The present study focuses on the development and evaluation of the resveratrol (RV)loaded cationic solid lipid nanoparticles (RV-c-SLNs) for the management of hepatocellular carcinoma (HCC). Materials and Methods: Optimization of formulation was performed using factorial design, and further in vitro drug release, cytotoxicity, biodistribution, in vivo preclinical, and biochemical evaluation were carried out. Results: The optimized formulation exhibited uniform size, homogeneous disparity, positive zeta potential, and stability over 12-week storage at 25°C/60% RH. The in vitro drug release and cytotoxicity study showed 60% drug release within the first 6 hours and comparatively higher cytotoxicity on HepG2 cell line by resveratrol-solid lipid nanoparticle (RV-SLN) as compared to the RV solution. In addition, an anticancer action and biodistribution study on a rat model of HCC showed significant reduction of tumor volume and higher accumulation in the tumor tissue from RV-c-SLN (P<0.01) over RV solution and RV-SLN. Furthermore, RV-c-SLN showed significant downregulation in the levels of pro-inflammatory cytokines and balancing of antioxidant enzymes. Histopathological investigation showed reduced occurrence of hepatic nodules, necrosis formation, infiltration of inflammatory cells, blood vessels inflammation, and cell swelling. Conclusion: Overall, the obtained results construed that RV-c-SLN with improved antitumor activity as clearly evident from in vitro, in vivo, and biochemical investigations.

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The current study focuses on the development and evaluation of nano lipidic carriers (NLCs) for codelivery of sorafenib (SRF) and ganoderic acid (GA) therapy in order to treat hepatocellular carcinoma (HCC). The dual drug-loaded NLCs were prepared by hot microemulsion technique, where SRF and GA as the drugs, Precirol ATO5, Capmul PG8 as the lipids, while Solutol HS15 and ethanol was used as surfactant and cosolvents. The optimized drug-loaded NLCs were extensively characterized through in vitro and in vivo studies. The optimized formulation had particle size 29.28 nm, entrapment efficiency 93.1%, and loading capacity 14.21%. In vitro drug release studies revealed>64% of the drug was released in the first 6 h. The enzymatic stability analysis revealed stable nature of NLCs in various gastric pH, while accelerated stability analysis at 25 ◦ C/60% RH indicated the insignificant effect of studied condition on particle size, entrapment efficiency, and loading capacity of NLCs. The cytotoxicity performed on HepG2 cells indicated higher cytotoxicity of SRF and GA-loaded NLCs as compared to the free drugs (p < 0.05). Furthermore, the optimized formulation suppressed the development of hepatic nodules in the Wistar rats and significantly reduced the levels of hepatic enzymes and nonhepatic elements against DEN intoxication. The SRF and GA-loaded NLCs also showed a significant effect in suppressing the tumor growth and inflammatory cytokines in the experimental study. Further, histopathology study of rats treated SRF and GA-loaded NLCs and DEN showed absence of necrosis, apoptosis, and disorganized hepatic parenchyma, etc. over other treated groups of rats. Overall, the dual drug-loaded NLCs outperformed over the plain drugs in terms of chemoprotection, implying superior therapeutic action and most significantly eliminating the hepatic toxicity induced by DEN in Wistar rat model.

Even with substantial advances in cardiovascular therapy, the morbidity and mortality rates of diabetic cardiomyopathy (DCM) continually increase. Hence, a feasible therapeutic approach is urgently needed. Objectives. This work is aimed at systemically reviewing literature and addressing cell targets in DCM through the possible cardioprotection of G. lucidum through its antioxidant effects by using the Open Targets Platform (OTP) website. Methods. The OTP website version of 19.11 was accessed in December 2019 to identify the studies in DCM involving G. lucidum. Results. Among the 157 cell targets associated with DCM, the mammalian target of rapamycin (mTOR) was shared by all evidence, drug, and text mining data with 0.08 score association. mTOR also had the highest score association 0.1 with autophagy in DCM. Among the 1731 studies of indexed PubMed articles on G. lucidum published between 1985 and 2019, 33 addressed the antioxidant effects of G. lucidum and its molecular signal pathways involving oxidative stress and therefore were included in the current work. Conclusion. mTOR is one of the targets by DCM and can be inhibited by the antioxidative properties of G. lucidum directly via scavenging radicals and indirectly via modulating mTOR signal pathways such as Wnt signaling pathway, Erk1/2 signaling, and NF-κB pathways.

