functioning, targeting dopaminergic neurons, and almost the entire functioning of the brain is affected. However, further exploration is required to determine the toxic dose of vitamin D in Parkinson's subjects. This "sunshine vitamin" surely can be a ray of sunshine for neurologically diseased subjects.

Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials.

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

Medicinal Plants and Isolated Molecules Demonstrating Immunomodulation Activity as Potential Alternative Therapies for Viral Diseases Including COVID-19.

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body's defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.