Warfarin-A natural anticoagulant: A review of research trends for precision medication.

BACKGROUND: Warfarin is a widely prescribed anticoagulant in the clinic. It has a more considerable individual variability, and many factors affect its variability. Mathematical models can quantify the quantitative impact of these factors on individual variability. PURPOSE: The aim is to comprehensively analyze the advanced warfarin dosing algorithm based on pharmacometrics and machine learning models of personalized warfarin dosage. METHODS: A bibliometric analysis of the literature retrieved from PubMed and Scopus was performed using VOSviewer. The relevant literature that reported the precise dosage of warfarin calculation was retrieved from the database. The multiple linear regression (MLR) algorithm was excluded because a recent systematic review that mainly reviewed this algorithm has been reported. The following terms of quantitative systems pharmacology, mechanistic model, physiologically based pharmacokinetic model, artificial intelligence, machine learning, pharmacokinetic, pharmacodynamic, pharmacokinetics, pharmacodynamics, and warfarin were added as MeSH Terms or appearing in Title/Abstract into query box of PubMed, then humans and English as filter were added to retrieve the literature. RESULTS: Bibliometric analysis revealed important co-occuring MeShH and index keywords. Further, the United States, China, and the United Kingdom were among the top countries contributing in this domain. Some studies have established personalized warfarin dosage models using pharmacometrics and machine learning-based algorithms. There were 54 related studies, including 14 pharmacometric models, 31 artificial intelligence models, and 9 model evaluations. Each model has its advantages and disadvantages. The pharmacometric model contains biological or pharmacological mechanisms in structure. The process of pharmacometric model development is very time- and labor-intensive. Machine learning is a purely data-driven approach; its parameters are more mathematical and have less biological interpretation. However, it is faster, more efficient, and less time-consuming. Most published models of machine learning algorithms were established based on cross-sectional data sourced from the database. CONCLUSION: Future research on personalized warfarin medication should focus on combining the advantages of machine learning and pharmacometrics algorithms to establish a more robust warfarin dosage algorithm. Randomized controlled trials should be performed to evaluate the established algorithm of warfarin dosage. Moreover, a more user-friendly and accessible warfarin precision medicine platform should be developed.

Exploring the pathophysiological influence of heme oxygenase-1 on neuroinflammation and depression: A study of phytotherapeutic-based modulation.

BACKGROUND: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses. METHODOLOGY: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer. RESULTS: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations. CONCLUSION: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression.

Fermented formulation of Silybum marianum seeds: Optimization, heavy metal analysis, and hepatoprotective assessment.

BACKGROUND: Fermented formulations are extensively used in Ayurveda due to several benefits like improved palatability, bioavailability, pharmacological potential, and shelf life. These formulations can also quench the heavy metals from the plant material and thus reduce the toxicity. Seeds of Silybum marianum (L.) Gaertn. are widely used for the management of many liver diseases. STUDY DESIGN AND METHODS: In the present study, we developed a novel fermented formulation of S. marianum seeds and evaluated parameters like safety (heavy metal analysis) and effectiveness (hepatoprotective). As the developed formulation's validation is crucial, the critical process variables (time, pH, and sugar concentration) are optimized for alcohol and silybin content using the Box-Behnken design (BBD). RESULTS: The response surface methodology coupled with BBD predicted the optimized conditions (fermentation time (28 days), pH 5.6, and sugar concentration (22.04%)) for the development of a fermented formulation of the selected herb. Moreover, the alcohol content (6.5 ± 0.9%) and silybin concentration (26.1 ± 2.1%) were confirmed in optimized formulation by GC-MS and HPTLC analysis. The optimized formulation was also analyzed for heavy metals (Pb, As, Hg, and Cd); their concentration is significantly less than the decoction of herbs. Further, the comparative evaluation of the developed formulation with the marketed formulation also confirmed that the fermented formulation's silybin concentration and percentage release were significantly enhanced. In addition, the developed fermented formulation's percentage recovery of HepG2 cell lines after treatment with CCl4 was significantly improved compared with the marketed formulation. CONCLUSION: It can be summarized that the developed fermented formulation improves safety and effectiveness compared to other market formulations. Finally, it can be concluded that the developed fermented formulation could be further explored as a better alternative for developing Silybum marianum preparation.