Thymoquinone (TQ), an active constituent of Nigella sativa, has been reported to exert a broad spectrum of pharmacological effects, including neuroprotective, anticancer, anti-inflammatory, antidiabetic, antiepileptic, antioxidant, and other modulatory roles in inflammation in experimental studies. The present study aims to evaluate the potential effects of TQ on vincristine-induced neuropathy in mice, as well as the possible role of oxidative stress, and pro- and anti-inflammatory cytokine in neuropathy development. A Swiss strain of male albino mice were randomly divided into seven groups, comprising of five animals each. Vincristine sulfate (0.1 mg/kg, i.p.) was administered for 10 consecutive days for the induction of peripheral neuropathy. The animals received their respective treatment of TQ (2.5, 5, and 10 mg/kg, p.o.) and pregabalin (10 mg/kg, p.o.) concurrently with vincristine for 10 days followed by 4 days post treatment. The animals were assessed for pain and related behavior on day 7 and 14 using hot and cold plates, and a rotarod test. TQ preventive treatment attenuated vincristine induced neuropathy in a dose dependent manner evidenced as a significant (p < 0.001) increase in reaction time on the hot plate and the cold plate, and a fall off time on the rotarod test. Further, TQ preventive treatment resulted in a significant (p < 0.001) reduction in the number of flinches and duration of paw elevation in a formalin test. Preventative treatment with TQ abolished the vincristine-induced rise in malondialdehyde and glutathione depletion in sciatic nerve tissue, as well as the blood IL-6 levels. In conclusion, TQ at 2.5, 5, and 10 mg/kg dose produced significant attenuation of neuropathic pain induced by vincristine which may be due to its antinociceptive, antioxidant, and anti-proinflammatory activity.

With an increase in the global burden of cancer-related deaths, the quest for developing new therapeutic solutions has taken momentum. In this regard, the idea of using cancer vaccines came to existence approximately 30 years ago, where gene therapy interventions have shown significant improvement in the therapeutic outcomes against several types of cancers. Cancer vaccines usually encounter a number of challenges with limited targeting ability to the tumors. Nanocarriers have been studied as a technological innovation for tumor targeting of gene therapeutics. This article provides a critical insight into the recent progress made in nanotherapeutic strategies for genetic vaccine delivery for treatment against various types of cancers. Moreover, the article intends to provide a summary of the research work being done on this topic.

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Aim: A monoterpene and bioactive component of the plant Rhodiola rosea (R. rosea), rosiridin has beneficial effects on the human central nervous system and enhances brain function. The goal of this scientific study was to determine if rosiridin might shield rats from neurocognitive problems induced by scopolamine. Methods: To track the potential toxicities in rats, the acute toxicity in rats was clarified. Rosiridin at a dose of 10 mg/kg was tested in rats for 14 days. At the conclusion of the investigation, behavioral parameters that were used to identify the rats’ cognitive and motor abilities were evaluated. Several biochemical parameters were estimated using the prepared homogenate, including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), radical scavengers produced by the body (Catalase-CAT, superoxide dismutase-SOD, and reduced glutathione-GSH), indicators of oxidative and nitrative burnout, pro-inflammatory (Interleukins- IL-1β, IL-6, interferon gamma IFN-ꝩ, and tumor necrosis factor-TNF-α), and cell apoptosis caspases 3 and 9. Results and Conclusion: A significant behavioral parameter restoration was seen in the rosiridin-treated group, including reduction in latency time during acquisition and retention trial in the Morris water maze test, and percentage of spontaneous alterations in the y-maze test, when compared to the disease control group that received scopolamine; rosiridin also altered the oxidative stress and neuroinflammatory markers, as well as restoring Ach and ChAT activities and normalizing GSH, SOD, MDA, TNF-α, nitrate, IL-1β, IL-6, IFN-ꝩ, caspases 3 and 9 levels. The results imply that rosiridin limits the effect of scopolamine on rat cognitive function.