COMPARATIVE BOTANICAL AND GENETIC CHARACTERIZATION OF CERTAIN SOLANUM SPECIES GROWN IN EGYPT

Objective: Urgent need for proper identification and characterization has emerged for some Solanum species as their toxicity to humans and animals ranges from mildly irritating to fatal. The objective of this work was targeted towards discrimination between Solanum seaforthianum Andrews and Solanum macrocarpon L.Methods: For establishment of different botanical and genetic criteria, this study presents a comparative investigation of the botanical features of the roots, stems and leaves of both plants through microscopical investigation of the prepared entire, transverse sections and powdered forms of different organs of both plants under study. Furthermore, the DNA of both plants was extracted from leaf samples and Random Amplified polymorphic DNA (RAPD) analysis using ten primers of arbitrary sequences.Results: Comparative botanical characters of different organs were identified. On the other hand a total 101 fragments were generated in S. macrocarpon while 105 fragments were generated in S. seaforthianum. Where the highest degree of similarities (70%) was recorded using primer B16 therefore could be used as an indicator for obtaining genetic markers, followed by 65.38% for Z13 and the lowest degree of similarity (38.1%) was recorded using primer O14 which could be used to discriminate between the two Solanum species depending on their low values of similarity coefficients and high level of polymorphism.Conclusion: For the present study, macro and micro-morphological characters, as well as, DNA fingerprinting can be considered as the identifying parameters to authenticate and differentiate between the two plants under study.Â

A comprehensive review on the techniques for extraction of bioactive compounds from medicinal cannabis

Cannabis is well-known for its numerous therapeutic activities, as demonstrated in pre-clinical and clinical studies primarily due to its bioactive compounds. The Cannabis industry is rapidly growing; therefore, product development and extraction methods have become crucial aspects of Cannabis research. The evaluation of the current extraction methods implemented in the Cannabis industry and scientific literature to produce consistent, reliable, and potent medicinal Cannabis extracts is prudent. Furthermore, these processes must be subjected to higher levels of scientific stringency, as Cannabis has been increasingly used for various ailments, and the Cannabis industry is receiving acceptance in different countries. We comprehensively analysed the current literature and drew a critical summary of the extraction methods implemented thus far to recover bioactive compounds from medicinal Cannabis. Moreover, this review outlines the major bioactive compounds in Cannabis, discusses critical factors affecting extraction yields, and proposes future considerations for the effective extraction of bioactive compounds from Cannabis. Overall, research on medicinal marijuana is limited, with most reports on the industrial hemp variety of Cannabis or pure isolates. We also propose the development of sustainable Cannabis extraction methods through the implementation of mathematical prediction models in future studies

Gastroprotective effects and metabolomic profiling of Chasteberry fruits against indomethacin-induced gastric injury in rats

Vitex agnus castus L. extract (VACE) was investigated for its gastroprotective properties and possible molecular mechanisms in rats. VACE (60 or 120 mg/kg) or Esomeprazole (20 mg/kg) were orally administered for 3 weeks before the induction of gastropathy using indomethacin (30 mg/kg, single oral dose). VACE ameliorated the indomethacin-induced gastric juice acidity and pathological changes. VACE significantly preserved GSH, SOD, NO and PGE2 contents, while decreased lipid-peroxide, TNF-α and MPO contents. Moreover, VACE downregulated NF-κB1, COX-2, Caspase-3 and upregulated Bcl-2 and HSP-70 expression. Ultra-high-performance liquid chromatography (UPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (qTOF-MS) enabled the tentative identification of 87 compounds allocated in seven main classes including flavonoids, glycosylated iridoid and labdane diterpenes. Notably, different agnuside derivatives and diterpenoids were reported in VACE for the first time. In conclusion, VACE contains an arsenal of bioactive metabolites which may exhibit gastroprotection by inhibiting inflammation, oxidative stress, and apoptosis

Synergistic interactions of cannabidiol with chemotherapeutic drugs in MCF7 cells : mode of interaction and proteomics analysis of mechanisms

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN−38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN−38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II β and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN−38 (CSN−38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN−38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of the combination of CBD and CSN−38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer

Mechanistic insights into the anti-proliferative action of gut microbial metabolites against breast adenocarcinoma cells

The gut microbiota undergoes metabolic processes to produce by-products (gut metabolites), which play a vital role in the overall maintenance of health and prevention of disease within the body. However, the use of gut metabolites as anticancer agents and their molecular mechanisms of action are largely unknown. Therefore, this study evaluated the anti-proliferative effects of three key gut microbial metabolites—sodium butyrate, inosine, and nisin, against MCF7 and MDA-MB-231 breast adenocarcinoma cell lines. To determine the potential mechanistic action of these gut metabolites, flow cytometric assessments of apoptotic potential, reactive oxygen species (ROS) production measurements and proteomics analyses were performed. Sodium butyrate exhibited promising cytotoxicity, with IC50 values of 5.23 mM and 5.06 mM against MCF7 and MDA-MB-231 cells, respectively. All three metabolites were found to induce apoptotic cell death and inhibit the production of ROS in both cell lines. Nisin and inosine indicated a potential activation of cell cycle processes. Sodium butyrate indicated the possible initiation of signal transduction processes and cellular responses to stimuli. Further investigations are necessary to ascertain the effective therapeutic dose of these metabolites, and future research on patient-derived tumour spheroids will provide insights into the potential use of these gut metabolites in cancer therapy

