Phytochemical profiling, antioxidant, cytotoxic, and anti-inflammatory activities of Plectranthus rugosus extract and fractions: in vitro, in vivo, and in silico approaches.

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.

Assessing Phytogenic and Chemogenic Silver Nanoparticles for Antibacterial Activity and Expedited Wound Recuperation.

Green silver nanoparticles (AgNPs) possess tremendous promise for diverse applications due to their versatile characteristics. Coriander and other plant extracts have become popular for greenly synthesizing AgNPs as an economical, biocompatible, cost-effective, and environmentally beneficial alternative to chemical processes. In this study, we synthesized AgNPs from coriander leaves and evaluated their antibacterial, anti-inflammatory, antioxidant, and wound-healing acceleration properties in comparison to chemically synthesized AgNPs. The zeta potentials of AgNPs extracted from green and chemical processes were -32.4 mV and -23.4 mV, respectively. TEM images showed a cuboidal shape of green and chemical AgNPs with a diameter of approximately 100 nm. The FTIR spectra of green AgNPs showed an extreme absorption peak at 3401 cm-1, which signifies O-H stretching vibrations, typically linked to hydroxyl groups. In vitro results elaborated that AgNPs from coriander exerted a stronger effect on anti-Klebsiella pneumoniae (KP) through interrupting cell integrity, generating ROS, depleting ATP, and exhibiting significant antioxidant activity, compared with AgNPs synthesized chemically. In vivo experiments showed that AgNPs from coriander, as opposed to chemically manufactured AgNPs, greatly accelerated the healing of wounds contaminated with Klebsiella pneumoniae bacteria by effectively eliminating the bacteria on the wounds and stimulating skin regeneration and the deposition of dense collagen. In vivo assays further demonstrated that green AgNPs effectively enhanced Klebsiella pneumoniae-infected wound healing by extenuating local inflammatory responses and up-regulating VEGF and CD31 expression. In conclusion, green AgNPs significantly alleviated the inflammation without significantly harming the organism.

An Exploratory Review on the Hypoglycemic Action of Unani Anti-diabetic Drugs via Possible Modulation of Gut Microbiota.

BACKGROUND AND AIM: Diabetes mellitus is a chronic, multi-factorial metabolic disorder and also an important public health issue that requires multi-dimensional therapeutic strategies for effective control. Unani herbs have long been used to effectively mitigate diabetes through various mechanisms. In recent years, it has been speculated that the alteration of gut microbiome ecology is potentially one of the important mechanisms through which the Unani drugs exert hypoglycemic action. This review aims at the trans-disciplinary interpretation of the holistic concepts of the Unani system of medicine and the molecular insights of contemporary medicine for novel strategies for diabetes management. METHODOLOGY: We searched scientific databases such as PubMed, Google Scholar, and Science-Direct, etc. Unani classical texts (Urdu, Arabic, and Persian), and medical books, for diabetic control with Unani medicine through the gut microbiome. RESULTS: Unani medicine defines, diabetes as a urinary system disorder disrupting the transformational faculty (Quwwat Mughayyira) in the gastrointestinal tract. The Unani system and contemporary biomedicine use different epistemology and ontology for describing diabetes through gutderived factors in whole-body glucose homeostasis. Unani Pharmaceutics have reported in clinical and preclinical (in vitro/ in vivo) trials in improving diabetes by altering gut microbiota composition, microvascular dysfunction, and inflammation. However, the preventive plan is the preservance of six essential factors (Asbab Sitta Daruriyya) as a lifestyle plan. CONCLUSION: This is the first study on the integrative strategy about the hypoglycemic effects of Unani herbs that could serve as a prerogative novel approach for cost-effective, holistic, rationalistic, and multi-targeted diabetes management.

Bioinformatics Analysis, Expression Profiling, and Functional Characterization of Heat Shock Proteins in Wolfi-poria cocos.