Current trends in natural products for the treatment and management of dementia: Computational to clinical studies.

The number of preclinical and clinical studies evaluating natural products-based management of dementia has gradually increased, with an exponential rise in 2020 and 2021. Keeping this in mind, we examined current trends from 2016 to 2021 in order to assess the growth potential of natural products in the treatment of dementia. Publicly available literature was collected from various databases like PubMed and Google Scholar. Oxidative stress-related targets, NF-κB pathway, anti-tau aggregation, anti-AChE, and A-ß aggregation were found to be common targets and pathways. A retrospective analysis of 33 antidementia natural compounds identified 125 sustainable resources distributed among 65 families, 39 orders, and 7 classes. We found that families such as Berberidaceae, Zingiberaceae, and Fabaceae, as well as orders such as Lamiales, Sapindales, and Myrtales, appear to be important and should be researched further for antidementia compounds. Moreover, some natural products, such as quercetin, curcumin, icariside II, berberine, and resveratrol, have a wide range of applications. Clinical studies and patents support the importance of dietary supplements and natural products, which we will also discuss. Finally, we conclude with the broad scope, future challenges, and opportunities for field researchers.

Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation.

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.

The role of nanomaterials in enhancing natural product translational potential and modulating endoplasmic reticulum stress in the treatment of ovarian cancer.

Ovarian cancer, and particularly its most frequent type, epithelial ovarian carcinoma, constitutes one of the most dangerous malignant tumors among females. Substantial evidence has described the potential of phytochemicals against ovarian cancer. The effect of natural compounds on endoplasmic reticulum (ER) stress is of great relevance in this regard. In ovarian cancer, the accumulation of misfolded proteins in the ER lumen results in decompensated ER stress. This leads to deregulation in the physiological processes for the posttranslational modification of proteins, jeopardizes cellular homeostasis, and increases apoptotic signaling. Several metabolites and metabolite extracts of phytochemical origin have been studied in the context of ER stress in ovarian cancer. Resveratrol, quercetin, curcumin, fucosterol, cleistopholine, fucoidan, and epicatechin gallate, among others, have shown inhibitory potential against ER stress. The chemical structure of each compound plays an important role concerning its pharmacodynamics, pharmacokinetics, and overall effectiveness. Studying and cross-comparing the chemical features that render different phytochemicals effective in eliciting particular anti-ER stress actions can help improve drug design or develop multipotent combination regimens. Many studies have also investigated the properties of formulations such as nanoparticles, niosomes, liposomes, and intravenous hydrogel based on curcumin and quercetin along with some other phytomolecules in ovarian cancer. Overall, the potential of phytochemicals in targeting genetic mechanisms of ovarian cancer warrants further translational and clinical investigation.

Twitter Poll as a Medium for Questionnaire-Based Health Survey: An Experience of a Pilot Study on the Preference of Systems of Medicine for Various Health Conditions.

