Computational profiling of natural compounds as promising inhibitors against the spike proteins of SARS-CoV-2 wild-type and the variants of concern, viral cell-entry process, and cytokine storm in COVID-19.

The continuous spread and evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the rapid surge in infection cases in the coronavirus disease 2019 (COVID-19) evoke a dire need for effective therapeutics. In this study, we explored the inhibitory potential of a library of 605 phytocompounds, selected from Indian medicinal plants with reported antiviral and anti-inflammatory activities, against the receptor-binding domain of spike proteins of the SARS-CoV-2 wild-type and the variants of concern, including variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Our approach was based on extensive molecular docking, assessment of drug-likeness, and robust molecular dynamics simulations. We also identified promising inhibitory candidates against the host (human) proteins associated with SARS-CoV-2 spike activation and attachment, namely, ACE2 receptor, proteases TMPRSS2 and CTSL, and the endocytic regulator AAK1. In addition, we screened promising inhibitory compounds against the human proinflammatory cytokines- IL-6, IL-1ß, TNF-α, and IFN-γ, that are associated with the adverse cytokine storm in COVID-19 patients. Our analysis returned an encouraging list of promising inhibitory candidates that includes: abietatriene against the spike proteins of the SARS-CoV-2 wild-type and the variants of concern; taraxerol against the human ACE2, CTSL and TNF-α; ß-amyrin against the human TMPRSS2; cynaroside against the human AAK1 and IL-1ß; and friedelin against the human IL-6 and IFN-γ. Our findings provide substantial evidence for the inhibitory potential of these compounds and encourage further in vitro and in vivo studies to validate their use as safe and effective therapeutics against COVID-19.

Chemical Composition and Cytotoxic Activity of the Essential Oil and Oleoresins of In Vitro Micropropagated Ansellia africana Lindl: A Vulnerable Medicinal Orchid of Africa.

Orchids are rich treasure troves of various important phytomolecules. Among the various medicinal orchids, Ansellia africana stands out prominently in the preparing of various herbal medicines due to its high therapeutic importance. The nodal explants of A. africana were sampled from asymbiotically germinated seedlings on basal Murashige and Skoog (MS) medium and were micropropagated in MS medium supplemented with 3% sucrose and 10 µM meta topolin (mT) + 5 µM naphthalene acetic acid (NAA) +15 µM indole butyric acid (IBA) + 30 µM phloroglucinol (PG). In the present study, the essential oil was extracted by hydrodistillation and the oleoresins by the solvent extraction method from the micropropagated A. africana. The essential oil and the oleoresins were analysed by Gas Chromatography (GC) and GC/MS (Mass spectrometry). A total of 84 compounds were identified. The most predominant components among them were linoleic acid (18.42%), l-ascorbyl 2,6-dipalmitate (11.50%), linolenic acid (10.98%) and p-cresol (9.99%) in the essential oil; and eicosane (26.34%), n-butyl acetate (21.13%), heptadecane (16.48%) and 2-pentanone, 4-hydroxy-4-methyl (11.13%) were detected in the acetone extract; heptadecane (9.40%), heneicosane (9.45%), eicosane (6.40%), n-butyl acetate (14.34%) and styrene (22.20%) were identified and quantified in the ethyl acetate extract. The cytotoxic activity of essential oil and oleoresins of micropropagated A. africana was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide) assay on Vero cells compared to the standard drug doxorubicin chloride. The present research contains primary information about the therapeutic utility of the essential oil and oleoresins of A. africana with a promising future research potential of qualitative and quantitative improvement through synchronised use of biotechnological techniques.