Heat shock proteins (HSPs) play critical roles in regulating different mechanisms under high-temperature conditions. HSPs have been identified and well-studied in different plants. However, there is a lack of information about their genomic organization and roles in medicinal plants and fungi, especially in Wolfi-poria cocos (W. cocos). We identified sixteen heat shock proteins (HSPs) in W. cocos and analyzed in terms of phylogenetic analysis, gene structure, motif distribution patterns, physiochemical properties, and expression comparison in different strains. Based on phylogenetic analysis, HSPs were divided into five subgroups (WcHSP100, WcHSP90, WcHSP70, WcHSP60, and WcsHSP). Subgroups WcHSP100s, WcHSP90s, WcHSP70s, WcHSP60, and WcsHSPs were further divided into 3, 2, 3, 1, and 6 subfamilies, respectively. Moreover, the expression profiling of all HSP genes in five strains of W. cocos under different temperature extremes revealed that expression of most HSPs were induced by high temperature. However, every subfamily showed different expression suggesting distinctive role in heat stress tolerance. WcHSP70-4, WcHSP90-1, and WcHSP100-1 showed the highest response to high temperature stress. Heterologous expression of WcHSP70-4, WcHSP90-1, and WcHSP100-1 genes in Escherichia coli enhanced survival rate of E. coli during heat stress. These findings suggest the role of W. cocos heat shock genes in the high temperature stress tolerance.

Concept of Unani Jali (detergents/cleansers) drugs and its scientific validation: scope for new opportunities in dermatological pharmacotherapeutics.

OBJECTIVES: The use of detergent-action drugs in traditional Unani therapeutic intervention has been a long-standing Unani medicinal practice. The key aim of the article is to provide thorough information on the novel, unexplored idea of Unani Jali (detergent/cleansers) drugs for the treatment of skin ailments, as well as to identify medicinal plants that have detergent action and correlate these findings with scientific studies that may support evidence for the drug's detergent effect. CONTENT: The ethnobotanical classical literature of Unani medicine was investigated in order to have a comprehensive insight of Unani detergents/cleansers. Scientific studies were carried from databases including PubMed, Scopus, Science Direct, and google Scholar, among others. More than fifty exclusive plant, mineral, and animal-based detergents are found specifically for skin disorders in Unani therapy. These drugs basically evacuate impurities from the body's excretory system and and have been found to have keratolytic and debris-peeling effects, as well as the ability to maintain skin tone consistency. Unani Jali drugs have also been found to have anti-inflammatory, antibacterial, analgesic, and tonic properties, suggesting its usefulness holistically. SUMMARY AND OUTLOOK: Based on phyto constituents, prospective therapeutic response, and scientific data, this review proposes that Unani Jali drugs could be a safe and promising therapeutic option for dermatological illnesses such as vitiligo, acne, dermatitis, psoriasis, and skin sensitivity.

Interventions of Unani medicine for maintenance of health with special reference to air quality: an evidence-based review.

OBJECTIVES: This article aims to discuss the impact of air quality on human health, measures to achieve the goal of good indoor air quality and proposed benefits of interventions of Unani Medicine with an evidence-based approach. CONTENT: The significance of air quality on the health of the community cannot be denied. Recent evidences from WHO illustrated data on severe air pollutants and their impacts on human health ranges from minor upper respiratory irritation to chronic respiratory ailments including lung carcinoma and heart disease associated with premature mortality and reduced life expectancy. In Unani Medicine, air has been included in the list of factors, which are six in number and play the central role in prevention of diseases and maintenance of health. Air is considered as the medium of most of the extrinsic factors such as chemical and biological pollutants affecting health and their exposure results in short and long-term health issues. The literature of Unani Medicine proposes many simple and effective measures, which help to improve indoor and outdoor air quality. The goal of outdoor clean air is achieved through implementation of measures to tackle the source of pollution, while indoor clean air is attained through various means e.g., fumigation with herbal drugs. Hence, an extensive literature survey on Unani reserve was conducted to collect information about the concept of air discussed under the heading of six essential factors and its implication in prevention of diseases and maintenance of health. Further, research databases such as Pub Med, Google Scholar, and Science-Direct were broadly searched for evidence on the efficacy of herbals mentioned in Unani literature for the indoor air purification and subsequent air quality improvement. SUMMARY AND OUTLOOK: Recent studies showed good air quality leads to decrease in mortality, particularly of respiratory and cardiovascular deaths whereas poor air quality results in a variety of diseases. Unani scholars prescribed several regimens such as Bukhoor (Fumigation), Sa'oot (Nasal instillation) and use of Abeer (Perfumes) and Nadd (Incense) for the improvement of air quality. Likewise various herbal fumigants and sprays containing drugs like mi'a sa'ila (Liquidambar orientalis Mill.), mastagi (Pistacia lentiscus L.), mushk (Moschus moschiferus L.), loban (Styrax benzoides W. G. Craib), abnoos (Diospyros ebenum J. Koenig ex Retz), za'fran (Crocus sativus L.) and sirka (vinegar) etc. has been well explained and used exclusively for air purification and improvement of AQI. Therefore, in the present scenario of altered air quality, we forward certain measures described in Unani system of medicine for health promotion and protection. Scientific evidence on several drugs reveal the presence of a number of pharmacologically active substances, which may provide a new approach into the purification of air.

