Current Pharmaceutical Biotechnology - Volume 25, Issue 5, 2024

Japanese encephalitis (JE) is a mosquito-borne disease that causes neuronal damage and inflammation of microglia, and in severe cases, it can be fatal. JE infection can resist cellular immune responses and survive in host cells. Japanese encephalitis virus (JEV) infects macrophages and peripheral blood lymphocytes. In addition to regulating biological signaling pathways, microRNAs in cells also influence virus-host interactions. Under certain circumstances, viruses can change microRNA production. These changes affect the replication and spread of the virus. Host miRNAs can contain viral pathogenicity by downregulating the antiviral immune response pathways. Simultaneous profiling of miRNA and messenger RNA (mRNA) could help us detect pathogenic factors, and dual RNA detection is possible. This work highlights important miRNAs involved in human JE infection. In this study, we have shown the important miRNAs that play significant roles in JEV infection. We found that during JEV infection, miRNA-155, miRNA-29b, miRNA-15b, miRNA-146a, miRNA-125b-5p, miRNA-30la, miRNA-19b-3p, and miRNA-124, cause upregulation of human genes whereas miRNA-432, miRNA-370, miRNA- 33a-5p, and miRNA-466d-3p are responsible for downregulation of human genes respectively. Further, these miRNAs are also responsible for the inflammatory effects. Although several other miRNAs critical to the JEV life cycle are yet unknown, there is currently no evidence for the role of miRNAs in persistence.

Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain.

Background: Wikstroemia (the family Thymelaeaceae) consists of medicinal plants which established great value in traditional medicines for many years. For instance, W. indica is always recommended for treatments of syphilis, arthritis, whooping cough, and cancer. No systematic review of bioactive compounds from this genus has been recorded to date. Objectives: The objective of the current study is to review phytochemical investigations and pharmacological effects of Wikstroemia plant extracts and isolates. Methods: By searching on the internet, the relevant data about Wikstroemia medicinal plants were retrieved from internationally renowned scientific databases, such as Web of Science, Google Scholar, Sci-Finder, Pubmed, and so on. Results: More than 290 structurally diverse metabolites were separated and identified from this genus. They include terpenoids, lignans, flavonoids, coumarins, mono-phenols, diarylpentanoids, fatty acids, phytosterols, anthraquinones, and others. Pharmacological records indicated that Wikstroemia plant crude extracts and their isolated compounds bring out various beneficial effects, such as anticancer, antiinflammatory, anti-aging, anti-viral, antimicrobacterial, antimalarial, neuroprotective, and hepatoprotective activities. Conclusion: Wikstroemia has been regarded as a worthy genus with numerous phytochemicals and various pharmacological potentials. Modern pharmacological studies have successfully provided evidence for traditional uses. Nonetheless, their action mechanisms need to be further investigated. Although various secondary metabolites were identified from Wikstroemia plants, the current pharmacological research mainly concentrated on terpenoids, lignans, flavonoids, and coumarins.

Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However, their therapeutic uses are limited due to drawbacks, such as gastric perforation, diarrhea, intestinal bleeding, abdominal cramps, hair loss, nausea, vomiting, weight loss, and adverse reactions. Hence, there is a continuous quest for safe and effective medicines to manage human health problems, like CRC. In this context, herbal medicines are considered an alternative disease control system. It has become popular in countries, like American, European, and Asian, due to its safety and effectiveness, which has been practiced for 1000 years. During the last few decades, herbal medicines have been widely explored through multidisciplinary fields for getting active compounds against human diseases. Several herbal bioactives, like curcumin, glycyrrhizin, paclitaxel, chlorogenic acid, gallic acid, catechin, berberine, ursolic acid, betulinic acid, chrysin, resveratrol, quercetin, etc., have been found to be effective against CRC. However, their pharmacological applications are limited due to low bioavailability and therapeutic efficacy apart from their several health benefits. An effective delivery system is required to increase their bioavailability and efficacy. Therefore, targeted novel drug delivery approaches are promising for improving these substances’ solubility, bioavailability, and therapeutic effects. Novel carrier systems, such as liposomes, nanoparticles, micelles, microspheres, dendrimers, microbeads, and hydrogels, are promising for delivering poorly soluble drugs to the target site, i.e., the colon. Thus, the present review is focused on the pathophysiology, molecular pathways, and diagnostic and treatment approaches for CRC. Moreover, an emphasis has been laid especially on herbal bioactive-based novel delivery systems and their clinical updates.