Anethum sowa Roxb. ex fleming: A review on traditional uses, phytochemistry, pharmacological and toxicological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Anethum sowa Roxb. ex Fleming (Syn. Peucedanum sowa Roxb. ex Fleming, Family: Apiaceae) is a pharmacologically important as aromatic and medicinal plant. Various parts of this plant are used in traditional medicine systems for carminative, uterine and colic pain, digestion disorder, flatulence in babies, appetite-stimulating agent and used to treat mild flue and cough. The essential oil is used for aromatherapy. It is also used as a spice for food flavouring and culinary preparations in many Asian and European countries. AIM OF THE REVIEW: This review aims to provide a comprehensive and critical assessment from the reported traditional and pharmaceutical uses and pharmacological activities of the extracts, essential oil and phytoconstituents with emphasis on its therapeutic potential as well as toxicological evaluation of A. sowa. MATERIALS AND METHODS: Online search engines such as SciFinder®, GoogleScholar®, ResearchGate®, Web of Science®, Scopus®, PubMed and additional data from books, proceedings and local prints were searched using relevant keywords and terminologies related to A. sowa for critical analyses. RESULTS: The literature studies demonstrated that A. sowa possesses several ethnopharmacological activities, including pharmaceutical prescriptions, traditional applications, and spice in food preparations. The phytochemical investigation conducted on crude extracts has been characterized and identified various classes of compounds, including coumarins, anthraquinone, terpenoids, alkaloid, benzodioxoles, phenolics, polyphenols, phenolic and polyphenols, fatty acids, phthalides and carotenoids. The extracts and compounds from the different parts of A. sowa showed diverse in vitro and in vivo biological activities including antioxidant, antiviral, antibacterial, analgesic and anti-inflammatory, Alzheimer associating neuromodulatory, cytotoxic, anticancer, antidiabetes, insecticidal and larvicidal. CONCLUSION: A. sowa is a valuable medicinal plant which is especially used in food flavouring and culinary preparations. This review summarized the pertinent information on A. sowa and its traditional and culinary uses, as well as potential pharmacological properties of essential oils, extracts and isolated compounds. The traditional uses of A. sowa are supported by in vitro/vivo pharmacological studies; however, further investigation on A. sowa should be focused on isolation and identification of more active compounds and establish the links between the traditional uses and reported pharmacological activities with active compounds, as well as structure-activity relationship and in vivo mechanistic studies before integrated into the medicine. The toxicological report confirmed its safety. Nonetheless, pharmacokinetic evaluation tests to validate its bioavailability should be encouraged.

Isolation and in silico prediction of potential drug-like compounds from Anethum sowa L. root extracts targeted towards cancer therapy.

Anethum sowa L. has been used as a spice herb in the Asian and European culinary systems to add flavour and taste. The studied plant has diverse folkloric medicinal value. Present study was designed to isolate phytochemicals from the hexane, chloroform and ethyl acetate extracts of the roots by various chromatographic techniques. Based on spectral analysis (IR, LC-MS, NMR) the isolated compounds were identified as physcione (1), ß-sitosterol (2), stigmasterol (3), 2-oxo-3-propyl-2H-chromene-7-carboxylic acid (4), bergapten (5), 3-ethyl-7-hydroxy-2H-chromen-2-one (6) and graveolone (7). The mentioned compounds have been isolated for the first time from the roots part of the plant. Based on extensive literature review, physcione and bergapten were inferred to exhibit crucial bioactivities including inhibitory efficacy against various forms of cancer. Accordingly, in the present research approach molecular docking investigations of the isolated phytochemicals have been robustly executed with different oncogenes that have been reported to be actively involved in various forms of carcinoma. In silico investigations encompassing molecular docking analysis and drug-likeness profiling was executed to estimate the potential therapeutic tendencies of the phytochemicals targeted towards effective cancer therapy. Current investigation offers meaningful know-how pertaining to potential anticancer activities of the phytochemicals extracted from the roots of Anethum sowa L. and might open up new revenues towards effective drug development against cancer.

