Next-generation probiotics (NGPs) represent an innovative group of beneficial bacteria that are currently undergoing research and development. NGPs are designed not only for conventional use as foods or dietary supplements but are also tailored for pharmaceutical applications. Research indicates that NGPs show therapeutic promise in addressing various chronic ailments. Offering multiple advantages over conventional probiotics, NGPs present opportunities for personalized probiotic therapies, involvement in synthetic biology and gene editing, participation in combination therapies, targeted delivery methods, and application in therapeutic settings. Our review discusses the potential therapeutic effect of the NGPs, covering diverse research trajectories for NGPs, including their identification, characterization, and targeted delivery. Furthermore, this review elucidates the influence of NGPs on critical aspects of human health, specifically, gut health, immune function, and broader health outcomes. Mechanistic insights encompass the production of bioactive compounds, competitive interactions with pathogenic bacteria, the modulation of immune cell activity, and the reinforcement of the gut barrier. What is noteworthy is that the current review points out the prevalent NGP strains and their diverse sources, providing a highlight for the comprehensive framework for understanding their potential applications and their future benefits in the domain of advanced therapeutics.

Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring polyphenolic stilbene compound produced by certain plant species in response to biotic and abiotic factors. Resveratrol has sparked a lot of interest due to its unique structure and approved therapeutic properties for the prevention and treatment of many diseases such as neurological disease, cardiovascular disease, diabetes, inflammation, cancer, and Alzheimer’s disease. Over the last few decades, many studies have focused on the production of resveratrol from various natural sources and the optimization of large-scale production. Endophytic fungi isolated from various types of grapevines and Polygonum cuspidatum, the primary plant sources of resveratrol, demonstrated intriguing resveratrol-producing ability. Due to the increasing demand for resveratrol, one active area of research is the use of endophytic fungi and metabolic engineering techniques for resveratrol’s large-scale production. The current review addresses an overview of endophytic fungi as a source for production, as well as biosynthesis pathways and relevant genes incorporated in resveratrol biosynthesis. Various approaches for optimizing resveratrol production from endophytic fungi, as well as their bio-transformation and bio-degradation, are explained in detail.

The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds.

Oxidative stress is involved in the pathophysiology of multiple health complications, and it has become a major focus in targeted research fields. As known, black seeds are rich sources of bio-active compounds and widely used to promote human health due to their excellent medicinal and pharmaceutical properties. The present study investigated the antioxidant potency of various black seeds from plants and their derived mycoendophytes, and determined the total phenolic and flavonoid contents in different extracts, followed by characterization of major constituents by HPLC analysis. Finally, in silico docking determined their binding affinities to target myeloperoxidase enzymes. Ten dominant mycoendophytes were isolated from different black seed plants. Three isolates were then selected based on high antiradical potency and further identified by ITS ribosomal gene sequencing. Those isolated were Aspergillus niger TU 62, Chaetomium madrasense AUMC14830, and Rhizopus oryzae AUMC14823. Nigella sativa seeds and their corresponding endophyte A. niger had the highest content of phenolics in their n-butanol extracts (28.50 and 24.43 mg/g), flavonoids (15.02 and 11.45 mg/g), and antioxidant activities (90.48 and 81.48%), respectively, followed by Dodonaea viscosa and Portulaca oleracea along with their mycoendophytic R. oryzae and C. madrasense. Significant positive correlations were found between total phenolics, flavonoids, and the antioxidant activities of different tested extracts. The n-butanol extracts of both black seeds and their derived mycoendophytes showed reasonable IC₅₀ values (0.81–1.44 mg/ml) compared to the control with significant correlations among their phytochemical contents. Overall, seventeen standard phenolics and flavonoids were used, and the compounds were detected in different degrees of existence and concentration in the examined extracts through HPLC analysis. Moreover, the investigation of the molecular simulation results of detected compounds against the myeloperoxidase enzyme revealed that, as a targeted antioxidant, rutin possessed a high affinity (−15.3184 kcal/mol) as an inhibitor. Taken together, the black seeds and their derived mycoendophytes are promising bio-prospects for the broad industrial sector of antioxidants with several valuable potential pharmaceutical and nutritional applications.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.

Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects. Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, C. pentandra ethyl acetate extract showed powerful in vitro radical-scavenging potential (IC50 = 0.0716) comparable to those of the standard natural (ascorbic acid, IC50 = 0.045) and synthetic (BHA, IC50 = 0.056) antioxidants. The effect of C. pentandra ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.). C. pentandra showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. C. pentandra also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, C. pentandra inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture. Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (1), cinchonains 1a (2) and 1b (3), cis-clovamide (4), trans-clovamide (5), and glochidioboside (6); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that C. pentandra exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms. Functional Disorder, Traditional Medicine, Herbal Medicine.