Background The easy accessibility of smartphones and internet connections enables people to stay virtually connected to communities via social media. However, social media is also being explored for health care education and dissemination of health-related information. Twitter (Twitter, Inc., San Francisco, California) is one of the popular social media used for spreading health-related information. Twitter enables users to create polls to get opinions from their users. The Twitter poll is a less-explored avenue for health surveys. Objective In this pilot study, we aimed to explore the feasibility of conducting a questionnaire-based health survey (on the preference of different systems of medicine for the treatment of various health problems) as a Twitter poll. Methods This observational study was conducted on Twitter for five consecutive days starting from May 31, 2021. We posted five Twitter polls, one poll each day, for five days in a #INPST unique Twitter campaign. Preferences on the use of modern medicine, traditional medicine, a combination of these two systems, and self-medication were collected on five health conditions. We collected the data from the landing poll page and Tweet Analytics (insight about the engagement of tweets provided free by Twitter). The Chi-square test, binomial test, and one-way Analysis of Variance were used to compare data, and Spearman's rank correlation coefficient was used to find a correlation between categorical variables. Results We had a mean 4358.6±590.3 poll reach with the engagement of 108.2±36.87 Twitter users and 67.6±28.06 votes. Most of the responses were received on the first day of posting the poll. The participation then gradually decreased. Modern medicine was the first choice for emergency medical care (85.1%, P <0.0001), treatment of cancer (43.6%, P <0.0001), and sexual disorder or transmitted diseases (48.9%, P <0.0001). Traditional medicine was the first choice (37.5%, P = 0.63) for the treatment of common illnesses, and a combination of modern and traditional medicine was the first choice (37.5%, P = 0.01) for the treatment of chronic diseases. Conclusion A medical survey with short questions with a maximum of four response options can be conducted on Twitter. Survey results can be obtained without any third-party analytic service. The response rate is highest on the first day and participation may decrease when multiple polls are posted within a Twitter campaign. Preference for systems of medicine found in this study can be used for designing large-scale surveys in the future.

Multifunctional role of natural products for the treatment of Parkinson's disease: At a glance.

Natural substances originating from plants have long been used to treat neurodegenerative disorders (NDs). Parkinson's disease (PD) is a ND. The deterioration and subsequent cognitive impairments of the midbrain nigral dopaminergic neurons distinguish by this characteristic. Various pathogenic mechanisms and critical components have been reported, despite the fact that the origin is unknown, such as protein aggregation, iron buildup, mitochondrial dysfunction, neuroinflammation and oxidative stress. Anti-Parkinson drugs like dopamine (DA) agonists, levodopa, carbidopa, monoamine oxidase type B inhibitors and anticholinergics are used to replace DA in the current treatment model. Surgery is advised in cases where drug therapy is ineffective. Unfortunately, the current conventional treatments for PD have a number of harmful side effects and are expensive. As a result, new therapeutic strategies that control the mechanisms that contribute to neuronal death and dysfunction must be addressed. Natural resources have long been a useful source of possible treatments. PD can be treated with a variety of natural therapies made from medicinal herbs, fruits, and vegetables. In addition to their well-known anti-oxidative and anti-inflammatory capabilities, these natural products also play inhibitory roles in iron buildup, protein misfolding, the maintenance of proteasomal breakdown, mitochondrial homeostasis, and other neuroprotective processes. The goal of this research is to systematically characterize the currently available medications for Parkinson's and their therapeutic effects, which target diverse pathways. Overall, this analysis looks at the kinds of natural things that could be used in the future to treat PD in new ways or as supplements to existing treatments. We looked at the medicinal plants that can be used to treat PD. The use of natural remedies, especially those derived from plants, to treat PD has been on the rise. This article examines the fundamental characteristics of medicinal plants and the bioactive substances found in them that may be utilized to treat PD.

Selenium-enriched yeast modulates the metal bioaccumulation, oxidant status, and inflammation in copper-stressed broiler chickens.

