The discovery of herbal drugs and natural compounds as inhibitors of SARS-CoV-2 infection in vitro

Atopic Dermatitis (AD) is a prolonged reverting skin ailment with characteristically distributed skin lesions. In the previous decades, researchers had shown a marked interest in AD due to its increased prevalence in developed countries. Although different strategies including biological and immune modulators are available for the treatment of AD, each has certain limitations. The researchers had shown considerable interest in the management of AD with herbal medicines. The establishment of herbal drugs for AD might eliminate local as well as systemic adverse effects associated with long term use of corticosteroids and also higher cost of therapy with biological drugs. The present review discusses the traditional East Asian herbal medicines and scientific data related to newer herbal extracts or compositions for the treatment of AD. In vivo animal models and in vitro cell cultures, investigated with herbal medicines to establish a possible role in AD treatment, have also been discussed in the paper. The paper also highlights the role of certain new approaches, i.e. pharmacopuncture, a combination of allopathic and herbal medicines; and novel carriers (liposomes, cubosomes) for herbal drugs on atopic skin. In conclusion, herbal medicines can be a better and safe, complementary and alternative treatment option for AD.

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Natural Compounds Isolated from Stachybotrys chartarum Are Potent Inhibitors of Human Protein Kinase CK2

Molecules ◽

10.3390/molecules26154453 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4453

Author(s):

Samer Haidar ◽

Franziska M. Jürgens ◽

Dagmar Aichele ◽

Annika Jagels ◽

Hans-Ulrich Humpf ◽

...

Keyword(s):

Cell Proliferation ◽

Natural Compounds ◽

Breast Adenocarcinoma ◽

Stachybotrys Chartarum ◽

Mcf7 Cells ◽

A431 Cells ◽

Ic50 Values ◽

Human Lung Carcinoma ◽

Kinase Ck2

A large number of secondary metabolites have been isolated from the filamentous fungus Stachybotrys chartarum and have been described before. Fourteen of these natural compounds were evaluated in vitro in the present study for their inhibitory activity towards the cancer target CK2. Among these compounds, stachybotrychromene C, stachybotrydial acetate and acetoxystachybotrydial acetate turned out to be potent inhibitors with IC50 values of 0.32 µM, 0.69 µM and 1.86 µM, respectively. The effects of these three compounds on cell proliferation, growth and viability of MCF7 cells, representing human breast adenocarcinoma as well as A427 (human lung carcinoma) and A431 (human epidermoid carcinoma) cells, were tested using EdU assay, IncuCyte® live-cell imaging and MTT assay. The most active compound in inhibiting MCF7 cell proliferation was acetoxystachybotrydial acetate with an EC50 value of 0.39 µM. In addition, acetoxystachybotrydial acetate turned out to inhibit the growth of all three cell lines completely at a concentration of 1 µM. In contrast, cell viability was impaired only moderately, to 37%, 14% and 23% in MCF7, A427 and A431 cells, respectively.

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The Effects of Bergamot Polyphenolic Fraction, Cynara cardunculus, and Olea europea L. Extract on Doxorubicin-Induced Cardiotoxicity

Nutrients ◽

10.3390/nu13072158 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2158

Author(s):

Jessica Maiuolo ◽

Irene Bava ◽

Cristina Carresi ◽

Micaela Gliozzi ◽

Vincenzo Musolino ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Apoptotic Cell ◽

Natural Compounds ◽

Cynara Cardunculus ◽

Unfolded Protein ◽

Wide Range ◽

Vitro Model ◽

The Unfolded Protein Response ◽

Protein Response

Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Treatment with anthracyclines causes heart failure in 15–17% of patients, resulting in mitochondrial dysfunction, the accumulation of reactive oxygen species, intracellular calcium dysregulation, the deterioration of the cardiomyocyte structure, and apoptotic cell death. Polyphenols have a wide range of beneficial properties, and particular importance is given to Bergamot Polyphenolic Fraction; Oleuropein, one of the main polyphenolic compounds of olive oil; and Cynara cardunculus extract. These natural compounds have particular beneficial characteristics, owing to their high polyphenol contents. Among these, their antioxidant and antoproliferative properties are the most important. The aim of this paper was to investigate the effects of these three plant derivatives using an in vitro model of cardiotoxicity induced by the treatment of rat embryonic cardiomyoblasts (H9c2) with doxorubicin. The biological mechanisms involved and the crosstalk existing between the mitochondria and the endoplasmic reticulum were examined. Bergamot Polyphenolic Fraction, Oleuropein, and Cynara cardunculus extract were able to decrease the damage induced by exposure to doxorubicin. In particular, these natural compounds were found to reduce cell mortality and oxidative damage, increase the lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin.