Ethnobotany, phytochemistry and pharmacology of Arctotis arctotoides (L.f.) O. Hoffm.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the genus Arctotis. Arctotis is an African genus of approximately 70 species that occur widely in the African continent with diverse medicinal values. This plant is used for the treatment of indigestion and catarrh of the stomach, epilepsy, topical wounds and skin disorders among the ethnic groups in South Africa and reported to have a wide spectrum of pharmacological properties. AIM OF THE REVIEW: The aim of the present review is to appraise the botany, traditional uses, phytochemistry, pharmacological potential, analytical methods and safety issues of A. arctotoides. Additionally, this review will help to fill the existing gaps in knowledge and highlight further research prospects in the field of phytochemistry and pharmacology. MATERIALS AND METHODS: Information on A. arctotoides was collected from various resources, including books on African medicinal herbs and Zulu medicinal plants, theses, reports and the internet databases such as SciFinder, Google Scholar, Pubmed, Scopus, Web of Science, and Mendeley by using a combination of various meaningful keywords. This review surveys the available literature of the species from 1962 to April 2017. RESULTS: In vitro and in vivo studies of the medicinal properties of A. arctotoides were reviewed. The main isolated and identified compounds were reported as sesquiterpenes, farnesol derivatives, germacranolide, guaianolides and some steroids, of which, nine were reported as antimicrobial. Monoterpenoids and sesquiterpenoids were the predominant essential oil compound classes of the leaves, flowers, stems and roots. The present review revealed potential pharmacological properties such as anti-oxidant, antibacterial, antifungal and anticancer activities of plant extracts as well as isolated compounds. Moreover, the review reports the safety profile (toxicity) of the crude extracts that had been screened on brine shrimps, rats and human cell lines. CONCLUSIONS: The present review has focused on the phytochemistry, botany, ethnopharmacology, biological activities and toxicological information of A. arctotoides. On the basis of reported data, A. arctotoides has emerged as a good source of natural medicine for the treatment of microbial infections, skin diseases, anti-inflammatory and anticancer agents and also provides new insights for further isolation of new bioactive compounds, especially the discovery of antimicrobial, anti-inflammatory and anticancer novel therapeutic lead drug molecules. Additionally, intensive investigations regarding pharmacological properties, safety assessment and efficacy with their mechanism of action could be future research interests before starting clinical trials for medicinal practices.

Chemical composition and pharmacological significance of Anethum Sowa L. Root.

BACKGROUND: Medicinal herbs are used for the treatment of different ailments since antiquity. Different parts of Anethum sowa L. is used in folk medicine as a carminative for the treatment of flatulence, colic and hiccups of infants and children, antioxidant, antimicrobial and antispasmodic agent. The aim of our present study is to evaluate the chemical composition of the essential oil, proximate and elemental composition, amino acid, fatty acid profile and thermal behaviour of its root part as well as different pharmacological activities like antioxidant, antimicrobial and cytotoxicity of the root essential oil. METHODS: The air-dried roots of Anethum sowa L. were subjected to hydro-distillation to yield the essential oil. The antioxidant activity of the essential oil was studied by DPPH radical scavenging activity. The antimicrobial activity was tested against four Gram-positive, six Gram-negative bacteria and four fungi species. The minimum inhibitory concentration (MIC) and Minimum bacterial concentration (MBC) for each examined microorganism were determined using the micro-dilution method. The LC50 value of the oil was also evaluated by brine shrimp lethality assay. The subsequent proximate analysis was also done by AOAC methods. The elemental analysis of the root powder was analysed by ICP-MS, AAS and FP system. The fatty acid was extracted by hot and cold extraction method and the analyses were carried out by GC. The amino acid profile was done by the amino acid analyzer. The DTA, DTG and TG of the root powder were taken by the thermogravimetric analyzer. RESULTS: A total of 24 constituents was identified and quantified in the essential oil and its water extract portion by GC and GC-MS. Apiol (81.99 and 74.779%) was found the highest phenylpropanoid constituent followed by m-diaminobenzene (10.446 and 8.778%) in the essential oil and aqueous extract portion. On the other hand, ß-butyrolactone (5.13%) and isobutyl acetone (3.73%) were found in the major constituents in the water extract part. The IC50 value of the essential oil was found to be 3.07 mg/mL by DPPH radical assay methods. The LC50 value of the brine shrimp cytotoxicity assay of the essential oil was observed at 0.81 µg/mL. The essential oil showed better activity on Gram-negative bacteria than Gram-positive bacteria and fungi. The proximate composition showed that root contained 5.29% ash, 2.01% protein, 54.09% crude fibre, 0.15% essential oil and 1.14% fatty oil for hot extract and 0.23% for cold extract on the dried basis. The palmitic (33.81 & 31.58%) and linoleic acid (30.03 & 23.79%) were the major saturated and unsaturated fatty acids in the cold and hot extracted root powder respectively. Ca (23,600 mg/kg), Mg (7620.33 mg/kg) and K (1286.15 mg/kg) were the most predominant elements followed by Ni (1187.30 mg/kg), Se (913.79 mg/kg), Li (317.84 mg/kg), Na (288.72 mg/kg) and Fe (206.88 mg/kg). The toxic elements were found to be within the permissible limit. Glutamic acid (19.37%), glycine (14.53%) and lysine (17.08%) were found as the major amino acids. The decomposition rates were obtained by TG, DTG and DTA curve of the powder sample at various temperature ranges. CONCLUSIONS: The results demonstrated that the root part of Anethum sowa L. is a rich source of mineral elements, essential amino acid and fatty acids. The essential oil is the highly potential as bioactive oil for pharmaceuticals and medical applications, possessing antioxidant, antimicrobial and cytotoxic activities. The thermal analysis suggested as a simple, effective and rapid method to characterize the Anethum sowa L. species as well as to assess for herbal formulation.