Copper (Cu) could be seriously hazardous when present at excessive levels, despite its vital contribution to various cellular processes. Selenium-enriched yeast (SeY) was reported to improve the health and metabolic status in broiler chicken. Hence, our study was endeavored to illustrate the mitigating efficacy of SeY on Cu-induced hepatic and renal damage. Cobb chicks aged 1 day were allocated into four experimental groups and offered a basal diet, SeY (0.5 mg/kg), CuSO4 (300 mg/kg), or SeY plus CuSO4 in their diets for 42 days. Our results revealed that SeY supplement antagonized significantly the Cu accumulation in livers and kidneys of exposed birds. Marked declines were also detected in the AST, ALT, urea, and creatinine levels, besides marked increases in total protein, glycerides, and cholesterol in the SeY-supplemented group. Moreover, enhancement of cellular antioxidant biomarkers (superoxide dismutase, CAT, GPx, and GSH) along with lowered MDA contents were achieved by SeY in hepatic and renal tissues. Further, SeY exerted a noteworthy anti-inflammatory action as indicated by decreased inflammatory biomarkers (IL-1ß and TNF-α) and NO levels in both organs. Noticeable histopathological alterations of both organs further validated the changes in the markers mentioned above. To sum up, our findings indicate that SeY can be considered a potential feed supplement for alleviating Cu-induced hepatic and renal damage in broilers, possibly via activation of antioxidant molecules and lessening the inflammatory stress.

Natural products derived from medicinal plants and microbes might act as a game-changer in breast cancer: a comprehensive review of preclinical and clinical studies.

Breast cancer (BC) is the most prevalent neoplasm among women. Genetic and environmental factors lead to BC development and on this basis, several preventive - screening and therapeutic interventions have been developed. Hormones, both in the form of endogenous hormonal signaling or hormonal contraceptives, play an important role in BC pathogenesis and progression. On top of these, breast microbiota includes both species with an immunomodulatory activity enhancing the host's response against cancer cells and species producing proinflammatory cytokines associated with BC development. Identification of novel multitargeted therapeutic agents with poly-pharmacological potential is a dire need to combat advanced and metastatic BC. A growing body of research has emphasized the potential of natural compounds derived from medicinal plants and microbial species as complementary BC treatment regimens, including dietary supplements and probiotics. In particular, extracts from plants such as Artemisia monosperma Delile, Origanum dayi Post, Urtica membranacea Poir. ex Savigny, Krameria lappacea (Dombey) Burdet & B.B. Simpson and metabolites extracted from microbes such as Deinococcus radiodurans and Streptomycetes strains as well as probiotics like Bacillus coagulans and Lactobacillus brevis MK05 have exhibited antitumor effects in the form of antiproliferative and cytotoxic activity, increase in tumors' chemosensitivity, antioxidant activity and modulation of BC - associated molecular pathways. Further, bioactive compounds like 3,3'-diindolylmethane, epigallocatechin gallate, genistein, rutin, resveratrol, lycopene, sulforaphane, silibinin, rosmarinic acid, and shikonin are of special interest for the researchers and clinicians because these natural agents have multimodal action and act via multiple ways in managing the BC and most of these agents are regularly available in our food and fruit diets. Evidence from clinical trials suggests that such products had major potential in enhancing the effectiveness of conventional antitumor agents and decreasing their side effects. We here provide a comprehensive review of the therapeutic effects and mechanistic underpinnings of medicinal plants and microbial metabolites in BC management. The future perspectives on the translation of these findings to the personalized treatment of BC are provided and discussed.

Role of Shankhpushpi (Convolvulus pluricaulis) in neurological disorders: An umbrella review covering evidence from ethnopharmacology to clinical studies.

C. pluricaulis Choisy (C. pluricaulis), a perennial herb aka C. microphyllus Sieb. and C. Prostratus Forsk. is being used as a traditional folk medicine for a variety of ailments. In this article, we collected information about C. pluricaulis through electronic search using PubMed, SciFinder, Google Scholar, and Web of Science as well as network pharmacology is done. This comprehensive review sheds light on the plant profile, phytochemistry, neuropharmacological, and toxicological data of C. pluricaulis. The crude herb and its metabolites have exhibited a wide range of in vitro and in vivo neuropharmacological effects, including memory enhancement, anxiolytic, tranquilizing, anti-depressant, anti-stress, neurodegenerative, anti-inflammatory, anti-oxidant, analgesic, sedative, anti-convulsant, and Alzheimer's disease-reversing effects. Network pharmacology results indicate that compounds from C. pluricaulis interact with various proteins, neuro synapses, signaling pathways, and serotonergic synapse which plays a crucial role in neurotransmission, Alzheimer's disease, long-term depression, addictions to alcohol, cognitive disorders, psychological conditions, and increasing serotonin concentration in synapses.

