Natural compounds against nonalcoholic fatty liver disease: A review on the involvement of the LKB1/AMPK signaling pathway.

Although various therapeutic approaches are used to manage nonalcoholic fatty liver disease (NAFLD), the best approach to NAFLD management is unclear. NAFLD is a liver disorder associated with obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to cirrhosis and end-stage liver disease. Hepatic kinase B1 (LKB1) is an upstream kinase of 5'-adenosine monophosphate-activated protein kinase (AMPK), a crucial regulator in hepatic lipid metabolism. Activation of LKB1/AMPK inhibits fatty acid synthesis, increases mitochondrial ß-oxidation, decreases the expression of genes encoding lipogenic enzymes, improves nonalcoholic steatohepatitis, and suppresses NAFLD progression. One potential opening for new and safe chemicals that can tackle the NAFLD pathogenesis through the LKB1-AMPK pathway includes natural bioactive compounds. Accordingly, we summarized in vitro and in vivo studies regarding the effect of natural bioactive compounds such as a few members of the polyphenols, terpenoids, alkaloids, and some natural extracts on NAFLD through the LKB1/AMPK signaling pathway. This manuscript may shed light on the way to finding a new therapeutic agent for NAFLD management.

Efficacy and Safety of Valproic Acid in Myelodysplastic Syndrome and Acute Myeloid Leukemia; a Narrative Review.

Loads of new therapeutic regimes have been turned up to manage Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly in elderly patients who are unfit for intensive chemotherapy. Despite accumulating research, the best MDS and AML management approach is indeterminate. Myelodysplastic syndrome implies a group of various hematopoietic stem cell disorders that may progress to acute myeloid leukemia. These disorders are more frequent in older adults. To the high rate of morbidity and abundant toxicities related to the therapeutic approaches, also, the treatment would be challenging. The clinical effectiveness of valproic acid, a histone deacetylase inhibitor, in MDS and AML patients is unknown, even though it has demonstrated positive activities to promote differentiation and apoptosis in cancer cells. We investigated the clinical research on the effects of valproic acid in conjunction with various drugs, including low-dose cytarabine, all-trans retinoic acid, DNA-hypomethylating agents, hydrazine, and theophylline. We conclude that VPA is a safe and effective treatment option for MDS and AML patients, particularly when used in conjunction with all-trans retinoic acid, DNA-hypomethylating drugs, and hydralazine. However, more randomized clinical studies are required to identify an ideal regimen.

Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disorder and is usually accompanied by obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to impaired functions of hepatocytes such as alternations in expression and function of hepatic transporters. The present study aimed to summarize and discuss the results of clinical and preclinical human studies that investigate the effect of NAFLD on hepatic transporters. METHODS: The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to 1 March 2022. The risk of bias was assessed for cross-sectional studies through the Newcastle-Ottawa Scale score. RESULTS: Our review included ten cross-sectional studies consisting of 485 participants. Substantial alternations in hepatic transporters were seen during NAFLD progression to non-alcoholic steatohepatitis (NASH) in comparison with control groups. A significant reduction in expression and function of several hepatic uptake transporters, upregulation of many efflux transporters, downregulation of cholesterol efflux transporters, and mislocalization of canalicular transporter ABCC2 are associated with NAFLD progression. CONCLUSION: Since extensive changes in hepatic transporters could alter the pharmacokinetics of the drugs and potentially affect the safety and efficacy of drugs, close monitoring of drug administration is highly suggested in patients with NASH.

Induction of JAK2/STAT3 pathway contributes to protective effects of different therapeutics against myocardial ischemia/reperfusion.

Insufficiency in coronary blood supply results in myocardial ischemia and consequently, various clinical syndromes and irreversible injuries. Myocardial damage occurs as a result of two processes during acute myocardial infarction (MI): ischemia and subsequent reperfusion. According to the available evidence, oxidative stress, excessive inflammation reaction, reactive oxygen species (ROS) generation, and apoptosis are crucial players in the pathogenesis of myocardial ischemia/reperfusion (IR) injury. There is emerging evidence that Janus tyrosine kinase 2 (JAK2) signal transducer and activator of the transcription 3 (STAT3) pathway offers cardioprotection against myocardial IR injury. This article reviews therapeutics that exert cardioprotective effects against myocardial IR injury through induction of JAK2/STAT3 pathway.

Protective effect of luteolin against chemical and natural toxicants by targeting NF-κB pathway.

Humans are continuously exposed to environmental, occupational, consumer and household products, food, and pharmaceutical substances. Luteolin, a flavone from the flavonoids family of compounds, is found in different fruits and vegetables. LUT is a strong anti-inflammatory (via inhibition of NF-κB, ERK1/2, MAPK, JNK, IL-6, IL-8, and TNF-α) and antioxidant agent (reducing ROS and enhancement of endogenous antioxidants). LUT can chelate transition metal ions responsible for ROS generation and consequently repress lipoxygenase. It has been proven that NF-κB, as a commom cellular pathway plays a considerable role in the progression of inflammatory process and stimulates the expression of genes encoding inducible pro-inflammatory enzymes (iNOS and COX-2) and cytokines including IL-1ß, IL-6, and TNF-α. This review summarizes the available literature discussing LUT and its potential protective role against pharmaceuticals-, metals-, and environmental compounds-induced toxicities. Furthermore, the review explains the involved protective mechanisms, especially inhibition of the NF-κB pathway.

Recent advances in neurogenic and neuroprotective effects of curcumin through the induction of neural stem cells.

Curcumin is extensively used in the prevention and treatment of various diseases. Recently, growing attention has been paid to the use of curcumin as a neurogenic and neuroprotective agent. This review study is aimed to collect and categorize the recent findings regarding the effects of curcumin on various neurological diseases through the induction of neural stem cell proliferation and differentiation. In addition, we have discussed the molecular mechanisms modulated by curcumin that contribute to this efficacy and have summarized the recent advancements in the novel delivery strategies used to improve the induction of neural stem cells by curcumin.