Antiviral zinc oxide nanoparticles mediated by hesperidin and in silico comparison study between antiviral phenolics as anti-SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. These phytopharmaceuticals and nutraceuticals can be more economic, available, safe and lower side effects. This is in silico comparison study of ten phenolic antiviral agents against SARS-CoV-2, as well as isolation of the most active metabolite from natural sources. Zinc oxide nanoparticles (ZnO NPs) were also then prepared using these metabolite as a reducing agent. All tested compounds showed predicted anti-SARS-CoV-2 activity. Hesperidin showed the highest docking score, this leads us to isolate it from the orange peels and we confirmed its structure by conventenional spectroscopic analysis. In addition, synthesis of hesperidin zinc oxide nanoparticles was characterized by UV, IR, XRD and TEM. In vitro antiviral activity of hesperidin and ZnO NPs was evaluated against hepatitis A virus as an example of RNA viruses. However, ZnO NPs and hesperidin showed antiviral activity against HAV but ZnO NPs showed higher activity than hesperidin. Thus, hesperidin and its mediated ZnO nanoparticles are willing antiviral agents and further studies against SARS-CoV-2 are required to be used as a potential treatment.

Anti-infective and cytotoxic properties of Bupleurum marginatum.

BACKGROUND: Bupleurum marginatum Wall. ex DC (Apiaceae) is a perennial herb widely used in traditional Chinese and Kampo medicine for the treatment of various infectious diseases. The biological activities of B. marginatum have not been fully investigated. This study aims to investigate the antitrypanosomal, antimicrobial and antiviral activities of methanol (ME) and dichloromethane (DCM) extracts of B. marginatum aerial parts and the ability of both extracts to inhibit the growth of different cancer cell lines. METHODS: Phytochemical characterization of the extracts was performed by LC-MS profiling. The antitrypanosomal activity was evaluated using the resazurin method. The antimicrobial activity was assessed using agar diffusion and microdilution methods, and the minimum inhibitory concentration (MIC) values were determined. The antiviral activity was determined for 6.25, 12.5, and 50 µg/mL doses using a plaque reduction assay. Cytotoxicity was investigated in eight cancer cell lines (Caco-2, CCL-81, CCRF-CEM, COS-7, HL-60, MIA PaCa-2, MCF-7, and PANC-1) using the MTT assay and the caspase 3/7 activity was determined over the range of 62.5-1000 µg/mL. RESULTS: Phytochemical analyses resulted in the characterization of 15 components, mainly flavonoids and lignans. The DCM extract showed significant antitrypanosomal activity (IC50: 36.21 µg/mL) and moderate activity against Streptococcus pyogenes (MIC value: 0.25 mg/mL). At a dose of 12.5 µg/mL, the DCM extract inhibited 73.6% of the plaque production by hepatitis A virus. CCRF-CEM cells were the most sensitive to both extracts (IC50: 12.5-22.7 µg/mL). The cytotoxicity was mediated by induction of apoptosis (19-fold increase in the cellular caspase 3/7 level after treatment with the DCM extract at 1 mg/mL). CONCLUSIONS: ME and DCM extract of B. marginatum showed anti-infective and antiproliferative effects.

Cytotoxicity of some Cameroonian spices and selected medicinal plant extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants and spices are used traditionally to treat cancers in Cameroon. AIM: Methanol extracts from thirty-four spices and plants, with related ethnobotanical use were investigated for their in vitro cytotoxicity on the human pancreatic cancer cell line MiaPaCa-2, leukemia CCRF-CEM cells and their multidrug resistant (MDR) subline CEM/ADR5000, and the normal human umbilical vein endothelial cells (HUVECs). In addition the anti-angiogenic properties of the most active extracts were investigated. MATERIAL AND METHODS: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay was used for cytotoxic studies and the CAM-assay (chicken-chorioallantoic-membrane-assay) for anti-angiogenesis test. RESULTS: The results of the cytotoxicity tests indicated that, when tested at 20 µg/ml, extracts from Xylopia aethiopica, Echinops giganteus, Imperata cylindrica, Dorstenia psilirus and Piper capense were able to inhibit more that 50% the proliferation of the three tested cancer cells (MiaPaCa-2, CEM/ADR5000 CCRF-CEM). The lowest IC(50) values of 6.86 µg/ml on MiaPaCa-2 and 3.91 µg/ml on CCRF-CEM cells were obtained with X. aethiopica, while the corresponding value of 6.56 µg/ml was obtained with P. capense on CEM/ADR5000 cells. Against leukemia cells, no cross-resistance was observed with I. cylindrica, P. capense and Zinziber officinalis. Extracts from D. psilirus and E. giganteus were able to inhibit angiogenesis by more than 50% in quail embryo. CONCLUSION: The overall results of the present study provide supportive data on the use of some Cameroonian plants for cancer treatment.