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives.

Ethnopharmacological relevance: The genus Alternanthera (Amaranthaceae) comprises 139 species including 14 species used traditionally for the treatment of various ailments such as hypertension, pain, inflammation, diabetes, cancer, microbial and mental disorders. Aim of the review: To search research gaps through critical assessment of pharmacological activities not performed to validate traditional claims of various species of Alternanthera. This review will aid natural product researchers in identifying Alternanthera species with therapeutic potential for future investigation. Materials and methods: Scattered raw data on ethnopharmacological, morphological, phytochemical, pharmacological, toxicological, and clinical studies of various species of the genus Alternanthera have been compiled utilizing search engines like SciFinder, Google Scholar, PubMed, Science Direct, and Open J-Gate for 100 years up to April 2021. Results: Few species of Alternanthera genus have been exhaustively investigated phytochemically, and about 129 chemical constituents related to different classes such as flavonoids, steroids, saponins, alkaloids, triterpenoids, glycosides, and phenolic compounds have been isolated from 9 species. Anticancer, antioxidant, antibacterial, CNS depressive, antidiabetic, analgesic, anti-inflammatory, and immunomodulator effects have been explored in the twelve species of the genus. A toxicity study has been conducted on 3 species and a clinical study on 2 species. Conclusions: The available literature on pharmacological studies of Alternanthera species reveals that few species have been selected based on ethnobotanical surveys for scientific validation of their traditional claims. But most of these studies have been conducted on uncharacterized and non-standardized crude extracts. A roadmap of research needs to be developed for the isolation of new bioactive compounds from Alternanthera species, which can emerge out as clinically potential medicines.

Natural Kinase Inhibitors for the Treatment and Management of Endometrial/Uterine Cancer: Preclinical to Clinical Studies.

Endometrial cancer (EC) is the sixth most prevalent type of cancer among women. Kinases, enzymes mediating the transfer of adenosine triphosphate (ATP) in several signaling pathways, play a significant role in carcinogenesis and cancer cells' survival and proliferation. Cyclin-dependent kinases (CDKs) are involved in EC pathogenesis; therefore, CDK inhibitors (CDKin) have a noteworthy therapeutic potential in this type of cancer, particularly in EC type 1. Natural compounds have been used for decades in the treatment of cancer serving as a source of anticancer bioactive molecules. Many phenolic and non-phenolic natural compounds covering flavonoids, stilbenoids, coumarins, biphenyl compounds, alkaloids, glycosides, terpenes, and terpenoids have shown moderate to high effectiveness against CDKin-mediated carcinogenic signaling pathways (PI3K, ERK1/2, Akt, ATM, mTOR, TP53). Pharmaceutical regimens based on two natural compounds, trabectedin and ixabepilone, have been investigated in humans showing short and midterm efficacy as second-line treatments in phase II clinical trials. The purpose of this review is twofold: the authors first provide an overview of the involvement of kinases and kinase inhibitors in the pathogenesis and treatment of EC and then discuss the existing evidence about natural products' derived kinase inhibitors in the management of the disease and outline relevant future research.

Natural Products for the Prevention and Control of the COVID-19 Pandemic: Sustainable Bioresources.