Pharmacological effects of the phytochemicals of Anethum sowa L. root extracts.

BACKGROUND: Anethum sowa L. is widely used as an important spice and traditional medicinal plants to treat various ailments. On the basis of scientific ethnobotanical information, this study was undertaken to evaluate the antioxidant, antimicrobial and cytotoxic activity of the crude extracts of Anethum sowa L. roots as well as to identify the classes of phytochemicals by chemical tests. METHODS: The antioxidant potential of the extracts was ascertained with the stable organic free radical (2, 2-diphenyl-1-picryl-hydrazyl). The agar well diffusion method was used to determine the susceptibility of bacterial and fungal strains of the crude extracts. The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) were determined by the microdilution test. Cytotoxic activities were screened using brine shrimps (Artemia salina) lethality assay. Finally, phytochemicals were profiled using standard procedures. RESULTS: A preliminary phytochemical screening of the different crude extracts by methanol, ethyl acetate and chloroform showed the presence of secondary metabolites such as flavonoids, alkaloids, saponin, cardiac glycosides and tannins while cyanogenetic glycosides were not detected. The methanol, ethyl acetate and chloroform extracts displayed high antioxidant activity (IC50 = 13.08 ± 0.03, 33.48 ± 0.16 and 36.42 ± 0.41 µg/mL, respectively) in the DPPH assay comparable to that of the standard ascorbic acid and BHT (IC50 = 3.74 ± 0.05 and 11.84 ± 0.29 µg/mL). The cytotoxic activity of the crude ethyl acetate and chloroform extracts possessed excellent activity (LC50 = 5.03 ± 0.08, 5.23 ± 0.11 and 17.22 ± 0.14 µg/mL, respectively) against brine shrimp larvae after 24 h of treatment and compared with standard vincristine sulphate (LC50 = 0.46 ± 0.05 µg/mL). The extracts also showed good antimicrobial activity against both Gram-positive and Gram-negative bacteria when compared with two standard antibiotics ciprofloxacin and tetracycline. CONCLUSION: These results showed that the Anethum sowa root extracts are the important source of the antioxidant, antimicrobial and cytotoxic agent. So, further research is necessary to isolate and characterize of different phytoconstituents for pharmaceutical drug lead molecules and also to verify its traditional uses.