Toxicogenomics for the prediction of toxicity related to herbs from traditional Chinese medicine.

Toxicogenomics represents the integration of genomics and toxicology to investigate the interaction between genes and environmental stress in human health. It is a scientific field that studies how the genome is involved in responses to environmental stressors and toxicants. The patterns of altered gene expression that are caused by specific exposures or disease outcomes reveal how toxicants may act and cause disease. Nowadays, toxicogenomics faces great challenges in discriminating the molecular basis of toxicity. We do believe that advances in this field will eventually allow us to describe all the toxicological interactions that occur within a living system. Toxicogenomic responses of a toxic agent in one species (e.g., laboratory animals) may predict the mode of action in another species (e.g., humans) (predictive toxicology). Development and application of toxicogenomic databases and new bioinformatics tools are among the most important aspects of toxicogenomic research which will facilitate sharing and interpretation of the huge amount of biological information generated in this field. Medicinal herbs have played an important role in pharmacy from ancient to modern times. Nowadays, there is a revival of interest in medicinal plants and an increasing scientific interest in bioactive natural products. Medicinal herbs are usually considered to be nontoxic. However, the consumption of herbs could produce prominent toxic effects either due to inherent toxicity or to contaminants (heavy metals, microorganisms, pesticides, toxic organic solvents, radioactivity, etc.). Therefore, a critical assessment of their toxicity is an urgent issue. This review explores the field of toxicogenomics, pinpoints some of its research approaches and describes the challenges it faces. In particular, Chinese herbal preparations have been implicated.

Biological activity of the essential oil of Kadsura longipedunculata (Schisandraceae) and its major components.

OBJECTIVES: The aim was to determine the chemical composition of the essential oil of Kadsura longipedunculata and the biological activity of the oil and its major components. METHODS: The essential oil from stem bark of Kadsura longipedunculata was analysed by capillary gas chromatography (GLC/FID) and gas chromatography-mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(*)) was used to evaluate the antioxidant activity. Inhibition of both lipoxygenase and prostaglandin E(2) was used to assess the anti-inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi using diffusion and microdilution methods. Inhibition of trypanosome proliferation was assessed using resazurin as vital stain. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, MIA PaCa-2, HeLa, HL-60, MDA-MB-231 and SW-480) was examined using the MTT assay. KEY FINDINGS: Fifty compounds, representing 97.63% of total oil, were identified. delta-Cadinene (21.79%), camphene (7.27%), borneol (6.05%), cubenol (5.12%) and delta-cadinol (5.11%) were found to be the major components of the oil. The oil exerted a good antimicrobial activity against all Gram-positive bacteria tested, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Streptococcus pyogenes and S. agalactiae were the most sensitive bacteria with a minimal inhibitory concentration (MIC) of 60 microg/ml oil. The essential oil showed a moderate fungicidal activity against yeasts, but it did not show any activity against Gram-negative bacteria. The essential oil showed a good trypanocidal activity in Trypanosoma b. brucei with an IC50 value of 50.52 +/- 0.029 microg/ml. Radical scavenging activity had an IC50 value of 3.06 +/- 0.79 mg/ml. 5-Lipoxygenase inhibition (IC50 = 38.58 microg/ml) and prostaglandin E(2) production inhibition (28.82% at 25 microg/ml) accounted for anti-inflammatory activity of the oil. The oil exhibited some degree of cytotoxic activity against MIA PaCa-2, HepG-2 and SW-480 cell lines with IC50 values of 133.53, 136.96 and 136.62 microg/ml, respectively. The oil increased caspase 3/7 activity (an indicator of apoptosis) 2.5-4 fold in MIA Paca-2 cells. Camphene and borneol did not show antioxidant activity. However, both compounds exhibited some degree of antimicrobial, trypanocidal, anti-inflammatory and cytotoxic activity. CONCLUSIONS: This investigation provided evidence for, and confirmed the efficacy of, K. longipedunculata, a traditionally used Chinese medicinal plant for the treatment of inflammation and infection.

Berberine inhibits cell growth and mediates caspase-independent cell death in human pancreatic cancer cells.