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model : promising activity without the risk of hepatic adverse effect

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk

Adventures in natural products drug discovery : metabolomic, proteomic, synergy and deep learning studies

In the present project, integrated untargeted metabolomic profiling and antiproliferative assays were implemented for smart identification of the antiproliferative metabolites of Australian propolis against MCF7 breast cancer cells. The synergistic chemotherapeutic combinations of the Australian propolis or cannabinoids such as cannabidiol were investigated and validated against different synergy quantitation models and designs. Moreover, label-free quantification proteomics studies were employed to elucidate the potential mechanism of action and biological targets of the mono treatment or the synergistic chemotherapeutic combinations. The holistic metabolomic profiling was performed for black cohosh roots and rhizomes, purslane seeds, and chasteberry fruits with the exploration of its potential effects and molecular targets in vivo for polycystic ovarian syndrome (PCOS), acrylamide-induced neurotoxicity and indomethacin-Induced gastric injury, respectively. Synpredict, a deep machine learning model, was developed to outperform the current state-of-the-art deep learning predictive model of the pairwise anticancer synergistic combinations. Intermediate and early fusion architectures were explored by comparing two publicly available anticancer drug interaction data sources over different synergy metrics. Several natural products were reviewed for their potential pharmacological effects and possible interactions, including ginger, cannabis, and avocado. Firstly, the potential ameliorative and protective effects of ginger and its metabolites were recapitulated against natural, chemical, and radiation-induced toxicities. Secondly, the potential interactions of medicinal cannabis were reviewed together with the recent advances in the mass spectrophotometric-based quantitation of phytocannabinoids in different biological matrices. Finally, the synergistic effects of Chinese herbal medicine (CHM) and biological networks were summarised to highlight the quantitative system pharmacology methods either at molecular or network levels and their applications in CHM. The interdisciplinary approaches and advanced technologies implemented in the current project will help to develop the evidence base for Traditional and Complementary Medicines and their integration with the conventional healthcare systems

Medicinal Cannabis—Potential Drug Interactions

The endocannabinoids system (ECS) has garnered considerable interest as a potential therapeutic target in various carcinomas and cancer-related conditions alongside neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy-induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed light on the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug–drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (Glycoprotein p, breast cancer resistance proteins, and multidrug resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP-glucuronosyltransferases). Caution should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions

Medicinal cannabis : potential drug interactions

The endocannabinoids system (ECS) has garnered considerable interest as a potential therapeutic target in various carcinomas and cancer-related conditions alongside neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy-induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed light on the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug–drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (Glycoprotein p, breast cancer resistance proteins, and multidrug resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP-glucuronosyltransferases). Caution should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions

Zn2SnO4 ternary metal oxide for ultraviolet radiation filter application: a comparative study with TiO2 and ZnO

Ultraviolet (UV) radiation causes serious health risks. Inorganic metal oxides, such as titanium dioxide (TiO2) and zinc oxide (ZnO), have long been recognized for their effectiveness as UV radiation filters/blockers in sunscreen formulations. TiO2 and ZnO as UV-blocking materials have some limitations and issues such as producing harmful radicals and toxicity, respectively. As a result, there is a growing need to develop efficient and safe UV-blocking materials to overcome these limitations associated with the conventional TiO2 and ZnO materials. Zinc stannate (Zn2SnO4), as a ternary metal oxide, is expected to be a promising candidate due to its optical properties and potential for UV-blocking capability. This study presents a comprehensive investigation into the development and characterization of Zn2SnO4 as a potential alternative UV filter to TiO2 and ZnO. The fundamental characteristics, including structural, optical, and photocatalytic characteristics, as well as cell viability, were investigated for two Zn2SnO4 morphologies: cubic aggregate Zn2SnO4 nanoparticles (ZTO CANP) and Zn2SnO4 nanoparticles (ZTO NP), which were compared with the performance of TiO2 nanoparticles (TiO2 NP) and ZnO nanoparticles (ZnO NP). Interestingly, in addition to their promising UVB and partial UVA blocking properties, ZTO CANP and ZTO NP were found to be relativity photocatalytically inactive materials, which means they produce less free radical species as in the case of TiO2 NP, and they cannot be considered as toxic materials as in the case of ZnO NP. To the best of our knowledge, this is the first direct comparison study examining the performance of Zn2SnO4 ternary metal oxide for its potential use as a UV filter. Further research and optimization need to be conducted on these materials, particularly on ZTO CANP as a promising alternative UV filter