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Preparation of Tablet from Naagdon Plant by Wet Granulation Method for Treatment of Excessive Bleeding in Piles

International Journal for Research in Applied Science and Engineering Technology ◽

10.22214/ijraset.2021.39508 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1654-1665

Author(s):

Sushma Kamble

Keyword(s):

The Body ◽

Wet Granulation ◽

Herbal Drugs ◽

Excessive Bleeding ◽

In Vitro Drug Release ◽

Acceptable Range ◽

Weight Variation ◽

Natural Drugs ◽

Evaluation Parameters

Abstract: The objective of present study was to formulate and evaluate the tablets for piles with different combination of herbal drugs. Material and Method: The tablet for piles containing lactose and mannitol as diluent and containing natural drugs like naagdon which was prepared by wet granulation method. The wet and compressed formulations were subject to several evaluation parameters like appearance, thickness, weight variation, hardness and friability. Results: The results of all evaluation parameters of piles tablet were within the acceptable limit. Pre-compression studies of piles tablet show satisfactory results. The thickness, hardness, weight variation, and friability of pilestablet were found to in acceptable range. The in-vitro drug release of eugenol from optimised for treatment piles formulation was found to be 90.23%. Significant results were obtained from present study. Discussion: The finding of current investigation clearly found that the health promotion of the body could be done by piles

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Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i54a33716 ◽

2021 ◽

pp. 30-42

Author(s):

Abdulaziz Bin Dukhyil

Keyword(s):

Molecular Docking ◽

Physicochemical Properties ◽

Methanolic Extract ◽

Natural Compounds ◽

Physicochemical Analysis ◽

Dynamics Simulation ◽

Carbohydrate Hydrolysis ◽

Catalytic Active Site ◽

Inhibitory Potential

Aims: Diabetes mellitus (DM) is chronic disorder well known for increased glucose level in blood. This disease can be controlled by inhibiting the enzyme (e.g., α-amylase) involve in carbohydrate hydrolysis. Senna auriculata leaves methanolic extract (SALME) have potential antidiabetic properties and it was also found to be safe in preclinical studies. In this study the aim was to explore the molecular interactions of α-amylase and bioactive compounds in SALME and their physicochemical properties. Methodology: Computational approach such as molecular docking and physicochemical analysis prediction was applied to understand the antidiabetic potential of natural compounds present in SALME. Results: The results showed from physicochemical analysis that out of 11 only 7 compounds are having drug like properties which are orally and intestinally better bioavailable. Furthermore, molecular docking analysis explained that three compounds (C3, C4, and C7) have lower binding energy, ΔG (-8, -9.1, -9.5 kcal/mol) and better binding affinity, Ki (7.31 x 105, 4.68 x 106, and 9.2 x 106 M-1, respectively) than the acarbose ΔG (-7.8 kcal/mol) and Ki (6.18 x 105 M-1), a well-known FDA approved medication for DM. The study also explained the binding pattern that the catalytic residue such as Asp197, Glu233 and Asp300 are involved in stabilizing the natural compounds with in the catalytic active site of target enzyme. Conclusions: From the results it has been concluded that these three compounds found in SALME have better inhibitory potential for α-amylase in comparison with acarbose. Further validation of the findings is required through molecular dynamics simulation, ADME-T study, and in-vitro enzyme inhibition by the purified compounds.

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Exemplifying the next generation of antibiotic susceptibility intensifiers of phytochemicals by LasR-mediated quorum sensing inhibition

Scientific Reports ◽

10.1038/s41598-021-01845-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Arpit Shukla ◽

Gaurav Shukla ◽

Paritosh Parmar ◽

Baldev Patel ◽

Dweipayan Goswami ◽

...

Keyword(s):

Quorum Sensing ◽

Metabolic Pathways ◽

Single Unit ◽

Antimicrobial Properties ◽

Well Being ◽

Natural Compounds ◽

Human Pathogens ◽

Quorum Sensing Inhibition ◽

In Silico Studies

AbstractThere persists a constant threat from multidrug resistance being acquired by all human pathogens that challenges the well-being of humans. This phenomenon is predominantly led by Pseudomonas aeruginosa which is already resistant to the current generations of antibiotic by altering its metabolic pathways to survive. Specifically for this microbe the phenomenon of quorum sensing (QS) plays a crucial role in acquiring virulence and pathogenicity. QS is simply the cross talk between the bacterial community driven by signals that bind to receptors, enabling the entire bacterial microcosm to function as a single unit which has led to control P. aeruginosa cumbersome even in presence of antibiotics. Inhibition of QS can, therefore, be of a significant importance to curb such virulent and pathogenic strains of P. aeruginosa. Natural compounds are well known for their antimicrobial properties, of which, information on their mode of action is scarce. There can be many antimicrobial phytochemicals that act by hindering QS-pathways. The rationale of the current study is to identify such natural compounds that can inhibit QS in P. aeruginosa driven by LasR, PhzR, and RhlR dependent pathways. To achieve this rationale, in silico studies were first performed to identify such natural compounds which were then validated by in vitro experiments. Gingerol and Curcumin were identified as QS-antagonists (QSA) which could further suppress the production of biofilm, EPS, pyocyanin, and rhamnolipid along with improving the susceptibility to antibiotics.