Background: The world has been unprecedentedly hit by a global pandemic which broke the record of deadly pandemics that faced humanity ever since its existence. Even kids are well-versed in the terminologies and basics of the SARS-CoV-2 virus and COVID-19 now. The vaccination program has been successfully launched in various countries, given that the huge global population of concern is still far behind to be vaccinated. Furthermore, the scarcity of any potential drug against the COVID-19-causing virus forces scientists and clinicians to search for alternative and complementary medicines on a war-footing basis. Aims and Objectives: The present review aims to cover and analyze the etiology and epidemiology of COVID-19, the role of intestinal microbiota and pro-inflammatory markers, and most importantly, the natural products to combat this deadly SARS-CoV-2 virus. Methods: A primary literature search was conducted through PubMed and Google Scholar using relevant keywords. Natural products were searched from January 2020 to November 2020. No timeline limit has been imposed on the search for the biological sources of those phytochemicals. Interactive mapping has been done to analyze the multi-modal and multi-target sources. Results and Discussion: The intestinal microbiota and the pro-inflammatory markers that can serve the prognosis, diagnosis, and treatment of COVID-19 were discussed. The literature search resulted in yielding 70 phytochemicals and ten polyherbal formulations which were scientifically analyzed against the SARS-CoV-2 virus and its targets and found significant. Retrospective analyses led to provide information about 165 biological sources that can also be screened if not done earlier. Conclusion: The interactive analysis mapping of biological sources with phytochemicals and targets as well as that of phytochemical class with phytochemicals and COVID-19 targets yielded insights into the multitarget and multimodal evidence-based complementary medicines.

Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment.

In the rural communities of sub-Saharan African (sSA) countries, malaria is being managed using phytocompounds. Artesunate is reported to inhibit Gephyrin E, a central, multi-domain scaffolding protein of inhibitory post-synapses. Neem plant and its metabolites like azadirachtin are being indicated for management of malaria by traditional healers. The present study was aimed to cheminformatically analyse the binding potential of artesunate and azadirachtin with various reactive moieties of Gephyrin E, to reduce malaria scourge. With molecular dynamics (MD), binding free energy estimation and binding affinity of artesunate and azadirachtin to Gephyrin E was done. GRIP docking was done to study the interactions of these test ligands with Gephyrin E (6FGC). MD simulation gave insights to structural changes upon binding of artesunate and azadirachtin in the ligand-binding pocket of Gephyrin E. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were calculated. From the estimation, azadirachtin had a total binding energy of -36.97 kcal/mol; artesunate had a binding energy of -35.73 kcal/mol. The GRIP docking results provided a clearer evidence that artesunate has comparatively better binding affinity to Gephyrin E than azadirachtin, and the critical binding sites (in activity order) were cavity 3, 2, 8, and 6 for artesunate while for azadirachtin, it was cavity 6, 3, 8, and 2. The GRIP docking provided detailed interactions at the atomic levels, providing evidence; both compounds have chances to overcome the drug resistance problem, albeit higher for artesunate. Our findings added another piece of evidence that azadirachtin may be effective as an anti-malarial agent. The results herein may provide impetus for more studies into bioactive components of plant origin towards the effective management of malaria disease phenotype.

Isolation, Docking and In Silico ADME-T Studies of Acacianol: Novel Antibacterial Isoflavone Analogue Isolated from Acacia leucophloea Bark.

BACKGROUND: The plant Acacia leucophloea (Roxb.) Willd. of the family Fabaceae is of paramount importance in Indian medicine. OBJECTIVES: We sought to evaluate the in vitro anti-microbial activity of A. leucophloea stem bark extract together with its phytochemical characterization and exploration of drug-likeness attributes. METHODS: In vitro Kirby-Bauer disc-diffusion and tube-dilution assays were exploited for determining the anti-microbial activity of the methanolic bark extracts against several bacterial test strains. Spectral characterization of the isolated phytoconstituents was performed using spectroscopy techniques viz., UV, IR, 1H NMR, and mass spectroscopy followed by the in silico studies like docking and ADME-T studies. RESULTS: The crude methanolic extracts were active against all the bacterial test strains, albeit weakly or moderately, as indicated by the zone of inhibition and minimum inhibitory concentration in the anti-microbial assays. The isolated phytoconstituent was identified to be 3-(3,4-dihydro-5-methoxy-2H-chromen-6-yl)-2,5- dimethoxy-2H-chromen-7-ol (hereby coined as acacianol), a novel isoflavone analog. Acacianol demonstrated a strong binding affinity towards the bacterial DNA gyrase over clorobiocin, especially in the case of cavity 4 with no predicted toxicities in silico, except skin sensitization and chromosome damage.