Hypocalcaemia As A Rare Reversible Cause Of Dilated Cardiomyopathy.

Dilated cardiomyopathy is characterized by dilation and enlargement of one or both ventricles with reduced systolic function. Calcium plays a key role in myocardial contraction. Hypocalcaemia can lead to a decrease in contraction, left ventricular systolic dysfunction, and heart failure with reduced ejection fraction (EF). Hypocalcaemia is a rare reversible cause of dilated cardiomyopathy. The author presents a case who presented with complaints of shortness of breath on exertion, orthopnoea, paroxysmal nocturnal dyspnoea, numbness and crampy muscular pains. He had a high JVP, systolic murmur on auscultation, hepatomegaly, pedal oedema and crackles on chest auscultation. His ECG showed sinus rhythm with prolonged QT interval. His echocardiography showed dilated cardiomyopathy with reduced ejection fraction, moderate mitral regurgitation and mild tricuspid regurgitation. His Calcium levels and PTH levels were both low. He was treated with ionotrophes, diuretics, vitamin D and calcium supplements, including both intravenous and oral. With the correction of calcium levels, he was weaned off the ionotrophic support and his ejection fraction improved. Calcium levels if low should be corrected in patients with dilated cardiomyopathy.

Phyto-Synthesis, Characterization, and In Vitro Antibacterial Activity of Silver Nanoparticles Using Various Plant Extracts.

Aloe vera, Mentha arvensis (mint), Coriandrum sativum (coriander), and Cymbopogon citratus (lemongrass) leaf extracts were used to synthesize stable silver nanoparticles (Ag-NPs) by green chemistry. UV-vis spectrophotometry, X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) spectroscopy techniques were used to characterize these biosynthesized nanoparticles. The data indicated that the silver nanoparticles were successfully synthesized, and the narrower particle size distribution was at 10-22 nm by maintaining a specific pH. As a short-term post-sowing treatment, Ag-NP solutions of different sizes (10 and 50 ppm) were introduced to mung bean seedlings, and the overall increase in plant growth was found to be more pronounced at 50 ppm concentration. The antibacterial activity of Ag-NPs was also investigated by disc diffusion test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) test. The zones of inhibition (ZOI) were shown by Escherichia coli (E. coli) (1.9, 2.1, 1.7, and 2 mm), followed by Staphylococcus aureus (S. aureus) (1.8, 1.7, 1.6, and 1.9 mm), against coriander, mint, Aloe vera, and lemongrass, respectively. MIC and MBC values of E. coli, and S. aureus ranged from 7 to 8 µg/mL. Overall, this study demonstrates that Ag-NPs exhibit a strong antimicrobial activity and thus might be developed as a new type of antimicrobial agent for the treatment of bacterial infection.

CAREPATH: Developing Digital Integrated Care Solutions for Multimorbid Patients with Dementia.

CAREPATH project is focusing on providing an integrated solution for sustainable care for multimorbid elderly patients with dementia or mild cognitive impairment. The project has a digitally enhanced integrated patient-centered care approach clinical decision and associated intelligent tools with the aim to increase patients' independence, quality of life and intrinsic capacity. In this paper, the conceptual aspects of the CAREPATH project, in terms of technical and clinical requirements and considerations, are presented.

Structural interactions of phytoconstituent(s) from cinnamon, bay leaf, oregano, and parsley with SARS-CoV-2 nucleocapsid protein: A comparative assessment for development of potential antiviral nutraceuticals.

