Validating Interactions of Pathogenic Proteins of Staphylococcus aureus and E. coli with Phytochemicals of Ziziphus jujube and Acacia nilotica.

This study focused on the assessment of the antimicrobial resistance of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) isolated from bovine mastitis milk samples and the revealing anti-mastitis potential of phytocompounds of Ziziphus jujube and Acacia nilotica through molecular docking analysis. The mastitis milk samples were collected from various dairy farms for the isolation of the bacteria (S. aureus and E. coli) and their response to antibiotics. Ethanolic extracts of both plants were prepared. Their antibacterial activity was evaluated, and they were processed for phytochemical analysis after which, molecular docking analysis with pathogenic proteins of the bacteria was carried out. Parametric and non-parametric statistical analyses were performed to reach the conclusions of this study. The findings of the study revealed a higher drug resistance (≥40%) of E. coli against ampicillin, amikacin, and vancomycin, while S. aureus exhibited the highest resistance to ampicillin, erythromycin, and ciprofloxacin. The ethanolic extracts of the Ziziphus jujube and Acacia nilotica plants produced a ZOI between 18 and 23 mm against multidrug-resistant S. aureus and E. coli. Gas chromatography-mass spectrophotometry (GC-MS) was used to explore 15 phytocompounds from Ziziphus jujube and 18 phytocompounds from Acacia nilotica. The molecular docking analysis of 2cyclopenten-1-one,3,4,4 trimethyl and Bis (2ethylhexyl) phthalate of Ziziphus jujube showed a binding affinity of -4.8 kcal/mol and -5.3 kcal/mol and -5.9 kcal/mol and -7.1 kcal/mol against the DNA Gyrase and toxic shock syndrome toxin-1 proteins of S. aureus and E. coli, respectively. The suberic acid monomethyl ester of Acacia nilotica showed a binding affinity of -5.9 kcal/mol and -5 kcal/mol against the outer membrane protein A and Topoisomerase IV protein of E. coli and -5.1 kcal/mol and -5.8 kcal/mol against the toxic shock syndrome toxin-1 and Enterotoxin B proteins of S. aureus. Similarly, 2,2,4-trimethyl-1,3-pentanediol di-iso-butyrate showed a binding affinity of -6.5 kcal/mol and -5.3 kcal/mol against the outer membrane protein A and Topoisomerase IV of E. coli and -5.2 kcal/mol and -5.9 kcal/mol against the toxic shock syndrome toxin-1 and Enterotoxin B proteins of S. aureus, respectively. The study concluded that there was an increasing trend for the antimicrobial resistance of S. aureus and E. coli, while the Ziziphus jujube and Acacia nilotica plant extracts expressed significant affinity to tackle this resistance; hence, this calls for the development of novel evidence-based therapeutics.

Phytochemical profiling and cytotoxic potential of Arnebia nobilis root extracts against hepatocellular carcinoma using in-vitro and in-silico approaches.

Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H2O2 radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC50 value: 22.77 µg/mL) than ANH extract (IC50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of - 7.2, - 9.2, - 7.2 and - 9.2 kcal/mol against TNF-α, TGF-ßR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations.

In Vitro Evaluation of Cytotoxic Potential of Caladium lindenii Extracts on Human Hepatocarcinoma HepG2 and Normal HEK293T Cell Lines.

Data regarding the therapeutic potential of Caladium lindenii (C. lindenii) are insufficient. It becomes more important to explore plants as an alternative or palliative therapeutics in deadly diseases around the globe. The current study was planned to explore C. lindenii for its anticancer activity of ethanolic and hexane extracts of C. lindenii leaves against hepatic carcinoma (HepG2) and human embryonic kidney (HEK293T) cell lines. HepG2 and HEK293T cells were treated with 10, 50, 100, 200, and 400 µg/mL of ethanolic and hexane extracts of C. lindenii and were incubated for 72 h. Antiproliferative activity was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, and percentage viability were calculated through crystal violet staining and cellular morphology by Floid Cell Imaging Station. The study showed ethanolic extract exhibiting a significantly higher antiproliferative effect on HepG2 (IC50 = 31µg/mL) in a concentration-dependent manner, while HEK293T (IC50 = 241µg/mL) cells showed no toxicity. Hexane extract exhibited lower cytotoxicity (IC50 = 150µg/mL) on HepG2 cells with no effect on HEK293T (IC50 = 550µg/mL). On the other hand, the percentage viability of HepG2 cells was recorded as 78%, 67%, 50%, 37%, and 28% by ethanolic extracts, and 88%, 80%, 69%, 59%, and 50% by hexane extracts at tested concentrations of both extracts. Toxicity assay showed significantly safer ranges of percentage viabilities in normal cells (HEK293T), i.e., 95%, 90%, 88%, 76%, and 61% with ethanolic extract and 97%, 95%, 88%, 75%, and 62% with hexane extract. The assay validity revealed 100% viability in the control negative (dimethyl sulfoxide treated) and less than 45% in the control positive (cisplatin) on both HepG2 and HEK293T cells. Morphological studies showed alterations in HepG2 cells upon exposure to >50 µg/mL of ethanolic extracts and ≥400 µg/mL of hexane extracts. HEK293T on the other hand did not change its morphology against any of the extracts compared to the aggressive changes on the HepG2 cell line by both extracts and positive control (cisplatin). In conclusion, extracts of C. lindenii are proved to have significant potential for cytotoxicity-induced apoptosis in human cancer HepG2 cells and are less toxic to normal HEK293T cells. Hence C. lindenii extracts are proposed to be used against hepatocellular carcinoma (HCC) after further validations.

Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review.

Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo studies met the inclusion criteria of this review. The inferences from scientific literature review, focusing on potential therapeutic consequences of medicinal plants on experimental models of HIV, HSV, influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral potential of plants. Fifty-four medicinal plants belonging to 36 different families having antiviral potential were documented. Out of 54 plants, 27 individually belong to particular plant families. On the basis of the work of several independent research groups, the therapeutic potential of medicinal plants against listed common viral diseases in the region has been proclaimed. In this context, the herbal formulations as alternative medicine may contribute to the eradication of complicated viral infection significantly. The current review consolidates the data of the various medicinal plants, those are Sambucus nigra, Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific antiviral activities scientifically proven through studies on experimental animal models. Consequently, the original research addressing the development of novel nutraceuticals based on listed medicinal plants is highly recommended for the management of viral disorders.