Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.
Saussurea costus (Falc.) Lipsch., commonly known as costus, is a perennial herb that has been traditionally used in various indigenous medicinal systems across Asia. Its historical prominence in traditional remedies underscores the need to explore its phytochemical composition, pharmacological properties, and potential therapeutic benefits. This review aims to provide a comprehensive overview of the available literature on the pharmacological properties, phytochemical constituents, ethnobotanical uses, and therapeutic potential of S. costus. An exhaustive search was performed across multiple electronic databases, including PubMed/MedLine, Google Scholar, Web of Science, Scopus, TRIP database, and Science Direct. Both experimental and clinical studies, as well as traditional ethnobotanical records, were considered for inclusion. The phytochemical analysis revealed that S. costus contains a plethora of bioactive compounds, including sesquiterpenes, flavonoids, and essential oils, which are responsible for its myriad of medicinal properties. The pharmacological studies have demonstrated its anti-inflammatory, anti-oxidant, anti-cancer, hepatoprotective, and immunomodulatory effects, among others. Ethnobotanical data showcased its extensive use in treating ailments like asthma, digestive disorders, and skin conditions. Some clinical trials also underscore its efficacy in certain health conditions, corroborating its traditional uses. S. costus possesses significant therapeutic potential, largely attributable to its rich phytochemical composition; the convergence of its traditional uses and modern pharmacological findings suggests promising avenues for future research, especially in drug development and understanding its mechanism of action in various ailments.
SRS27, an andrographolide analogue, had been proven to have therapeutic properties at a dose of 3 mg/kg in both in vitro and in vivo asthma models of our previous study. The present study focuses on the pharmacokinetic and toxicity profile of this compound to provide further evidence for the development of this compound as an anti-asthma agent. A simple pharmacokinetic study was performed in female BALB/c mice to measure blood plasma concentration of the compound at therapeutic dose. At a single dose of 3 mg/kg, SRS27 had a relatively short half-life but was able to achieve a concentration range of 13-19 μM that is related to its in vitro bioactivities. With regard to toxicity profile, SRS27 appears to be safe, as no histopathological changes were observed in the liver, kidneys and ovaries of SRS27-treated female BALB/c mice. In addition, there was no significant change in the mean body weight and organ weight of the animals in the SRS27-treated groups compared with the vehicle-treated control group at the end of the treatment. This fully supports the absence of any significant changes in peripheral blood leukocyte counts of SRS27-treated mice. Rewardingly, this acute toxicity study also revealed that SRS27 has a wide therapeutic window as no toxicity symptoms were detected with a dose up to 60 mg/kg daily when tested for 14 days. These results provide strong justification for further investigation of SRS27 as a potential new anti-asthma agent.
Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.
The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.
The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
Cancer is a complex disease characterized by dysregulated cell growth and division, posing significant challenges for effective treatment. Hispidulin, a flavonoid compound, has shown promising biological effects, particularly in the field of anticancer research. The main objective of this study is to investigate the anticancer properties of hispidulin and gain insight into its mechanistic targets in cancer cells. A comprehensive literature review was conducted to collect data on the anticancer effects of hispidulin. In vitro and in vivo studies were analyzed to identify the molecular targets and underlying mechanisms through which hispidulin exerts its anticancer activities. Hispidulin has shown significant effects on various aspects of cancer, including cell growth, proliferation, cell cycle regulation, angiogenesis, metastasis, and apoptosis. It has been observed to target both extrinsic and intrinsic apoptotic pathways, regulate cell cycle arrest, and modulate cancer progression pathways. The existing literature highlights the potential of hispidulin as a potent anticancer agent. Hispidulin exhibits promising potential as a therapeutic agent for cancer treatment. Its ability to induce apoptosis and modulate key molecular targets involved in cancer progression makes it a valuable candidate for further investigation. Additional pharmacological studies are needed to fully understand the specific targets and signaling pathways influenced by hispidulin in different types of cancer. Further research will contribute to the successful translation of hispidulin into clinical settings, allowing its utilization in conventional and advanced cancer therapies with improved therapeutic outcomes and reduced side effects.
Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).