SARS-CoV-2 has been responsible for causing 6,218,308 deaths globally till date and has garnered worldwide attention. The lack of effective preventive and therapeutic drugs against SARS-CoV-2 has further worsened the scenario and has bolstered research in the area. The N-terminal and C-terminal RNA binding domains (NTD and CTD) of SARS-CoV-2 nucleocapsid protein represent attractive therapeutic drug targets. Naturally occurring compounds are an excellent source of novel drug candidates due to their structural diversity and safety. Ten major bioactive compounds were identified in ethanolic extract (s) of Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare, and Petroselinum crispum using HPLC and their cytotoxic potential was determined against cancer and normal cell lines by MTT assay to ascertain their biological activity in vitro. To evaluate their antiviral potential, the binding efficacy to NTD and CTD of SARS-CoV-2 nucleocapsid protein was determined using in silico biology tools. In silico assessment of the phytocomponents revealed that most of the phytoconstituents displayed a druglike character with no predicted toxicity. Binding affinities were in the order apigenin > catechin > apiin toward SARS-CoV-2 nucleocapsid NTD. Toward nucleocapsid CTD, the affinity decreased as apigenin > cinnamic acid > catechin. Remdesivir displayed lesser affinity with NTD and CTD of SARS-CoV-2 nucleocapsid proteins than any of the studied phytoconstituents. Molecular dynamics (MD) simulation results revealed that throughout the 100 ns simulation, SARS-CoV-2 nucleocapsid protein NTD-apigenin complex displayed greater stability than SARS-CoV-2 nucleocapsid protein NTD-cinnamic acid complex. Hence, apigenin, catechin, apiin and cinnamic acid might prove as effective prophylactic and therapeutic candidates against SARS-CoV-2, if examined further in vitro and in vivo. PRACTICAL APPLICATIONS: Ten major bioactive compounds were identified in the extract(s) of four medicinally important plants viz. Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare and Petroselinum crispum using HPLC and their biological activity was also evaluated against cancer and normal cell lines. Interestingly, while all extract(s) wielded significant cytotoxicity against cancer cells, no significant toxicity was found against normal cells. The outcome of the results prompted evaluation of the antiviral potential of the ten bioactive compounds using in silico biology tools. The present study emphasizes on the application of computational approaches to understand the binding interaction and efficacy of the ten bioactive compounds from the above plants with SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal RNA binding domains in preventing and/or treating COVID-19 using in silico tools. Druglikeness and toxicity profiles of the compounds were carried out to check the therapeutic application of the components. Additionally, molecular dynamics (MD) simulation was performed to check the stability of ligand-protein complexes. The results provided useful insights into the structural binding interaction(s) that can be exploited for the further development of potential antiviral agents targeting SARS-CoV-2 especially since no specific therapy is still available to combat the rapidly evolving virus and the existing treatment is more or less symptomatic which makes search for novel antiviral agents all the more necessary and crucial.

Profiling of phytochemicals from aerial parts of Terminalia neotaliala using LC-ESI-MS2 and determination of antioxidant and enzyme inhibition activities.

OBJECTIVES: Owing to extraordinary healing power, Terminalia species have been used in traditional medicine systems to treat various diseases. Many folklore uses of Terminalia neotaliala (Madagascar's almond) included treating arterial hypertension, diabetes, diarrhea, dysentery, colic, oral and digestive candidiasis, intestinal parasitic infections, inflammatory skin conditions, postpartum care, and mycotic infections but nevertheless scientifically explored for its medicinal and pharmacological importance. Therefore, the current study intended to prepare methanolic extract and its fractionation with hexane, chloroform, and butanol followed by evaluation of their polyphenolic content, biological activities, and LCMS analysis. The biological study included antioxidant activity and enzyme inhibition assay i.e., α-glucosidase and urease. The insight study of biologically active secondary metabolites of butanol fraction (BUAE) was performed through LCMS. METHODS: The total phenolic content (TPC) and total flavonoid content (TFC) of hydroalcoholic and its fractions were estimated using the Folin-Ciocalteu and aluminum chloride method. The total tannin content (TTC) was determined using the Folin-Denis spectrophotometric method. Similarly, the antioxidant potential of HAAE, HEAE, CFAE, and BUAE was determined using four methods as DPPH (1,1-diphenyl-2-picrylhydrazyl), 2,2-azinobis(3-ethylbenothiazoline)-6-sulfonic acid, cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP). The sample extracts were also evaluated against two clinically important enzymes i.e., α-glucosidase and urease. RESULTS: The BUAE (butanol aerial fraction) showed the highest TPC (234.79 ± 0.12 mg.GAE.g-1 DE), TFC (320.75 ± 12.50 mg.QE.g-1 DE), and TTC (143.36 ± 4.32 mg.TA.Eq.g-1 DE). The BUAE also showed the highest scavenging potential determined by DPPH (642.65 ± 1.11 mg.TEq.g-1 DE) and ABTS (543.17 ± 1.11 mg.TEq.g-1 DE), and the metal-reducing capacity determined by CUPRAC (1510.41 ± 4.45 mg.TEq.g-1 DE) and FRAP (739.81 ± 19.32 mg.TEq.g-1 DE). The LCMS of BUAE identified 18 different biologically active phytoconstituents validating a rich source of hydrolyzable tannins including ellagitannins and gallitannins. CONCLUSION: The present study concluded that T. neotaliala is a rich source of polyphenols capable of neutralizing the damage caused by free radical accumulation in the cells and tissues. The significant antioxidant results and identification of high molecular weight hydrolyzable tannins enlightened the medicinal importance of T. neotaliala.

