Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

Purpose: Smoking is a global public health concern, with a significant negative impact on human health and healthcare spending. Vaping, or the use of electronic cigarettes (e-cigarettes), has emerged as a popular alternative to traditional nicotine replacement therapies (NRTs) for smoking cessation. While considered less harmful than combustible cigarettes, the long-term health effects of e-cigarettes (vaping) are unknown. Therefore, this study aimed to identify and provide a comprehensive overview of the performance of vaping in clinical trials. Patients and Methods: A search was conducted in the ClinicalTrials.gov database on April 14th, 2023, using the search term “smoking cessation, e-cigarettes, NRTs, and vaping”. Inclusion and exclusion criteria were defined to identify relevant clinical trials. Randomized controlled trials (RCTs) and non-randomized clinical trials that evaluated vaping as a therapeutic approach to smoking cessation were included. Results: A total of 87 clinical trials were identified, of which only seven were related to smoking cessation through vaping as a form of treatment. The primary endpoint was the effect of vaping as smoking cessation, and the secondary endpoints were patients’ abstinence rate, withdrawal symptoms, and adverse events of e-cigarettes. Most of the trials used e-cigarettes as an intervention, with some trials including a combination of e-cigarettes and other NRTs. The trials lasted from 4 weeks to 12 months. The overall results of the trials indicated that vaping was effective in helping smokers to quit. It was also associated with a lower risk of adverse events than combustible cigarettes. Conclusion: Vaping appears to be an effective method for smoking cessation, and it is associated with a lower risk of adverse events than combustible cigarettes.

Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aβ42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3β. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin’s promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties.

Sleep deprivation (SD) has been revealed to provoke anxiety-like behavior. Phytochemicals and nanotechnology-based interventions have emerged as promising alternatives due to their pleiotropic activity and enhanced bioavailability. Here we investigated the effect of sodium selenite, Epigallocatechin-3-gallate (EGCG), and EGCG–Selenium nanoparticles (SeNPs) on SD-provoked cortical impairment and tried to recognize the possible underlying mechanisms in addition to in silico analysis of EGCG. SD was provoked in rats utilizing a modified multiple platform model. We performed an in silico analysis of EGCG docked on Bcl2 and MMP2. Forty animals were divided into five groups of eight animals each: animals were given saline orally for 8 days (control); animals were given saline orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD); animals were given Na₂SeO₃ orally with 0.5 mg/kg/day for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/Na₂SeO₃); animals were given 100 mg/kg/day EGCG orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/EGCG); animals were given SeNPs biosynthesized using EGCG and 0.5 mg/kg/day orally for 8 days, and on day 7 animals were exposed to 24 h of SD (24 h SD/EGCG-SeNPs). Behavioral tests were performed, including the sucrose preference test and the open-field test. Neurotransmitters (norepinephrine, serotonin, and dopamine), monoamine oxidase, ACh, GABA, AChE, neurotropic and glial markers (BDNF and GFAP), as well as neuro-inflammatory, oxidative stress, and apoptotic markers were assessed. Interestingly, sodium selenite, EGCG, and EGCG-SeNP employment mitigated cognitive functions and cortical histopathological alterations in SD-subjected rats. These potential impacts elicited by sodium selenite, EGCG, and EGCG-SeNPs may be related to their impact of elucidating corticosterone increase, cortical neurotransmitter decrease, and neurotropic and glial markers alterations, while also inhibiting the inflammatory and apoptotic axis and upregulating Nrf2 antioxidant cascade. These results prove the neuroprotective potential of sodium selenite, EGCG, and EGCG-SeNPs, especially EGCG-SeNPs in sleep deprivation-subjected rats by ameliorating cortical neuroinflammation, prooxidant alterations, and apoptotic events likely caused by modulating the NOS-2/Nrf2 axis.

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen’s damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.

Renal damage is a devastating adverse effect for cyclosporine; a widely used immunosuppressant drug. The present work examined the potential of camel milk, a natural agent with marked anti-inflammatory/antioxidant properties, to attenuate cyclosporine-induced renal injury. The kidney tissue was examined with the aid of Western blotting, immunohistochemistry, biochemical assays, including colorimetric and ELISA kits. The present findings revealed that camel milk (10 mL/kg/day; for 3 weeks by gavage) significantly lowered serum creatinine, BUN, and KIM-1 renal dysfunction markers. Mechanistically, camel milk inhibited renal inflammation, as seen by significant decrease of the pro-inflammatory cytokines (MCP-1, TNF-α, IL-1β, and IL-18) and extracellular degradation signals (MMP-2 and MMP-9) and enhanced the generation of the anti-inflammatory IL-10. Moreover, it inhibited the upstream pro-inflammatory p38/ERK/JNK MAPK pathway by lowering the phosphorylation of the 3 subfamilies of MAPKs (p38 MAPK, JNK1/2, and ERK1/2). Furthermore, camel milk curbed the NF-κB pathway activation by downregulating the protein expression of activated NF-κBp65, p-NF-κBp65, and p-IκBα proteins. Additionally, camel milk inhibited renal oxidative stress by lowering the MPO activity and augmenting the reduced/oxidized glutathione ratio and total antioxidant capacity. These findings propose that camel milk may be a promising agent that inhibits cyclosporine-triggered renal inflammation via curtailing the p38/ERK/JNK MAPK and NF-κB pathways, matrix metalloproteinases, and pro-inflammatory cytokines.