Herbal Resources to Combat a Progressive & Degenerative Nervous System Disorder- Parkinson's Disease.

Parkinson's disease is one of the most common adult-onset, a chronic disorder involving neurodegeneration, which progressively leads to deprivation of dopaminergic neurons in substantia nigra, causing a subsequent reduction of dopamine levels in the striatum resulting in tremor, myotonia, and dyskinesia. Genetics and environmental factors are believed to be responsible for the onset of Parkinson's disease. The exact pathogenesis of Parkinson's disease is quite complicated and the present anti-Parkinson's disease treatments appear to be clinically insufficient. Comprehensive researches have demonstrated the use of natural products such as ginseng, curcumin, ashwagandha, baicalein, etc. for the symptomatic treatment of this disease. The neuroprotective effects exhibited by these natural products are mainly due to their ability to increase dopamine levels in the striatum, manage oxidative stress, mitochondrial dysfunction, glutathione levels, clear the aggregation of α- synuclein, induce autophagy and decrease the pro-inflammatory cytokines and lipid peroxidation. This paper reviews various natural product studies conducted by scientists to establish the role of natural products (both metabolite extracts as well as pure metabolites) as adjunctive neuroprotective agents.

Topical Capsaicin for the Treatment of Neuropathic Pain.

BACKGROUND: Neuropathic pain (NP) is an egregious problem worldwide. Due to the side-effects of oral drugs, drugs delivered directly to the affected area of pain are preferred. OBJECTIVE: Capsaicin, a chemical compound isolated from chili peppers, is used as an analgesic in topical ointments and dermal patches to alleviate pain. Objective of the study is to review the application and functionality of topical capsaicin in treatment of neuropathic pain. DATA SOURCES: To systematically review capsaicin's functions on NP, we retrieved articles from the PubMed database published in the last ten years. STUDY ELIGIBILITY CRITERIA: The inclusion criteria were capsaicin and the use of capsaicin for the treatment of NP; on the other hand, articles were excluded according to the mentioned criteria such as abstracts, articles written in any language other than English, incomplete articles, and conference papers. PARTICIPANTS AND INTERVENTIONS: Out of 265 articles, 108 articles were selected after filtering through the inclusion and exclusion criteria. The data and knowledge currently existing for capsaicin treatment in NP are summarized. RESULTS: This review indicates that capsaicin effectively improves NP treatment without affecting the motor and large nerve fibres involved in sensory function. Transient receptor potential channel vanilloid type 1 (TRPV1) is the capsaicin receptor expressed in central and peripheral terminals of a sensitive primary nerve cell. Conclusions and implications of key findings: Topical capsaicin has a sensible safety profile and is effective in reducing NP. Therefore, studies over the last decade suggest that capsaicin might be a potential drug for NP treatment.

Data-driven translational prostate cancer research: from biomarker discovery to clinical decision.

Prostate cancer (PCa) is a common malignant tumor with increasing incidence and high heterogeneity among males worldwide. In the era of big data and artificial intelligence, the paradigm of biomarker discovery is shifting from traditional experimental and small data-based identification toward big data-driven and systems-level screening. Complex interactions between genetic factors and environmental effects provide opportunities for systems modeling of PCa genesis and evolution. We hereby review the current research frontiers in informatics for PCa clinical translation. First, the heterogeneity and complexity in PCa development and clinical theranostics are introduced to raise the concern for PCa systems biology studies. Then biomarkers and risk factors ranging from molecular alternations to clinical phenotype and lifestyle changes are explicated for PCa personalized management. Methodologies and applications for multi-dimensional data integration and computational modeling are discussed. The future perspectives and challenges for PCa systems medicine and holistic healthcare are finally provided.