Improving boron use efficiency via different application techniques for optimum production of good quality potato (Solanum tuberosum L.) in alkaline soil.

Boron (B) deficiency is a widespread problem in alkaline soils which affects yield and quality of potato but is often ignored by the growers. That's why, we compared the impact of different methods of boron application (foliar spray, fertigation and soil dressing) along with control on boron use efficiency (BUE), quality and yield of potato in alkaline soils. Boron (0.5 kg ha-1) applied as a foliar spray had significantly increased plant height, tuber per plant, tuber volume and enhanced the quality in terms of vitamin C, starch and B content of potato compared to other methods. Moreover, foliar applied B significantly improved B uptake and it use efficiency over other application methods. B concentration in tubers were strongly correlated with vitamin C and starch contents. The application methods were ranked as foliar spray>fertigation>soil dressing in term of their effectiveness towards potato yield and quality improvement. Thus, for optimum production of good quality potato, B should be applied as foliar spray at the rate of 0.5 kg B ha-1 in existing agro-climatic conditions.

Virtual screening of phytoconstituents from miracle herb nigella sativa targeting nucleocapsid protein and papain-like protease of SARS-CoV-2 for COVID-19 treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-PRO; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL-PRO-cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Cα atoms throughout the simulation run time. Interestingly, PL-PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

Flavonol morin targets host ACE2, IMP-α, PARP-1 and viral proteins of SARS-CoV-2, SARS-CoV and MERS-CoV critical for infection and survival: a computational analysis.

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-α and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further. Communicated by Ramaswamy H. Sarma.

Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis.

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.

Understanding Holism in the light of principle underlying practice of Unani Medicine.

The holistic Unani medicine is fundamentally different from the reductionist conventional medicine. It asserts the self-integration amongst its basic disciplines, without considering them underlying principles of Unani system of medicine cannot be understood. The diagnosis, selection of drugs, and plan of treatment is also overlooked. Unani scholars attribute health to the functions or actions of the body in a normal way. The constitution is considered as the result of need based on the amalgamation of Arkan (primordial essence). Umoor Tabiya (basic principles) interact at many levels and manifest into Kaifiyyat (Mizaj), Akhlat (Humour), Arwaah (Pneuma), Quwa (faculties), and Tabiyat (Physis) which need to be understood properly for effective management and diagnosis of disease in Unani medicine as well as its treatment. Ilmul Asbab is applied in the prevention of disease as well as in disease causation. In Unani medicine, there should be conformity in between, Asbab (causes), Alamaat (symptoms), and therapeutics. Therefore; the treatment strategy needs the knowledge of Ilmul Asbab. This paper will examine the basic relationship amongst disciplines i.e. Basic principles, diagnosis, and principles of treatment. It will attempt to illustrate the need for awareness of the basic principles of health and disease for a physician for effective management of disease which is what Unani medicine claims to be holistic.

Exploring nature's bounty: identification of Withania somnifera as a promising source of therapeutic agents against COVID-19 by virtual screening and in silico evaluation.

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19.

Soybean herbage yield, nutritional value and profitability under integrated manures management.