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Antiepileptic and Antioxidant Activity of Some Medicinal Plants: A Review

International Journal of Pharmacognosy and Phytochemical Research ◽

10.25258/phyto.v9i10.10452 ◽

2017 ◽

Vol 9 (10) ◽

Author(s):

Jeenu Joseph ◽

Lincy Joseph ◽

Mathew George

Keyword(s):

Medicinal Plants ◽

Cell Activity ◽

Acorus Calamus ◽

Herbal Drugs ◽

Clinical Testing ◽

Bacopa Monniera ◽

Ficus Religiosa ◽

Antiepileptic Agents

Medicinal plants are the oldest form of healthcare known to mankind. Antioxidants are considered to be important in fighting against the damages done by the free radicals produced due to oxidative stress. Antiepileptic drugs help to minimize or to irradiate the convulsive shocks and seizures as a result of abnormal and excessive nerve cell activity. Standardized, well established in vitro and in vivo methods are available for experimental evaluation of antioxidant and antiepileptic agents. A step wise procedure from in vitro and in vivo seems reasonable to reduce the large quantity of potential drugs to a few promising agents for further clinical testing. This review has focused on some herbal drugs with both antioxidant and antiepileptic property such as Brassica nigra, Bacopa monniera, Ficus religiosa, Convolvulus pluricalis, Jatamansi and Acorus calamus.

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High Throughput in Silico Identification of Novel Phytochemical Inhibitors for the Master Regulator of Inflammation (TNFα)

10.26434/chemrxiv.14178212.v2 ◽

2021 ◽

Author(s):

Pratap Kumar Parida ◽

Dipak Paul ◽

Debamitra Chakravorty

Keyword(s):

Small Molecule ◽

High Throughput ◽

In Silico ◽

Small Molecule Inhibitors ◽

Binding Free Energy ◽

Natural Compounds ◽

Free Energy Calculations ◽

Compound Libraries ◽

Relative Binding

<a>The over expression of Tumor necrosis factor-α (TNFα) has been implicated in a variety of disease and is classified as a therapeutic target for inflammatory diseases (Crohn disease, psoriasis, psoriatic arthritis, rheumatoid arthritis).Commercially available therapeutics are biologics which are associated with several risks and limitations. Small molecule inhibitors and natural compounds (saponins) were identified by researchers as lead molecules against TNFα, however, </a>they were often associated with high IC50 values which can lead to their failure in clinical trials. This warrants research related to identification of better small molecule inhibitors by screening of large compound libraries. Recent developments have demonstrated power of natural compounds as safe therapeutics, hence, in this work, we have identified TNFα phytochemical inhibitors using high throughput in silico screening approaches of 6000 phytochemicals followed by 200 ns molecular dynamics simulations and relative binding free energy calculations. The work yielded potent hits that bind to TNFα at its dimer interface. The mechanism targeted was inhibition of oligomerization of TNFα upon phytochemical binding to restrict its interaction with TNF-R1 receptor. MD simulation analysis resulted in identification of two phytochemicals that showed stable protein-ligand conformations over time. The two compounds were triterpenoids: Momordicilin and Nimbolin A with relative binding energy- calculated by MM/PBSA to be -190.5 kJ/Mol and -188.03 kJ/Mol respectively. Therefore, through this work it is being suggested that these phytochemicals can be used for further in vitro analysis to confirm their inhibitory action against TNFα or can be used as scaffolds to arrive at better drug candidates.

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Virtual screening of natural compounds as combinatorial agents from indian medicinal plants against estrogen positive breast cancer

International Journal on Integrated Education ◽

10.31149/ijie.v3i10.750 ◽

2020 ◽

Vol 3 (10) ◽

pp. 266-275

Author(s):

Shaleen Jain ◽

Dr. Asmita Das

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Virtual Screening ◽

Medicinal Plants ◽

Natural Compounds ◽

Binding Energies ◽

Common Amino Acid ◽

Estrogen Receptor Positive ◽

Positive Breast Cancer

Facing worldwide challenges associated with multifactorial etiology of breast cancer, designing of combinatorial therapies using natural compounds is currently the emergent way of treating several cancers including breast cancer in a synergistic way, which may mitigate several problems associated with multiple receptor targeting. In this research, Estrogen receptor positive breast cancer was taken as prototype and several key receptors associated with this particular disease were targeted by virtual screening of natural compounds found in Indian originated medicinal plants using Computer aided Drug Designing (CADD) strategies. We found the combination of Carpusin, Paulownin Cornigerine, Nororientaline, Oryzalexin B, Romucosine H and Colchicine as effective against six potential receptors i.e. FGFR2, ESR1, PIK3CA, PIK3CB, PIK3CD and AR in Estrogen receptor positive breast cancer with their binding energies in the range of ∆G ≤ -8.0 Kcal/mol as well as significant number of common amino acid binding residues as compared with binding sites of receptors. Thus this research holds significant implications for the designing of combinatorial therapeutic agents against breast cancer which can be further tested in-vitro and in-vivo to prove their synergistic efficiency.

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