Objectives: Obesity is regarded as the main cause of metabolic diseases and a core factor for all-cause mortality in the general population, notably from cardiovascular disease. The majority of people with type 2 diabetes have obesity and insulin resistance. Some evidence indicates that an individual with obesity is approximately 10 times more likely to develop type 2 diabetes than someone with moderate body weight. One of the most significant therapeutic herbs, Salvia officinalis (Lamiaceae) (SAGE), possesses potent medicinal importance. The aim of this article was to evaluate the anti-diabetic and antiobesity activity of SAGEAE against HFD-induced obesity in rats. Methods: Thirty adult albino rats were randomly divided into five equal groups: control, High-fat Diet (HFD) administrated rats, HFD +Salvia officinalis Aqueous Extract (SAGEAE) (150 mg/kg.bw.), HFD + SAGEAE (300 mg/kg.bw.) and HFD + metformin (500 mg/kg.bw.). Body weight, plasma biochemical parameters, oxidative stress, inflammatory indicators, hepatic Phosphoenolpyruvate Carboxykinase 1 (PCK1), Glucokinase (GK), brain Leptin Receptor (LepRb), Glucose Transporter-4 (GLUT4), Sirtuin 1 (SIRT1) and mRNA33-5P gene signalling mRNA levels were all assessed after 8 weeks. A histological examination of the liver was also performed to check for lipid accumulation. Results: The administration of HFD resulted in increased body weight, glucose, insulin, leptin, Total Cholesterol (TC), Triglycerides (TG), Thiobarbaturic Acid Reactive Substances (TBARS), Monocyte Chemoattractant Protein-1 (MCP1), Interleukine-6 (IL-6) and tumor necrosis factor-α (TNF- α) as well as hepatic PCK1, brain LepRb and adipose tissue mRNA33-5P gene expression. However, our findings revealed a significant reduction in adiponectin, High-density Lipoproteincholesterol (HDL-C), reduced glutathione (GSH) and Superoxide Dismutase (SOD) levels as well as the expression of hepatic GK and adipose tissue SIRT1 and GLUT4 genes. Also, administration of SAGEAE significantly normalized body weight, glucose, insulin, leptin, adiponectin, TC, TG, HDL-C, TBARs, SOD, IL-6, MCP-1 and TNF-α in plasma and liver tissue of HFD-treated rats. On the other hand, PCK1, GK, LepRb, SIRT1, GLUT4 and mRNA33-5P gene expression was enhanced in obese rats when administrated with SAGEAE. Histological and US studies support the biochemical, PCR and electrophoretic results. Conclusion: The findings imply that SAGEAE could be used as a new pharmaceutical formula in the treatment of obesity.

Background: Plants that have therapeutic features for humans or animals are commonly referred to as "medicinal plants". They produce secondary metabolites with antioxidant, antimicrobial and/or anti-cancer effects. Lithospermum officinale, known as European stone seed, is a famous medicinal herb. However, due to the pyrrolizidine alkaloids (PzAl) in the root extract of L.officinal, there are therapeutic limitations to this herb. Objective: This research was devoted to the evaluation of the anti-inflammatory capacity of methanolic extracts of L. officinale callus (LoE) (fresh cells) on rat microglial cells, the immune cells of the Central Nervous System, which play an essential role in the responses to neuroinflammation. Methods: Primary microglia were obtained from neonatal Wistar rats (1 to 3-days old), and then treated with various concentration of CfA and methanolic extracts of 17 and 31-day-old L. officinale callus before LPS-stimulation. In addition to HPLC analysis of the extracts, viability, nitric oxide production, and evaluation of pro-inflammatory genes and cytokines in the inflamed microglia were investigated by MTT, Griess methos, qrt-PCR, and ELISA. Results: Methanolic extract of the 17-day-old callus of L. officinale exhibited anti-inflammatory effects on LPS-stimulated microglial cells much higher than observed for CfA. The data were further supported by the decreased expression of Nos2, Tnf-α, and Cox-2 mRNA and the suppression of TNF-α and IL-1β release in the activated microglial cells pretreated with the effective dose of LoE (0.8 mg mL-1). Conclusion: It was assumed that the better anti-neuroinflammatory performance of LoE than CfA in LPS-activated primary microglia could be a result of the synergism of the components of the extract and the lipophilic nature of RsA as the main phenolic acid of LoE. Considering that LoE shows a high antioxidant capacity and lacks PzAl, it is anticipated that LoE extract might be considered a reliable substitute to play a key role in the preparation of neuroprotective pharmaceutical formulas, which require in vivo research and further experiments.

Background: Pro-inflammatory cytokines secreted from activated macrophages and astrocytes are crucial mediators of inflammation for host defense. Among them, the secretion of IL-1β, a major pro-inflammatory cytokine, is especially mediated by the activation of NLRP3 inflammasome. Pro-IL-1β, which is produced in response to the invaded pathogens, such as LPS, is cleaved and matured in the NLRP3 inflammasome by the recognition of ATP. Excessively activated IL-1β induces other immune cells, resulting in the up-regulation of inflammation. Therefore, regulation of NLRP3 inflammasome can be a good strategy for alleviating inflammation. Objective: Our study aimed to examine whether 5-methylthiopentyl isothiocyanate, a sulforaphane analogue (berteroin), has an anti-inflammatory effect on the NLRP3 inflammasome activation induced by LPS and ATP. Methods: Primary bone marrow-derived macrophages (BMDMs) and astrocytes were stimulated by LPS and ATP with the treatment of 5-methylthiopentyl isothiocyanate, a sulforaphane analogue. The secretion of pro-inflammatory cytokines was measured by ELISA, and the expression level of NLRP3 inflammasome-associated proteins was detected by western blot. The association of NLRP3 inflammasome was assessed by co-immunoprecipitation, and the formation of ASC specks was evaluated by fluorescent microscope. Results: 5-methylthiopentyl isothiocyanate, a sulforaphane analogue (berteroin), decreased the release of pro-inflammatory cytokines, IL-1β, and IL-6 in the BMDMs. Berteroin notably prevented the formation of both NLRP3 inflammasome and ASC specks, which reduced the secretion of IL-1β. Additionally, berteroin reduced the IL-1β secretion and cleaved IL-1β expression in the primary astrocytes. Discussion and Conclusion: These results indicated the anti-inflammatory effects of 5- methylthiopentyl isothiocyanate (berteroin) by regulating NLRP3 inflammasome activation, suggesting that berteroin could be the potential natural drug candidate for the regulation of inflammation.