Organic manures are more preferred and environmentally friendly than chemical fertilizers for minimally contaminating soil, water and environmental resources, but the determination of right source of organic manures continues to remain an unexplored aspect. Considering the important issue, a multi-year field trial was carried out to determine the response of forage soybean to four sources of nutrients such as chemical fertilizers (IF), poultry litter (PL), bovine's farm yard slurry (BFYS) and sewage sludge (SS) and their seven binary combinations (PL+BFYS, PL+SS, PL+IF, BFYS+SS, BFYS+IF, SS+IF and PL+BFYS+SS). Supplementation of organic manures with mineral fertilizers remained superior to their sole application, particularly BFYS + IF was found significantly (p≤0.05) superior for yielding the highest fresh biomass (23.9, 26.4 and 25.7 t ha-1) with improved nutritional quality. The same combination of integrated fertilizer management also recorded higher sustainability as per sustainable forage yield index along with the highest net income and the benefit-cost ratio. PL and SS applied in conjunction with IF performed better than sole or binary application of organic manures. Therefore, BFYS + IF may be recommended for adoption to produce comparable forage yield and nutritional quality of soybean along with reducing dependency on chemical fertilizers.

Design, Synthesis, Molecular Modelling, and Biological Evaluation of Oleanolic Acid-Arylidene Derivatives as Potential Anti-Inflammatory Agents.

INTRODUCTION: Oleanolic acid, a pentacyclic triterpenic acid, is widely distributed in medicinal plants and is the most commonly studied triterpene for various biological activities, including anti-allergic, anti-cancer, and anti-inflammatory. METHODS: The present study was carried out to synthesize arylidene derivatives of oleanolic acid at the C-2 position by Claisen Schmidt condensation to develop more effective anti-inflammatory agents. The derivatives were screened for anti-inflammatory activity by scrutinizing NO production inhibition in RAW 264.7 cells induced by LPS and their cytotoxicity. The potential candidates were further screened for inhibition of LPS-induced interleukin (IL-6) and tumour necrosis factor-alpha (TNF-α) production in RAW 264.7 cells. RESULTS: The results of in vitro studies revealed that derivatives 3d, 3e, 3L, and 3o are comparable to that of the oleanolic acid on the inhibition of TNF-α and IL-6 release. However, derivative 3L was identified as the most potent inhibitor of IL-6 (77.2%) and TNF-α (75.4%) when compared to parent compound, and compounds 3a (77.18%), 3d (71.5%), and 3e (68.8%) showed potent inhibition of NO than oleanolic acid (65.22%) at 10µM. Besides, from docking score and Cyscore analysis analogs (3e, 3L, 3n) showed greater affinity towards TNF-α and IL-1ß than dexamethasone. CONCLUSION: Herein, we report a series of 15 new arylidene derivatives of oleanolic acid by Claisen Schmidt condensation reaction. All the compounds synthesized were screened for their anti-inflammatory activity against NO, TNF-α and IL-6. From the data, it was evident that most of the compounds exhibited better anti-inflammatory activity.

Origanum vulgare L.: In vitro Assessment of Cytotoxicity, Molecular Docking Studies, Antioxidant and Anti-inflammatory Activity in LPS Stimulated RAW 264.7 Cells.

BACKGROUND: Inflammation involves a dynamic network that is highly regulated by signals that initiate the inflammation process as well as signals that downregulate it. However, an imbalance between the two leads to tissue damage. Throughout the world, inflammatory disease becomes common in the aging society. The drugs which are used clinically have serious side effects. Natural products or compounds derived from natural products show diversity in structure and play an important role in drug discovery and development. OBJECTIVE: Oreganum Vulgare is used in traditional medicine for various ailments including respiratory and rheumatic disorders, severe cold, suppression of tumors. The current study aims to evaluate the anti-inflammatory potential by evaluating various in vitro parameters. METHODS: Inflammation-induced in macrophages via LPS is the most accepted model for evaluating the antiinflammatory activity of various plant extracts and lead compounds. RESULTS: The extracts (OVEE, OVEAF) as well as the isolated compound(OVRA)of Oreganum Vulgare inhibit the pro-inflammatory cytokines (IL-6 and TNF-α) and NO without affecting cell viability. CONCLUSION: Our study established that the leaf extracts of Oreganum vulgare L. exhibit anti-inflammatory activity and thus confirm its importance in traditional medicine.