Pancreatic cancer is one of the most aggressive human malignancies with an increasing incidence worldwide. In addition to the poor survival rates, combinations using gemcitabine as a backbone have failed to show any benefit beyond monotherapy. These facts underscore an urgent need for novel therapeutic options and motivated us to study the effect of berberine on pancreatic cancer cells. Here, we undertook an mRNA-based gene expression profiling study in order to get deeper insight into the molecular targets mediating the growth inhibitory effects of berberine on pancreatic cancer cells compared to normal ones. Twenty-four hours after treatment, berberine showed preferential selectivity toward pancreatic cancer cells compared to normal ones. Moreover, expression profiling and Ingenuity pathway analysis results showed that the cytotoxicity of berberine was accompanied with an activation of BRCA1-mediated DNA damage response, G1/S and G2/M cell cycle checkpoint regulation, and P53 signalling pathways. The activation of these signalling pathways might be explained by the fact that berberine intercalates DNA and induces DNA strand break through inhibition of topoisomerases and induction of DNA lesions.

Traditional Chinese medicines (TCMs) for molecular targeted therapies of tumours.

Scientific progress in genetics, cell and molecular biology has greatly ameliorated our comprehensive understanding of the molecular mechanisms of neoplastic transformation and progression. The rapidly advancing identification of molecular targets in human cancers during the last decade has provided an excellent starting point for the development of novel therapeutics. A huge variety of potential molecular targets have been identified, many of which are already in the market for therapeutic purposes. It is now becoming possible to target pathways and/or molecules that are crucial in maintaining the malignant phenotype. Traditional Chinese medicine (TCM) is often considered as alternative or complementary medicine. TCM represents a holistic approach and lacks high-quality scientific evidence on its effectiveness. Therefore, it is frequently regarded with some scepticism by western academic medicine. In this review, we report that application of modern technologies allowed identification of novel molecular targets modulating the anti-tumour activity of natural products derived from TCM. Moreover, we tried to cross the bridge between TCM and Western modern medicine to be able to implement them for the sake of cancer patients.

Chemical composition and biological activity of the essential oil obtained from Bupleurum marginatum (Apiaceae).

OBJECTIVES: Bupleurum marginatum is a herb indigenous to the southern and southwestern part of China. It is widely used in many Chinese prescriptions. We aimed to investigate the chemical composition, antioxidant, anti-inflammatory, antimicrobial and in-vitro cytotoxic activity of the hydrodistilled and extracted essential oil from B. marginatum to validate some of its ethnopharmacologial uses. METHODS: The essential oil of the aerial parts of B. marginatum was analysed by capillary gas chromatography (GLC/FID) and gas chromatography-mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(.)) and to prevent the degradation of deoxyribose were used to evaluate the antioxidant activity. Inhibition of both prostaglandin E(2) production and lipoxygenase were used to assess the anti-inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, Caco-2, CCRF-CEM, HeLa, MiaPaCa-2 and MCF-7) was examined using the MTT assay. KEY FINDINGS: Seventy-two components, comprising almost 94.29% of the total peak area, were identified in the analysis. The main components were tridecane (13.18%), undecane (10.42%), pentadecane (8.71%), beta-caryophyllene (5.53%) and beta-caryophyllene oxide (5.29%). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(.)) and to prevent the degradation of deoxyribose were used to evaluate the antioxidant activity and the corresponding IC50 values (drug concentration which resulted in a 50% reduction in inhibition of the activity) were found to be 3.66 mg/ml and 17.4 microg/ml, respectively. Inhibition of both prostaglandin E(2) production and lipoxygenase were used to assess the anti-inflammatory activity (IC50 of 63.64 microg/ml for lipoxygenase, 26.04% inhibition of prostaglandin E(2) at 25 microg/ml dose). The oil also showed a significant in-vitro antimicrobial activity against Gram positive pathogens (Streptococcus pyogenes and Streptococcus agalactiae) with minimum inhibitory concentration (MIC) values ranging from 0.125 up to 4.00 mg/ml. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, Caco-2, CCRF-CEM, HeLa, MiaPaCa-2 and MCF-7) examined using the MTT assay revealed the highest activity to be in the CCRF-CEM cell line with an IC50 (concentration which resulted in a 50% reduction in cell viability) of 46.01 microg/ml after 24 h treatment. CONCLUSIONS: The essential oil of B. marginatum exhibited a promising anti-inflammatory activity along with strong cytotoxicity against many cancer cells (CCRF-CEM and HepG2) mediated through induction of apoptosis, and this in-vitro activity make its local traditional uses rational. However, its limited antimicrobial activity indicates that a combination with other drugs is essential for effective use. Further selectivity testing is required to evaluate the effect of the oil against normal cells.